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Opass Putcharoen

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DOI: 10.1007/s12072-020-10072-8
2020
Cited 217 times
Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)
COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.
DOI: 10.1002/jmv.26005
2020
Cited 74 times
Evaluating the efficiency of specimen pooling for PCR‐based detection of COVID‐19
In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.
DOI: 10.1371/journal.pone.0240502
2020
Cited 69 times
Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019
Background A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. Aim To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. Methods Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. Results A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8–93.6) and 84.8% (95% CI: 76.2–91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). Conclusion The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.
DOI: 10.1186/s40635-020-00362-8
2020
Cited 64 times
Endotoxemia and circulating bacteriome in severe COVID-19 patients
When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19.We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome.Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime.Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.
DOI: 10.1186/s12981-021-00335-1
2021
Cited 64 times
COVID-19 and HIV infection co-pandemics and their impact: a review of the literature
Abstract Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.
DOI: 10.12932/ap-250721-1197
2022
Cited 26 times
Short-term immune response after inactivated SARS-CoV-2 (CoronaVac®, Sinovac) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-AstraZeneca) vaccinations in health care workers
Background: Inactivated SARS-CoV-2 (CoronaVac®, Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs).Objective: To determine the short-term immune response after the SV and AZ vaccinations in HCWs. Methods:In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included.Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody.Blood samples were analyzed at 4 and 12 weeks after the complete vaccination.The primary outcome was the seroconversion rate at 4-weeks after complete immunization.Results: Overall, 185 HCWs with a median (IQR) age of 40.5 (30.3-55.8)years (94 HCWs in the SV group and 91 in the AZ group) were included.At 4 weeks after completing the SV vaccination, 60.6% (95%CI: 50.0-70.6%)had seroconversion evaluated by sVNT (≥ 68% inhibition), comparable to the patients recovered from mild COVID-19 infection (69.0%), with a rapid reduction to 12.2% (95%CI: 6.3-20.8)at 12 weeks.In contrast, 85.7% (95%CI: 76.8-92.2%)HCWs who completed two doses of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients (92.5%), with a reduction to 39.2% (95%CI: 28.4-50.9%)at 12 weeks.When using the anti-SARS-CoV-2 total antibody level (≥ 132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group at 4 weeks. Conclusion:A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.
DOI: 10.1038/s41564-022-01246-1
2022
Cited 23 times
SARS-CoV-2 Omicron variant emerged under immune selection
The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.
DOI: 10.3390/vaccines10050639
2022
Cited 19 times
Dynamics of Neutralizing Antibody and T-Cell Responses to SARS-CoV-2 and Variants of Concern after Primary Immunization with CoronaVac and Booster with BNT162b2 or ChAdOx1 in Health Care Workers
Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declines within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants who received ChAdOx1 and forty-two participants who received BNT162b2 were enrolled into this study, which evaluated immune responses, including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript), five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization, as well as 4 and 12 weeks after receiving the booster. This study showed a significant increase in anti-SARS-CoV-2 spike total antibodies, sVNT, and T-cell immune response after the booster, including against the Omicron variant. Immune responses rapidly decreased in the booster group at 12 weeks after booster but were still higher than post-primary vaccination. A fourth dose or a second booster should be recommended, particularly in health care workers.
DOI: 10.1111/tid.13388
2020
Cited 32 times
A case of successful treatment of severe COVID‐19 pneumonia with favipiravir and tocilizumab in post–kidney transplant recipient
We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.
DOI: 10.1038/s10038-021-01009-6
2022
Cited 16 times
Host genetic factors of COVID-19 susceptibility and disease severity in a Thai population
Host genetic factors have been shown to play a role in SARs-CoV-2 infection in diverse populations. However, the genetic landscape differs among various ethnicities; therefore, we explored the host genetic factors associated with COVID-19 disease susceptivity and disease severity in a Thai population. We recruited and genotyped 212 unrelated COVID-19 Thai patients and 36 controls using AxiomTM Human Genotyping SARs-COV-2 array, including 847,384 single nucleotide polymorphisms related to SARs-COV-2 pathogenesis, immune response, and related comorbidity No SNPs passed the genome-wide significance threshold of p value <1 × 10-8. However, with a threshold of p value <1 × 10-5, a locus on chromosome 5q32 was found to have a suggestive association with COVID-19 disease susceptibility (p value 6.9 × 10-6; Q-Q plot λ = 0.805, odds ratio 0.02). Notably, IL17B is a gene located in this linkage disequilibrium block and is previously shown to play a part in inflammation and pneumonia. Additionally, a suggestive locus on chromosome 12q22, harboring EEA1 and LOC643339, was associated with COVID-19 disease severity (p value 1.3 × 10-6 - 4.4 × 10-6, Q-Q plot λ = 0.997, odds ratio 0.28-0.31). EEA1 is involved in viral entry into cells, while LOC643339 is a long non-coding RNA. In summary, our study suggested loci on chromosomes 5q32 and 12q22 to be linked to COVID-19 disease susceptibility and disease severity, respectively. The small sample size of this study may lessen the likelihood that the association found is real, but it could still be true. Further study with a larger cohort is required to confirm these findings.
DOI: 10.1016/j.jmii.2022.09.001
2022
Cited 16 times
Impact of SARS-CoV-2 infection on the profiles and responses of innate immune cells after recovery
SARS-CoV-2 infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic to severe symptoms and death. Most COVID-19 pathogenesis is associated with hyperinflammatory conditions driven primarily by myeloid cell lineages. The long-term effects of SARS-CoV-2 infection post recovery include various symptoms.We performed a longitudinal study of the innate immune profiles 1 and 3 months after recovery in the Thai cohort by comparing patients with mild, moderate, and severe clinical symptoms using peripheral blood mononuclear cells (n = 62).Significant increases in the frequencies of monocytes compared to controls and NK cells compared to mild and moderate patients were observed in severe patients 1-3 months post recovery. Increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were observed in all recovered patients, even after 3 months. Increased IL-6 and TNFα levels in monocytes were observed 1 month after recovery in response to lipopolysaccharide (LPS) stimulation, while decreased CD86 and HLA-DR levels were observed regardless of stimulation. A multiplex analysis of serum cytokines performed at 1 month revealed that most innate cytokines, except for TNFα, IL4/IL-13 (Th2) and IFNγ (Th1), were elevated in recovered patients in a severity-dependent manner. Finally, the myelopoiesis cytokines G-CSF and GM-CSF were higher in all patient groups. Increased monocytes and IL-6- and TNFα-producing cells were significantly associated with long COVID-19 symptoms.These results reveal that COVID-19 infection influences the frequencies and functions of innate immune cells for up to 3 months after recovery, which may potentially lead to some of the long COVID symptoms.
DOI: 10.1038/s41598-023-28715-9
2023
Cited 5 times
Simultaneous detection of omicron and other SARS-CoV-2 variants by multiplex PCR MassARRAY technology
The rapid emergence of SARS-CoV-2 variants with high severity and transmutability adds further urgency for rapid and multiplex molecular testing to identify the variants. A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/µl. The panel has shown a 100% concordant with the Next Generation Sequencing (NGS) results testing on 256 clinical specimens with real-time PCR cycle threshold (Ct) values less than 26. It showed a higher sensitivity over NGS; 25/28 samples were positive by PMA but not NGS in the clinical samples with PCR Ct higher than 26. Due to the mass of nucleotide used to differentiate between wild-type and mutation strains, the co-infection or recombination of multiple variants can be determined by the PMA method. This method is flexible in adding a new primer set to identify a new emerging mutation site among the current circulating VOCs and the turnaround time is less than 8 h. However, the spike gene sequencing or NGS retains the advantage of detecting newly emerged variants.
DOI: 10.1097/qad.0000000000001496
2017
Cited 35 times
New-onset diabetes in HIV-treated adults
To determine the incidence and risk factors for developing diabetes mellitus in a cohort of Thai HIV-infected patients on long-term combination antiretroviral therapy (cART).Prospective study conducted between July 1996 and 30 April 2015.A total of 1748 patients (60% men) who did not have diabetes mellitus prior to ART were assessed twice a year. Incident diabetes mellitus was defined as either having two consecutive fasting glucose levels more than 126 mg/dl, or reporting antidiabetes mellitus medication/diabetes mellitus diagnosis after starting cART. Incidence rates were calculated per 1000 person-year follow-up. Multivariate Cox regression was used to determine risk factors for the development of diabetes mellitus.During a median follow-up of 9 years (16 274 person-year of follow-up), 123 patients developed new-onset diabetes mellitus, resulting in an incidence rate of 7.6 (95% confidence interval 6.3-9) per 1000 person-year of follow-up. From the multivariate models, age more than 35 years, male sex, BMI at least 25 kg/m, family history of diabetes, abnormal waist circumference, lipodystrophy and exposure to didanosine were significantly associated with incident diabetes mellitus. The diabetes mellitus group had higher mortality rate (8.1 vs. 4.1%, P = 0.04). A significantly higher proportion diabetes vs. nondiabetes patients developed cardiovascular and cerebrovascular complications (8.9 vs. 3.6%, P = 0.008) or chronic kidney disease stage III (estimated glomerular filtration rate <60 ml/min/1.73 m) (15.3 vs. 1.9%, P < 0.001) over total follow-up.In addition to traditional risk factors, lipodystrophy and use of didanosine were strongly associated with development of incident diabetes. Given the higher rate of cardiovascular-cerebrovascular complications and chronic kidney disease among patients with diabetes mellitus, careful assessment and appropriate management of diabetes mellitus are essential.
DOI: 10.1371/journal.pone.0246864
2021
Cited 22 times
Early detection of neutralizing antibodies against SARS-CoV-2 in COVID-19 patients in Thailand
The presence of neutralizing antibodies (NAbs) is an indicator of protective immunity for most viral infections. A newly developed surrogate viral neutralization assay (sVNT) offers the ability to detect total receptor binding domain-targeting NAbs in an isotype-independent manner, increasing the test sensitivity. Thus, specimens with low IgM/ IgG antibody levels showed strong neutralization activity in sVNT.This study aimed to measure the %inhibition of NAbs measured by sVNT in PCR-confirmed COVID-19 patients. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection and its kinetics were determined.Ninety-seven patients with PCR-confirmed SARS-CoV-2 infection were included in this study. Majority of the patients were 21-40 years old (67%) and 63% had mild symptoms. The sensitivity of sVNT for the diagnosis of SARS-CoV-2 infection was 99% (95% confidence interval (CI) 94.4-100%) and the specificity was 100% (95% CI 98.3-100%). The negative predictive value of sVNT from the samples collected before and after 7 days of symptom onset was 99.5% (95% CI 97.4-100%) and 100% (95% CI 93.8-100%), respectively. The level of inhibition at days 8-14 were significantly higher than days 0-7 (p<0.001). The median %inhibition values by severity of COVID-19 symptoms were 79.9% (interquartile range (IQR) 49.7-91.8%); 89.0% (IQR 71.2-92.4%); and 86.6% (IQR 69.5-92.8%), for mild, moderate and severe/critical symptoms respectively. The median level of sVNT %inhibition of severe was significantly higher than the mild group (p = 0.05).The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.
DOI: 10.1111/jgh.12613
2014
Cited 33 times
Advanced liver fibrosis by transient elastography, Fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: Role of vitamin D levels
Background and Aim Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. Methods Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2–9.4 kPa); severe (9.5–14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. Results A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20–5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70–14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09–5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05–0.65), P = 0.01. Conclusions HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.
DOI: 10.1128/jvi.06421-11
2012
Cited 29 times
HIV-1 Clinical Isolates Resistant to CCR5 Antagonists Exhibit Delayed Entry Kinetics That Are Corrected in the Presence of Drug
HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV-sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell β-lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV-resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population-derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance.
DOI: 10.1517/14656566.2012.729040
2012
Cited 29 times
Treatment of HIV infection with once-daily regimens
Introduction: Treatment for HIV infection requires a lifetime antiretroviral therapy. In order to improve adherence, once daily (OD) is thus a preferred regimen. Areas covered: Evidence-based information and most recent guidelines recommendation, both from resource-rich and resource-limited settings, on antiretroviral regimens that can be administered OD will be reviewed. Sources of evidences were from the late clinical development studies (Phase III and II) published in Medline or major international conferences. Expert opinion: Nine OD US FDA-approved regimens and one new integrase inhibitor OD regimen have been shown to be efficient and well tolerated. For the fixed-dose single-tablet regimens (STRs), there are two currently approved regimens: Atripla® and Complera®. Another STR elvitegravir/cobicistat/emtricitabine/tenofovir (QUAD, Stribild®) is recently approved by the US FDA (August 20, 2012), whereas two additional SRTs, including abacavir/lamivudine/dolutegravir and darunavir/cobicistat/emtricitabine/GS-7340 are undergoing Phase III and II trials, respectively. Three OD regimens are currently recommended by the US DHHS guidelines as the preferred regimens for treatment-naïve patients (efavirenz, boosted atazanavir and boosted darunavir). EFV-based regimen is the only OD regimen available for resource-limited countries. Nevertheless, it should be noted that each of these OD regimens has its own advantages and disadvantages and therefore should be selected accordingly.
DOI: 10.3201/eid2712.211772
2021
Cited 14 times
Limited and Short-Lasting Virus Neutralizing Titers Induced by Inactivated SARS-CoV-2 Vaccine
In vitro determination of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies induced in serum samples from recipients of the CoronaVac vaccine showed a short protection period against the original virus strain and limited protection against variants of concern. These data provide support for vaccine boosters, especially variants of concern circulate.
DOI: 10.1159/000515628
2021
Cited 13 times
Endotoxin Adsorbent Therapy in Severe COVID-19 Pneumonia
&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO&lt;sub&gt;2&lt;/sub&gt;/FiO&lt;sub&gt;2&lt;/sub&gt; ratio and decreased EAA level after EA therapy. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.
DOI: 10.21203/rs.3.rs-1362541/v1
2022
Cited 8 times
Differential escape of neutralizing antibodies by SARS-CoV-2 Omicron and pre-emergent sarbecoviruses
Abstract The SARS-CoV-2 B.1.1.529 lineage, Omicron variant, was first detected in November 2021 and carries 32 amino acid mutations in the spike protein (15 in RBD) and exhibits significant escape of neutralizing antibodies targeting the parental SARS-CoV-2 virus. Here, we performed a high-resolution multiplex (16-plex) surrogate virus neutralization assay covering all major SARS-CoV-2 variants and pre-emergent ACE2-binding sarbecoviruses against 20 different human serum panels from infected, vaccinated and hybrid immune individuals which had vaccine-breakthrough infections or infection followed by vaccination. Among all sarbecoviruses tested, we observed 1.1 to 4.7-, 2.3 to 10.3- and 0.7 to 33.3-fold reduction in neutralization activities to SARS-CoV-2 Beta, Omicron and SARS-CoV-1, respectively. Among the SARS-CoV-2 related sarbecoviruses, it is found that the genetically more distant bat RaTG13 and pangolin GX-P5L sarbecoviruses had less neutralization escape than Omicron. Our data suggest that the SARS-CoV-2 variants emerged from the changed immune landscape of human populations are more potent in escaping neutralizing antibodies, from infection or vaccination, than pre-emergent sarbecoviruses naturally evolved in animal populations with no or less immune selection pressure.
DOI: 10.1186/s40545-023-00538-z
2023
Telepharmacy during home isolation: drug-related problems and pharmaceutical care in COVID-19 patients receiving antiviral therapy in Thailand
Home isolation has been proposed for coronavirus disease 2019 (COVID-19) patients with mild symptoms to avoid hospital overcrowding. This study aimed to describe the drug-related problems (DRPs) and the pharmaceutical care of home-isolating COVID-19 patients in Thailand.Our cross-sectional study was undertaken from July 1 to September 30, 2021, at the King Chulalongkorn Memorial Hospital, Thailand. Patients who were ≥ 18 years old, were diagnosed with mild COVID-19 by real-time polymerase chain reaction (RT-PCR), and were able to isolate at home while receiving an antiviral agent and standard symptomatic treatment were enrolled. Infectious disease pharmacists provided a telepharmacy service on days 1 and 3 after the COVID-19 diagnosis.A total of 197 patients met the study criteria. Their median age was 45 years, and their most common underlying disease was hypertension (44.29%). All patients exhibited excellent anti-COVID-19 drug adherence. We identified 125 DRPs, including adverse reactions (68%), and the unnecessary use of products (62.40%). Moreover, 91 patients (46.19%) reported the use of supplements or herbs, with vitamin C being the main supplement (37.36%). Pharmacists provided 36 recommendations and received 33 questions from COVID-19 patients.Our study demonstrates that telepharmacy is an essential service for detecting and preventing DRPs in home-isolating COVID-19 patients.
DOI: 10.3390/v15040876
2023
SARS-CoV-2 Variants Detection Strategies in Wastewater Samples Collected in the Bangkok Metropolitan Region
Wastewater surveillance is considered a promising approach for COVID-19 surveillance in communities. In this study, we collected wastewater samples between November 2020 and February 2022 from twenty-three sites in the Bangkok Metropolitan Region to detect the presence of SARS-CoV-2 and its variants for comparison to standard clinical sampling. A total of 215 wastewater samples were collected and tested for SARS-CoV-2 RNA by real-time PCR with three targeted genes (N, E, and ORF1ab); 102 samples were positive (42.5%). The SARS-CoV-2 variants were determined by a multiplex PCR MassARRAY assay to distinguish four SARS-CoV-2 variants, including Alpha, Beta, Delta, and Omicron. Multiple variants of Alpha-Delta and Delta-Omicron were detected in the wastewater samples in July 2021 and January 2022, respectively. These wastewater variant results mirrored the country data from clinical specimens deposited in GISAID. Our results demonstrated that wastewater surveillance using multiple signature mutation sites for SARS-CoV-2 variant detection is an appropriate strategy to monitor the presence of SARS-CoV-2 variants in the community at a low cost and with rapid turn-around time. However, it is essential to note that sequencing surveillance of wastewater samples should be considered complementary to whole genome sequencing of clinical samples to detect novel variants.
DOI: 10.1186/s12985-024-02296-z
2024
An unusual diarrheal outbreak in the community in Eastern Thailand caused by Norovirus GII.3[P25]
Abstract Background Sentinel laboratory surveillance for diarrheal disease determined norovirus to be the most common cause of non-bacterial gastroenteritis in people during the COVID-19 pandemic in Thailand. An increase in patients presenting with diarrhea and vomiting in hospitals across Chanthaburi province between December 2021 and January 2022 led to the need for the identification of viral pathogens that may be responsible for the outbreak. Methods Fecal samples (rectal swabs or stool) from 93 patients, of which 65 patients were collected during the December 2021 to January 2022 outbreak, were collected and screened for viral infection by real-time RT-PCR. Positive samples for norovirus GII were then genotyped by targeted amplification and sequencing of partial polymerase and capsid genes. Full genome sequencing was performed from the predominant strain, GII.3[P25]. Results Norovirus was the most common virus detected in human fecal samples in this study. 39 of 65 outbreak samples (60%) and 3 of 28 (10%) non-outbreak samples were positive for norovirus genogroup II. One was positive for rotavirus, and one indicated co-infection with rotavirus and norovirus genogroups I and II. Nucleotide sequences of VP1 and RdRp gene were successfully obtained from 28 of 39 positive norovirus GII and used for dual-typing; 25/28 (89.3%) were GII.3, and 24/28 (85.7) were GII.P25, respectively. Norovirus GII.3[P25] was the predominant strain responsible for this outbreak. The full genome sequence of norovirus GII.3[P25] from our study is the first reported in Thailand and has 98.62% and 98.57% similarity to norovirus found in China in 2021 and the USA in 2022, respectively. We further demonstrate the presence of multiple co-circulating norovirus genotypes, including GII.21[P21], GII.17[P17], GII.3[P12] and GII.4[P31] in our study. Conclusions An unusual diarrhea outbreak was found in December 2021 in eastern Thailand. Norovirus strain GII.3[P25] was the cause of the outbreak and was first detected in Thailand. The positive rate during GII.3[P25] outbreak was six times higher than sporadic cases (GII.4), and, atypically, adults were the primary infected population rather than children.
DOI: 10.7189/jogh.14.03016
2024
Charting the path forward in Southeast Asia: Learning from the COVID-19 vaccination challenges in six ASEAN countries
DOI: 10.2217/fvl-2024-0016
2024
Conference proceedings from the 26th Bangkok International Symposium on HIV Medicine
The first Bangkok International Symposium on HIV Medicine was launched in January 1998 with the aim to provide up-to-date information on HIV to professional heathcare workers in Thailand and surrounding countries who cannot afford to attend conferences abroad. After several virtual conferences during the COVID-19 pandemic, this is the second face-to-face meeting held in Bangkok from 17 to 19 January 2024. There were a total of six plenary sessions each morning and two afternoon workshops on Wednesday and Thursday. The symposium had expert speakers from Thailand, Australia, Taiwan, India, Malaysia, the UK, the USA, Japan, Singapore, the Philippines and Vietnam.
DOI: 10.3390/v16040534
2024
Comparative Performance in the Detection of Four Coronavirus Genera from Human, Animal, and Environmental Specimens
Emerging coronaviruses (CoVs) are understood to cause critical human and domestic animal diseases; the spillover from wildlife reservoirs can result in mild and severe respiratory illness in humans and domestic animals and can spread more readily in these naïve hosts. A low-cost CoV molecular method that can detect a variety of CoVs from humans, animals, and environmental specimens is an initial step to ensure the early identification of known and new viruses. We examine a collection of 50 human, 46 wastewater, 28 bat, and 17 avian archived specimens using 3 published pan-CoV PCR assays called Q-, W-, and X-CoV PCR, to compare the performance of each assay against four CoV genera. X-CoV PCR can detect all four CoV genera, but Q- and W-CoV PCR failed to detect δ-CoV. In total, 21 (42.0%), 9 (18.0%), and 21 (42.0%) of 50 human specimens and 30 (65.22%), 6 (13.04%), and 27 (58.70%) of 46 wastewater specimens were detected using Q-, W-, and X-CoV PCR assays, respectively. The X-CoV PCR assay has a comparable sensitivity to Q-CoV PCR in bat CoV detection. Combining Q- and X-CoV PCR assays can increase sensitivity and avoid false negative results in the early detection of novel CoVs.
2024
Prevalence and incidence rates of tuberculosis in people with HIV during the coronavirus 2019 pandemic: a single center retrospective analysis.
Tuberculosis (TB) poses a significant risk to people with HIV (PWH), with heightened incidence and prevalence rates, especially in countries with a high TB burden. This study assesses the prevalence and incidence rates of TB among PWH during the COVID-19 pandemic, and on treatment outcomes in TB-HIV co-infections.
DOI: 10.1258/ijsa.2009.009152
2012
Cited 18 times
Assessing adherence in Thai patients taking combination antiretroviral therapy
In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19-8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01-4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence.
DOI: 10.1371/journal.pone.0154221
2016
Cited 13 times
Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study
Introduction Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Methods Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. Results 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). Conclusion The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.
DOI: 10.1111/1346-8138.15567
2020
Cited 10 times
Skin manifestations in COVID‐19: The tropics experience
Reports concerning cutaneous manifestations in coronavirus disease 2019 (COVID-19) have been mostly from temperate regions, namely Western countries and China, with prevalence rates of 0.20–20.45%.1 Information on other races, ethnicities and locales is lacking. Thailand is located in the tropical region; thus, we hypothesize that different patterns of skin manifestations may ensue. From 9 March to 18 April 2020, 187 patients with COVID-19 were diagnosed at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. We conducted a retrospective chart review and telephone interview to investigate the epidemiology of skin findings in COVID-19. This study was approved by the institutional review board of the Faculty of Medicine, Chulalongkorn University (IRB 291/63). All 187 cases were confirmed by positive testing for SARS-CoV-2 by reverse transcription polymerase chain reaction. Patient interviews using a standardized questionnaire were accomplished by telephone. If skin rashes were present, photographs were requested. If unavailable, a picture chart showing various clinical patterns of skin findings was used to describe ones that best represented their lesions. All medical records were reviewed by two dermatologists. Of the 187 patients, 153 participated in the survey, with a median (interquartile range) age of 36.7 years (range, 27–47), including six children aged less than 15 years old. The severity of COVID-19 was mild in 91 patients, moderate in 30, severe in 24 and critical in eight. The interviews were conducted at a mean of 61 days (standard deviation [SD], 10) after the onset of COVID-19. Skin lesions were present in 23 (15.0%) patients. Baseline demographic and details of skin manifestations are shown in Table 1. Skin manifestations were categorized by the proposed classification.2 The most common skin lesions observed were urticaria in five of the 23 patients with rash (21.7%), followed by maculopapules in four (17.4%), vesicular eruptions in two (8.6%) and necrosis in one (4.4%). There were no patients with pseudo-chilblain. Urticaria or vesicular lesions were found early in the clinical course with a mean onset of 6.8 days (SD, 5.4). Purpura/necrosis was detected in one critically ill patient on day 40 of the disease. We found no clinically significant association between the presence of skin manifestations with systemic symptoms, disease severity and laboratory data (Tables S2,S3). Pseudo-chilblain is the most commonly reported skin sign from the cold/temperate countries;1 however, there was none in our cohort. We speculate that the environment (hot vs cold weather), host factors and different strains of the virus may be responsible for this discrepancy. Interestingly, there were two cases of exacerbated psoriasis and atopic dermatitis (AD). Hyperinflammation and dysregulation of T-helper (Th)17 responses are found in severe COVID-19.3 Psoriasis and Asian AD are known to be mediated largely by Th17 inflammation.4 The exacerbation may be a coincident or bear a causal relationship; further studies are needed to clarify these issues. All six pediatric cases had mild COVID-19 symptoms and no Kawasaki-like rash. Even though dermatologists did not examine actual skin lesions due to limited access according to the infection prevention control policy, 13 cases had photographic documentation of the lesions. The follow-up telephone interview allowed us to include skin manifestations up to at least 1 month after diagnosis. In conclusion, we herein report our experience from Thailand, a country in the tropical region, of which the skin manifestations are slightly different from those reported from the USA and Europe (Fig. 1). The authors graciously thank the Skin and Allergy Research Unit and the Collection and Management of COVID-19 Related Clinical Data and Biological Specimens for Researches Task Force, Research Affairs, Faculty of Medicine, Chulalongkorn University, for their support. Funding was received from the Ratchadapisek Sompoch Endowment Fund RA (PO) 001/63, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. None declared. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
DOI: 10.1101/2020.05.29.20109785
2020
Cited 9 times
Endotoxemia and circulating bacteriome in severe COVID-19 patients
Abstract Purpose When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium are injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. Methods We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13 th March and 17 th April 2020. Blood samples on day 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1→3)-β-D-Glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. Results Of the 19 patients, 14 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. Conclusions Bacterial DNA and toxins were discovered in virtual all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease
DOI: 10.20944/preprints202203.0411.v1
2022
Cited 4 times
Dynamics of Neutralizing Antibody and T-cell Responses to SARS-CoV-2 and Variants of Concern After Primary Immunization With CoronaVac and Booster With BNT162b2 or ChAdOx1 in Health Care Workers
Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys&amp;reg;), surrogated viral neutralization test (sVNT) to ancestral strain (cPass&amp;trade;; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.
DOI: 10.3390/vaccines10081321
2022
Cited 4 times
Homologous or Heterologous COVID-19 Booster Regimens Significantly Impact Sero-Neutralization of SARS-CoV-2 Virus and Its Variants
We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs), in 125 healthcare workers who received CoronaVac as their primary vaccination and later received either a single ChAdOx1 or a combi-nation of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or two doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize all strains. After a single ChAdOx1 booster, the levels of neutralization at Day 30 varied significantly, with only a small proportion of participants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChAdOx1 as the booster induced the lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.
DOI: 10.1093/ofid/ofad234
2023
High-Sensitivity Troponins and Subclinical Coronary Atherosclerosis Evaluated by Coronary Calcium Score Among Older Asians Living With Well-Controlled Human Immunodeficiency Virus
Abstract Background Elevated levels of high-sensitivity cardiac troponin (hs-cTn) are suggestive of myocardial cell injury and coronary artery disease. We explored the association between hs-cTn and subclinical arteriosclerosis using coronary artery calcification (CAC) scoring among 337 virally suppressed patients with human immunodeficiency virus (HIV) who were ≥50 years old and without evidence of known coronary artery disease. Methods Noncontrast cardiac computed tomography and blood sampling for hs-cTn, both subunit I (hs-cTnI) and subunit T (hs-cTnT), were performed. The relationship between CAC (Agatston score) and serum hs-cTn levels was analyzed using Spearman correlation and logistic regression models. Results The patients, of whom 62% were male, had a median age of 54 years and had been on antiretroviral therapy for a median of 16 years; the CAC score was &amp;gt;0 in 50% of patients and ≥100 in 16%. Both hs-cTn concentrations were positively correlated with the Agatston score, with correlation coefficients of 0.28 and 0.27 (P &amp;lt; .001) for hs-cTnI and hs-cTnT, respectively. hs-cTnI and hs-cTnT concentrations of ≥4 and ≥5.3 pg/mL, respectively, provided the best performance for discriminating patients with Agatston scores ≥100, with a sensitivity and specificity of 76% and 60%, respectively, for hs-cTnI and 70% and 50% for hs-cTnT. In multivariable logistic regression analysis, each log unit increase in hs-cTnI level was independently associated with increased odds of having an Agatston score ≥100 (odds ratio, 2.83 [95% confidence interval, 1.69–4.75]; P &amp;lt;.001). Although not an independent predictor, hs-cTnT was also associated with an increased odds of having an Agatston score ≥100 (odds ratio, 1.58 [95% confidence interval, .92–2.73]; P = .10). Conclusions Among Asians aged ≥50 years with well-controlled HIV infection and without established cardiovascular disease, 50% had subclinical arteriosclerosis. Increasing hs-cTnI and hs-cTnT concentrations were associated with an increased risk of severe subclinical arteriosclerosis, and hs-cTn may be a potential biomarker to detect severe subclinical arteriosclerosis.
DOI: 10.22541/au.169096143.38866154/v1
2023
High transmission rates of early omicron sub-variant BA.2 in Bangkok, Thailand
Omicron emerged as the fifth variant of concern of SARS-CoV-2 coronavirus pandemic in late 2021 and rapidly overtook the previously predominant Delta variants with a significantly faster transmission rate and unique mutations on the spike gene. Hence, the ability to identify viral variants rapidly and affordably in large number of patients, which facilitates the monitoring of the transmission and clinical impact of new variants, is needed to obtain information for updating the public health policy. In this study, we evaluated the capability of two RT-PCR and mass spectrometry-based SARS-CoV-2 variant classification platforms to distinguish Delta, Omicron BA.1, and Omicron BA.2 variants in 618 COVID-19-positive samples from patients in Bangkok collected during November 2011-March 2022. Analysis of the time-evolution pattern of SARS-CoV-2 variant profiles indicated that the BA.1 and BA.2 possess up to 2-3 times higher transmission rates than the Delta variant. Our study showcases a cost-effective virus surveillance that enables a quantitative estimation of variant-specific public health impact.
DOI: 10.1128/jvi.00286-12
2012
Cited 9 times
Vicriviroc Resistance Decay and Relative Replicative Fitness in HIV-1 Clinical Isolates under Sequential Drug Selection Pressures
We previously described an HIV-1-infected individual who developed resistance to vicriviroc (VCV), an investigational CCR5 antagonist, during 28 weeks of therapy (Tsibris AM et al., J. Virol. 82:8210-8214, 2008). To investigate the decay of VCV resistance mutations, a standard clonal analysis of full-length env (gp160) was performed on plasma HIV-1 samples obtained at week 28 (the time of VCV discontinuation) and at three subsequent time points (weeks 30, 42, and 48). During 132 days, VCV-resistant HIV-1 was replaced by VCV-sensitive viruses whose V3 loop sequences differed from the dominant pretreatment forms. A deep-sequencing analysis showed that the week 48 VCV-sensitive V3 loop form emerged from a preexisting viral variant. Enfuvirtide was added to the antiretroviral regimen at week 30; by week 48, enfuvirtide treatment selected for either the G36D or N43D HR-1 mutation. Growth competition experiments demonstrated that viruses incorporating the dominant week 28 VCV-resistant env were less fit than week 0 viruses in the absence of VCV but more fit than week 48 viruses. This week 48 fitness deficit persisted when G36D was corrected by either site-directed mutagenesis or week 48 gp41 domain swapping. The correction of N43D, in contrast, restored fitness relative to that of week 28, but not week 0, viruses. Virus entry kinetics correlated with observed fitness differences; the slower entry of enfuvirtide-resistant viruses corrected to wild-type rates in the presence of enfuvirtide. These findings suggest that while VCV and enfuvirtide select for resistance mutations in only one env subunit, gp120 and gp41 coevolve to maximize viral fitness under sequential drug selection pressures.
DOI: 10.1016/j.sbsr.2018.06.003
2018
Cited 8 times
Rapid design and fielding of four diagnostic technologies in Sierra Leone, Thailand, Peru, and Australia: Successes and challenges faced introducing these biosensors
Febrile illnesses are among the most common reasons for visits to hospitals and clinics worldwide. Since fevers can arise from a wide range of diseases, identifying the causative pathogen is essential not only for effective personal treatment but also for early detection of outbreaks. The Defense Threat Reduction Agency (DTRA) tasked a coalition of commercial, academic, and government researchers with moving diagnostic technology concepts from ideation to field use as rapidly as possible using scientifically sound evaluations. DTRA's 24 Month Challenge program examined >30 technologies before fielding four technologies on four continents. >10,000 in field test results were recorded. Here we discuss our tiered evaluation system to assess candidate technologies developed by commercial partners and the process of field testing those technologies at various front-line clinics in Sierra Leone, Thailand, Peru, and Australia. We discuss successes and challenges for introducing two multiplexed lateral flow immunoassay (LFI) tests that detect malaria, dengue fever, melioidosis, and the plague. Additionally we discuss the use of a LFI reader that assisted the interpretation of the assay, communicated results to a data cloud, and greatly facilitated reach-back support. Lastly, we discuss the concurrent field testing of a multiplexed PCR assay on the FilmArray platform, which had an assay pouch specially designed for the 24 Month Challenge. Either standard-of-care or gold-standard testing were run alongside our fielded technologies to benchmark their performance.
DOI: 10.1089/aid.2019.0126
2019
Cited 7 times
Low CD4 Cell Counts Are Associated with Carotid Plaque and Intima–Media Thickness in Virologically Suppressed HIV-Infected Asians Older Than 50 Years
Information about the prevalence, and risk factors for subclinical atherosclerosis in an Asian HIV-infected population is limited. Carotid intima–media thickness (cIMT) is one predictor for the risk of cardiovascular disease (CVDs) and mortality. We evaluated the prevalence and risk factors related to carotid atherosclerosis among well-suppressed HIV-infected adults receiving long-term ART from Thailand. This was a cross-sectional study of HIV-infected adults >50 years of age and free from CVDs from Thailand during 1 March 2016 and 30 May 2017. Ultrasonography of the carotid was performed and read by cIMT experienced neurologists who were blinded from the patient care. Subclinical atherosclerosis was defined by carotid plaque or cIMT of the common carotid artery (CCA) >0.9 mm. Totally 316 HIV-infected adults (61% males) were included. Median age was 54.4 years and 15.8% were diabetic, 40.2% had hypertension, and 12.7% were current smokers. The median duration of ART was 16.3 years and 32% were currently on boosted protease inhibitor. The mean overall cIMT of the common carotid arteries were 0.63 (IQR 0.55–0.72) mm. Men had higher cIMT than women, 0.64 (IQR 0.56–0.76) vs. 0.60 (IQR 0.53–0.70), p = .03. Overall, 3.8% had cIMT >0.9 mm and 24.4% had carotid plaque. From the multivariate logistic regression analysis, age per 1 year increase [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.003–1.12; p = .04] and nadir CD4 < 200 cells/mm3 (OR 1.8; 95%CI 1.02–3.18, p = .04) were significantly associated with subclinical atherosclerosis. High-sensitivity C-reactive protein was not associated with subclinical atherosclerosis. In this well-suppressed HIV-infected Aging Asian cohort with relatively low prevalence of current smokers, 26.9% of them had subclinical atherosclerosis. Advanced age and low nadir CD4 cell count were significantly associated with subclinical atherosclerosis. Given that approximately a quarter of the patients had carotid plaques, longitudinal studies to evaluate the development of future overt coronary artery disease and stroke are warranted.
DOI: 10.1101/2021.08.27.21262721
2021
Cited 6 times
Short-Term Immune Response After Inactivated SARS-CoV-2 (CoronaVac®, Sinovac) And ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-AstraZeneca) Vaccinations in Thai Health Care Workers
Abstract Background Inactivated SARS-CoV-2 (CoronaVac®,Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®,Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs) in Thailand. Objective To determine the short-term immune response after the SV and AZ vaccinations in HCWs. Methods In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete SV vaccination and at 4 weeks after each dose of the AZ vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization. Results Overall, 185 HCWs with a median (IQR) age of 40.5(30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI:50.0-70.6%) had seroconversion evaluated by sVNT(≥68%inhibition), comparable to the patients recovered from mild COVID-19 infection(69.0%), with a rapid reduction to 12.2%(95%CI:6.3-20.8) at 12 weeks. In contrast, 85.7%(95%CI:76.8-92.2%) HCWs who completed the second dose of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients(92.5%). When using the anti-SAR-CoV-2 total antibody level(≥132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group. Conclusion A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SAR-CoV-2 variants of concern.
2012
Cited 7 times
Histoplasmosis and penicilliosis among HIV-infected Thai patients: a retrospective review.
Histoplasmosis and penicilliosis are fungal infections with similar clinical presentation and laboratory findings that were reported mainly in the era prior to highly active antiretroviral therapy. We conducted a retrospective review at two hospitals in Central Thailand of the medical records of HIV-positive patients with microbiologic evidence of histoplasmosis or penicilliosis between January 2003 to September 2007 when antiretrovirals became widely available in Thailand. Fifty patients met inclusion criteria; 36 had histoplasmosis, and 14 had penicilliosis. Symptoms and laboratory findings on presentation were similar between the two infections except for a greater incidence of tachypnea and neutropenia among patients with histoplasmosis (both p < 0.05). For histoplasmosis, blood culture had a significantly lower yield for detecting infection compared to tissue microscopic examination highlighting the importance of obtaining tissue for diagnosis (p < 0.05).
DOI: 10.2147/dddt.s63989
2015
Cited 6 times
Rationale and clinical utility of the darunavir&amp;ndash;cobicistat combination in the treatment of HIV/AIDS
This article is to provide an update overview of cobicistat (COBI)-boosted darunavir in response to its recent approval by the US Food and Drug Administration, and inclusion as an alternative first-line regime in the 2015 treatment guidelines in the US.COBI is a relatively new non-antiretroviral cytochrome P450 3A inhibitor or pharmacoenhancer.The rationale behind COBI development was to provide an alternative to ritonavir (RTV) as a protease inhibitor pharmacoenhancer, due to associated adverse events with short-and long-term RTV use, such as gastrointestinal intolerability, drug-drug interactions, insulin resistance, lipodystrophy, and hyperlipidemia.Although in vitro studies suggest that COBI may result in a lower incidence of undesired drug-drug interactions and lipid-associated disorders than RTV, not all Phase III studies have well addressed these issues, and the data are limited.However, Phase III studies have demonstrated tolerability, noninferiority, and bioequivalence of COBI compared to RTV.Two main advantages of COBI over RTV-containing regimes have been noted as follows: 1) COBI has no anti-HIV activity; therefore, resistance to COBI as a booster in addition to protease inhibitor resistance is of little concern, allowing for COBI-containing regimes in future.2) COBI's solubility and dissolution rate allow for co-formulated/fixed-dose combination products.Nonetheless, prior to initiating COBI-containing treatment regimens, the following should be considered: 1) COBI may increase serum creatinine levels and reduce estimated glomerular filtration rate (GFR) without affecting actual GFR; 2) potential drug-drug interaction data are insufficient, warranting caution when initiating COBI in conjunction with concomitant medication or in individuals with multiple comorbidities; 3) food plays a pivotal role in boosting darunavir exposure, warranting caution and patient education on the importance of taking COBI-containing regimens with appropriate amounts of food; and 4) data on the success of COBI-containing regimens in treatment-experienced patients are limited.
DOI: 10.1002/ccr3.3152
2020
Cited 6 times
Cold agglutinin disease following SARS‐CoV‐2 and <i>Mycoplasma pneumoniae</i> co‐infections
SARS-CoV-2 and other respiratory co-infections may occur. As Mycoplasma pneumoniae and various viruses can cause cold agglutinin disease (CAD), the presence of CAD in COVID-19 patients should indicate the need of investigations for those pathogens.
DOI: 10.1111/1348-0421.12883
2021
Cited 5 times
Multiple clades of SARS‐CoV‐2 were introduced to Thailand during the first quarter of 2020
In early January 2020, Thailand became the first country where a coronavirus disease 2019 (COVID-19) patient was identified outside China. In this study, 23 whole genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from patients who were hospitalized from January to March 2020 were analyzed, along with their travel histories. Six lineages were identified including A, A.6, B, B.1, B.1.8, and B.58, among which lineage A.6 was dominant. Seven patients were from China who traveled to Thailand in January and early February. Five of them were infected with the B lineage virus, and the other two cases were infected with different lineages including A and A.6. These findings present clear evidence of the early introduction of diverse SARS-CoV-2 clades in Thailand.
DOI: 10.1097/tp.0000000000004361
2022
Cited 3 times
The Predictors for Severe SARS-CoV-2 Omicron (B.1.1.529) and Pre-Omicron Variants Infection Among Kidney Transplant Recipients
At the present time, the substantial concern of COVID-19 is the subvariants of the Omicron, BA.4, and BA.5 that are surging globally. BA.4 and BA.5 might not be the final variants of Omicron.1,2 The future variants could lead to many other epidemic waves. In this cohort study, we evaluated the predictors for developing pneumonia to triage the COVID-19 infected kidney transplant recipients (KTRs)—determining which patients should be hospitalized—as well as the admission investigations used to predict disease progression defined as increasing severity of the disease as per the National Institutes of Health3 by at least 1 level during hospitalization. Variables with P < 0.10 in the univariate analysis were selected for multivariate analysis. Due to vaccine shortages, people who were fully vaccinated were defined as having at least 3 doses of any combination of the vaccines for >14 d, albeit the Centers for Disease Control and Prevention recommended that organ transplant patients should receive a complete primary series of 3-dose BNT162b2 or mRNA-1273.4 All 121 KTRs who underwent kidney transplantations at our hospital and had COVID-19 infections from March 2020 to June 2022 were assessed. Based on the epidemiologic data in Thailand, 76 KTRs who were infected from January to mid-May 2022 were assumed to have Omicron BA.1 or BA.2. In the first half of May, only 1 KTR was infected followed by another wave of infection after mid-May. Thirteen patients were infected from mid-May to June 2022. They were assumed to have Omicron BA.4 or BA.5. Only 3 patients died, all were infected in the pre-Omicron period. In the Omicron and pre-Omicron periods, 6.7% and 75.0% had pneumonia, respectively (adjusted odds ratio [OR] 0.04; 95% confidence interval [CI], 0.01-0.25; P < 0.001). In the Omicron period, the mean age of the patients with pneumonia was higher than those without pneumonia (56.3 ± 10.2 versus 45.9 ± 12.0 y; P = 0.04). Increasing age by 1 y increased the risk of developing pneumonia with an adjusted OR of 1.07 (95% CI, 1.01-1.13; P = 0.02). Increasing body mass index by 1 kg/m2 also increased the risk of developing pneumonia with an adjusted OR of 1.17 (95% CI, 1.02-1.35; P = 0.03) (Table 1). The symptoms of 15 (12.4%) patients progressed during hospitalization. Most of them (93.3%) were not fully vaccinated. Only increasing admission serum creatinine by 1 mg/dL was a significant risk for disease progression with an adjusted OR of 34.85 (95% CI, 1.84-661.07; P = 0.02) (Table 1). In BA.4/5 period, all patients had only mild symptoms. Of those, 91.7% were fully vaccinated. One patient was reinfected in BA.4/5 period after infection with the Omicron 79 d and had only mild symptoms. The patient received 2 doses of ChAdOx1 nCov-19, 1 dose of BNT162b2, and the mRNA-1273 vaccine. TABLE 1. - Univariate and multivariate logistic regression for predicting developing pneumonia and for predicting disease progression Univariate analysis Multivariate analysis Variables Unadjusted odds ratio (95% CI) P Adjusted odds ratio (95% CI) P For predicting developing pneumonia Omicron vs pre-Omicron 0.02 (0.01-0.08) <0.001 0.04 (0.01-0.25) <0.001 Patient characteristics Sex, female vs male 0.68 (0.29-1.58) 0.37 – – Age, per 1 y increase 1.05 (1.01-1.08) 0.01 1.07 (1.01-1.13) 0.02 BMI, per 1 kg/m2 increase 1.10 (0.99-1.20) 0.05 1.17 (1.02-1.35) 0.03 Hypertension, presence vs absence 1.18 (0.51-2.72) 0.70 – – Diabetes, presence vs absence 2.01 (0.78-5.19) 0.15 – – Coronary artery disease, presence vs absence 6.43 (0.56-73.58) 0.14 – – Transplant characteristics DDKT vs LDKT 1.79 (0.76-4.25) 0.19 – – Transplantation vintage 0.22 – – ≤0.5 y (ref) 1 – – 0.5-1 y 3.75 (0.33-42.47) – – >1 y 0.74 (0.14-4.07) – – Tacrolimus, use vs nonuse 0.83 (0.27-2.57) 0.75 – – MPA, use vs nonuse 0.65 (0.24-1.78) 0.40 – – Vaccination Vaccination, fully vaccinated vs not fully vaccinated 0.06 (0.02-0.18) <0.001 0.39 (0.07-2.19) 0.28 Duration after vaccination, per 1 d increase 1.00 (0.99-1.00) 0.94 – – Symptoms Fever 2.41 (1.04-5.59) 0.04 1.32 (0.33-5.21) 0.70 Cough 1.87 (0.72-4.82) 0.20 – – Diarrhea 13.71 (4.78-39.31) <0.001 2.96 (0.58-15.06) 0.19 Anosmia 0.75 (0.08-6.98) 0.80 – – Running nose 0.97 (0.40-2.32) 0.61 – – For predicting disease progression Omicron vs pre-Omicron 0.03 (0.01-0.16) <0.001 0.31 (0.03-3.32) 0.34 Vaccination, fully vaccinated vs not fully vaccinated 0.03 (0.01-0.30) 0.002 0.45 (0.03-8.05) 0.59 Admission investigations Age, per 1 y increase 1.06 (1.01-1.11) 0.02 0.99 (0.89-1.10) 0.83 Ct in RT-PCR 1.09 (0.96-1.23) 0.17 – – Cr, per 1 mg/dL increase 1.78 (1.09-2.91) 0.02 34.85 (1.84-661.07) 0.02 IL-6, per 1 pg/mL increase 1.03 (0.99-1.08) 0.16 – – hsCRP, per 1 mg/L increase 1.01 (0.99-1.03) 0.09 0.99 (0.94-1.03) 0.55 D-dimer, per 1 ng/mL increase 1.00 (0.99-1.00) 0.17 – – NLR, per 1 increase 1.11 (1.00-1.24) 0.04 1.12 (0.93-1.35) 0.23 BMI, body mass index; CI, confidence interval; Ct, cycle threshold; Cr, creatinine; DDKT, deceased donor kidney transplantation; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; LDKT, living donor kidney transplantation; MPA, mycophenolic acid; NLR, neutrophil-to-lymphocyte ratio; RT-PCR, reverse transcription polymerase chain reaction. There were some limitations in our study. First, it was a single-center study so the sample size was small‚ which could increase the risk of bias. Also, in our study, we used heterologous combination of the vaccines, hence, the efficacy of the vaccinations could be hardly assessed. Lastly, the virus variant was not individually confirmed by genomic sequencing. Nevertheless, the epidemic data showed that certain variants were mainly responsible for the outbreak in each period. From our study, in the Omicron period, though causing less disease severity, KTRs who are elderly or obese should be admitted into the hospital because of a high risk of developing pneumonia and those who have high admission serum creatinine should receive high-efficacy medications in a setting where there were medication shortages due to high risk of disease progression. BA.4/5 could cause another wave of infection‚ although almost KTRs received full vaccination or were previously infected.
2007
Cited 7 times
Salmonella gas-forming femoral osteomyelitis and pyomyositis: the first case and review of the literature.
The authors describe the first case of Salmonella serogroup D gas-forming femoral osteomyelitis and pyomyositis in a 51-year-old man with non-Hodgkin lymphoma. The patient was successfully treated with surgical debridement as well as clindamycin plus ceftriaxone, and then switched to ciprofloxacin. However, he eventually died due to multidrug-resistant Acinetobacter baumannii pneumonia. In addition, five cases of Salmonella gas-forming pyomyositis in the literature were reviewed.
DOI: 10.7448/ias.17.4.19740
2014
Cited 4 times
Rilpivirine versus etravirine validity in NNRTI‐based treatment failure in Thailand
Introduction Etravirine (ETR) and rilpivirine (RPV) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV‐1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI‐based regimen [ 1 ]. RPV has profile with similar properties to ETR but this agent is approved for treatment‐naïve patients [ 2 ]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI‐based regimens: efavirenz (EFV)‐ or nevirapine (NVP)‐based regimen. Materials and Methods Data of clinical samples with confirmed virologic failure during 2003–2010 were reviewed. We selected the samples from patients who failed EFV‐ or NVP‐based regimen. Resistance‐associated mutations (RAMs) were determined by IAS‐USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV. Results A total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP‐based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV‐based regimen treatment failure (EFV group) were included. 95% of samples were HIV‐1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI‐RAMs and 20% had four to seven NNRTI‐RAMs. 181C mutation was the most common NVP‐associated RAM (54.3% vs 14.7%, p&lt;0.01). 103N mutation was the most common EFV‐associated RAM (56.5% vs 19.1%, p&lt;0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly higher than NPV group (ETR susceptibility 32.2% vs 11.1%, p&lt;0.01, RPV susceptibility 31.6% vs 10.9%, p&lt;0.01), respectively. Conclusions RPV might be a cost saving and reasonable second line NNRTI for patients who failed EFV‐ or NVP‐containing regimens, especially in resource‐limited setting because these two agents have comparable susceptibility identified by genotyping. From our study, approximately 30% of patients who failed EFV‐based regimens had viruses that remained susceptible to RPV.
DOI: 10.1016/s2055-6640(20)30692-0
2016
Cited 4 times
A qualitative assessment of barriers and facilitators to antiretroviral adherence in Thai patients
Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV.Semi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok.Median informant age was 43 years (range 27-60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART into their daily routine were key components of good adherence. Supportive and trusting relationships, particularly with the clinic team, empowered patients to maintain good medication adherence.Changing public perceptions about HIV, and training of HIV clinic staff on the importance of trusting and supportive provider-patient relationships in promoting good health outcomes, will help Thailand achieve its aim of having zero new HIV infections, zero discrimination and zero AIDS-related deaths by 2030.
DOI: 10.1002/rcr2.733
2021
Cited 4 times
Multimodality treatment in immunocompromised patients with severe <scp>COVID</scp>‐19: the role of <scp>IL</scp>‐6 inhibitor, intravenous immunoglobulin, and haemoperfusion
Abstract Cytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID‐19). Multiple anti‐inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life‐threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID‐19‐related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO 2 :FiO 2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID‐19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.
2019
Cited 4 times
Comparable carotid intima-media thickness among long-term virologically suppressed individuals with HIV and those without HIV in Thailand.
This study compared the carotid intima-media thickness (cIMT) among well suppressed adult participants living with HIV and adults without HIV, aged >45 years.A cross-sectional, age and sex-matched study was conducted at two sites in Thailand: King Chulalongkorn Memorial Hospital (KCMH) and HIV-NAT. All participants had no evidence of coronary artery disease (CAD). Ultrasonography of the carotid artery was measured by one well-trained neurologist who was blinded to the participants' care. The primary endpoint was the difference in cIMT between participants with HIV and controls without HIV. Prevalence and predictive risk of cIMT≥0.9 mm were determined.Of 90 individuals, 60 were living with HIV. The overall median (IQR) age was 54.1 (52-60) years and 53.3% were male. For the group with HIV, the median duration of ART was 15 years and 33% were on boosted PIs. Compared to controls without HIV, the group with HIV had a higher proportion of hypertriglyceridaemia (48.3% vs 26.7%, P=0.049) but the median overall cIMT of the common carotid arteries (0.665 mm vs 0.649 mm, P=0.277) and serum high-sensitivity C-reactive protein (hs-CRP) (1.59 mg/dL vs 1.46 mg/dL, P=0.325) were not different. Hs-CRP was not correlated with cIMT ≥0.9 mm. However, carotid plaques (n=6) were found only among the group with HIV. From the multivariate analysis, only male sex and hypertension were significantly associated with cIMT ≥0.9 mm.Well-controlled and long-term treated participants living with HIV had comparable cIMT to Thai adults without HIV. Monitoring for progression of cIMT, carotid plaques and cardiovascular disease in this population is warranted to guide continued management.
DOI: 10.20944/preprints202207.0174.v1
2022
Homologous or Heterologous COVID-19 Boosters Regimens Significantly Impact Sero-neutralization of SARS-CoV-2 Virus and Variants
We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.
DOI: 10.4103/ijdvl.ijdvl_637_16
2017
Cited 3 times
Subcutaneous Saksenaea vasiformis infection presenting as disfiguring facial plaques
DOI: 10.1101/2020.05.02.20087221
2020
Cited 3 times
Evaluating efficiency of pooling specimens for PCR-based detection of COVID-19
ABSTRACT In the age of a pandemic, such as the ongoing one caused by SARS-CoV-2, the world faces limited supply of tests, PPE and reagents, and factories are struggling to meet the growing demands. This study aimed to evaluate the efficacy of pooling specimen for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten specimens were pooled for testing, containing either one or two known positive specimen of varying viral concentrations. Pooling specimens did not affect the sensitivity of detecting SARS-CoV-2, and the PCR cycle threshold (Ct) between testing of pooling specimen and subsequent individual testing was not significantly different using paired t-test. This study also identified cost savings garnered from pooling of specimen for testing at 4 differing prevalence rates, ranging from 0.1-10%. Pooling specimens to test for COVID-19 infection in low prevalence areas or in low risk population can dramatically decrease the resources burden on lab operations by up to 80%. This paves the possibility for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with low incidence of infection, or with lower risk populations.
DOI: 10.1101/2020.09.06.20189480
2020
Cited 3 times
Antibody Responses to SARS-CoV-2 in Coronavirus Diseases 2019 Patients with Different Severity
Abstract Background More understanding of antibody responses in the SARS-CoV-2 infected population is useful for vaccine development. Aim To investigate SARS-CoV-2 IgA and IgG among COVID-19 Thai patients with different severity. Methods We used plasma from 118 adult patients who have confirmed SARS-CoV-2 infection and 49 patients under investigation without infection, 20 patients with other respiratory infections, and 102 healthy controls. Anti-SARS-CoV-2 IgA and IgG were performed by enzyme-linked immunosorbent assay from Euroimmun. The optical density ratio cut off for positive test was 1.1 for IgA and 0.8 for IgG. The association of antibody response with the severity of diseases and the day of symptoms was performed. Results From Mar 10 to May 31, 2020, 289 participants were enrolled, and 384 samples were analyzed. Patients were categorized by clinical manifestations to mild (n = 59), moderate (n = 27) and severe (n = 32). The overall sensitivity of IgA and IgG from samples collected after day 7 is 87.9% (95% CI 79.8-93.6) and 84.8% (95% CI 76.2-91.3), respectively. The severe group had a significantly higher level of specific IgA and IgG to S1 antigen compared to the mild group. All moderate to severe patients have specific IgG while 20% of the mild group did not have any IgG detected after two weeks. Interestingly, SARS-CoV-2 IgG level was significantly higher in males compared to females among the severe group (p = 0.003). Conclusion The serologic test for SARS-CoV-2 has high sensitivity after the second week after onset of illness. Serological response differs among patients with different severity and different sex.
DOI: 10.1177/2050313x211024471
2021
Cited 3 times
The first report of kidney transplantation in a human immunodeficiency virus–positive recipient in Thailand and literature review: Encouragement for developing countries in Southeast Asia
Patients with human immunodeficiency virus infection are at risk of chronic kidney disease and end-stage renal disease. Human immunodeficiency virus infection impedes patients' accessibility to transplantation in Thailand and other developing countries in Southeast Asia, where the burdens of human immunodeficiency virus infection and chronic kidney disease are rapidly increasing. We report the successful kidney transplantation in a human immunodeficiency virus-positive recipient in Thailand and provide brief information about the current knowledge of human immunodeficiency virus medicine and transplantation that are needed for conducting kidney transplantations in such patients. Patient selection and evaluation, the choice of antiretroviral therapy, immunosuppressive regimens, and infectious complications are reviewed and discussed. The aim is to encourage kidney transplantation in end-stage renal disease patients with well-controlled human immunodeficiency virus infection, especially in countries where the prevalence of human immunodeficiency virus infection is high and the accessibility to transplantation is still limited.
DOI: 10.21203/rs.3.rs-2482226/v1
2023
Simultaneous Detection of Omicron and Other SARS-CoV-2 Variants by Multiplex PCR MassARRAY Technology
Abstract The rapid emergence of SARS-CoV-2 variants with high severity and transmutability adds further urgency for rapid and multiplex molecular testing to identify the variants. A nucleotide matrix-assisted laser-desorption-ionization time-of-flight mass spectrophotometry (MALDI-TOF MS)-based assay was developed (called point mutation array, PMA) to identify four major SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Delta, and Omicron (namely PMA-ABDO) and differentiate Omicron subvariant (namely PMA-Omicron). PMA-ABDO and PMA-Omicron consist of 24 and 28 mutation sites of the spike gene. Both PMA panels specifically identified VOCs with as low as 10 viral copies/ µl. The panel has shown a 100% concordant with the Next Generation Sequencing (NGS) results testing on 256 clinical specimens with real-time PCR cycle threshold (Ct) values less than 26. It showed a higher sensitivity over NGS; 25/28 samples were positive by PMA but not NGS in the clinical samples with PCR Ct higher than 26. Due to the mass of nucleotide used to differentiate between wild-type and mutation strains, the co-infection or recombination of multiple variants can be determined by the PMA method. This method is flexible in adding a new primer set to identify a new emerging mutation site among the current circulating VOCs and the turnaround time is less than 8 hours. However, the spike gene sequencing or NGS retains the advantage of detecting newly emerged variants.
DOI: 10.2217/fvl-2023-0019
2023
The 25th Bangkok International Symposium on HIV Medicine
Proceedings of: 25th Bangkok International Symposium on HIV Medicine, 18–20 January 2023, held virtually and on site at Samyan Mitrtown Hall, Bangkok, Thailand. The Bangkok International Symposium on HIV Medicine has commenced on the third Wednesday of January since 1998. The Symposium aims to provide professional healthcare workers in Thailand and the region an opportunity to receive the most up-to-date information on HIV and its related conditions if they are unable to attend other HIV conferences abroad. This year’s hybrid symposium was held from 18 January to 20 January 2023. A total of six plenary sessions were held in the mornings, and four afternoon workshops held on Wednesday and Thursday. Expert speakers from Thailand, China, Malaysia, Singapore, India, Hong Kong, the Philippines, Australia, the UK, The Netherlands and the USA participated in the symposium.
DOI: 10.1016/j.jvacx.2023.100334
2023
Long-term immunogenicity in previously vaccinated healthcare workers with inactivated virus vaccine after SARS-CoV-2 infection or booster vaccination
Immunity against SARS-CoV-2 infection in vaccinated individuals varies based on the vaccine type, duration after vaccination or infection, and SARS-CoV-2 variant type. We conducted a prospective observational study to evaluate the immunogenicity of a booster vaccination with AZD1222 after two doses of CoronaVac (booster group) compared to individuals who had SARS-CoV-2 infection after receiving two doses of CoronaVac (infection group). We used a surrogate virus neutralization test (sVNT) to evaluate immunity against wild-type and Omicron variant (BA.1) at 3 and 6 months after infection or booster dose. Of the 89 participants, 41 were in the infection group, and 48 were in the booster group. At 3 months post-infection or booster vaccination, the median (IQR) sVNT against wild-type was 97.87 % (97.57-97.93 %) and 97.65 % (95.38-98.00 %), p = 0.66, respectively, while the sVNT against Omicron was 18.8 % (0-47.10 %) and 24.46 (11.69-35.47 %), p = 0.72 respectively. At 6 months, the median (IQR) sVNT against wild-type was 97.68 % (95.86-97.92 %) in the infection group, higher than 94.7 % (95.38-98.00 %) in the booster group (p = 0.03). Results showed no significant difference in immunity against wild-type and Omicron at 3 months between the two groups. However, the infection group exhibited better immunity than the booster group at 6 months.
DOI: 10.1109/ssp53291.2023.10208057
2023
AI-assisted monitoring of COVID-19 community isolation in Thailand
By minimizing human movement and contact, community isolation is an effective containment measure for the COVID-19 pandemic, especially against later strains that cause less severe symptoms. Nonetheless, a significant number of patients who enter community isolation with mild symptoms eventually develop severe pneumonias and require hospitalization. Therefore, the ability to foresee severe cases would be indispensable for managing limited medical resources. Here, we developed a proof-of-concept machine learning model, using daily vital signs data from 1,123 community isolation patients in Bangkok, Thailand, that can predict future hospitalization events up to 3 days in advance with an area under the precision-recall curve of 0.95. The model requires simple inputs, including body temperature, pulse rate, peripheral oxygen saturation, and shortness of breath, that the patients can self-perform and report. Hence, our approach can aid clinicians in providing remote, proactive healthcare service in broad settings
DOI: 10.21203/rs.3.rs-3591227/v1
2023
An unusual diarrheal outbreak in the community in Eastern Thailand caused by Norovirus GII.3[P25]
Abstract Background Sentinel laboratory surveillance for diarrheal disease determined norovirus to be the most common cause of non-bacterial gastroenteritis in people during the COVID-19 pandemic in Thailand. An increase in patients presenting with diarrhea and vomiting in hospitals across Chanthaburi province between December 2021 and January 2022 led to the need for the identification of viral pathogens that may be responsible for the outbreak. Methods Feces samples (rectal swabs or stool) from 93 patients, of which 65 patients were collected during the December 2021 to January 2022 outbreak, were collected and screened for viral infection by real-time RT-PCR. Positive samples for norovirus GII were then genotyped by targeted amplification and sequencing of partial polymerase and capsid genes. Whole genome sequencing was performed from the predominant strain, GII.3[P25]. Results Norovirus was the most common virus detected in human fecal samples in this study. 39 of 65 outbreak samples (60%) and 3 of 28 (10%) non-outbreak samples were positive for norovirus genogroup II. One was positive for rotavirus, and one indicated co-infection with rotavirus and norovirus genogroups I and II. Nucleotide sequences of VP1 and RdRp gene were successfully obtained from 28 of 39 positive norovirus GII and used for dual-typing; 25/28 (89.3%) were GII.3, and 24/28 (85.7) were GII.P25, respectively. Norovirus GII.3[P25] was the predominant strain responsible for this outbreak. The whole genome sequence of norovirus GII.3[P25] from our study is the first reported in Thailand and has 98.62% and 98.57% similarity to norovirus found in China in 2021 and USA in 2022, respectively. We further demonstrate the presence of multiple co-circulating norovirus genotypes, including GII.21[P21], GII.17[P17], and unassignable RdRp in GII.3 and GII.4 in our study. Conclusions An unusual diarrhea outbreak was found in December 2021 in eastern Thailand. Norovirus strain GII.3[P25] was the cause of the outbreak and was first detected in Thailand. The positive rate during GII.3[P25] outbreak was six times higher than sporadic cases (GII.4), and, atypically, adults were the primary infected population rather than children.
DOI: 10.1093/ofid/ofad500.1973
2023
2352. The Dynamic Change in Humeral Immunity Against SARS-CoV-2 Omicron Subvariants in Patients with Breakthrough Infection: The Prospective Cohort Study
Abstract Background The SARS-CoV-2 continued to emerge new variants. Omicron variants had become world predominance. There were increase in number of breakthrough infections. This study aimed to evaluated immunity after breakthrough infections in Thai patients, given high varieties of vaccination regimens. Methods We conducted a cohort study at King Chulalongkorn Memorial Hospital (KCMH) and enrolled participants with breakthrough infections during April 2022 in outpatient setting. Serum sample was evaluated at baseline, 1-month, and 3-months post-infection. Surrogate virus neutralization test (sVNT), using cPASS GenScriptTM, was used to evaluate the neutralizing capacity against SARS-CoV-2 wild-type and Omicron variants. Results A total of 109 participants were enrolled, with a median age of 36 years (IQR: 28-45). Nine vaccination regimens were observed, with all but one participant receiving at least one dose of booster vaccination. The most common duration from last vaccination to enrollment was 3-4 months. SARS-CoV-2 Omicron BA.2 was the predominant strain (97.8%). At baseline, the highest sVNT was observed against wild-type, followed by Omicron BA.2 and Omicron BA.1. At 1-month post-infection, we observed a non-significant increase in sVNT against wild-type (p=0.11), but a significant increase in antibodies against Omicron BA.2 (p &amp;lt; 0.01) then stable at 3-month post-infection. Of the participants, 31 received a booster vaccine before the scheduled 3-month follow-up, and their sVNT levels at 3-month post-infection were similar to those who did not receive a booster. This study found no difference in post-infection sVNT level across previous vaccination regimens.Table 1Baseline characteristics of participants Table 1: Baseline characteristics of participants. Continuous data are presented as median and interquartile range (IQR). Categorical data are presented as number and percentage. Baseline sVNT against SARS-CoV-2 wild type, Omicron BA.1, and Omicron BA.2 Figure 1A Baseline sVNT (%) results for SARS-CoV-2 wild type, Omicron BA.1, and Omicron BA.2. Figure 1B Baseline sVNT (%) results for SARS-CoV-2 wild type, Omicron BA.1, and Omicron BA.2 stratified by time from last vaccination. Error bars represent 95% confidence interval of means. ns: non-significant, *p&amp;lt;0.05, **p&amp;lt;0.01.Figure 2shows the dynamics of sVNT (%) against SARS-CoV-2 wild type and Omicron BA.2. Participants who received booster vaccination before 3 months were excluded. Conclusion Our study suggests that, in outpatient setting, neutralizing antibody responses to wild-type and Omicron BA.2 are durable up to three months following natural infection regardless of previous vaccination regimens. Further research is needed to determine the long-term durability of these immune responses and the need for booster vaccination in the context of emerging SARS-CoV-2 variants Disclosures All Authors: No reported disclosures
DOI: 10.1093/ofid/ofad500.1432
2023
1597. Randomized-Controlled Trial Evaluating The Outcome Between Switching to Tenofovir Disoproxil Fumarate(TDF)/Lamivudine(3TC)/Dolutegravir(DTG) Versus Maintaining The Current NNRTI Or Boosted-PI-containing Regimen in PLWH in Thailand – A Pilot Study from Single Center
Abstract Background The Thai and WHO HIV 2022 guidelines have recently adopted TDF/3TC/DTG (TLD; single tablet) as the preferred regimen replacing NNRTI- or boosted-PI-based cART among both treatment-naïve and -experienced PLWH. Virologic and metabolic outcomes are scarce after switching to TLD compared with maintaining the same ART. Additionally, there are concerns regarding an increase in metabolic complications after switching to a DTG-based regimen, especially weight gain and possible subsequent metabolic syndrome. Previous data mostly consisted of the non-Asian population. Methods We enrolled virologically suppressed PLWH age ≥18 years currently on NNRTI or boosted-PI-containing cART and randomized to either switching to TLD or maintaining their current cART during 2019-2021 at our tertiary care center. The primary outcome was virological suppression &amp;lt; 50 copies/mL at 48 weeks. Secondary outcomes were changes in CD4 counts, body weight, waist circumferences, metabolic profile, 9 questions depression rating scale (9Q), and sleeping quality measure by the Thai version of the Pittsburgh sleep quality index (T-PSQI) questionnaires at 48 weeks. Results The study population comprised 48 persons; 23 were switched to TLD, and 25 continued their current cART. Seventy-eight and ninety-two percent of participants had an EFV-based regimen prior to switching in the TLD and cART group, respectively. The median age was 25 years and 80% were male. At 48 weeks, 19 and 20 in the TLD and current cART completed the follow-up. Baseline characteristics were shown in Table 1. Virological suppression was achieved in 100% vs. 90% in the TLD and current cART group, respectively (p=0.487). In addition to increasing sleeping quality, LDL and cholesterol significantly decreased after switching to TLD compared with the current ART (Figure 1). Waist circumference and BMI changes did not significantly differ between the two groups.Table 1.Baseline characteristics of all participants The baseline characteristics of all participants demonstrated differences in the baseline T-PSQI in which the TLD group had a slightly higher median than the cART group. Asterisk represented a significant difference. Figure 1. Mean changes of each parameter at 48 weeks post-switching There was a significant reduction of cholesterol, LDL, and T-PSQI at 48-week post-switching in the TLD group than cART group. The lower T-PSQI represented better sleeping quality. Conclusion Switching to TLD in PLWH maintained high virological suppression and achieved a favorable lipid profile and sleeping quality than maintaining NNRTI- or booster-PI-based regimen. Body weight and BMI changes were comparable and there was a trend toward a more favorable FIB-4 score in the TLD group. Our study supports the recommendation of switching to TLD among Thai PLWH. Disclosures All Authors: No reported disclosures
DOI: 10.1155/2023/4940767
2023
High Transmission Rates of Early Omicron Subvariant BA.2 in Bangkok, Thailand
The emergence of Omicron as the fifth variant of concern within the SARS-CoV-2 pandemic in late 2021, characterized by its rapid transmission and distinct spike gene mutations, underscored the pressing need for cost-effective and efficient methods to detect viral variants, especially given their evolving nature. This study sought to address this need by assessing the effectiveness of two SARS-CoV-2 variant classification platforms based on RT-PCR and mass spectrometry. The primary aim was to differentiate between Delta, Omicron BA.1, and Omicron BA.2 variants using 618 COVID-19-positive samples collected from Bangkok patients between November 2011 and March 2022. The analysis revealed that both BA.1 and BA.2 variants exhibited significantly higher transmission rates, up to 2-3 times, when compared to the Delta variant. This research presents a cost-efficient approach to virus surveillance, enabling a quantitative evaluation of variant-specific public health implications, crucial for informing and adapting public health strategies.
DOI: 10.1177/23259582231220513
2023
Treatment Outcomes After Switching to Second-Line Anti-Retroviral Therapy: Results From the Thai National Treatment Program
This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.
DOI: 10.1155/2018/4759807
2018
Orbital and Pulmonary Actinomycosis: The First Case Report and Literature Review
Orbital actinomycosis is a very rare clinical manifestation of orbital infection caused by Actinomyces species, anaerobic Gram-positive filamentous bacteria. We report herein a case of a 58-year-old man who presented with chronic progressive course of total ophthalmoparesis in association with productive cough, leading to the diagnosis after extensive investigation. In addition, all reported cases of orbital actinomycosis in the literature are reviewed.
DOI: 10.1016/j.virol.2020.12.012
2021
U.S.-Japan cooperative medical sciences program: 22nd International Conference on Emerging Infectious Diseases in the Pacific Rim
This review summarizes the presentations given at the 22nd International conference on Emerging Infectious Diseases in the Pacific Rim. The purpose of this annual meeting is to foster international collaborations and address important public health issues in the Asia-Pacific region. This meeting was held in Bangkok in February 2020 and focused on emerging virus infections. Unexpectedly, the SARS-CoV-2 pandemic was in the initial stages leading to a special session on COVID-19 in addition to talks on dengue, influenza, hepatitis, AIDS, Zika, chikungunya, rabies, cervical cancer and nasopharyngeal carcinoma.
DOI: 10.3855/jidc.14852
2022
Use of qRT-PCR for SARS-CoV-2 sgRNA leader for the therapeutic plan: a preliminary report on 10 patients
Introduction: Duration of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) shedding is important for infection control. The presence of SARS-CoV-2 subgenomic RNA (sgRNA) leader indicates that the virus is replicative. This study examined the shedding duration of SARS-CoV-2 sgRNA leader and genomic RNA (gRNA) in diverse respiratory specimens.&#x0D; Methodology: One hundred and eleven respiratory specimens collected sequentially from 10 COVID-19 patients with real-time RT-PCR SARS-CoV-2 orf1ab gene confirmed positive admitted to King Chulalongkorn Memorial Hospital were examined for SARS-CoV-2 E sgRNA leader and E gRNA by using Real-time reverse transcription PCR (qRT-PCR). These specimens included nasopharyngeal swab and throat swabs, nasal swab and throat swabs, sputum, and endotracheal aspirate, and were collected from the first day of admission until the time of orf1ab real-time RT-PCR negative of at least 2-4 consecutive days.&#x0D; Results: E sgRNA leader could only be detectable in specimens with ≥ 1E+05 virus E gene copies per ml within the first 15 days after hospitalization. SARS-CoV-2 sgRNA leader was undetectable from one to 15 days earlier than that of gRNA in all patients. Re-shedding of sgRNA was evident in 2 cases, both on a single occasion after being undetectable for 3-10 days.&#x0D; Conclusions: Assessment of the presence of sgRNA leader may be useful for therapeutic planning.
DOI: 10.1016/s0924-8579(07)70047-x
2007
O58 Presence of dengue virus genome in the bone marrow of asymptomatic adults in a dengue-hyperendemic country: implication for complicated dengue pathogenesis
A novel electrochemical method was employed to accurately measure the kinetics of H2O2 decomposition on the surface of magnetite at elevated temperatures and pressures. Electrochemical impedance spectroscopy was used to probe the decay of H2O2 concentration by tracking the charge transfer resistance on the surface of a platinum electrode. It was found that the decomposition kinetics follow a first-order rate law with respect to H2O2 concentration and vary from 8.1 × 10−4 to 7.9 × 10−2 min−1 when the temperature increases from 298 to 473 K (for a 0.2 g L−1 magnetite suspension). The mean calculated activation energy of 30 ± 1 kJ mol−1 showed that H2O2 decomposition on the surface of magnetite particles is a chemically controlled process.
DOI: 10.2217/fvl.12.135
2013
Rilpivirine in treatment-naive patients: what did we learn from the THRIVE and ECHO studies?
Rilpivirine is a new non-nucleoside reverse transcriptase inhibitor with potent activity against HIV-1. The THRIVE and ECHO studies are multinational, randomized, placebo-controlled, double-blinded clinical trials that evaluated the efficacy of rilpivirine once daily versus efavirenz once daily in initial antiretroviral regimen for treatment-naive patients. At week 48 of treatment, rilpivirine was noninferior to efavirenz by the intention-to-treat time-to-loss-of-virologic-response. Of note, patients treated with rilpivirine had a higher rate of virologic failure whereas those treated with efavirenz had a higher rate of adverse events-associated discontinuation. The lower response among patients on rilpivirine compared with efavirenz was observed when pretreated plasma viral load was &gt;100,000 copies/ml. Rilpivirine improved tolerability versus efavirenz particularly for dizziness, abnormal dream, rash and dyslipidemia. Patients with rilpivirine-associated mutations had a likelihood for reduced susceptibility to other non-nucleoside reverse transcriptase inhibitors, especially etravirine, in subsequent antiretroviral regimens. Rilpivirine is contraindicated for use with proton-pump inhibitors.
DOI: 10.1186/s12879-022-07439-7
2022
Behavioral–biological surveillance of emerging infectious diseases among a dynamic cohort in Thailand
Interactions between humans and animals are the key elements of zoonotic spillover leading to zoonotic disease emergence. Research to understand the high-risk behaviors associated with disease transmission at the human-animal interface is limited, and few consider regional and local contexts.This study employed an integrated behavioral-biological surveillance approach for the early detection of novel and known zoonotic viruses in potentially high-risk populations, in an effort to identify risk factors for spillover and to determine potential foci for risk-mitigation measures.Participants were enrolled at two community-based sites (n = 472) in eastern and western Thailand and two hospital (clinical) sites (n = 206) in northeastern and central Thailand. A behavioral questionnaire was administered to understand participants' demographics, living conditions, health history, and animal-contact behaviors and attitudes. Biological specimens were tested for coronaviruses, filoviruses, flaviviruses, influenza viruses, and paramyxoviruses using pan (consensus) RNA Virus assays.Overall 61/678 (9%) of participants tested positive for the viral families screened which included influenza viruses (75%), paramyxoviruses (15%), human coronaviruses (3%), flaviviruses (3%), and enteroviruses (3%). The most salient predictors of reporting unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) in the past year were having other household members who had unusual symptoms and being scratched or bitten by animals in the same year. Many participants reported raising and handling poultry (10.3% and 24.2%), swine (2%, 14.6%), and cattle (4.9%, 7.8%) and several participants also reported eating raw or undercooked meat of these animals (2.2%, 5.5%, 10.3% respectively). Twenty four participants (3.5%) reported handling bats or having bats in the house roof. Gender, age, and livelihood activities were shown to be significantly associated with participants' interactions with animals. Participants' knowledge of risks influenced their health-seeking behavior.The results suggest that there is a high level of interaction between humans, livestock, and wild animals in communities at sites we investigated in Thailand. This study highlights important differences among demographic and occupational risk factors as they relate to animal contact and zoonotic disease risk, which can be used by policymakers and local public health programs to build more effective surveillance strategies and behavior-focused interventions.
DOI: 10.1016/s0924-8579(07)71640-0
2007
P1801 Significance of Streptococcus bovis biotype II/2 bacteraemia in patients with chronic liver diseases
DOI: 10.22541/au.158938622.21516968
2020
Cold agglutinin disease following SARS-CoV-2 and Mycoplasma pneumoniae co-infections
During coronavirus disease 2019 (COVID-19) pandemic, coinfections with other viral infections are not uncommon, but concomitant atypical bacteria are rare.Herein, we describe a young female COVID-19 patient who developed acute cold agglutinin disease secondary to Mycoplasma pneumoniae.Using an azithromycin-containing COVID-19 therapeutic regimen, both pneumonia and anemia resolved uneventfully.
DOI: 10.1093/ofid/ofz360.2169
2019
2491. Virologic Response of Switching Tenofovir Disoproxil Fumarate (TDF)-Based Regimen to Abacavir (ABC)-Based Regimen vs. Lopinavir/Ritonavir(LPV/r) Plus Lamivudine(3TC) in HIV-Infected Patients with TDF-Induced Nephrotoxicity at 24 Weeks: A Prospective, Open-Label, Randomized, Controlled Trial
DOI: 10.21203/rs.3.rs-36338/v1
2020
Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)
Abstract Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon co morbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods : Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. Result: Altogether , 228 patients [ 185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR=2.1(1.1-3.7), p=0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR=8.1(1.9-38.8), p=0.002) predisposed more to liver injury than those without these . Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5(11.6%)] or acute decompensation [4(9%)]. Liver related complications increased (p&lt;0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC-0.94, HR=19.2(95CI 2.3-163.3), p&lt;0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis. Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.
DOI: 10.2217/fvl-2016-0017
2016
Updates on HIV treatment and prevention from Asia's HIV symposium: the 18th Bangkok International Symposium on HIV Medicine
The 18th Bangkok International Symposium on HIV Medicine, Queen Sirikit National Convention Centre, Bangkok, Thailand, 13–15 January 2016 Consistent with HIV-NAT's mission, quality training is provided to many professional healthcare workers in the region by taking the latest knowledge from research and presenting it locally at the Bangkok International Symposium of HIV Medicine. The symposium is offered every third week of January for 3 days. Some of the plenary session content is presented below.
DOI: 10.3410/f.718892783.793500534
2014
Faculty Opinions recommendation of A mechanistic theory to explain the efficacy of antiretroviral therapy.
2011
Disseminated invasive aspergillosis of the brain and spine
We report a case of 27-year-old female with steroid using presented with progressive headache for 2 months followed by lower back pain. Computed tomography of the brain revealed brain abscess at multiple sites and MRI of thoracolumbar spine showed spondylodiscitis at T9-10 level. Open brain biopsy was done and the histopathology demonstrated fungal with septate hyphae. Voriconazole was administered as a drug of choice. After 2 weeks of the treatment, symptoms were improved and follow-up imaging was improved also. (J Infect Dis Antimicrob Agents 2011;29:83-7.)
DOI: 10.2217/fvl-2017-0016
2017
Decades research and implementation science of HIV prevention, treatment and cure: highlights from Symposium 2017
The 19th Bangkok International Symposium on HIV Medicine, Bangkok, Thailand, 18–20 January 2017 This training is one of the most established and largest, with up-to-date information provided by well-renowned international speakers and hence considered one of the best in the Asia Pacific region. The Symposium is offered every third week of January for three full days. Celebrating HIV Netherlands Australia Thailand research collaboration's 20th anniversary, for the first time, the sessions were covered real-time through webcasts, streamed live via the internet. Speakers included community advocates voicing and addressing certain issues, and the entire third day was dedicated to symposiums. HIV Netherlands Australia Thailand research collaboration continues to strive to provide well-rounded trainings of quality to the region's professional healthcare workers, hoping to significantly impact the delivery of health services. Noteworthy sessions have been briefly summarized in this report.
DOI: 10.1093/ofid/ofx163.710
2017
Infectious Causes and Infectious Mimics of Acute Encephalitis: a Prospective Study from Thailand
Abstract Background Previous reports of infectious encephalitis in Thailand showed viruses as major pathogens similar to worldwide data. Major viruses in studies varied among Japanese encephalitis, Enteroviruses and Herpesviruses. Infectious etiologies vary by regions, seasons and preventive strategies done. Dynamic change of pathogen is believed to occur continually. Local data in each region is important to develop an algorithm of investigations for the cost-effectiveness. Methods This is a prospective study of patients with encephalitis between January 2014 to March 2017 at a tertiary hospital in Bangkok. Microbiological and serological studies were done according to an algorithm based on initial cerebrospinal fluid analysis. Initial tests were for bacteria, fungus, mycobacterium and commonly prevalent viruses. Further tests for infectious etiology were done by stepwise approach if initial tests yielded negative. Results Fifty-two patients were enrolled. Twenty-seven (51.9%) patients had no etiology identified. Three patients (5.8%) had bacterial etiology, 10 (19.2%) had viral etiology, and 12 (23%) had immune-mediated encephalitis. Among viral etiologies, VZV was identified in 4 cases, HSV in 3 cases, CMV in 2 cases and measles in 1 case. Baseline characteristic of HIV infection or skin rash was associated with viral infection (p 0.031, p 0.006). Patients with VZV encephalitis might not have active skin lesion. The presence of prodrome, duration of prodrome, neurological onset to peak and physical examination of focal neurodeficit, meningeal irritation signs, and reflex were similar across all etiologies. White blood cell [mean 7.0 (range 0–30) cells/µL] and protein [mean 32.5 (range 11–70.4) mg/dL] from the cerebrospinal fluid of noninfectious etiologies tended to be lower than the levels of infectious causes (p 0.009, p 0.020). All patients survived at 7 days after admission. Conclusion A quarter of patients presenting with acute encephalitis in this study had autoimmune and paraneoplastic encephalitis. Infections caused by herpesviruses was the most prevalent viral etiology. Autoimmune and paraneoplastic encephalitis should be kept in the differential diagnosis in patients with acute encephalitis. Disclosures S. Wacharapluesadee, USAID: Investigator, Research grant. O. Putcharoen, USAID: Grant Investigator, Research grant.
DOI: 10.5372/abm.v2i3.186
2008
It is time to change the starting point of initiating antiretroviral therapy and to advocate more active HIV testing
DOI: 10.22541/au.164864881.18046394/v1
2022
Benefits of Early Combination Antiviral Treatment Containing Favipiravir for COVID-19 in Thailand
We report the clinical outcomes following implementation of initial COVID-19 treatment guidelines in Thailand. A composite poor outcome was defined as death, ICU admission, requiring intubation, or high-flow oxygen. 744 COVID-19 patients (48.8% male) were included, median (IQR) age was 37 (27-48) years [8.4% &gt;60 years] and 21.4% had pneumonia at admission. Admission &lt;4 days from symptom onset had a reduced risk of poor outcome. In a subgroup analysis, favipiravir use reduced the risk of a poor outcome for patients admitted &lt;4 days from symptom onset (OR 0.320 (0.152-0.662), P=0.003). Thai guidelines now include favipiravir to treat all symptomatic COVID-19 patients.
DOI: 10.1016/s0016-5085(22)60675-9
2022
Sa1048: PREDICTORS OF VIRAL SHEDDING IN FECAL SAMPLES AMONG CORONAVIRUS DISEASE 2019 (COVID-19) PATIENTS AND SUBSEQUENT FUNCTIONAL GASTROINTESTINAL DISORDERS (FGIDS)
2022
Early switching of tenofovir disoproxil fumarate (TDF) in HIV-infected patients with TDF-induced nephrotoxicity: a prospective study.
Background: Tenofovir disoproxil fumarate (TDF) can induce proximal renal tubulopathy (PRT) and necessitate changes in treatment regimen. This prospective study aimed to compare tubular function recovery following early switching versus late switching of TDF in human immunodeficiency virus (HIV)-infected patients with TDF-induced PRT.Methods: For this prospective study, conducted during 2017-2019, we enrolled HIV-1-infected, virologically suppressed adults undergoing TDF-containing combination antiretroviral therapy. Patients were separated into a late-switching group (LSG) and an early-switching group (ESG). The LSG included patients having an estimated glomerular filtration rate (eGFR) decrease ≥25% from the pretreatment level or Fanconi syndrome. The ESG included patients having ≥2 of the following indicators of PRT: fractional excretion of phosphate (FEUP) ≥10%, low tubular maximum reabsorption of phosphate (TmP)/GFR, or uricosuria; fractional uric acid excretion ≥10%; urine protein-creatinine index (UPCI) ≥500 mg/g creatinine, normoglycemic glycosuria, or decrease in eGFR of 15%-24%. Recovery of proximal tubular function at 6 and 12 months after TDF discontinuation was assessed. Complete recovery was defined as normalization of all abnormal tubular markers.Results: Thirty-three HIV-infected patients were enrolled (70% male). Except for tubular function markers, baseline characteristics were not significantly different between the two groups. The proportion of patients having complete recovery was significantly higher in the ESG (p = 0.007, log-rank test). FEUP improved significantly in the ESG after TDF discontinuation; improvements of eGFR and UPCI were greater in the LSG. An eGFR change of 10% from baseline was the only independent predictor of failure to achieve complete recovery after switching. After median follow-up of 2.25 years post-trial, sustained recovery of eGFR within 5% of pre-TDF eGFR was achieved only in the ESG.Conclusions: Early-switching of TDF in HIV patients with PRT may allow complete recovery of proximal renal tubular function.
DOI: 10.1016/s0924-8579(07)70111-5
2007
O171 A comparative study of treatment outcome in cryptococcal meningitis in HIV-infected patients during period before versus after implementation of treatment guidelines for management of increased intracranial pressure
DOI: 10.1016/s0924-8579(07)70902-0
2007
P1062 Brucellosis in Thailand: emerging and enigmatic
To investigate the rabies antigen and antibody prevalences among stray dogs in Bangkok, Thailand, we took both a saliva and serum sample from each of 3314 stray dogs captured once each between December 2003 and June 2004. One 2-year-old female was antigen positive in the latex-agglutination test and confirmed by reverse transcription-polymerase chain reaction. The overall antibody seroprevalence from the enzyme-linked immunosorbent assay that we used was 62% (95% CI: 54, 70%). Antibody seroprevalence was greater for dogs captured within central Bangkok (86% of 1208 dogs captured) than in the dogs captured in the outskirts of the greater metropolitan area (49% of 2106 dogs captured). If our samples of stray dogs are representative, then the seroprevalence achieved from previous vaccination campaigns is too low to protect the dog and human populations.
2007
Detection of Dengue Virus in Bone Marrow by Reverse Transcription-Polymerase Chain Reaction
Backbround: Our country is considered endemic for dengue virus infection. Serosurveillance indicates that almost all adults have been infected, mostly asymptomatically. A long-held mechanism for clinical severity involves sequential infections by different serotypes. Even though some of its peer flaviviruses are known to reside persistently within the host and contribute to host illnesses, dengue virus has not been shown to behave in a similar fashion. As dengue is a hematotropic virus, we sought to find evidence of its persistence in the bone marrow of previously-infected persons. Methods: We studied patients clinically suspected of hematologic malignancies and indicated to have diagnostic bone marrow studies. A fraction of cellular marrow was employed for RNA extraction for reverse transcriptionpolymerase chain reaction (RT-PCR) by dengue-specific primers. Serologic assessment by hemagglutunation inhibition test (HI) and enzyme-linked immunosorbent assay (ELISA) was performed to minimize a chance of including patients with recent dengue infection. Demographic data of all patients were analyzed, especially for the history of prior recent febrile illness and diagnosis of dengue infection. Results: Of 73 enrolled patients, dengue genome was detected in cellular marrow of three cases. These patients had had no history of febrile illness prior to the bone marrow study, and HI and ELISA results of single or paired sera of from these patients were, similar to those of the rest, compatible with either remote or remote/no infection by flaviviviruses. An indication for bone marrow examination in these patients was a follow-up examination, and pathological results also confirmed they were in the stage of
DOI: 10.1093/ofid/ofz360.421
2019
348. Kidney Function Decline Among HIV-infected Thai Adults: Is Low Vitamin D One of the Factors?
Abstract Background The prevalence of both hypovitaminosis D and Chronic Kidney disease (CKD) are high among Thai HIV-infected adults. Therefore, we examined the association of hypovitaminosis D and kidney function decline among HIV-infected Thai adults. Methods Using data prospectively collected from the HIV-NAT long-term cohort, we selected patients who were on ART, and virologically suppressed for ≥6 months. Baseline was defined as when the patient had a serum 25 OHD measured, with estimated Glomerular filtration rate (eGFR) above 60 mL/minute. Participants with eGFR measured at least twice a year were analyzed in the study. The primary outcome was kidney function impairment assessed as eGFR decline. Generalised estimating equations (GEE) were used to assess associations between the outcome and patient comorbidities and disease-related characteristics, including age, sex, body mass index (BMI) hypertension, gout, diabetes mellitus, co-infections with Hepatitis B or C viruses HIV-viral load and co-variate interactions with vitamin D status defined as normal, insufficient or deficient. Results A total of 435 participants were observed longitudinally through observations over the median follow-up of 24 (IOR 12–48) months. The median age of the participants was 46.6 (IOR 38.06–54.29) years. Median serum 25 OHD was 23.4 (IQR 18.5–29) ng/mL, and 209 (48%) and 126(29%) had insufficient and deficient 25 OH levels, respectively. Median baseline eGFR was 95 (IQR 82.70–104.93) mL/minute/l.73 m2. We found a significant interaction between BMI and vitamin D concentration (P = 0.02). In our multivariate model, the adjusted mean predictions of eGFR change at 24 months for patients with BMI ≥25 kg/m2 and deficient, insufficient and sufficient vitamin D were 89.8 (88.3–91.4), 91.2 (90.1–92.4) and 92.8 (91.3–94.4), respectively. In those with BMI &lt;25 kg/m2 and deficient, insufficient and sufficient Vitamin D the adjusted mean predictions in eGFR change were 92.0 (91.1–93.0), 91.6 (90.9–92.3) and 92.3 (91.3–93.3), respectively. Conclusion HIV-infected Thai adults with high BMI (25 and above) but who are vitamin D deficient had a statistically significant eGFR decline. Further studies in larger populations with multi-ethnic groups are warranted. Disclosures All authors: No reported disclosures.
DOI: 10.2139/ssrn.3605137
2020
SARS-CoV-2 Pandemic Response, Clinical Characteristics and Outcomes at Bangkok's Largest Emerging Diseases Clinical Centre
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DOI: 10.2139/ssrn.3611970
2020
Pre-Existing Liver Disease Is Associated with Poor Outcome in Patients with SARS CoV-2 Infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)
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2021
Assessement of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
Thailand encountered its first coronavirus disease 2019 (COVID-19) outbreak in March 2020 and the Thailand Ministry of Public Health rapidly developed COVID-19 treatment guidelines. In this study we aimed to describe the outcomes among patients treated following those initial guidelines and determine factors significantly associated with poor outcomes in order to inform efforts to improve COVID-19 treatment guidelines for Thailand. Nine hospitals in Bangkok submitted data from their COVID-19 patients using standardized case record forms. A poor outcome was defined as death, ICU admission, requiring intubation or requiring high-flow oxygen. Factors associated with these outcomes were assessed. A total of 744 patients (48.8% male) were included in the study. The median (interquartile range) age of study subjects was 37 (27-48) years; 8.4% were aged >60 years, 5.6% of subjects were obese and 16.5% had underlying conditions: obesity, immunocompromised status, diabetes, chronic conditions of lungs, kidneys, liver, cardiovascular or cerebrovascular systems or had an absolute lymphocyte count 60 years (adjusted odds ratio (aOR): 2.50, 95% confidence interval (CI): 1.17-5.36, p = 0.018), having an underlying risk condition (aOR: 2.36, 95%CI: 1.27-4.39, p = 0.007), presenting with pneumonia (aOR: 6.60, 95%CI: 3.48-12.49,p 60 years, having an underlying risk condition, presenting with pneumonia and azithromycin use; and with lower odds of having a poor outcome was being treated with favipiravir within 4 days of symptom onset. Thai guidelines have been updated to include early initiation of favipiravir, particularly among those with underlying risk conditions. Further studies are needed to determine if implementation of guidelines taking into account of all these factors will result in improved outcomes.
DOI: 10.6084/m9.figshare.14420426
2021
Supplementary Material for: Endotoxin Adsorbent Therapy in Severe COVID-19 Pneumonia
<b><i>Introduction:</i></b> Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. <b><i>Methods:</i></b> We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. <b><i>Results:</i></b> Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO<sub>2</sub>/FiO<sub>2</sub> ratio and decreased EAA level after EA therapy. <b><i>Conclusions:</i></b> We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.
DOI: 10.6084/m9.figshare.13636358
2021
Minimal data set sVNT.xlsx
File includes raw data of surrogate neutralization assay and IgG/IgM.