Jiuyang Xu

<h2>Summary</h2><h3>Background</h3> A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. <h3>Methods</h3> All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. <h3>Findings</h3> By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. <h3>Interpretation</h3> The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. <h3>Funding</h3> Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

<h2>Summary</h2><h3>Background</h3> Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. <h3>Methods</h3> In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. <h3>Findings</h3> 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. <h3>Interpretation</h3> The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. <h3>Funding</h3> Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

<h2>Summary</h2><h3>Background</h3> The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. <h3>Methods</h3> We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. <h3>Findings</h3> In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% <i>vs</i> 58·5%) and median titres (19·0 <i>vs</i> 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m² or more at acute phase had eGFR less than 90 mL/min per 1·73 m² at follow-up. <h3>Interpretation</h3> At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. <h3>Funding</h3> National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

<h2>Summary</h2> Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have tried every effort to understand the disease, and a brief portrait of its clinical features have been identified. In clinical practice, we noticed that many severe or critically ill COVID-19 patients developed typical clinical manifestations of shock, including cold extremities and weak peripheral pulses, even in the absence of overt hypotension. Understanding the mechanism of viral sepsis in COVID-19 is warranted for exploring better clinical care for these patients. With evidence collected from autopsy studies on COVID-19 and basic science research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, we have put forward several hypotheses about SARS-CoV-2 pathogenesis after multiple rounds of discussion among basic science researchers, pathologists, and clinicians working on COVID-19. We hypothesise that a process called viral sepsis is crucial to the disease mechanism of COVID-19. Although these ideas might be proven imperfect or even wrong later, we believe they can provide inputs and guide directions for basic research at this moment.

The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19.We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes.1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls.Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population.Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.

Rapidly progressing hypoxemia and acute respiratory distress syndrome were commonly observed in patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) viral pneumonia [1]. Although several severity scores including Pneumonia Severity Index (PSI) [2], CURB-65 and CRB-65 (confusion, (urea >7 mmol·L−1), respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) ≤60 mmHg (diastolic), age ≥65 years), [3], A-DROP [4] and SMART-COP [5] have been developed to identify community acquired pneumonia (CAP) patients at high risk and offer therapeutic advice, the underestimation of risk of death from viral pneumonia in these scores has been reported by previous studies [6, 7]. The National Early Warning Score 2 (NEWS2) was developed by National Health Service (NHS) England [8] and, along with quick sequential organ failure assessment score (qSOFA), was proposed as a candidate for prognostic prediction for severe coronavirus disease 2019 (COVID-19) in the situation of limited medical source [9]. The aim of this study was to compare the accuracy of current score rules in hospitalised patients with COVID-19 pneumonia for predicting the risk of death and evaluate feasibility in improving medical decisions by adopting appropriate scores in clinical practice. A-DROP is a reliable tool for risk stratification of death in COVID-19 hospitalised patients on admission <https://bit.ly/3iDZipD> We acknowledge all healthcare workers involved in the diagnosis and treatment of patients in Wuhan, China.

The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.2019新型冠状病毒(2019-nCoV)是武汉不明原因肺炎的致病原。2019-nCoV在遗传学上与一种蝙蝠来源的新型冠状病毒比较接近，与SARS-CoV、MERS-CoV同为β属冠状病毒。目前临床上常用的抗病毒药物，包括神经氨酸酶抑制剂（奥司他韦、帕拉米韦、扎那米韦等）、更昔洛韦、阿昔洛韦、利巴韦林等药物对2019-nCoV均无效，不建议临床应用。目前研究证实可能有效的药物包括：瑞德西韦、洛匹那韦/利托那韦、洛匹那韦/利托那韦联合干扰素-β、恢复期血浆、单克隆抗体。但这些药物在2019-nCoV肺炎患者中的疗效和安全性有待进一步临床实验证实。.

The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up.At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial.In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed.A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate.Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Background There is a paucity of data on the natural trajectory of outcomes in survivors of COVID-19 beyond 2 years after symptom onset, and no evidence exists on the effect of re-infection in people with long COVID symptoms. We aimed to investigate the 3-year health outcomes of COVID-19 survivors and the effect of omicron re-infection. Methods In this single-centre, longitudinal cohort study, we recruited participants with confirmed COVID-19 who were discharged from the Jin Yin-tan hospital in Wuhan, China, between Jan 7 and May 29, 2020. Participants completed three follow-up visits at 6 months (June 16 to Sept 13, 2020), 1 year (Dec 16, 2020, to Feb 7, 2021), and 2 years (Nov 16, 2021, to Jan 10, 2022) since symptom onset (reported previously). At 1-year follow-up, community controls without a history of SARS-CoV-2 infection were recruited from two communities in Wuhan and at 2 years were matched (1:1) with survivors of COVID-19 who underwent pulmonary function tests. We did a 3-year follow-up from Feb 23, 2023, to April 20, 2023, after the omicron (B.1.1.529) wave in winter, 2022. All eligible survivors of COVID-19 and community controls matched at 2-year follow-up were invited to the outpatient clinic at the hospital to complete several face-to-face questionnaires, a 6-min walking test (6MWT), and laboratory tests. A subgroup of survivors of COVID-19 identified by stratified sampling on the basis of disease severity scale score during hospitalisation and community controls underwent pulmonary function tests. Survivors of COVID-19 who received high-resolution CT and showed abnormal lung images at 2-year follow-up were invited for another assessment. We identified participants with and without long COVID at 2 years. The primary outcomes were sequelae symptoms, omicron infection, lung function, and chest imaging at the 3-year follow-up. Findings Of 1359 COVID-19 survivors who completed 2-year and 3-year follow-up, 728 (54%) had at least one sequelae symptom at 3 years after symptom onset and before omicron infection, mainly mild to moderate severity. During the omicron wave, participants with long COVID at 2 years had a significantly higher proportion of re-infection (573 [76%] of 753 vs 409 [67%] of 606 without long COVID; p=0·0004), pneumonia (27 [5%] of 568 vs seven [2%] of 403; p=0·012). 3 months after omicron infection, 126 (62%) of 204 survivors with long COVID at 2 years had newly occurring or worse symptoms, which was significantly higher than the proportion in the non-long COVID group (85 [41%] of 205; p<0·0001) and community controls (81 [40%] of 205; p<0·0001), and not significantly different between COVID-19 survivors without long COVID and matched community controls (85 [41%] of 205 vs 81 [39%] of 206; p=0·66). Re-infection was a risk factor for dyspnoea (odds ratio 1·36 [95% CI 1·04 to 1·77]; p=0·023), anxiety or depression (OR 1·65 [1·24 to 2·20]; p=0·0007), EuroQol visual analogue scale score (β –4·51 [–6·08 to –2·95]; p<0·0001), but not for reduced daily activity (0·72 [0·38 to 1·37]; p=0·32) at 3 years. Lung function of survivors at 3 years was similar to that of matched community controls. We found irregular line, traction bronchiectasis, subpleural lines and ground glass opacity at 3 years, but the volume ratio of lung lesion to total lung was only 0·2–0·3%. Interpretation Most long COVID symptoms at 3 years were mild to moderate, with lung function recovering to levels of matched controls. Survivors with long COVID had a higher proportion of participants with re-infection and newly occurring or worse symptoms 3 months after omicron infection than those without long COVID. Re-infection had increased symptom occurrence but not increased reduced daily activity. Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012.The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern.However, no licensed therapeutic agents or vaccines against MERS-CoV are currently available and only a limited few have entered clinical trials.Among all the potential targets of MERS-CoV, the spike glycoprotein (S) has been the most well-studied due to its critical role in mediating viral entry and in inducing a protective antibody response in infected individuals.The most notable studies include the recent discoveries of monoclonal antibodies and development of candidate vaccines against the S glycoprotein.Structural characterization of MERS-CoV S protein bound with these monoclonal antibodies has provided insights into the mechanisms of humoral immune responses against MERS-CoV infection.The current review aims to highlight these developments and discuss possible hurdles and strategies to translate these discoveries into ultimate medical interventions against MERS-CoV infection.

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22–28, whereas HCoV-OC43 antibody titres increased until days 15–21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, −229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1–10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.

<h2>Abstract</h2><h3>Objectives</h3> Use of corticosteroids is common in the treatment of coronavirus disease 2019, but clinical effectiveness is controversial. We aimed to investigate the association of corticosteroids therapy with clinical outcomes of hospitalized COVID-19 patients. <h3>Methods</h3> In this single-centre, retrospective cohort study, adult patients with confirmed coronavirus disease 2019 and dead or discharged between 29 December 2019 and 15 February 2020 were studied; 1:1 propensity score matchings were performed between patients with or without corticosteroid treatment. A multivariable COX proportional hazards model was used to estimate the association between corticosteroid treatment and in-hospital mortality by taking corticosteroids as a time-varying covariate. <h3>Results</h3> Among 646 patients, the in-hospital death rate was higher in 158 patients with corticosteroid administration (72/158, 45.6% vs. 56/488, 11.5%, p < 0.0001). After propensity score matching analysis, no significant differences were observed in in-hospital death between patients with and without corticosteroid treatment (47/124, 37.9% vs. 47/124, 37.9%, p 1.000). When patients received corticosteroids before they required nasal high-flow oxygen therapy or mechanical ventilation, the in-hospital death rate was lower than that in patients who were not administered corticosteroids (17/86, 19.8% vs. 26/86, 30.2%, log rank p 0.0102), whereas the time from admission to clinical improvement was longer (13 (IQR 10–17) days vs. 10 (IQR 8–13) days; p < 0.001). Using the Cox proportional hazards regression model accounting for time varying exposures in matched pairs, corticosteroid therapy was not associated with mortality difference (HR 0.98, 95% CI 0.93–1.03, p 0.4694). <h3>Discussion</h3> Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality.

Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated.An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up.In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively.AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors.Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).

Cr 1 –O 4 as an active site in the Cr 1 /ZSM-5 SAC can catalyze the DOM to form value-added C1 oxygenated products with a productivity of 21 100 μmol g cat −1 h −1 and a selectivity of 99.8% at 50 °C within 30 min, which outperforms most state-of-the-art catalysts.

The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.

Background Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19. Methods Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR). Results Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51–0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41–0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42–0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49–0.78) with no increase in the risk of adverse events. Conclusion Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414 , identifier: CRD42021261414.

Aqueous zinc ion batteries are a promising alternative secondary battery technology due to their excellent safety and environmental friendliness. Vanadium-based compounds as a highly promising class of cathode materials still suffer from structural collapse and slow kinetics. Studies have shown that metal ion pre-introduction is an effective method to solve these problems and enhance battery performance. Here, the introduction of Al3+ , Cr3+ , Cu2+ and Fe3+ is found to effectively reduce the migration energy barrier of Zn2+ with the density functional theory calculations, while Al3+ exhibits the best induction effects. Subsequently, Al0.34 V5 O12 ·2.4H2 O (AlVOH) nanoribbons are synthesized by hydrothermal introduction of Al3+ , demonstratin excellent electrochemical properties (407.8 mAh g-1 at 0.2 A g-1 and 176.3 mAh g-1 after 2000 cycles at 20 A g-1 ). By further compounding with redox graphene (rGO), AlVOH/rGO exhibits high capacitance and specific capacity (460.4 mAh g-1 at 0.2 A g-1 and 180.6 mAh g-1 after 2000 cycles at 20 A g-1 ). In addition, it is found that the introduction of metal ions adjusts the structural water content of the material. Especially, the introduction of Al3+ can increase the interlayer structural water content and make the electrochemical properties of the material more stable.

Carbon material is considered a promising electrocatalyst for the CO2 reduction reaction (CO2RR); especially, N-doped carbon material shows high CO Faradic efficiency (FECO) when using pyridinic N species as the active site. However, in the past decade, more efforts were focused on the preparation of various carbon nanostructures containing abundant pyridinic N species and few researchers studied the electronic structure modulation of the pyridinic N site. The curvature of the carbon substrate is an easily controllable parameter for modulating the local electronic environment of catalytic sites. In this research, carbon nanotubes (CNTs) with different diameters are applied to modulate the electronic environment of pyridinic N by the curvature effect. The pyridinic N sites doped on CNTs with the average curvature of 0.04 show almost 100% FECO at the current density of 3 mA cm–2 at −0.6 V vs RHE and 91% FECO retention after 12 h test, which is superior to most of the carbon-based electrocatalysts. As demonstrated by density functional theory simulation, the pyridinic N site forms a strong local electric field around the nearby C active site and protrudes out of the curved CNT surface like a tip, which remarkably enriches the protons around the adsorbed CO2 molecule.

Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III interferon (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity.

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans.However, no approved prophylactic and therapeutic interventions are currently available.The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4).Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S).Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice.In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA).Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge.Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein.These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

Abstract Background The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known. Methods NAbs and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analyzed. Multivariable adjusted generalized linear mixed model for random effects were developed. Results After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (IgG), 100% for RBD-IgG, 91.1% for N-IgM, and 91.1% for NAbs. The NAbs titers increased over time in both survivors and nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope −2.11, 95% confidence interval [CI] −3.04 to −1.18, P &amp;lt; .0001), S-IgG (slope −2.44, 95% CI −3.35 to −1.54, P &amp;lt; .0001), and RBD-IgG (slope −1.43, 95% CI −1.98 to −.88, P &amp;lt; .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset. Conclusions IgM and IgG against N, S, and RBD and NAbs developed in most severe COVID-19 patients and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S, and RBD were related to viral clearance.

Abstract There have been arguments on whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) treatment alters the risk of coronavirus disease 2019 (COVID-19) susceptibility and disease severity. We identified a total of 102 eligible studies for systematic review, in which 49 studies adjusting for confounders were included in the meta-analysis. We found no association between prior ACEI/ARB use and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population (adjusted odds ratio [aOR], 1.00; 95% confidence interval [CI], .94–1.05). The risk of mortality (aOR, .87; 95% CI, .66–1.04) and severe outcomes (aOR, .95; 95% CI, .73–1.24) were also unchanged among COVID-19 patients taking ACEIs/ARBs. These findings remained consistent in subgroup analyses stratified by populations, drug exposures, and other secondary outcomes. This systematic review provides evidence-based support to current medical guidelines and position statements that ACEIs/ARBs should not be discontinued. Additionally, there has been no evidence for initiating ACEI/ARB regimen as prevention or treatment of COVID-19.

Coronavirus disease 2019 (COVID-19), an emerging respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading across the world rapidly and claiming tens of thousands of lives. On 11 March 2020, the WHO announced it to be a global pandemic. As of 6 April 2020, more than a million COVID-19 cases have been confirmed globally with over 60 000 deaths [1].

Aqueous zinc-ion batteries (ZIBs) stand out among the next generation of large-scale energy storage devices owing to their overwhelming advantages of high safety, low-cost and environmental benefit. However, this promising technology is still plagued by lack of superior cathode materials due to the inherent slow diffusion kinetics. Herein, with theoretical calculations as a guide, we proposed a new strategy to promote Zn2+ migration based on ion-exchange. Specifically, we first find the tendency of Mg2+ and Zn2+ exchange in inverse-spinel Mg2VO4 by molecular dynamics simulations. Density functional theory (DFT) calculations reveal that this ion exchange can moderate the electrostatic interaction between Zn2+ and host material, and reduce the diffusion energy barrier of Zn2+. Meanwhile, the Mg2+ of host leaves vacancies when it is detached, and both contribute to the improvement of Zn2+ diffusion kinetics. Based on theoretical calculations, we for the first time used a simple sol-gel method to synthesize inverse-spinel Mg2VO4 as an aqueous ZIBs cathode. As predicted in theoretical calculations, after optimization of Zn2+ and Mg2+ exchange, the Mg2VO4/Zn system demonstrates rewarding cyclic stability. This work provides a new insight into the development of cathode materials for high-performance ZIBs.

Oxygen species functionalized graphene (O-G) is an effective electrocatalyst for electrochemically synthesizing hydrogen peroxide (H2 O2 ) by a 2 e- oxygen reduction reaction (ORR). The type of oxygen species and degree of carbon crystallinity in O-G are two key factors for the high catalytic performance of the 2 e- ORR. However, the general preparing method of O-G by the precursor of graphite has the disadvantages of consuming massive strong oxidant and washing water. Herein, the biomass-based graphene with tunable oxygen species is rapidly fabricated by a CO2 laser. In a flow cell setup, the laser-induced graphene (LIG) with abundant active oxygen species and graphene structure shows high catalytic performance including high Faraday efficiency (over 78 %) and high mass activity (814 mmolgcatalyst-1 h-1 ), superior to most of the reported carbon-based electrocatalysts. Density function theory demonstrates the meta-C atoms at nearby C-O, O-C=O species are the key catalytic sites. Therefore, we develop one facile method to rapidly convert biomass to graphene electrocatalyst used for H2 O2 synthesis.

Past decade has witnessed the great improvement of carbon-based dual-single metal-site electrocatalysts. However, there are rare reports exploring the enhanced effect of a nonmetallic “dual-site” in carbon-based catalysts. Herein, a “H3BO3 template” method is proposed to fabricate highly active B–S pairs dispersed on a hierarchically microporous/mesoporous carbon matrix to electrochemically synthesize hydrogen peroxide by two-electron oxygen reduction reaction. Under the synergistic effect of B–S pairs and advantageous nanostructures, the catalytic performance outperforms the reported metal-free carbon catalysts in alkaline electrolytes, especially, with a high HO2– selectivity of 90–94% at a wide potential range of 0.3–0.7 V versus reversible hydrogen electrode (RHE) using a rotating ring-disk electrode, Faradaic efficiency of over 90% during 11 h stability testing, and high mass activity of 756 mmol gcatalyst–1 h–1 in a flow cell. Density functional theory demonstrates that the carbon atoms nearby B–S pairs exhibit predominant catalytic sites. This paper proposes a new approach to distinctly improve the catalytic performance by dual heteroatom pairs.

The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a great threat to public health worldwide. Approximately 5% of patients are complicated with critical illness, with some of them experiencing multi-organ dysfunction and even death.1,2

<h2>Summary</h2><h3>Background</h3> Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. <h3>Methods</h3> This single-centre, cross-sectional cohort study was done at China–Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18–33 days), 2 months (55–84 days), or 4 months (115–134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. <h3>Findings</h3> Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64–10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. <h3>Interpretation</h3> Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. <h3>Funding</h3> National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. <h3>Translation</h3> For the Chinese translation of the abstract see Supplementary Materials section.

<b>Solid pre-clinical investigations serve as the basis for clinical research. High quality clinical trials remain the definitive measure to evaluate an interventional therapy. Clinical decisions should be independent from media and political propaganda.</b>https://bit.ly/3iaNBsB

Objective The objective of this study was to investigate whether hepatitis B virus (HBV) infection plays a role in the regulation of autoimmunity for systemic lupus erythematosus (SLE). Method A total of 21 female BALB/c mice and 21 female HBV transgenic BALB/c mice aged two months were randomly divided into four groups: BALB/c mice, HBV Tg mice, pristane-injected BALB/c mice, and pristane-injected HBV Tg mice. BALB/c mice and HBV Tg mice were given an intraperitoneal injection of 0.5 ml normal saline, and the mice in the other two groups were given an intraperitoneal injection of 0.5 ml pristane. ANA and anti-dsDNA levels in serum were detected by indirect immunofluorescence. Interleukin 2 (IL-2), IL-4, IL-6, IL-17, and TNF-α were measured by Luminex technology. The serum BAFF level was measured using an Elisa kit. Twenty-four weeks after pristane administration, kidneys were removed, dissected, and stained with hematoxylin and eosin and periodic-acid Schiff. Result At six months after injecting, the ANA titers in pristane-injected HBV Tg mice were significantly lower than pristane-injected BALB/c mice. IL-17, TNF-α, and BAFF levels were significantly higher in pristane-injected BALB/c mice than BALB/c mice and pristane-injected HBV Tg mice. IL-2, IL-4, and IL-6 levels were much higher in pristane-injected HBV Tg mice than pristane-injected BALB/c mice. In pristane-injected HBV Tg mice and HBV Tg mice, fewer glomerulonephritis changes were found in the kidneys. Conclusions Our results showed that the incidence of SLE was much lower in HBV Tg mice, and that HBV infection helped the SLE mice survive high levels of inflammatory cytokines and severe renal damage. All these findings demonstrated the protective role of HBV in SLE patients via the immunoregulatory networks of the cytokines.

The design of efficient electrocatalysts is essential to enhance the performance of rechargeable metal-air cells, renewable fuel cells and overall water splitting. Based on this, how to improve the catalytic activity of oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) becomes self-evident. Currently, single atom catalysts (SACs) are widely used as structural design models for the OER, ORR and HER because of the single active site and maximum metal atom utilization, but significant challenges remain. Herein, the catalytic properties of the OER, ORR and HER with a single metal atom as the active site are discussed through first-principles calculations by introducing a single metal atom in the Mn vacancy of Mn2B2 (TM@Mn2B2, TM = Au, Ag, Co, Cd, Cu, Ir, Pd, Ni, Rh, Ru and Pt). The results show that Ni@Mn2B2 is suitable as a dual-function electrocatalyst for the OER/ORR with overpotentials of 0.38 V and 0.37 V, which are lower than those of the OER overpotential of RuO2/IrO2 (0.42 V/0.56 V) and the ORR overpotential of Pt (0.45 V). Meanwhile, Pt@Mn2B2 is available as an OER/HER dual-function electrocatalyst for overall water splitting with a lower overpotential of OER (0.45 V) and lower |ΔGH| (-0.15eV) under 1/4 hydrogen coverage for the HER. This work proposes a practical strategy for developing single metal atom doped MBene as a dual-function electrocatalyst.

Human metapneumovirus (HMPV) is a non-segmented, negative strand RNA virus belonging to the family Pneumoviridae, previously a subfamily of Paramyxoviridae. It is a leading cause of lower respiratory tract infection in infants, children, and adults with underlying medical conditions. HMPV grows poorly in cell culture and requires trypsin to cleave and mature the virus particles, which adds to the challenge of HMPV research. Currently, an indirect immuno-staining assay is commonly used to titrate HMPV, which is time-consuming and costly. In order to simplify virus quantification for HMPV, a direct plaque assay was developed. By optimizing trypsin concentration and other supplements in the agarose overlay, it was found that HMPV strains from all four subgroups formed clear and countable plaques 5-7 days post-infection. Animal tissue homogenate can also be directly titrated with this assay. Compared with the traditional assay, the direct plaque assay yields similar titer result, but saves time and eliminates the use of antibodies. Potentially, it can also be applied to plaque purification for HMPV clinical isolates. The direct plaque assay will be a valuable tool in HMPV research.

The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 3 years, with an enormous impact on global health and economies. In some patients, symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which cannot be explained by an alternate diagnosis; this condition has been defined as long COVID. Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants. The most common symptoms include fatigue, dyspnea, and other symptoms involving multiple organs. Vaccination results in lower rates of long COVID. To date, the mechanisms of long COVID remain unclear. In this narrative review, we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.

The pandemic of Coronavirus Disease 2019 (COVID-19) is rapidly evolving as a major threat to global health. Cardiovascular and metabolic comorbidities including hypertension, diabetes, coronary artery disease (CAD) are common among COVID-19 patients, and are associated with increased mortality and adverse outcomes in COVID-19 [1]. However, clinical or physiological evidence is lacking regarding the causal relationship between cardiovascular diseases and the severity of COVID-19, and whether management of cardiovascular risk factors would benefit the outcome of COVID-19.

Community acquired pneumonia and other lower respiratory tract infections are major health issues in China and around the world.1Vos T Lim SS Abbafati C et al.Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396: 1204-1222Summary Full Text Full Text PDF PubMed Scopus (5227) Google Scholar Many patients with community acquired pneumonia are treated with empirical antibiotics before pathogen identification and knowledge about the causes of the disease is therefore essential. For a long time, bacteria have been considered as the major pathogen for community acquired pneumonia among immunocompetent adults. Viral causes of pneumonia have received attention in children and immunocompromised adults, but have received insufficient attention in the immunocompetent adult population. In the past 20 years, the outbreaks of severe acute respiratory syndrome (SARS), influenza A H1N1, influenza A H7N9, Middle East respiratory syndrome (MERS), and the ongoing COVID-19 pandemic have highlighted the importance of viral causes of community acquired pneumonia. Monitoring the circulating and emerging viruses that cause community acquired pneumonia and implementing rapid and timely responses are necessary public health tasks. In 2010, we estimated that viruses could account for about 10% of community acquired pneumonia cases in China,2Cao B Ren L-L Zhao F et al.Viral and Mycoplasma pneumoniae community-acquired pneumonia and novel clinical outcome evaluation in ambulatory adult patients in China.Eur J Clin Microbiol Infect Dis. 2010; 29: 1443-1448Crossref PubMed Scopus (47) Google Scholar but the data were from a single-centre study. At that time, several multicentre research and surveillance networks for pneumonia had been established globally, such as the Competence Network for Community Acquired Pneumonia and the Community Acquired Pneumonia Organization, which coordinated large-scale longitudinal studies on the epidemiology, diagnosis, and treatment of the disease. These research networks are highly productive and have facilitated further understanding of the disease. In response to the public health challenges of community acquired pneumonia in China, we established the Community Acquired Pneumonia-China (CAP-China) network to mitigate research gaps in surveillance, rapid diagnosis, and optimal treatment. The network was initially established in Beijing with 12 hospitals as the Beijing Network for Adult Community-Acquired Pneumonia, and then expanded to 72 medical institutions (mainly tertiary hospitals) across the country as the CAP-China network. Through a multicentre registry within the network, data from another cohort in China, and advances in pathogen detection techniques, it is now estimated that viruses are present in 27·5–39·2% of immunocompetent patients with community acquired pneumonia.3Qu J-X Gu L Pu Z-H et al.Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity.BMC Infect Dis. 2015; 15: 89Crossref PubMed Scopus (49) Google Scholar, 4Zhou F Wang Y Liu Y et al.Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.Eur Respir J. 2019; 541802406Crossref PubMed Scopus (65) Google Scholar, 5Zhan Y Yang Z Chen R Wang Y Guan W Zhao S Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls.BMC Pulm Med. 2014; 14: 144Crossref PubMed Scopus (19) Google Scholar Although rhinovirus was predominant in patients with community acquired pneumonia in the USA,6Jain S Self WH Wunderink RG et al.Community-acquired pneumonia requiring hospitalization among US adults.N Engl J Med. 2015; 373: 415-427Crossref PubMed Scopus (1425) Google Scholar the most common virus among immunocompetent patients with pneumonia in China was influenza (28·4%), followed by respiratory syncytial virus (3·6%), human adenovirus (3·3%), and human coronavirus (3·0%).4Zhou F Wang Y Liu Y et al.Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.Eur Respir J. 2019; 541802406Crossref PubMed Scopus (65) Google Scholar Disease severity on hospital admission, the occurrence of severe complications, and 90-day mortality of patients with non-influenza viral pneumonia were similar to those of viral pneumonia caused by influenza.4Zhou F Wang Y Liu Y et al.Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.Eur Respir J. 2019; 541802406Crossref PubMed Scopus (65) Google Scholar Unlike the previous notion that non-influenza viruses mainly affect children and immunosuppressed populations, non-influenza viral pneumonia also had an important role in community acquired pneumonia in immunocompetent adults.4Zhou F Wang Y Liu Y et al.Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.Eur Respir J. 2019; 541802406Crossref PubMed Scopus (65) Google Scholar Human adenovirus 55 was also identified as an emerging cause of community acquired pneumonia among immunocompetent individuals in China.7Cao B Huang G-H Pu Z-H et al.Emergence of community-acquired adenovirus type 55 as a cause of community-onset pneumonia.Chest. 2014; 145: 79-86Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar The CAP-China network studies emphasised the crucial role of viral causes of community acquired pneumonia in adults and contributed to the latest guidelines on the disease in China.8Cao B Huang Y She D-Y et al.Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.Clin Respir J. 2018; 12: 1320-1360Crossref PubMed Scopus (130) Google Scholar Surveillance and observational studies are vital for rapid responses to viral pneumonia, including vaccine development, the rational use of antibiotics, and drug development. As shown by the example of annual influenza vaccines, surveillance data provide crucial information for the prediction of circulating viral strains and rational vaccine design. Also, considering the generally limited resources for vaccine development, it is important to prioritise vaccines for viruses with higher incidence and mortality, which again is dependent on information from aetiological surveillance. Antibiotic resistance and the potential epidemic of multidrug resistant bacteria pose substantial public health threats in China. The use of antibiotics in patients with viral community acquired pneumonia without bacterial co-infection might further exacerbate the current situation. Knowledge about disease characteristics from large-scale, multicentre observational studies and information about common circulating viruses from aetiological surveillance will promote early identification of viral pneumonia. The use of rapid molecular testing for respiratory viruses might also help to reduce intravenous antibiotic use.9Shengchen D Gu X Fan G et al.Evaluation of a molecular point-of-care testing for viral and atypical pathogens on intravenous antibiotic duration in hospitalized adults with lower respiratory tract infection: a randomized clinical trial.Clin Microbiol Infect. 2019; 25: 1415-1421Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar Aetiological surveillance can guide the allocation of research resources for the development of antiviral therapies. Unlike bacterial infection, the choice of antivirals for respiratory viruses is very limited and drug resistance is emerging, which necessitates the development of more potent therapies to reduce complications and mortality from community acquired viral pneumonia.10Zumla A Memish ZA Maeurer M et al.Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.Lancet Infect Dis. 2014; 14: 1136-1149Summary Full Text Full Text PDF PubMed Scopus (86) Google Scholar The repurposing of available antiviral drugs and the development of novel drugs and drug combinations are crucial. Moreover, because immune dysfunction is a key mechanism in the pathogenesis of severe viral pneumonia, the development or repurposing of host-directed therapies is also important. The surveillance and clinical research coordinated by the CAP-China network and similar networks around the world will continue to benefit the health community. Apart from guiding vaccine development and therapy, the CAP-China network will also aid in identifying novel emerging pathogens and contribute to global understanding of viral respiratory illness. With the close collaboration of researchers in China, knowledge about community acquired viral pneumonia in immunocompetent adults has progressed rapidly in the past 10 years, and the substantial role of viral pathogens as causes of community acquired pneumonia has been gradually recognised.2Cao B Ren L-L Zhao F et al.Viral and Mycoplasma pneumoniae community-acquired pneumonia and novel clinical outcome evaluation in ambulatory adult patients in China.Eur J Clin Microbiol Infect Dis. 2010; 29: 1443-1448Crossref PubMed Scopus (47) Google Scholar, 3Qu J-X Gu L Pu Z-H et al.Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity.BMC Infect Dis. 2015; 15: 89Crossref PubMed Scopus (49) Google Scholar, 4Zhou F Wang Y Liu Y et al.Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.Eur Respir J. 2019; 541802406Crossref PubMed Scopus (65) Google Scholar, 5Zhan Y Yang Z Chen R Wang Y Guan W Zhao S Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls.BMC Pulm Med. 2014; 14: 144Crossref PubMed Scopus (19) Google Scholar The experience from CAP-China and other networks shows the importance of regional and global collaboration in research. Although confronted with many unknowns and challenges, we believe these difficulties can be addressed if researchers unite as a close community. BC is one of the cofounders of the CAP-China network. The other authors declare no competing interests.

The coronavirus 2019 (COVID-19) pandemic is circulating worldwide and threatening global health. Although the initial wave of the outbreak in China in March–April 2020 has well abated, multiple sporadic community outbreaks have been reported ever since. In particular, Beijing, the capital city of China with more than 20 million residents, experienced a second wave in June–July 2020, after a 56-consecutive day period of no new local cases.1 This outbreak, linked to the massive Xinfadi Agricultural Wholesale Food Market, was likely to have been triggered by contamination from cold-chain food imported from overseas.2 The epidemic was quickly contained within only 1 month from identification of the first clustered cases,1 and the market was soon reopened for wholesale trade. Experience from this and other outbreaks in China again highlighted the importance of boosting capacity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing in epidemic control.3 During the epidemic, the Beijing municipal government has stepped up testing capacity to ensure all who should be tested get tested, and all who want to get tested can as well. These key population groups in need of testing include close contacts of COVID-19 cases, inbound travellers, patients in fever clinics, staff working at medical institutions, quarantine and inspection staff and nursing home workers, among others. The policy that all those in need should be tested, quarantined, hospitalized and treated has ensured rapid and early case identification and prevented further community spread of the disease. From 11 June to 14 July, a massive campaign of 11.88 million nucleic acid tests was conducted, covering about half of the residents in the city.3 Mobile testing points were deployed quickly across the city. Among the 335 confirmed cases and 33 asymptomatic infections, over half were identified in active screening and follow-up of close contacts, instead of self-reporting or visits to fever clinics. The shift of new case identification from symptomatic hospital visits to screening in the asymptomatic population indicates efficient containment of the outbreak. This experience holds lessons for other countries. Prompt targeted testing with the aid of new measures such as makeshift test sites and mobile nucleic acid testing vehicles could also contain virus re-emergence, without wide-reaching, cross-border lockdown. It is noteworthy that only high-risk areas were locked down at the community level in Beijing during the outbreak, and most other areas remained normal. This practice has reduced the effect of outbreak containment on business, social activities and residents' daily lives (Fig. 1). Apart from massive nucleic acid testing, another key experience during the COVID-19 outbreak in Hubei and later in Beijing is the importance of rapid source tracing. This cannot be fulfilled without laborious epidemiological investigation. In no more than 1 day after the first case identification on 11 June, the Xinfadi Market was recognized as the possible origin of the outbreak.1 The market was soon shut down when it was associated with both of the first two cases.1 This enabled rapid identification of the new outbreak and ensured timely response in contact tracing. Furthermore, boosting the capacity of next-generation sequencing has enabled rapid virological source tracing and provided clues for policy-makers of possible sources of infection. The community-level public health measures and digital management for a matrix of urban communities have been the key to China's achievement in controlling the COVID-19 pandemic.4 The populated urban city is divided into several levels with integrated functions as districts, residential neighbourhoods (jie dao), communities (she qu) and sub-divided into grids (wang ge). Multiple tasks were conducted at the community or grid level with incredible efficiency, including coordination of nucleic acid tests, collection of epidemiological information, quarantine of suspected cases and close contacts, and public health education, among others. The fine division of the city into individual functional units as communities or grids has enabled rapid responses to the emergence of new outbreaks. On the other hand, concentrating medical resources into designated hospitals was proven effective for the treatment and management of confirmed COVID-19 cases. All 335 patients, including 21 severe and 5 critical cases, were treated in the designated hospital (Ditan Hospital) by a team of experienced medical experts gathered from across the city. The zero rate of both case fatalities and nosocomial infections during this wave of the outbreak highlights the importance of concentrated medical resources during the pandemic. Although COVID-19 community spread has been sporadic and remained low, the ‘war-time’ for COVID-19 epidemic control in China seems to be continuing. The emphasis has shifted from medical treatment to active surveillance and disease prevention, and the situation is far from being back to normal. There have been confirmed local COVID-19 cases in multiple regions in the Chinese mainland in November 2020, including in heavily populated cities such as Shanghai, Qingdao and Tianjin. In the meantime, China is under rising pressure to guard against imported cases of COVID-19, as total confirmed cases worldwide continue to rise. It is noted that regular measures have been taken in pandemic prevention and control, including social distancing, mask-wearing, health certificates in the form of QR codes (quick response codes) and active screening of nucleic acid tests in key populations. There are continuing challenges facing China, especially Beijing, in coping with the COVID-19 pandemic. (i) Both the pressure of imported cases and the possibility of resurgence in domestic cases pose threats to resuming economic and social development, which has only just recovered from the pandemic hit early this year. (ii) In winter, the superinfection or co-infection of influenza virus and other respiratory pathogens in COVID-19 patients is worthy of attention, given that SARS-CoV-2 vaccine is not commercialized and influenza vaccination has not had large-scale public health implementation. (iii) Special attention needs to be paid to potential nosocomial spread of COVID-19, as learned from the experience from Qingdao, where sharing the same computed tomography (CT) suite without effective de-contamination turned out to be the source for transmission.5 Active surveillance, massive polymerase chain reaction (PCR) testing, stringent lockdown and isolation, as well as other measures can certainly contain the epidemic but the total cost may be high. We have been probing the perfect balance between cost and safety. The experience from Beijing was an attempt of targeted and scientific epidemic control, and may serve as a model for other cities.

The monolayer MoSeTe is a two-dimensional material similar to graphene. Herein, the adsorption characteristic of NO2, CH4, CO and NO molecules on the monolayer MoSeTe has been studied by first-principles calculations. All of the above gas molecules are tending to adsorb on the Te-layer surface rather than the Se-layer surface, and the values of their adsorption energies on the monolayer MoSeTe surface are all negative. Among them, the adsorption energy of NO2 gas molecule on the monolayer MoSeTe is obviously stronger than that of other gas molecules, indicating the strong interaction between them. Because the charge transfer between the N-based molecules and monolayer MoSeTe are more than that of the C-based molecules, the monolayer MoSeTe can be used as the gas sensor material for detecting the N-based gases. These theoretical outcomes may provide useful guidance for the monolayer MoSeTe as an ideal material for detecting the N-based gases.

By using the density functional theory (DFT), we have investigated CO molecules adsorbed on palladium atom doped (Pd-doped) (5, 5) and (6, 6) boron nitride nanotubes (BNNTs). In order to investigate the electronic and structural properties of all the research objects, we calculated the band gap (Eg), bind energy (Eb), and density of state (DOS). The results show that energy gaps of BNNTs reduced by doped impurity Pd atom, but there are no obvious changes with the tube diameter of Pd-BNNTs change. One impurity Pd atom substituting one B (PdB) or N atom (PdN) of pristine BNNTs can increase the reactivity with CO molecule. The energy gaps for CO molecule adsorption on the tube wall of Pd-BNNTs reduced. This indicates that Pd-doped BNNTs can be considered as nano gas sensitive material.

Effectively removal of air pollutants using adsorbents is one of the most important methods to purify the air. In this work, we proposed for the first time that PtN 3 -CNT is an effective adsorbent for air purification. Its air purification performance was studied by calculating the adsorption behaviors and electronic structures of 12 gas molecules, including the main components of air (N 2 , O 2 , H 2 O, CO 2 ) and the most common air pollutants (NO, NO 2 , SO 3 , SO 2 , CO, O 3 , NH 3 , H 2 S), on the surface of PtN 3 -CNT using first-principles calculations. The results showed that these gases were adsorbed stably via the coordination between Pt and the coordinated atoms (C, N, O, and S atoms) in the gas molecules, and the adsorption energies vary in the range of −0.81∼−4.28 eV. The obvious chemical interactions between PtN 3 -CNT and the adsorbed gas molecules are mainly determined by the apparent overlaps between the Pt 5d orbitals and the outmost p orbitals of the coordination atoms. PtN 3 -CNT has strong adsorption capacity for the toxic gas molecules, while relatively weaker adsorption performance for the main components of the air except oxygen. The recovery time of each adsorbed molecule calculated at different temperatures showed that, CO 2 , H 2 O, and N 2 can be desorbed gradually at 298∼498 K, while the toxic gases are always adsorbed stably on the surface of PtN 3 -CNT. Considering the excellent thermal stability of PtN 3 -CNT at up to 1000 K proved by AIMD, PtN 3 -CNT is very suitable to act as an adsorbent to remove toxic gases to achieve the purpose of air purification. Our findings in this report would be beneficial for exploiting possible carbon-based air purification adsorbents with excellent adsorbing ability and good recovery performance.

Abstract Influenza virus infection poses a heavy burden on global health and economics. With the advancement in viral pathogen detection methods, the role of virus infection in community-acquired pneumonia has been increasingly recognized. The disease spectrum of influenza ranges from asymptomatic infection to severe or even fatal illness. Progress has been made in recent years to identify risk factors including lymphopenia and hypoxia for influenza mortality. Immunopathology plays an important role in influenza pathogenesis. The disturbed homeostasis after virus infection consists of both an excessive inflammatory phase and an immune suppression phase, collectively described as viral sepsis. Multiple antiviral therapies have been tested and some were advanced to late-phase clinical trials, including polymerase inhibitors, hemagglutinin inhibitors, host-acting antivirals, monoclonal antibodies, and adjunctive immunomodulatory therapies. Combination therapies have been shown to increase antiviral efficacy and genetic resistance barrier. In this review, we summarized the recent advances in our understanding of the disease pathogenesis, as well as the progress in antiviral therapy development. We also pointed out current key knowledge gaps in influenza research. Hopefully, experience gained from seasonal influenza research will prepare us for the next influenza pandemic and emerging respiratory pathogens.

Expanding on the recommendation of Assaf et al. (2022), this research note provides insights and recommendations for the post-COVID-19 future of tourism research. We reviewed 56 recent papers related to COVID-19 published in the top three high quality tourism journals. Whilst there was a glut of relatively descriptive research on the pandemic, especially involving the economic impacts as a result of the virus, the results indicate that inadequate attention has been given to technology adoption and tourists’ well-being. Recent discussions of post-COVID-19 tourism have emphasised crisis management, which remains an important direction for future research. We recommend tourism recovery and resilience as one of the major focuses for tourism research and for greater importance to be attached to crisis planning and preparation so that lessons can be learned from COVID-19. Rather than a single country, cross-sectional studies, the adoption of cross-cultural, cross-contextual, and longitudinal study approaches is also recommended. Keywords COVID-19; Tourism; Future; Post-COVID-19 tourism research

The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P < 0.001) were more common in non-immunocompromised patients than in immunocompromised ones, and angio-invasive CT signs were more common in immunocompromised patients (55.3% vs.72.7%, P = 0.013). Typical angio-invasive CT signs were delayed in non-immunocompromised IPA patients, whereas airway-invasive signs appear earlier. Host immunocompromised condition was associated with ICU admission and/or intubation (OR 1.095; 95% CI 1.461–6.122; P = 0.003). Poor prognosis (35.5% vs. 21.1%, P = 0.005) was more common in immunocompromised patients. Airway-invasion-associated CT presentations at early stages of the disease are characteristic of IPA in non-immunocompromised hosts.

"Pulmonary Mucorcycosis with Rib Involvement in an Immunocompromised Patient." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –

Antimicrobials are powerful tools for managing infectious diseases and provide a safe cornerstone for breakthroughs in other medical practices (surgery, chemotherapy, immunomodulatory treatments, etc.) Since the discovery of penicillin, antimicrobials have revolutionized modern medicine. However, the emergence of antimicrobial resistance (AMR) has threatened to reverse the advancement [ [1] Marston H.D. Dixon D.M. Knisely J.M. Palmore T.N. Fauci A.S. Antimicrobial resistance. JAMA. 2016; 316: 1193-1204https://doi.org/10.1001/jama.2016.11764 Crossref PubMed Scopus (417) Google Scholar ]. Inappropriate use of broad-spectrum antimicrobials promotes the emergence of AMR through the selection of resistant mutants. Facing the challenge of AMR, various antimicrobial stewardship (AMS) programmes have been implemented to promote appropriate and responsible antimicrobial use [ [2] Dyar O.J. Huttner B. Schouten J. Pulcini C. ESGAP (ESCMID Study Group for Antimicrobial stewardshiP). What is antimicrobial stewardship?. Clin Microbiol Infect. 2017; 23: 793-798https://doi.org/10.1016/j.cmi.2017.08.026 Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar ], but the current situation is still challenging, especially in the primary healthcare facility (PHF). Inappropriate antibiotic prescribing in primary healthcare facilities in China: a nationwide survey, 2017–2019Clinical Microbiology and InfectionVol. 29Issue 5PreviewWe aimed to generate comprehensive estimates of the appropriateness of outpatient antibiotic prescriptions at primary healthcare facilities (PHFs) in China. Full-Text PDF

&lt;p&gt;The susceptibility of the elderly to respiratory viral infections and the challenges posed by an aging population necessitate imperative development of advanced preventive and therapeutic strategies for elderly individuals. The clinical outcome of such infections is intricately determined by the complex interplay among viruses, host tissues, and immune cells. Elderly individuals exhibit a diminished efficacy of their immune system to clear viruses, consequently leading to prolonged viral insults, tissue damage, and an excessive activation of inflammatory cells. These ultimately result in worse clinical outcomes. Targeting the dysregulated antiviral immune responses has emerged as a potential approach to improve the prognosis of geriatric patients. It is noteworthy that the impacts of aging on antiviral immune responses are highly heterogenous. Thus, individualized patient assessment and management assume paramount importance. This review aims to summarize the current evidence elucidating the effects of aging on immune responses to respiratory viruses, with the ultimate goal of identifying knowledge gaps that can inform future research and enhance the management of elderly individuals.&lt;/p&gt;

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

Abstract Background To explore the suitable cutoff value of aldosterone to renin concentration ratio (ARR) detected by chemiluminescence immunoassay for primary aldosteronism (PA) screening among hypertensive population in Sichuan, China. Methods 423 hypertensive patients screened for PA in Department of Endocrinology and Metabolism of West China Hospital of Sichuan University from October 2020 to May 2022 were included in this study. Blood samples were collected 2 hours after the patients were in an upright position. Chemiluminescence was used to measure the concentrations of aldosterone and renin. Receiver operating characteristic curve was used to determine the optimal cutoff value of ARR. Results The 423 patients with hypertension included 199 PA and 224 essential hypertension. Youden index was the highest when the upright ARR was 2.4 (ng/dl)/(mU/l), and the sensitivity and specificity for PA were 95.5% and 94.2%, respectively. The most suitable upright ARR cutoff values for male and female were 2.0 and 2.4 (ng/dl)/(mU/l), and the sensitivity were 96.5%, 95.6%, the specificity was 95.3%, 91.5%, respectively. The most suitable cutoff values of upright ARR in the ≤40, &amp;gt;40 to &amp;lt;60, and ≥60-year-old patients with hypertension were 1.4, 2.3, and 2.7 (ng/dl)/(mU/l), respectively. Conclusions The suitable upright ARR cutoff value may be 2.4 (ng/dl)/(mU/l) for PA among hypertensive population in Sichuan. In male, the suitable cutoff value of ARR is lower than female. The cutoff value of ARR is increased with age.

As of May 5, 2020, the coronavirus disease 2019 (COVID-19) outbreak had spread to 215 countries, areas, or territories and led to more than 3·4 million confirmed cases worldwide,1 within just 4 months of the first reported cases. The global pursuit of antiviral treatments and vaccines is in progress, but unfortunately none have proven to be effective yet. Without effective treatments, we have to rely on public health interventions to fight the pandemic, by controlling the source of infection, blocking the transmission route, and preventing new infections.

Introduction: Human metapneumovirus (HMPV) is a member of the Pneumoviridae, formerly a subfamily of Paramyxoviridae. HMPV is a leading cause of lower respiratory infection in infants, children, and adults. The disease outcome of HMPV infection ranges from mild upper respiratory infection to severe pneumonia. Despite the clinical and economic burden, mechanisms of HMPV pathogenesis are not fully understood. In addition, no licensed vaccines or anti-viral drugs are available. Results: Most published HMPV studies use a few laboratory-adapted strains of the A2 lineage. Here, we tested eight HMPV clinical isolates from different genetic lineages in comparison to a laboratory reference strain in an established C57BL/6 mouse model. The clinical isolates induced variable disease severity. While mice infected by laboratory strain TN/94-49 (A2) did not lose weight, mice infected by clinical strains showed significant weight loss and greater lung histopathology. Several clinical isolates caused lethal disease, which is unusual in mouse models of HMPV. Viral replication in lungs was variable, but peak lung viral titer did not correlate with disease outcome. Higher proinflammatory cytokine production in mouse lungs was associated with more severe disease and death. Virulent clinical isolates of HMPV exhibited diminished innate immune responses and decreased antigen-presenting cells, suggesting active inhibition of innate immunity. The findings were confirmed in BALB/c and DBA/2 inbred mice. Conclusion: Our results indicate that severe disease caused by HMPV clinical isolates was due to exuberant immune response and immunopathology. These data suggest that distinct HMPV strains may engage host immune mediators differently.

The ability to stop a response promptly when a stop signal is presented is named response inhibition. It is generally accepted that the process of response inhibition requires a subject to pay attention to the stop instruction and then cancel the action. A wealth of converging evidence suggests that physical activity (PA) can promote response inhibition, but the potential contributions of attentional capture to the relationship between PA and response inhibition are currently unknown. In this study, the standard stop-signal task (SST) and two novel versions of the SST were used to solve this gap. A total of 58 college students were divided into a higher PA group and a lower PA group, respectively. In Experiment 1, the classical SST determined that the participants in the higher PA group displayed a significantly faster stop-signal reaction time (SSRT) than those in the lower PA group. Experiment 2 separated the attentional capture in the SST and revealed that the participants in the higher PA group could detect the signal faster than those in the lower PA group. Experiment 3 further added a stop signal to Experiment 2 and demonstrated that the participants in the higher PA group could more effectively deploy attentional resources to complete the task. Overall, these findings indicate that PA is positively associated with response inhibition and that the positive relationship is associated with effective allocation of attentional resources for faster attentional capture.

With the continuous increase in the scale of photovoltaic grid connection, the impact of the safe and stable operation of photovoltaic power generation systems on the grid cannot be ignored. When a short-term failure of the power grid occurs, the large-scale disconnection of the unit will seriously affect the stability of the grid voltage and frequency. Therefore, this paper proposes a non-linear control method for photovoltaic power generation low voltage ride through (LVRT) based on adaptive maximum power tracking. This method adaptively adjusts the power tracking trajectory through the feedforward control of the voltage drop amplitude. Cooperating with the nonlinear control of the grid-connected inverter, this method can quickly and effectively control the power output of photovoltaic cells on the basis of providing appropriate reactive power support, so as to realize the rapid response of grid system. Through the simulation in PSCAD, it is verified that the control method described in this article can well realize the LVRT in different amplitudes of the photovoltaic system, especially when zero voltage drops occur.

Treatment of a chelating silane 1-(dimethylsilyl)-2-silylbenzene (4) with Pd(PEt3)4 in the ratio of 2:1 selectively afforded a unique mononuclear palladium complex [{1,2-C6H4(SiMe2)(SiH)}2Pd(PEt3)2] (6), which was formed by two Si–Si coupling reactions between the SiH2 groups and the SiMe2 moieties from two hydrosilane ligands. Complex 6 was structurally characterized by single crystal X-ray analysis and multinuclear NMR spectroscopic studies and is one of the very few examples of cis-bis(silyl)palladium(II) complexes containing in situ formed Si–Si single bonds.

We thank the clinicians and researchers around the world for their comprehensive interpretation of the results of our randomised controlled trial of remdesivir for COVID-19.1 They shared valuable thoughts from different perspectives according to related evidence from in vitro and animal models, and pharmacogenomic studies. A suggestion was made for subgroup analyses by concomitant lopinavir-ritonavir use. Concerns for not reaching the predetermined sample size in our study were also expressed. These comments are appreciated and helpful for future conduct and interpretation of COVID-19 therapy studies.

Abstract Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in infants and children. The disease outcome of HMPV infection ranges from mild infection to severe bronchiolitis and fatal pneumonia. HMPV was discovered in 2001 and its disease mechanisms are not fully understood. To gain insight into HMPV pathogenesis, we tested nine HMPV clinical isolates in an established C57BL/6 mouse model. HMPV clinical isolates induced variable disease severity ranging from mild to fatal disease. Mice infected by non-virulent strain TN/94-49 did not show significant weight loss, but mice infected with virulent isolate C2-202 showed dramatic weight loss and 40% mortality within 5 days post-infection. These findings were confirmed in other inbred mouse strains. C2-202 infected mice also suffered from impaired pulmonary function post-recovery. Lung virus replication did not correlate with disease severity, suggesting immune-mediated pathogenesis. Further investigation revealed increased type I and III interferons, pro-inflammatory cytokine production, and neutrophil infiltration in C2-202 infected mice. HMPV C2-202 infection also inhibited dendritic cell recruitment and down-regulated MHC-II surface expression on macrophages. Stat1/Stat2 double knockout mice lacking interferon signaling exhibited reduced weight loss, lessened disease severity, and increased dendritic cell recruitment after C2-202 infection. Our results indicate that severe disease caused by HMPV clinical isolates was due to exuberant interferon response leading to immuno-pathological tissue damage. These data suggest interferon signaling plays an important role in HMPV pathogenesis, and thus serves as a potential therapeutic target.

Abstract Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in infants and children. The disease outcome of HMPV infection ranges from mild infection to severe bronchiolitis and fatal pneumonia. HMPV was discovered in 2001 and its disease mechanisms are not fully understood. To study HMPV pathogenesis, we tested nine HMPV clinical isolates in an established C57BL/6 mouse model. HMPV clinical isolates induced variable disease severity ranging from mild to fatal disease. Mice infected by non-virulent strain TN/94-49 did not show significant weight loss, but mice infected with virulent isolate C2-202 showed dramatic weight loss and 40% mortality within 5 days post-infection. These findings were confirmed in other inbred mouse strains. C2-202 infected mice also suffered from impaired pulmonary function post-recovery. Lung virus replication did not correlate with disease severity, suggesting immune-mediated pathogenesis. Further investigation revealed increased type I and III interferons, pro-inflammatory cytokine production, and neutrophil infiltration in C2-202 infected mice. HMPV C2-202 infection also inhibited dendritic cell recruitment and down-regulated MHC-II surface expression on macrophages. Stat1/Stat2 double knockout mice lacking interferon signaling exhibited reduced weight loss, lessened disease severity, and increased dendritic cell recruitment after C2-202 infection. Our results indicate that severe disease caused by HMPV clinical isolates was due to exuberant interferon response leading to immuno-pathological tissue damage. These data suggest interferon signaling plays an important role in HMPV pathogenesis, and thus serves as a potential therapeutic target.

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

Abstract Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in children and adults. However, mechanisms of pathogenesis are not fully understood. Methods We tested HMPV clinical and laboratory isolates in an established C57BL/6 mouse model and measured weight loss, airway function, and viral titers. Immune responses were determined using cytokine quantitation and flow cytometry. Results HMPV clinical isolates induced variable disease severity ranging from mild to fatal disease. Laboratory strain TN/94-49 did not cause weight loss, but mice infected with clinical isolate C2-202 showed dramatic weight loss and 40% mortality within 5 days post-infection (Figure 1). These findings were confirmed in other inbred mouse strains. C2-202-infected mice also suffered from impaired pulmonary function post-recovery. Lung viral titer did not correlate with disease severity, suggesting immune-mediated pathogenesis. C2-202-infected mice exhibited increased production of type I and III interferons (IFN) and pro-inflammatory cytokines, and lung neutrophil infiltration. However, neutrophil depletion or inflammasome inactivation did not reduce disease. Stat1/Stat2 double knockout (KO) mice lacking type I and III IFN signaling exhibited reduced weight loss but increased lung viral titer after C2-202 infection (Figure 2). Type I IFN receptor (IFNAR) KO mice infected with C2-202 had reduced weight loss but unchanged lung viral titer (Figure 3), while the addition of type III IFN blockade to C2-202-infected IFNAR mice had no effect on disease but increased lung viral titer (Figure 4). Conclusion These results suggest that severe disease caused by virulent HMPV was due to exuberant IFN response. Moreover, type I IFN was primarily associated with disease, while type III IFN was associated with viral clearance. These data suggest that IFN signaling plays an important role in HMPV pathogenesis, and thus serves as a potential therapeutic target. Disclosures All Authors: No reported Disclosures.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Problem: Coronavirus disease 2019 (COVID-2019) caused by SARS-CoV-2 has been an ongoing pandemic and worldwide public health emergency, having drawn a lot of attention around the world. There is concern about whether COVID-19 is closely related to male reproduction. Method of Study: In this review, we investigated the viral, biological, and clinical data of male reproductive dysfunction associated with the infection of SARS-CoV-2 and its possible immunological explanations and clinical remedies. Results: The pathogenesis of COVID-19 is characterized by infecting ACE-2-expressing cells, including testis-specific cells, namely Leydig, Sertoli, and spermatogenic cells, which are closely related to male reproduction. This leads to aberrant hyperactivation of the immune system generating damage to the infected organs. An impairment in testicular function through uncontrolled immune responses alert more attention to male infertility. Meanwhile, the recent clinical data indicate that the infection of human testis with SARS-CoV-2 may impair male germ cell development, lead to germ cell loss and higher immune cells infiltration. Conclusions: Conclusively, the issue of SARS-CoV-2 likely infecting human testis, especially the patients with severe COVID-19, cannot be ignored, and the germ cells loss in the patients with COVID-19 should raise alarming attention to the potential impairment of the reproductive function of the patients, especially the reproductive-aged men.

Additional file 1: Table S1. Underlying conditions of IPA patients. Figure S1. Radiological presentations of IPA patients.

In order to improve the accuracy of the evaluation results, BP algorithm is introduced to design the automatic reliability evaluation model of relay protection equipment. In order to ensure the effectiveness of the model evaluation results, the method of expanding the reliability automatic evaluation data samples i s adopted to mine the operation rules of the data set. According to the time series of data output, the output data set and the training sample data set are fused. At the same time, it describes the possibility of failure of relay protection equipment in different operation stages, and estimates the least square parameters of equipment operation reliability through Weibull index, and obtains the reliability evaluation results of relay protection equipment. And th rough the way of experimental demonstration, it is proved that the designed model can control the error of evaluation results within the range of 0.01.

Grant-free access successfully reduces the overhead and delay of signaling in the scenario of ultra-reliable low-latency communications (URLLC). However, it is also prone to conflict in the case of high load, resulting the lose of spectrum efficiency, reduced reliability and increased delay. In this paper, we realize K-multipacket reception (K-MPR) with sparse code multiple access (SCMA) technology to improve spectrum efficiency and throughput, and yet its implementation greatly increases the difficulty of ensuring the reliability of data transmission. Therefore, we propose an optimization method to maximize service quality of SCMA grant-free access with MPR. First, we investigate the behaviors of transient system via Markov chain to obtain reliability under delay constraints. Furthermore, we use dichotomy to calculate the minimum MPR ability value <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$K$</tex> . The simulation results show the validity of theoretical analysis. The proposed scheme maintains the increasing trend of reliability under delay constraints and tradeoff between throughput and reliability under delay constraints is presented, while optimal tradeoff between spectrum efficiency and reliability is achieved.

In the battle against COVID-19, scientists all over the world are doing their best to fight. From January 24, 2020, when the SARS-CoV-2 cases were first reported,1 to today (February 16, 2021), more than 100,000 related articles have been published. These scientific discoveries have enabled us to better understand our enemies.

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

<b><i>Objectives:</i></b> The determinants leading to different renal outcomes in community-acquired acute kidney injury (CA-AKI) and the influence of renal histological damage on the prognosis and recovery of CA-AKI are scarcely reported. <b><i>Methods:</i></b> Adult patients with CA-AKI admitted to Shanghai Changzheng Hospital with renal biopsy profiles from January 1, 2010, to December 31, 2018, were enrolled in our cohort. After 3 months of follow-up, clinical outcomes, including patient survival, dialysis requirement during hospitalization and at 3 months, CKD stage 3–5, and renal functional recovery at 3 months, were analyzed, and risk factors were identified. <b><i>Results:</i></b> A total of 294 patients with CA-AKI with renal pathology were identified for this cohort. Among 282 patients who survived 3 months after AKI, 59.6% completely recovered, 21.3% partially recovered, 21.3% progressed to stage 3–5 CKD without dialysis, and 17.7% maintained dialysis. Moreover, 70.4% of patients in the cohort presented with de novo intrinsic renal disease, except acute tubular necrosis or acute interstitial nephritis, on renal biopsy. In the multivariate analyses, clinical factors were more related to short-term outcomes and severity of CA-AKI, represented by mortality, in-hospital dialysis, and CRRT requirement, while pathological elements were more involved with CKD progression, including dialysis-dependent or stage 3–5 CKD, and renal function recovery at the 3-month follow-up. The detrimental influence of glomerular and arterial lesions on renal prognosis of CA-AKI was as critical as tubular and interstitial lesions. <b><i>Conclusions:</i></b> Clinical and pathological parameters both contribute to patient and renal outcomes after CA-AKI. The value of renal biopsy should be recognized in prognostic prediction.