HLA-B*15:245:02Q differs from HLA-B*15:01:01:01 by two nonsynonymous nucleotides exchanges in exon 3.

HLA-A*02:889 differs from HLA-A*02:01:01:01 by one nucleotide exchange at position 506(C>G) with an amino exchange.

Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18 th 2020 to April 26 th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate. Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Background Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases. Methods We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020. Results Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality. Conclusions A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.

BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING: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.

Background: Different positive end-expiratory pressure (PEEP) strategies are available for subjects with coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. We aimed to evaluate three conventional PEEP strategies on their effects on respiratory mechanics, gas exchanges, and hemodynamics.Methods: This is a prospective, physiologic, multicenter study conducted in China. We recruited 20 intubated subjects with ARDS and confirmed COVID-19. We first set PEEP by the ARDSnet low PEEP–fraction of inspired oxygen (FIO2) table. After a recruitment maneuver, PEEP was set at 15, 10, and 5 cm H2O for 10 min, respectively. Among these three PEEP levels, best-compliance PEEP was the one providing the highest respiratory system compliance; best-oxygenation PEEP was the one providing the highest PaO2 (partial pressure of arterial oxygen)/FIO2.Results: At each PEEP level, we assessed respiratory mechanics, arterial blood gas, and hemodynamics. Among three PEEP levels, plateau pressure, driving pressure, mechanical power, and blood pressure improved with lower PEEP. The ARDSnet low PEEP–FIO2 table and the best-oxygenation strategies provided higher PEEP than the best-compliance strategy (11 ± 6 cm H2O vs. 11 ± 3 cm H2O vs. 6 ± 2 cm H2O, p = 0.001), leading to higher plateau pressure, driving pressure, and mechanical power. The three PEEP strategies were not significantly different in gas exchange. The subgroup analysis showed that three PEEP strategies generated different effects in subjects with moderate or severe ARDS (n = 12) but not in subjects with mild ARDS (n = 8).Conclusions: In our cohort with COVID-19–induced ARDS, the ARDSnet low PEEP/FIO2 table and the best-oxygenation strategies led to higher PEEP and potentially higher risk of ventilator-induced lung injury than the best-compliance strategy.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04359251.

AbstractIt is crucial to maintain continuity of essential services for people affected by tuberculosis (TB). Efforts to deliver these essential services in many global settings have been complicated by the emergence and global spread of SARS-CoV-2 and the pandemic of COVID-19. Understanding how the COVID-19 pandemic has impacted the availability of TB diagnostic and treatment services is critical for identifying policies that can mitigate disruptions of these essential services. China has a dual burden of TB and COVID-19. We conducted a survey and collected data from 13 provinces in China to evaluate the early impact of COVID-19 on TB services and to document interventions that were adopted to maintain the continuity services for TB patients during the pandemic. We use these data to identify additional opportunities which will improve the ability of TB programs to maintain essential services during this crisis. While health systems and underlying epidemiology differ between countries, we believe that sharing China’s experience can inform the design of locally tailored strategies to maintain essential TB services during the COVID-19 pandemic.

majority (67-85%) of critically ill patients who

Background 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. Methods 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. Findings 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 TNF alpha. Interpretation 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

BackgroundIn December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.MethodsIn this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.FindingsOf the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.InterpretationThe 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.FundingNational Key R&D Program of China.

Background The clinical correlates, prognosis and determinants of acute kidney injury (AKI) in patients with coronavirus disease 2019 (Covid-19) remain largely unclear. Methods We retrospectively reviewed medical records of all adult patients with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. Results Among 210 patients, 131 were males (62.4%). The median Age was 64 years (IQR: 56–71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) were classified as being at stage 1, 2 and 3, respectively. 54 patients (58.7%) received continuous renal replacement therapy. Age, sepsis, nephrotoxic drug, invasive mechanical ventilation and elevated baseline serum creatinine levels were associated with the occurrence of AKI. Renal recovery during hospitalization was identified among 16 patients with AKI (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher ratio of partial pressure of oxygen to the fraction of inspired oxygen. Of 210 patients, 93 deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater Age and the lowest ratio of partial pressure of oxygen to the fraction of inspired oxygen being < 150 mmHg were independently associated with death. Conclusions Among patients with Covid-19, the incidence of AKI was high. Our findings of the risk factors of the development of AKI and factors associated with renal function recovery may inform clinical management of patients with critical illness of Covid-19.

Background: Since December 2019, a novel coronavirus (2019-nCoV) associated pneumonia has emerged in Wuhan, China. The study aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.Methods: 99 cases admitted to Wuhan Jinyintan Hospital during January 1 to 20, 2020 and confirmed by real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) test were analyzed for epidemiological, demographic, clinical, radiological features, and laboratory data. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the South China Seafood Wholesale Market. The average age of the patients was 62.85 ± 11.99 years, including 67 males and 32 females. 2019-nCoV was detected in all patients by RT-PCR, and some of them also by serological testing, and metagenomics sequencing analysis. 50 cases (50.51%) had chronic basic diseases. Patients had clinical manifestations of fever (83%), cough (82%), shortness of breath (31%), muscle aches (11%), headache (8%), fuzzy confusion (7%), chest pain (2%), and diarrhea (2%). According to imaging examination, 74 patients showed bilateral pneumonia (74.75%), 25 patients showed multiple mottled and ground-glass opacity, and 1 patient had pneumothorax. Most patients received antiviral, antibiotics, supportive treatments, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), and had good prognosis. 17 patients developed acute Respiratory Distress Syndrome (ARDS) and among them, 2 patients worsened in a short period of time and died of multiple organ failure.Interpretation: The infection of the 2019-nCoV can result in severe and even fatal respiratory disease like ARDS. It is very important to actively prevent complications and secondary infections, treat underlying diseases, and provide timely organ function support. Early diagnosis, early isolation, multiple treatment, and intervention of CRRT and ECMO when necessary can effectively reduce mortality caused by severe coronavirus pneumonia.Funding: National Key R&D Program of China (No. 2017YFC1309700)Declaration of Interest: The author reports no conflicts of interest in this work.Ethical Approval: The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from all patients involved before enrolment.

Backs round An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26,2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59.7 (SD 13.3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61.5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64.6 years [11.2] vs 51.9 years [12.9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13.5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Background: A cluster of cases infected with the novel coronavirus (COVID-19) pneumonia outbroke in Wuhan, China. Recovered patients may remain virus carriers. Data therefore have been collected to formulate integrated guidelines for hospital discharge or discontinuation of quarantine. Methods: From January 2020 to March 2020, we investigated 30 patients with unstable conditions which indicates shifting results of virus RNA detections in Wuhan Jin Yin-tan Hospital (Wuhan, China). Evidences like clinical records, nursing records, laboratory and Radiology examinations for all confirmed positive patients by viral nucleic acid detections were collected beforehand. Dataset were then analyzed to identify the relationship between the RNA detection and symptoms. Findings: The median age of parents was 60.5-year-old, with 14 patients (46.7%) aged between 15 and 49, and 10 (33.3%) older than 65 years (as shown in table 1). 14 patients (46.7%) were male, slightly less than female (16, 53.3%). 17 patients (56.7%) had chronic diseases which include diabetes, hypertension, bronchial asthma, tumor post-operation, bullae of lung post- operation, hepatitis B cirrhosis, cerebrovascular diseases, gout, postpartum, pituitary adenoma. The most common symptoms were fever (93.3%), cough (90%), and dyspnoea (63·3%). The median duration from the onset of symptoms to admission into the hospital was 13 (IQR 5–31) days. A majority of the patients received intravenous antibiotics (90.0%) and broad-spectrum antivirus therapy (86.7%) while 26 patients (86.7%) received nutrition support therapy. Systemic glucocorticoids were administrated to 8 patients (26.7%). Oxygen therapy by nasal cannula was adopted in all cases while invasive ventilation not engaged in any treatment. All of the 30 patients were being followed up during the study. Nobody was transferred to ICU or treated with the use of invasive mechanical ventilation. All of them are still alive. Interpretation: The disease course of confirmed patients, which can be evaluated by clinical manifestation and radiological examination results, may not reciprocate mono-directional reversion of positive RT-PCR test results into negative ones. Patients infected with COVID-19 may become asymptomatic in the process of treatment and recovery, combined with promising chest CT findings, however, unpredictable changes in RT-PCR test results between positives and negatives have been identified. Due to the unavailability of quantitative studies and the lack of specific medicine for COVID-19 infected pneumonia, longer periods of hospitalization and quarantine, integrated specimens for RT-PCR test are therefore suggested.Funding Statement: This study is funded by The National Natural Science Foundation of China (No: 81802137).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study was approved by the Ethics Commission of Wuhan Jin-Yintan Hospital. Due to the severity of this highly contagious disease, the patients' verbal agreements to participate in the research were obtained and the written informed consent was waived.

Abstract Background The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. Methods Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. Results Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. Conclusions Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Background Covid-19 is an emerging and evolving infectious and communicable diseases which gravely endanger the lives of critically ill patients with it. It is crucial to determine the clinical implication of secondary pulmonary bacterial infection for the outcome of critically ill patients with severe Covid-19.Methods All critically ill patients with Covid-19(30 deceased and 35 discharged) between January 26, 2020 and March 15, 2020 in two ICUs of Jinyintan Hospital, Wuhan, China, were retrospectively reviewed, to investigate the clinical implication of secondary pulmonary bacterial infection in the prognosis of critically ill patients with severe Covid-19.Results The fatality rate between patients with positive and negative sputum bacterial culture is 75.0%vs 33.3% (P = 0.003). The ROC analyses demonstrate that NLR[0.921(0.858–0.984)P༜0.001], CRP[0.908(0.837–0.978)P༜0.001],neutrophil[0.832(0.728–0.937)P༜0.001],lymphocyte[0.858(0.755–0.960)P༜0.001],leucocyte[0.753(0.626–0.879)P༜0.001] and PCT [0.733(0.605–0.860)P = 0.001] have the discrimination power for the fatality. The Kaplan-Meier analyses show that the patients with negative sputum bacterial culture(P༜0.001) have higher cumulative overall survival rates, in comparison with the opposite. The positive sputum bacterial culture is positively correlated with leukocyte(r = 0.706), CRP(r = 0.733), NLR(r = 0.554) and PCT(r = 0.549)(all P༜0.001). A multivariate Cox regression analysis shows that sputum bacterial culture[15.36(4.291–54.980) P༜0.001], CRP[2.022(2.013–2.030) P༜0.001] and NLR[2.012(2.000-2.024) P = 0.045] are positively correlated with the fatality of the patients.Conclusions The critically ill patients with severe Covid-19 who are complicated with secondary pulmonary bacterial infection may have an unfavorable outcome, in comparison with those who are not. Secondary pulmonary bacterial infection is an independent factor for the fatality of critically patients with Covid-19.

HLA‐B*46:01:21 differs from HLA‐B*46:01:01 by one nucleotide exchange at position 834(G>A) with no amino exchange.