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1.
Lancet ; 2020 Jul 20.
Article in English | MEDLINE | ID: covidwho-666142

ABSTRACT

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

2.
Lancet ; 395(10223): 497-506, 2020 02 15.
Article in English | MEDLINE | ID: covidwho-665705

ABSTRACT

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 TNFα. 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. FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Age Distribution , Aged , China/epidemiology , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/transmission , Cough/epidemiology , Cough/virology , Female , Fever/epidemiology , Fever/virology , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Myalgia/epidemiology , Myalgia/virology , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Prognosis , Radiography, Thoracic , Respiratory Distress Syndrome, Adult/epidemiology , Respiratory Distress Syndrome, Adult/virology , Time Factors , Tomography, X-Ray Computed , Young Adult
3.
Respir Res ; 21(1): 172, 2020 Jul 06.
Article in English | MEDLINE | ID: covidwho-656136

ABSTRACT

BACKGROUND: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear. RESEARCH QUESTION: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score-matching (PSM) analysis. STUDY DESIGN AND METHODS: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients' outcomes and PSM analysis to further validate the abovementioned effect. RESULTS: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709-6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients' mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19. CONCLUSION: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Hospital Mortality , Hypertension/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Age Factors , Aged , China/epidemiology , Clinical Laboratory Techniques/methods , Cohort Studies , Comorbidity , Female , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Hypertension/diagnosis , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Propensity Score , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , Survival Analysis , Survivors , Tertiary Care Centers
4.
Sci Rep ; 10(1): 10263, 2020 06 24.
Article in English | MEDLINE | ID: covidwho-617065

ABSTRACT

COVID-19 is "public enemy number one" and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 -12), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10-6). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman's Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.


Subject(s)
Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , Tomography, X-Ray Computed/methods , Adult , Aged , Betacoronavirus , Female , Humans , Male , Middle Aged , Pandemics , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies
5.
Respir Res ; 21(1): 157, 2020 Jun 22.
Article in English | MEDLINE | ID: covidwho-610251

ABSTRACT

BACKGROUND: Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined. METHOD: We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020 in a tertiary hospital in Wuhan. Patients were classified as having mild or severe COVID-19 based on their respiratory rate, SpO2, and PaO2/FiO2 levels. Patients' symptoms, computer tomography (CT) images, preadmission drugs received, and the serum biochemical examination on admission were compared between the mild and severe groups. Significant variables were enrolled into logistic regression model to predict the factors affecting disease severity. A receiver operating characteristic (ROC) curve was applied to validate the predictive value of predictors. RESULT: Age; temperature; anorexia; and white blood cell count, neutrophil percentage, platelet count, lymphocyte count, C-reactive protein, aspartate transaminase, creatine kinase, albumin, and fibrinogen values were significantly different between patients with mild and severe COVID-19 (P < 0.05). Logistic regression analysis confirmed that lymphopenia (P = 0.010) indicated severe prognosis in previously healthy young adults with COVID-19, with the area under the curve (AUC) was 0.791(95% Confidence Interval (CI) 0.704-0.877)(P < 0.001). CONCLUSION: For previously healthy young adults with COVID-19, lymphopenia on admission can predict severe prognosis.


Subject(s)
Coronavirus Infections/epidemiology , Hospital Mortality , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Age Factors , China/epidemiology , Clinical Laboratory Techniques/methods , Cohort Studies , Coronavirus Infections/diagnosis , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Logistic Models , Male , Pneumonia, Viral/diagnosis , Predictive Value of Tests , Prognosis , ROC Curve , Radiography, Thoracic/methods , Retrospective Studies , Risk Assessment , Survival Rate , Tertiary Care Centers , Tomography, X-Ray Computed/methods , Young Adult
6.
Emerg Microbes Infect ; 9(1): 1489-1496, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-599991

ABSTRACT

In December 2019, Wuhan, China suffered a serious outbreak of a novel coronavirus infectious disease (COVID) caused by novel severe acute respiratory syndrome-related coronavirus (SARS-CoV 2). To quickly identify the pathogen, we designed and screened primer sets, and established a sensitive and specific qRT-PCR assay for SARS-CoV 2; the lower limit of detection (LOD) was 14.8 (95% CI: 9.8-21) copies per reaction. We combined this qRT-PCR assay with an automatic integration system for nucleic acid extraction and amplification, thereby establishing an automatic integrated gene detection system (AIGS) for SARS-CoV 2. Cross reactive analysis performed in 20 other respiratory viruses and 37 nasopharyngeal swabs confirmed a 100% specificity of the assay. Using two fold diluted SARS-CoV 2 culture, the LOD of AIGS was confirmed to be 365 copies/ml (95% CI: 351-375), which was Comparable to that of conventional q RT-PCR (740 copies/ml, 95% CI: 689-750). Clinical performances of AIGS assay were assessed in 266 suspected COVID-19 clinical respiratory tract samples tested in parallel with a commercial kit. The clinical sensitivity of the AIGS test was 97.62% (95% CI: 0.9320-0.9951) based on the commercial kit test result, and concordance analysis showed a high agreement in SARS-CoV-2 detection between the two assays, Pearson R was 0.9623 (95% CI: 0.9523-0.9703). The results indicated that this AIGS could be used for rapid detection of SARS-CoV 2. With the advantage of simple operation and less time consuming, AIGS could be suitable for SARS-CoV2 detection in primary medical institutions, thus would do a great help to improve detection efficiency and control the spread of COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , Automation, Laboratory , China , DNA Primers , Humans , Limit of Detection , Pandemics , RNA, Viral/analysis , Sensitivity and Specificity , Virus Cultivation
7.
Shock ; 2020 Jun 02.
Article in English | MEDLINE | ID: covidwho-526044

ABSTRACT

BACKGROUND AND OBJECTIVE: The effects of corticosteroid treatment on non-severe COVID-19 pneumonia patients are unknown. To determine the impacts of adjuvant corticosteroid administrated to patients with non-severe COVID-19 pneumonia. METHOD: A retrospective cohort study based on propensity score analysis was designed to explore the effects of corticosteroid on several clinical outcomes. RESULTS: 132 patients satisfied the inclusion criteria and 35 pairs were generated according to propensity score matching. Compared to non-corticosteroid group, the CT score on day 7 was significantly higher in corticosteroid group (8.6 (IQR, 2.8-11.5) versus 12.0 (IQR, 5.0-19.3), P = 0.046). In corticosteroid group, more patients progressed to severe cases (11.4% versus 2.9%, P = 0.353), hospital stay (23.5 days (IQR, 19-29 d) versus 20.2 days (IQR, 14-25.3 d), P = 0.079) and duration of viral shedding (20.3 days (IQR, 15.2-24.8 d) versus 19.4 days (IQR, 11.5-28.3 d), P = 0.669) were prolonged, while fever time (9.5 days (IQR, 6.5-12.2 d) versus 10.2 days (IQR, 6.8-14 d), P = 0.28) was shortened, however all these data revealed no statistically significant differences. CONCLUSION: Corticosteroid might have a negative effect on lung injury recovery in non-severe COVID-19 pneumonia patients, however the results of this study must be interpreted with caution because of confounding factors.

8.
Lancet ; 395(10240): 1845-1854, 2020 06 13.
Article in English | MEDLINE | ID: covidwho-342974

ABSTRACT

BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. METHODS: We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. FINDINGS: Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. INTERPRETATION: The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. FUNDING: National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/administration & dosage , Adenoviridae , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Immunity, Humoral , Injections, Intramuscular , Male , Middle Aged , T-Lymphocytes/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/therapeutic use , Viral Vaccines/adverse effects , Viral Vaccines/therapeutic use , Young Adult
9.
Trials ; 21(1): 422, 2020 May 24.
Article in English | MEDLINE | ID: covidwho-342726

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Alanine/administration & dosage , Alanine/adverse effects , Antiviral Agents/adverse effects , Betacoronavirus/pathogenicity , China , Clinical Trials, Phase III as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Double-Blind Method , Equivalence Trials as Topic , Female , Humans , Infusions, Intravenous , Male , Multicenter Studies as Topic , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome
10.
J Med Virol ; 2020 May 21.
Article in English | MEDLINE | ID: covidwho-326869

ABSTRACT

Although emerging data demonstrated mortality of young COVID-19 patients, no data have reported the risk factors of mortality for these young patients, and whether obesity is a risk for young COVID-19 patients remains unknown. We conducted a retrospective study including 13 young patients who died of COVID-19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID-19 patients. Most of the young deceased COVID-19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by a higher severity of patchy shadows (100.00% vs 48.70%; P = .006), pleural thickening (61.50% vs 12.80%; P = .012), and mild pericardial effusion (76.90% vs 0.00%; P < .001). Most importantly, the deceased patients manifested higher body mass index (odds ratio [OR] = 1.354; 95% confidence interval [CI] = 1.075-1.704; P = .010), inflammation-related index C-reactive protein (OR = 1.014; 95% CI = 1.003-1.025; P = .014), cardiac injury biomarker hs-cTnI (OR = 1.420; 95% CI = 1.112-1.814; P = .005), and increased coagulation activity biomarker D-dimer (OR = 418.7; P = .047), as compared with that of survivors. Our data support that obesity could be a risk factor associated with high mortality in young COVID-19 patients, whereas aggravated inflammatory response, enhanced cardiac injury, and increased coagulation activity are likely to be the mechanisms contributing to the high mortality.

12.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Article in English | MEDLINE | ID: covidwho-141774

ABSTRACT

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , Betacoronavirus , China , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Negative Results , Pandemics
13.
Nature ; 580(7803): E7, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-73543

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

15.
Ann Am Thorac Soc ; 17(7): 839-846, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-38758

ABSTRACT

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%.Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia.Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020.Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively.Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.


Subject(s)
Betacoronavirus , Coronavirus Infections , Critical Care/methods , Multiple Organ Failure , Pandemics , Pneumonia, Viral , Respiratory Insufficiency , Aged , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , China/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Mortality , Multiple Organ Failure/diagnosis , Multiple Organ Failure/etiology , Outcome and Process Assessment, Health Care , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prognosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Risk Assessment , Risk Factors
16.
PLoS One ; 15(3): e0230548, 2020.
Article in English | MEDLINE | ID: covidwho-10200

ABSTRACT

Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.


Subject(s)
Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Aged , China , Comorbidity , Coronavirus Infections/pathology , Female , Humans , Lung/pathology , Male , Middle Aged , Pneumonia, Viral/pathology , Predictive Value of Tests , Prognosis , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
17.
Chin Med J (Engl) ; 133(9): 1032-1038, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-3344

ABSTRACT

BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ±â€Š6.60 vs. 41.27 ±â€Š4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adult , Aged , Female , Hospitals , Humans , Logistic Models , Male , Middle Aged , Risk Factors
20.
Nature ; 579(7798): 265-269, 2020 03.
Article in English | MEDLINE | ID: covidwho-258

ABSTRACT

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.


Subject(s)
Betacoronavirus/classification , Communicable Diseases, Emerging/complications , Communicable Diseases, Emerging/virology , Coronavirus Infections/complications , Coronavirus Infections/virology , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/virology , Adult , Betacoronavirus/genetics , China , Communicable Diseases, Emerging/diagnostic imaging , Communicable Diseases, Emerging/pathology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Genome, Viral/genetics , Humans , Lung/diagnostic imaging , Male , Phylogeny , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , RNA, Viral/genetics , Recombination, Genetic/genetics , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/pathology , Tomography, X-Ray Computed , Whole Genome Sequencing
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