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1.
Lancet ; 398(10314): 1872-1873, 2021 11 20.
Article in English | MEDLINE | ID: covidwho-1521621

Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Survivors
2.
BMC Pulm Med ; 21(1): 308, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1439539

ABSTRACT

BACKGROUND: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). METHODS: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. RESULTS: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021). CONCLUSIONS: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.

3.
Lancet ; 398(10302): 747-758, 2021 08 28.
Article in English | MEDLINE | ID: covidwho-1376121

ABSTRACT

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.


Subject(s)
COVID-19/complications , Survivors , Aged , Anxiety/etiology , COVID-19/physiopathology , COVID-19/psychology , Depression/etiology , Exercise Tolerance , Fatigue/etiology , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lung/physiopathology , Male , Middle Aged , Muscle Weakness/etiology , Quality of Life , SARS-CoV-2 , Walk Test
4.
BMJ Open ; 11(8): e049515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-1346064

ABSTRACT

INTRODUCTION: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate. METHODS AND ANALYSIS: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission. ETHICS AND DISSEMINATION: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04682899.


Subject(s)
Bacterial Infections , Pulmonary Disease, Chronic Obstructive , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Humans , Inpatients , Multicenter Studies as Topic , Procalcitonin , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic
5.
Lancet ; 398(10296): 188-190, 2021 07 17.
Article in English | MEDLINE | ID: covidwho-1313500
6.
Med Phys ; 48(8): 4334-4349, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1265402

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused hundreds of thousands of infections and deaths. Efficient diagnostic methods could help curb its global spread. The purpose of this study was to develop and evaluate a method for accurately diagnosing COVID-19 based on computed tomography (CT) scans in real time. METHODS: We propose an architecture named "concatenated feature pyramid network" ("Concat-FPN") with an attention mechanism, by concatenating feature maps of multiple. The proposed architecture is then used to form two networks, which we call COVID-CT-GAN and COVID-CT-DenseNet, the former for data augmentation and the latter for data classification. RESULTS: The proposed method is evaluated on 3 different numbers of magnitude of COVID-19 CT datasets. Compared with the method without GANs for data augmentation or the original network auxiliary classifier generative adversarial network, COVID-CT-GAN increases the accuracy by 2% to 3%, the recall by 2% to 4%, the precision by 1% to 3%, the F1-score by 1% to 3%, and the area under the curve by 1% to 4%. Compared with the original network DenseNet-201, COVID-CT-DenseNet increases the accuracy by 1% to 3%, the recall by 4% to 9%, the precision by 1%, the F1-score by 1% to 3%, and the area under the curve by 2%. CONCLUSION: The experimental results show that our method improves the efficiency of diagnosing COVID-19 on CT images, and helps overcome the problem of limited training data when using deep learning methods to diagnose COVID-19. SIGNIFICANCE: Our method can help clinicians build deep learning models using their private datasets to achieve automatic diagnosis of COVID-19 with a high precision.


Subject(s)
COVID-19 , COVID-19 Testing , Humans , Radionuclide Imaging , SARS-CoV-2 , Tomography, X-Ray Computed
7.
Clin Infect Dis ; 72(11): e901-e913, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249298

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.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , SARS-CoV-2
8.
Clin Infect Dis ; 72(10): e545-e551, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232187

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 < .0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, P < .0001), and RBD-IgG (slope -1.43, 95% CI -1.98 to -.88, P < .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.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Antibody Formation , China/epidemiology , Humans , Immunoglobulin M , SARS-CoV-2
9.
Lancet ; 397(10287): 1807-1808, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1228178

Subject(s)
COVID-19 , Humans , Kidney , SARS-CoV-2
10.
The Lancet ; 397(10270):220-232, 2021.
Article in English | APA PsycInfo | ID: covidwho-1164655

ABSTRACT

Presents a study which aims to examine consequences of COVID-19 in patients discharged from hospital for 6-months. This ambidirectional cohort study was done at Jin Yin-tan Hospital, the first designated hospital for patients with COVID-19 in Wuhan, Hubei, China. Clinical data for acute phase were retrieved from electronic medical records, including demographic characteristics, clinical characteristics, laboratory test results;and treatment. The disease severity was characterized by the highest seven-category scale during the hospital stay. Data were managed using REDCap electronic data capture tools in order to minimize missing inputs and allow for real-time data validation and quality control. Follow-up consultations were done in the outpatient clinic of Jin Yin-tan Hospital. All participants were interviewed face-to-face by trained physicians and asked to complete a series of questionnaires. For the symptom questionnaire, participants were asked to report newly occurring and persistent symptoms, or any symptoms worse than before COVID-19 development. A total of 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7, and May 29, 2020, and the follow-up study was done from June 16, 2020, to Sept 3, 2020. This is the largest cohort study with the longest follow-up duration assessing the health consequences of adult patients discharged from hospital recovering from COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

11.
Emerg Microbes Infect ; 10(1): 664-676, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1139855

ABSTRACT

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.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronavirus OC43, Human/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Severity of Illness Index , Young Adult
13.
Lancet ; 397(10270): 220-232, 2021 01 16.
Article in English | MEDLINE | ID: covidwho-1065678

ABSTRACT

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


Subject(s)
COVID-19/complications , Quality of Life , Aged , COVID-19/epidemiology , COVID-19/psychology , COVID-19 Serological Testing/statistics & numerical data , China/epidemiology , Cohort Studies , Comorbidity , Fatigue/epidemiology , Fatigue/etiology , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Muscle Weakness/epidemiology , Muscle Weakness/etiology , Pandemics , SARS-CoV-2 , Severity of Illness Index , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Surveys and Questionnaires
14.
Emerg Microbes Infect ; 9(1): 2707-2714, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-953975

ABSTRACT

To identify the association between the kinetics of viral load and clinical outcome in severe coronavirus disease 2019 (COVID-19) patients, a retrospective study was performed by involved 188 hospitalized severe COVID-19 patients in the LOTUS China trial. Among the collected 578 paired throat swab (TS) and anal swab (AS) samples, viral RNA was detected in 193 (33.4%) TS and 121 (20.9%) AS. A higher viral RNA load was found in TS than that of AS, with means of 1.0 × 106 and 2.3 × 105 copies/ml, respectively. In non-survivors, the viral RNA in AS was detected earlier than that in survivors (median of 14 days vs 19 days, P = 0.007). The positivity and viral load in AS were higher in non-survivors than that of survivors at week 2 post symptom onset (P = 0.006). A high initial viral load in AS was associated with death (OR 1.368, 95% CI 1.076-1.741, P = 0.011), admission to the intensive care unit (OR 1.237, 95% CI 1.001-1.528, P = 0.049) and need for invasive mechanical ventilation (OR 1.340, 95% CI 1.076-1.669, P = 0.009). Our findings indicated viral replication in extrapulmonary sites should be monitored intensively during antiviral therapy.


Subject(s)
Anal Canal/virology , COVID-19/virology , SARS-CoV-2/isolation & purification , Viral Load , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Female , Humans , Male , Middle Aged , Pharynx/virology , RNA, Viral/analysis , Retrospective Studies , Time Factors , Virus Replication , Young Adult
15.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Article in English | MEDLINE | ID: covidwho-824547

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 , COVID-19 , China , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Negative Results , Pandemics , SARS-CoV-2
17.
Clin Microbiol Infect ; 27(1): 112-117, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-802088

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). DISCUSSION: Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , SARS-CoV-2/pathogenicity , Aged , Antiviral Agents/therapeutic use , COVID-19/pathology , China , Critical Illness , Drug Administration Schedule , Female , Hospital Mortality/trends , Hospitals , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , Retrospective Studies , SARS-CoV-2/drug effects , Severity of Illness Index , Treatment Outcome
18.
Eur Respir Rev ; 29(157)2020 Sep 30.
Article in English | MEDLINE | ID: covidwho-662439

ABSTRACT

According to the Third International Consensus Definition for Sepsis and Septic Shock, sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Epidemiological data about sepsis from the 2017 Global Burden of Diseases, Injuries and Risk Factor Study showed that the global burden of sepsis was greater than previously estimated. Bacteria have been shown to be the predominant pathogen of sepsis among patients with pathogens detected, while sepsis caused by viruses is underdiagnosed worldwide. The coronavirus disease that emerged in 2019 in China and now in many other countries has brought viral sepsis back into the vision of physicians and researchers worldwide. Although the current understanding of the pathophysiology of sepsis has improved, the differences between viral and bacterial sepsis at the level of pathophysiology are not well understood. Diagnosis methods that can broadly differentiate between bacterial and viral sepsis at the initial stage after the development of sepsis are limited. New treatments that can be applied at clinics for sepsis are scarce and this situation is not consistent with the growing understanding of pathophysiology. This review aims to give a brief summary of current knowledge of the epidemiology, pathophysiology, diagnosis and treatment of viral sepsis.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Sepsis/diagnosis , Sepsis/epidemiology , Cause of Death , China/epidemiology , Consensus , Coronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Humans , Male , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Infections/therapy , Risk Assessment , Sepsis/therapy , Shock, Septic/diagnosis , Shock, Septic/epidemiology , Shock, Septic/therapy , Survival Analysis
20.
Front Med ; 14(5): 601-612, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-632554

ABSTRACT

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.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , Coronavirus Infections , Hypertension/drug therapy , Pandemics , Pneumonia, Viral , Antihypertensive Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Hospital Mortality , Humans , Hypertension/epidemiology , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
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