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1.
Stem Cell Res Ther ; 13(1): 220, 2022 05 26.
Article in English | MEDLINE | ID: covidwho-1865311

ABSTRACT

BACKGROUND: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. METHODS: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. RESULTS: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. CONCLUSIONS: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. TRIAL REGISTRATION: MEXCOVID, NCT04276987.


Subject(s)
COVID-19 , Exosomes , Mesenchymal Stem Cells , Adipose Tissue , COVID-19/therapy , Female , Humans , Male , Middle Aged , Pilot Projects
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332766

ABSTRACT

Background: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0×10 8 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (IQR, 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61×10 9 /L vs. 1.78×10 9 /L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0×10 9 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration MEXCOVID, NCT04276987

3.
Nat Commun ; 13(1): 1788, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1773979

ABSTRACT

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the generation of variants that may diminish host immune responses to vaccine formulations. Here we show a registered observational clinical trial (NCT04795414), we assess the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine BBIBP-CorV in a cohort of 1006 vaccine recipients. No serious adverse events are observed during the term of the study. Detectable virus-specific antibody is measured and determined to be neutralizing in 698/760 (91.84%) vaccine recipients on day 28 post second vaccine dose and in 220/581 (37.87%) vaccine recipients on day 180 post second vaccine dose, whereas vaccine-elicited sera show varying degrees of reduction in neutralization against a range of key SARS-CoV-2 variants, including variant Alpha, Beta, Gamma, Iota, and Delta. Our work show diminished neutralization potency against multiple variants in vaccine-elicited sera, which indicates the potential need for additional boost vaccinations.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , SARS-CoV-2/genetics
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325163

ABSTRACT

We assessed the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine BBIBP-CorV, especially measured the resistance of four global variants of concern: Lineage B.1.1.7, Lineage B.1.351, Lineage P.1, and Lineage B.1.526 to neutralizing activity of vaccine-elicited sera. Among 1006 enrolled participants, no serious adverse event was reported within 28 days post-vaccination. Seroconversion of neutralizing antibodies was seen in 698 (91.84%) of 760 healthcare workers, and the geometric mean titres (GMTs) of neutralizing antibody titre was 62.68 (57.02–68.91) after the second immunization. We found that 57 (12.13%), 99 (20.97%), and 114 (24.26%) vaccine-elicited sera showed complete or partial loss of neutralizing activity against lineage B.1.1.7, lineage B.1.526, and lineage P.1, respectively, while 199 (42.34%) vaccine-elicited sera preserved neutralizing activity against lineage B.1.351, albeit at relatively low dilutions. These data indicated that humoral responses against SARS-CoV-2 could be effectively induced in vaccine recipients, although diminished neutralization potency against multiple variants was observed.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-293751

ABSTRACT

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.<br><br>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. <br><br>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.<br><br>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.<br><br>Funding: National Key R&D Program of China (No. 2017YFC1309700)<br><br>Declaration of Interest: The author reports no conflicts of interest in this work.<br><br>Ethical Approval: The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from all patients involved before enrolment.

7.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
8.
Cell Res ; 31(11): 1148-1162, 2021 11.
Article in English | MEDLINE | ID: covidwho-1493088

ABSTRACT

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107alow classical monocytes, intermediate monocytes, non-classical monocytes and CD62Lhi CD8+ Tnaïve cells, reduced plasma STC1 level but an increased frequency of CD4+ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.


Subject(s)
Asymptomatic Infections , COVID-19/immunology , Carrier State/immunology , Adult , B-Lymphocytes/immunology , COVID-19/pathology , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Natural Killer T-Cells/immunology , SARS-CoV-2/physiology , T-Lymphocytes/immunology
9.
Sci Bull (Beijing) ; 66(22): 2312-2319, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1331219

ABSTRACT

The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019 (COVID-19) patients. Recently, according to reports from several studies, the vaccine-induced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4 (PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients. It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis. In this prospective study, we recruited 406 healthcare workers who received two doses, 21 days apart, of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBP-CorV, Sinopharm). Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies, including anticardiolipin (aCL), anti-ß2 glycoprotein I (aß2GP1), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-PF4-heparin. The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81% (389/406) four weeks after vaccination. None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks. There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination: for aCL, IgG (7 vs. 8, P = 0.76), IgM (41 vs. 44, P = 0.73), IgA (4 vs. 4, P = 1.00); anti-ß2GP1, IgG (7 vs. 6, P = 0.78), IgM (6 vs. 5, P = 0.76), IgA (3 vs. 5, P = 0.72); aPS/PT IgG (0 vs. 0, P = 1.00), IgM (6 vs. 5, P = 0.76); aPF4-heparin (2 vs. 7, P = 0.18), and antinuclear antibody (ANA) (18 vs. 21, P = 0.62). Notably, seven cases presented with anti-PF4-heparin antibodies (range: 1.18-1.79 U/mL) after vaccination, and none of them exhibited any sign of thrombotic disorder. In conclusion, inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.

10.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1327867

ABSTRACT

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Subject(s)
COVID-19/complications , Lymphohistiocytosis, Hemophagocytic/etiology , Adult , Aged , Aspartate Aminotransferases/blood , COVID-19/epidemiology , COVID-19/therapy , China/epidemiology , Comorbidity , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/virology , Female , Ferritins/blood , Humans , Incidence , Lymphocyte Count , Lymphohistiocytosis, Hemophagocytic/epidemiology , Lymphohistiocytosis, Hemophagocytic/mortality , Male , Middle Aged , Mortality , Retrospective Studies , Risk Factors
11.
Front Public Health ; 9: 646780, 2021.
Article in English | MEDLINE | ID: covidwho-1256408

ABSTRACT

Background: The COVID-19 pandemic is a significant health threat. Health care worker (HCWs) are at a significant risk of infection which may cause high levels of psychological distress. The aim of this study was to investigate the psychological impact of the COVID-19 on HCWs and factors which were associated with these stresses during the first outbreak in Shanghai. Methods: Between February 9 and 21, 2020, a total of 3,114 frontline HCWs from 26 hospitals in Shanghai completed an online survey. The questionnaire included questions on their sociodemographic characteristics, 15 stress-related questions, and General Health Questionnaire-12 (GHQ-12). Exploratory factor analysis was applied to the 15 stress-related questions which produced four distinct factors for evaluation. Multiple linear regression models were performed to explore the association of personal characteristics with each score of the four factors. Binary logistic analysis was used to explain the association of personal characteristics and these four factors with the GHQ-12. Results: There were 2,691 valid surveys received. The prevalence of emotional distress (defined as GHQ-12 ≥ 12) was noted in 47.7% (95%CI:45.7-49.6%) HCWs. Females (OR = 1.43, 95%CI:1.09-1.86) were more likely to have a psychological distress than males. However, HCWs who work in secondary hospitals (OR = 0.71, 95% CI:0.58-0.87) or had a no contact history (OR = 0.45, 95%CI: 0.35-0.58) were less likely to suffer psychological distress. HCWs who were nurses, married, and had a known contact history were highly likely to have anxiety. HCWs working at tertiary hospitals felt an elevated anxiety regarding the infection, a lack of knowledge, and less protected compared to those who worked at secondary hospitals. Conclusions: Our study shows that the frontline HCWs had a significant psychosocial distress during the COVID-19 outbreak in Shanghai. HCWs felt a lack of knowledge and had feelings of being not protected. It is necessary for hospitals and governments to provide additional trainings and psychological counseling to support the first-line HCWs.


Subject(s)
COVID-19 , Pandemics , China/epidemiology , Cross-Sectional Studies , Disease Outbreaks , Female , Health Personnel , Humans , Male , SARS-CoV-2
12.
Front Pharmacol ; 12: 638556, 2021.
Article in English | MEDLINE | ID: covidwho-1221963

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender. Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6-7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04)." The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7. Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

13.
Eur Respir J ; 57(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1190024

ABSTRACT

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.


Subject(s)
COVID-19/therapy , Hospitalization , Adrenal Cortex Hormones/therapeutic use , Adult , Humans , Meta-Analysis as Topic , Respiration, Artificial , Systematic Reviews as Topic
14.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1112385

ABSTRACT

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Aged , COVID-19/complications , Disease-Free Survival , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/etiology , Retrospective Studies , Severity of Illness Index , Survival Rate
15.
ACS Chem Biol ; 16(3): 491-500, 2021 03 19.
Article in English | MEDLINE | ID: covidwho-1084488

ABSTRACT

The outbreak of novel coronavirus SARS-CoV-2 has caused a worldwide threat to public health. COVID-19 patients with SARS-CoV-2 infection can develop clinical symptoms that are often confused with the infections of other respiratory pathogens. Sensitive and specific detection of SARS-CoV-2 with the ability to discriminate from other viruses is urgently needed for COVID-19 diagnosis. Herein, we streamlined a highly efficient CRISPR-Cas12a-based nucleic acid detection platform, termed Cas12a-linked beam unlocking reaction (CALIBURN). We show that CALIBURN could detect SARS-CoV-2 and other coronaviruses and influenza viruses with little cross-reactivity. Importantly, CALIBURN allowed accurate diagnosis of clinical samples with extremely low viral loads, which is a major obstacle for the clinical applications of existing CRISPR diagnostic platforms. When tested on the specimens from SARS-CoV-2-positive and negative donors, CALIBURN exhibited 73.0% positive and 19.0% presumptive positive rates and 100% specificity. Moreover, unlike existing CRISPR detection methods that were mainly restricted to respiratory specimens, CALIBURN displayed consistent performance across both respiratory and nonrespiratory specimens, suggesting its broad specimen compatibility. Finally, using a mouse model of SARS-CoV-2 infection, we demonstrated that CALIBURN allowed detection of coexisting pathogens without cross-reactivity from a single tissue specimen. Our results suggest that CALIBURN can serve as a versatile platform for the diagnosis of COVID-19 and other respiratory infectious diseases.


Subject(s)
Bacterial Proteins/genetics , COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , CRISPR-Associated Proteins/genetics , CRISPR-Cas Systems , Endodeoxyribonucleases/genetics , RNA, Viral/analysis , SARS-CoV-2/chemistry , Adenoviridae/chemistry , Animals , COVID-19/genetics , Fluorescent Dyes/chemistry , Humans , Limit of Detection , Mice, Inbred BALB C , Nucleic Acid Amplification Techniques , RNA Probes/genetics , RNA, Viral/genetics , Specimen Handling , Spectrometry, Fluorescence
16.
Ann Transl Med ; 9(2): 111, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1079876

ABSTRACT

BACKGROUND: Chest computed tomography (CT) has been found to have high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at the early stage, giving it an advantage over nucleic acid detection during the current pandemic. In this study, we aimed to develop and validate an integrated deep learning framework on chest CT images for the automatic detection of NCP, focusing particularly on differentiating NCP from influenza pneumonia (IP). METHODS: A total of 148 confirmed NCP patients [80 male; median age, 51.5 years; interquartile range (IQR), 42.5-63.0 years] treated in 4 NCP designated hospitals between January 11, 2020 and February 23, 2020 were retrospectively enrolled as a training cohort, along with 194 confirmed IP patients (112 males; median age, 65.0 years; IQR, 55.0-78.0 years) treated in 5 hospitals from May 2015 to February 2020. An external validation set comprising 57 NCP patients and 50 IP patients from 8 hospitals was also enrolled. Two deep learning schemes (the Trinary scheme and the Plain scheme) were developed and compared using receiver operating characteristic (ROC) curves. RESULTS: Of the NCP lesions, 96.6% were >1 cm and 76.8% were of a density <-500 Hu, indicating them to have less consolidation than IP lesions, which had nodules ranging from 5-10 mm. The Trinary scheme accurately distinguished NCP from IP lesions, with an area under the curve (AUC) of 0.93. For patient-level classification in the external validation set, the Trinary scheme outperformed the Plain scheme (AUC: 0.87 vs. 0.71) and achieved human specialist-level performance. CONCLUSIONS: Our study has potentially provided an accurate tool on chest CT for early diagnosis of NCP with high transferability and showed high efficiency in differentiating between NCP and IP; these findings could help to reduce misdiagnosis and contain the pandemic transmission.

17.
COVID-19 ; : ix-x, 2021.
Article in English | ScienceDirect | ID: covidwho-893386
18.
COVID-19 ; : 89-97, 2021.
Article in English | ScienceDirect | ID: covidwho-893385

ABSTRACT

We have been continuously deepening our understanding of 2019 coronavirus disease (COVID-19)—an emerging disease. Further knowledge on varying clinical manifestations, phenotypes, clinical course, acute and chronic conditions, susceptibility, as well as research to improve our ability in identification of susceptible populations and tracking the direction of evolution of the virus, are urgently needed.

19.
COVID-19 ; : 75-88, 2021.
Article in English | ScienceDirect | ID: covidwho-893384

ABSTRACT

The control of infectious disease is more dependent on prevention than on treatment. The first task is to isolate the source of infection. Suspected patients, mildly affected patients, and close contacts of confirmed cases should be placed under medical observation. No matter whether there is an etiological diagnosis or not, suspected patients should be kept in strict isolation. It is difficult to identify the source of infection completely unless compulsory measures are taken, such as door-to-door screening. Therefore, the focus of prevention is how to cut off the transmission routes. Given that droplet transmission and contact transmission appear to be the main routes of transmission of COVID-19, the general public need to refrain from going outdoors as much as possible, wear masks in public, and keep good hygiene including frequent handwashing, and wiping and disinfecting door handles and elevator buttons. It is recommended to stop using central air-conditioning because COVID-19 may also spread through aerosol transmission.

20.
COVID-19 ; : 55-74, 2021.
Article in English | ScienceDirect | ID: covidwho-893383

ABSTRACT

Suspected and confirmed cases should be treated in a designated hospital with effective isolation and protective conditions. The isolation condition of suspected cases should be the highest, and treatment should be carried out in a single room instead of mixed accommodation. Only confirmed cases should be admitted to the same ward, and critically ill patients should be admitted to ICU as soon as possible. At this stage, asymptomatic infected persons should also be isolated for observation. If a severe epidemic occurs in the area and medical resources are limited, mild cases and asymptomatic infected persons can be treated and observed at home, but registration and management should be carried out by the local disease prevention and control institutions and community health service centers, so as to guide, observe, and treat the quarantine at home. Moreover, the referral and transfer of severe patients should be safe, evaluated well, and no problems should be caused on the way.

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