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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22280020

RESUMO

BackgroundThe first case of COVID-19 in South Africa was reported in March 2020 and the country has since recorded over 3.6 million laboratory-confirmed cases and 100 000 deaths as of March 2022. Transmission and infection of SARS-CoV-2 virus and deaths in general due to COVID-19 have been shown to be spatially associated but spatial patterns in in-hospital deaths have not fully been investigated in South Africa. This study uses national COVID-19 hospitalization data to investigate the spatial effects on hospital deaths after adjusting for known mortality risk factors. MethodsCOVID-19 hospitalization data and deaths were obtained from the National Institute for Communicable Diseases (NICD). Generalized structured additive logistic regression model was used to assess spatial effects on COVID-19 in-hospital deaths adjusting for demographic and clinical covariates. Continuous covariates were modelled by assuming second-order random walk priors, while spatial autocorrelation was specified with Markov random field prior and fixed effects with vague priors respectively. The inference was fully Bayesian. ResultsThe risk of COVID-19 in-hospital mortality increased with patient age, with admission to intensive care unit (ICU) (aOR=4.16; 95% Credible Interval: 4.05-4.27), being on oxygen (aOR=1.49; 95% Credible Interval: 1.46-1.51) and on invasive mechanical ventilation (aOR=3.74; 95% Credible Interval: 3.61-3.87). Being admitted in a public hospital (aOR= 3.16; 95% Credible Interval: 3.10-3.21) was also significantly associated with mortality. Risk of in-hospital deaths increased in months following a surge in infections and dropped after months of successive low infections highlighting crest and troughs lagging the epidemic curve. After controlling for these factors, districts such as Vhembe, Capricorn and Mopani in Limpopo province, and Buffalo City, O.R. Tambo, Joe Gqabi and Chris Hani in Eastern Cape province remained with significantly higher odds of COVID-19 hospital deaths suggesting possible health systems challenges in those districts. ConclusionThe results show substantial COVID-19 in-hospital mortality variation across the 52 districts. Our analysis provides information that can be important for strengthening health policies and the public health system for the benefit of the whole South African population. Understanding differences in in-hospital COVID-19 mortality across space could guide interventions to achieve better health outcomes in affected districts.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22279197

RESUMO

IntroductionThe Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. MethodsData from South Africas national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models. ResultsIn-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality. ConclusionOverall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africas first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22277575

RESUMO

BackgroundThe B.1.1.529 (Omicron BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global resurgence of coronavirus disease 2019 (Covid-19). The contribution of BA.1 infection to population immunity and its effect on subsequent resurgence of B.1.1.529 sub-lineages warrant investigation. MethodsWe conducted an epidemiologic survey to determine the sero-prevalence of SARS-CoV-2 IgG from March 1 to April 11, 2022, after the BA.1-dominant wave had subsided in Gauteng (South Africa), and prior to a resurgence of Covid-19 dominated by the BA.4 and BA.5 (BA.4/BA.5) sub-lineages. Population-based sampling included households in an earlier survey from October 22 to December 9, 2021 preceding the BA.1 dominant wave. Dried-blood-spot samples were quantitatively tested for IgG against SARS-CoV-2 spike protein and nucleocapsid protein. Epidemiologic trends in Gauteng for cases, hospitalizations, recorded deaths, and excess deaths were evaluated from the inception of the pandemic to the onset of the BA.1 dominant wave (pre-BA.1), during the BA.1 dominant wave, and for the BA.4/BA.5 dominant wave through June 6, 2022. ResultsThe 7510 participants included 2420 with paired samples from the earlier survey. Despite only 26.7% (1995/7470) of individuals having received a Covid-19 vaccine, the overall sero-prevalence was 90.9% (95% confidence interval [CI], 90.2 to 91.5), including 89.5% in Covid-19 unvaccinated individuals. Sixty-four percent (95%CI, 61.8-65.9) of individuals with paired samples had serological evidence of SARS-CoV-2 infection during the BA.1 dominant wave. Of all cumulative recorded hospitalisations and deaths, 14.1% and 5.9% were contributed by the BA.1 dominant wave, and 5.1% and 1.6% by the BA.4/BA.5 dominant wave. The SARS-CoV-2 infection fatality risk was lower in the BA.1 compared with pre-BA.1 waves for recorded deaths (0.02% vs. 0.33%) and Covid-19 attributable deaths based on excess mortality estimates (0.03% vs. 0.67%). ConclusionsGauteng province experienced high levels of infections in the BA.1 -dominant wave against a backdrop of high (73%) sero-prevalence. Covid-19 hospitalizations and deaths were further decoupled from infections during BA.4/BA.5 dominant wave than that observed during the BA.1 dominant wave. (Funded by the Bill and Melinda Gates Foundation.)

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22270594

RESUMO

BackgroundPost COVID-19 Condition (PCC) as defined by WHO refers to a wide range of new, returning, or ongoing health problems experienced by COVID-19 survivors, and represents a rapidly emerging public health priority. We aimed to establish how this developing condition has impacted patients in South Africa and which population groups are at risk. MethodsIn this prospective cohort study, participants [≥]18 years who had been hospitalised with laboratory-confirmed SARS-CoV-2 infection during the second and third wave between December 2020 and August 2021 underwent telephonic follow-up assessment up at one-month and three-months after hospital discharge. Participants were assessed using a standardised questionnaire for the evaluation of symptoms, functional status, health-related quality of life and occupational status. Multivariable logistic regression models were used to determine factors associated with PCC. FindingsIn total, 1,873 of 2,413 (78%) enrolled hospitalised COVID-19 participants were followed up at three-months after hospital discharge. Participants had a median age of 52 years (IQR 41-62) and 960 (51.3%) were women. At three-months follow-up, 1,249 (66.7%) participants reported one or more persistent COVID-related symptom(s), compared to 1,978/2,413 (82.1%) at one-month post-hospital discharge. The most common symptoms reported were fatigue (50.3%), shortness of breath (23.4%), confusion or lack of concentration (17.5%), headaches (13.8%) and problems seeing/blurred vision (10.1%). On multivariable analysis, factors associated with new or persistent symptoms following acute COVID-19 were age [≥]65 years [adjusted odds ratio (aOR) 1.62; 95%confidence interval (CI) 1.00-2.61]; female sex (aOR 2.00; 95% CI 1.51-2.65); mixed ethnicity (aOR 2.15; 95% CI 1.26-3.66) compared to black ethnicity; requiring supplemental oxygen during admission (aOR 1.44; 95% CI 1.06-1.97); ICU admission (aOR 1.87; 95% CI 1.36-2.57); pre-existing obesity (aOR 1.44; 95% CI 1.09-1.91); and the presence of [≥]4 acute symptoms (aOR 1.94; 95% CI 1.19-3.15) compared to no symptoms at onset. InterpretationThe majority of COVID-19 survivors in this cohort of previously hospitalised participants reported persistent symptoms at three-months from hospital discharge, as well as a significant impact of PCC on their functional and occupational status. The large burden of PCC symptoms identified in this study emphasises the need for a national health strategy. This should include the development of clinical guidelines and training of health care workers, in identifying, assessing and caring for patients affected by PCC, establishment of multidisciplinary national health services, and provision of information and support to people who suffer from PCC.

5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268475

RESUMO

BackgroundClinical severity of patients hospitalised with SARS-CoV-2 infection during the Omicron (fourth) wave was assessed and compared to trends in the D614G (first), Beta (second), and Delta (third) waves in South Africa. MethodsWeekly incidence of 30 laboratory-confirmed SARS-CoV-2 cases/100,000 population defined the start and end of each wave. Hospital admission data were collected through an active national COVID-19-specific surveillance programme. Disease severity was compared across waves by post-imputation random effect multivariable logistic regression models. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, intensive-care admission or death. Results335,219 laboratory-confirmed SARS-CoV-2 admissions were analysed, constituting 10.4% of 3,216,179 cases recorded during the 4 waves. In the Omicron wave, 8.3% of cases were admitted to hospital (52,038/629,617) compared to 12.9% (71,411/553,530) in the D614G, 12.6% (91,843/726,772) in the Beta and 10.0% (131,083/1,306,260) in the Delta waves (p<0.001). During the Omicron wave, 33.6% of admissions experienced severe disease compared to 52.3%, 63.4% and 63.0% in the D614G, Beta and Delta waves (p<0.001). The in-hospital case fatality ratio during the Omicron wave was 10.7%, compared to 21.5%, 28.8% and 26.4% in the D614G, Beta and Delta waves (p<0.001). Compared to the Omicron wave, patients had more severe clinical presentations in the D614G (adjusted odds ratio [aOR] 2.07; 95% confidence interval [CI] 2.01-2.13), Beta (aOR 3.59; CI: 3.49-3.70) and Delta (aOR 3.47: CI: 3.38-3.57) waves. ConclusionThe trend of increasing cases and admissions across South Africas first three waves shifted in Omicron fourth wave, with a higher and quicker peak but fewer admitted patients, who experienced less clinically severe illness and had a lower case-fatality ratio. Omicron marked a change in the SARS-CoV-2 epidemic curve, clinical profile and deaths in South Africa. Extrapolations to other populations should factor in differing vaccination and prior infection levels.

6.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21268096

RESUMO

BackgroundWe conducted a seroepidemiological survey from October 22 to December 9, 2021, in Gauteng Province, South Africa, to determine SARS-CoV-2 immunoglobulin G (IgG) seroprevalence primarily before the fourth wave of coronavirus disease 2019 (Covid-19), in which the B.1.1.529 (Omicron) variant was dominant. We evaluated epidemiological trends in case rates and rates of severe disease through to January 12, 2022, in Gauteng. MethodsWe contacted households from a previous seroepidemiological survey conducted from November 2020 to January 2021, plus an additional 10% of households using the same sampling framework. Dry blood spot samples were tested for anti-spike and anti-nucleocapsid protein IgG using quantitative assays on the Luminex platform. Daily case, hospital admission, and reported death data, and weekly excess deaths, were plotted over time. ResultsSamples were obtained from 7010 individuals, of whom 1319 (18.8%) had received a Covid-19 vaccine. Overall seroprevalence ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) in children aged <12 years to 79.7% (95% CI, 77.6 to 81.5) in individuals aged >50 years. Seropositivity was more likely in vaccinated (93.1%) vs unvaccinated (68.4%) individuals. Epidemiological data showed SARS-CoV-2 infection rates increased and subsequently declined more rapidly than in previous waves. Infection rates were decoupled from Covid-19 hospitalizations, recorded deaths, and excess deaths relative to the previous three waves. ConclusionsWidespread underlying SARS-CoV-2 seropositivity was observed in Gauteng Province before the Omicron-dominant wave. Epidemiological data showed a decoupling of hospitalization and death rates from infection rate during Omicron circulation.

7.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21253184

RESUMO

IntroductionSouth Africa experienced its first wave of COVID-19 peaking in mid-July 2020 and a larger second wave peaking in January 2021, in which the SARS-CoV-2 501Y.V2 lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves of COVID-19. MethodsWe analysed data from the DATCOV national active surveillance system for COVID-19 hospitalisations. We defined four wave periods using incidence risk for hospitalisation, pre-wave 1, wave 1, pre-wave 2 and wave 2. We compared the characteristics of hospitalised COVID-19 cases in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using multivariable logistic regression. ResultsPeak rates of COVID-19 cases, admissions and in-hospital deaths in the second wave exceeded the rates in the first wave (138.1 versus 240.1; 16.7 versus 28.9; and 3.3 versus 7.1 respectively per 100,000 persons). The weekly average incidence risk increase in hospitalisation was 22% in wave 1 and 28% in wave 2 [ratio of growth rate in wave two compared to wave one: 1.04, 95% CI 1.04-1.05]. On multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 20% increased risk of in-hospital mortality in the second wave (adjusted OR 1.2, 95% CI 1.2-1.3). In-hospital case fatality-risk (CFR) increased in weeks of peak hospital occupancy, from 17.9% in weeks of low occupancy (<3,500 admissions) to 29.6% in weeks of very high occupancy (>12,500 admissions) (adjusted OR 1.5, 95% CI 1.4-1.5). Compared to the first wave, individuals hospitalised in the second wave, were more likely to be older, 40-64 years [OR 1.1, 95% CI 1.0-1.1] and [≥]65 years [OR 1.1, 95% CI 1.1-1.1] compared to <40 years; and admitted in the public sector [OR 2.2, 95% CI 1.7-2.8]; and less likely to have comorbidities [OR 0.5, 95% CI 0.5-0.5]. ConclusionsIn South Africa, the second wave was associated with higher incidence and more rapid increase in hospitalisations, and increased in-hospital mortality. While some of this is explained by increasing pressure on the health system, a residual increase in mortality of hospitalised patients beyond this, could be related to the new lineage 501Y.V2. RESEARCH IN CONTEXT O_TEXTBOXEvidence before this studyMost countries have reported higher numbers of COVID-19 cases in the second wave but lower case-fatality risk (CFR), in part due to new therapeutic interventions, increased testing and better prepared health systems. South Africa experienced its second wave which peaked in January 2021, in which the variant of concern, SARS-CoV-2 501Y.V2 predominated. New variants have been shown to be more transmissible and in the United Kingdom, to be associated with increased hospitalisation and mortality rates in people infected with variant B.1.1.7 compared to infection with non-B.1.1.7 viruses. There are currently limited data on the severity of lineage 501Y.V2. Added value of this studyWe analysed data from the DATCOV national active surveillance system for COVID-19 hospitalisations, comparing in-hospital mortality and other patient characteristics between the first and second waves of COVID-19. The study revealed that after adjusting for weekly COVID-19 hospital admissions, there was a 20% increased risk of in-hospital mortality in the second wave. Our study also describes the demographic shift from the first to the second wave of COVID-19 in South Africa, and quantifies the impact of overwhelmed hospital capacity on in-hospital mortality. Implications of all the available evidenceOur data suggest that the new lineage (501Y.V2) in South Africa may be associated with increased in-hospital mortality during the second wave. Our data should be interpreted with caution however as our analysis is based on a comparison of mortality in the first and second wave as a proxy for dominant lineage and we did not have individual-level data on lineage. Individual level studies comparing outcomes of people with and without the new lineage based on sequencing data are needed. To prevent high mortality in a potential third wave, we require a combination of strategies to slow the transmission of SARS-CoV-2, to spread out the peak of the epidemic, which would prevent hospital capacity from being breached. C_TEXTBOX

8.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20248409

RESUMO

BackgroundThe interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis (TB) are unclear, particularly in low- and middle-income countries in Africa. South Africa has a national adult HIV prevalence of 19% and TB prevalence of 0.7%. Using a nationally representative hospital surveillance system in South Africa, we investigated the factors associated with in-hospital mortality among individuals with COVID-19. MethodsUsing data from national active hospital surveillance, we describe the demographic characteristics, clinical features, and in-hospital mortality among hospitalised individuals testing positive for SARS-CoV-2, during 5 March 2020 to 27 March 2021. Chained equation multiple imputation was used to account for missing data and random effect multivariable logistic regression models were used to assess the role of HIV-status and underlying comorbidities on in-hospital COVID-19 mortality. FindingsAmong the 219,265 individuals admitted with laboratory confirmed SARS-Cov-2, 51,037 (23.3%) died. Most commonly observed comorbidities among individuals with available data were hypertension (61,098/163,350; 37.4%), diabetes (43,885/159,932; 27.4%), and HIV (13,793/151,779; %), while TB was reported in 3.6% (5,282/146,381) of individuals. While age was the most important predictor, other factors associated with in-hospital COVID-19 mortality were HIV infection [aOR 1.34, 95% CI: 1.27-1.43), past TB [aOR 1.26, 95% CI: 1.15-1.38), current TB [aOR 1.42, 95% CI: 1.22-1.64) and both past and current TB [aOR 1.48, 95% CI: 1.32-1.67) compared to never TB, as well as other described risk factors for COVID-19, such as male sex, non-white race, and chronic underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy. After adjusting for other factors, PLWH not on ART [aOR 1.45, 95% CI: 1.22-1.72] were more likely to die in-hospital compared to PLWH on ART. Among PLWH, the prevalence of other comorbidities was 29.2% compared to 30.8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased mortality risk in both PLWH and HIV-uninfected individuals. InterpretationIdentified high risk individuals (older individuals and those with chronic comorbidities and PLWH, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation, as well as early referral and treatment. FundingSouth African National Government Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince the emergence of the COVID-19 pandemic, studies have identified older age, male sex and presence of underlying comorbidities including heart disease and diabetes as risk factors for severe disease and death. There are very few studies, however, carried out in low- and middle-income countries (LMIC) in Africa, many of whom have high poverty rates, limited access to healthcare, and high prevalence of chronic communicable diseases, such as HIV and tuberculosis (TB). Data are also limited from settings with limited access to HIV treatment programmes. Early small cohort studies mainly from high income countries were not conclusive on whether HIV or TB are risk factors for disease severity and death in COVID-19 patients. Large population cohort studies from South Africas Western Cape province and the United Kingdom (UK) have found people living with HIV (PLWH) to have a moderately increased risk of COVID-19 associated mortality. Of these, only the Western Cape study presented data on mortality risk associated with presence of high viral load or immunosuppression, and found similar levels of severity irrespective of these factors. Recent meta-analyses have confirmed the association of HIV with COVID-19 mortality. No studies reported on the interaction between HIV-infection and other non-communicable comorbidities on COVID-19 associated mortality. We performed separate literature searches on PubMed using the following terms: "COVID-19" "risk factors" and "mortality"; "HIV" "COVID-19" and "mortality"; "TB" "COVID-19" and "mortality". All searches included publications from December 1, 2019 until May 5, 2021, without language restrictions. Pooled together, we identified 2,786 published papers. Additionally, we performed two literature searches on MedRxiv using the terms "HIV" "COVID-19" and "mortality", and "TB" "COVID-19" and "mortality" from April 25, 2020 until May 5, 2021, without language restrictions. Pooled together, we identified 7,744 pre-prints. Added value of this studyAmong a large national cohort of almost 220,000 individuals hospitalised with COVID-19 in a setting with 19% adult HIV prevalence and 0.7%TB prevalence, we found that along with age, sex and other comorbidities, HIV and TB were associated with a moderately increased risk of in-hospital mortality. We found increasing risk of in-hospital mortality among PLWH not on ART compared to those on ART. Among PLWH, the prevalence of other comorbidities was high (29%) and the effect of increasing numbers of comorbidities on mortality was similar in PLWH and HIV-uninfected individuals. Our study included 13,793 PLWH from all provinces in the country with varying levels of access to HIV treatment programmes. Implications of all the available evidenceThe evidence suggests that PLWH and TB-infected individuals should be prioritised for COVID-19 prevention and treatment programmes, particularly those with additional comorbidities. Increasing age and presence of chronic underlying illness are important additional factors associated with COVID-19 mortality in a middle-income African setting. The completeness of data is a limitation of this national surveillance system, and additional data are needed to confirm these findings.

9.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20155218

RESUMO

ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 17th report, is a part of a series published over the past 2 years. Data have been entered for 800,459 individuals from 1701 partner institutions and networks across 60 countries. The comprehensive analyses detailed in this report includes hospitalised individuals of all ages for whom data collection occurred between 30 January 2020 and up to and including 5 January 2022, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 699,014 cases who meet eligibility criteria for this report, selected findings include: O_LImedian age of 58 years, with an approximately equal (50/50) male:female sex distribution C_LIO_LI29% of the cohort are at least 70 years of age, whereas 4% are 0-19 years of age C_LIO_LIthe most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time C_LIO_LIthe five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports C_LIO_LIage-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above C_LIO_LI16% of patients with relevant data available were admitted at some point during their illness into an intensive care unit (ICU), which is slightly lower than previously reported (19%) C_LIO_LIantibiotic agents were used in 35% of patients for whom relevant data are available (669,630), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions; in ICU/HDU admitted patients with data available (50,560), 91% received antibiotics C_LIO_LIuse of corticosteroids was reported in 24% of all patients for whom data were available (677,012); in ICU/HDU admitted patients with data available (50,646), 69% received corticosteroids C_LIO_LIoutcomes are known for 632,518 patients and the overall estimated case fatality ratio (CFR) is 23.9% (95%CI 23.8-24.1), rising to 37.1% (95%CI 36.8-37.4) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease C_LI To access previous versions of ISARIC COVID-19 Clinical Data Report please use the link below: https://isaric.org/research/covid-19-clinical-research-resources/evidence-reports/

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