COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: An observational cohort study during 2020-2022 (preprint)

Background: There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-naive population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods We performed an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results By end 2022, only 41% of surviving adults had completed vaccination and 8% a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92% for death (range across periods), 45-92% for admission with severe disease or death, and 25-90% for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity.

Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town, South Africa (preprint)

Abstract Background In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19.

The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa (preprint)

Background COVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden. Methods This was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers' Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA). Findings Among 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p <0.001], previous stroke [(1% vs 4.1%, waves II and I, respectively), p = 0.046]. In terms of clinical and laboratory findings, our study found that wave I patients had higher haemoglobin and HIV viral loads. Wave II, on the other hand, had statistically significant higher chest radiography abnormalities, fraction of inspired oxygen (FiO2), and uraemia. The adjusted odds ratio for death vs discharge between waves I and II was similar (0.94, 95%CI: 0.84-1.05). Wave I had a longer average survival time (8.0 vs 6.1 days) and a shorter average length of stay among patients discharged alive (9.2 vs 10.7 days). LCA revealed that the cardiovascular phenotype had the highest mortality, followed by diabetes and CKD phenotypes. Only Diabetes and hypertension phenotypes had the lowest mortality. Conclusion Even though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.

COVID-19 among adults living with HIV: Correlates of mortality in a general population in a resource-limited setting (preprint)

Introduction: While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower income settings. We studied the association between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH. Methods: We analysed observational cohort data on all PWH aged [≥]15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results: Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17 831 first diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions: Mortality was strongly associated with suboptimal HIV control, and prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimised.

Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa (preprint)

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. We assessed the severity of BA.4/BA.5 infections using the presence/absence of the S-gene target for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We linked national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assessed severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.71, 95%CI 0.41–1.25) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 continue to show reduced clinical severity compared to previous variants, as observed for Omicron BA.1.

Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa (preprint)

ObjectiveWe aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. MethodsWe included public sector patients aged [≥]20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. ResultsAmong 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for boosted vs. no vaccine) were protective. ConclusionDisease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective.

The epidemiological and clinical characteristics of COVID-19 in a high HIV/TB burden district level hospital setting (preprint)

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature.Methods: A retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020 – December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters.Findings: This cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37–54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141–457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariate analysis, smoking (risk ratio [RR]: 2.86 (1.75–4.69)), neutrophilia [RR]: 1.024 (1.01–1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007–1.01) were associated with mortality.Conclusion: The district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.

Evaluation of a Public COVID-19 Dashboard in the Western Cape, South Africa: a tool for communication, trust, and transparency (preprint)

Background: Public health dashboards have been used extensively in the past to communicate and guide local responses to outbreaks, epidemics, and a host of various health conditions. During the first year of the COVID-19 pandemic, digital dashboards proliferated but the availability and quality of these dashboards differed vastly across the world. This study aimed to evaluate one such dashboard in the Western Cape province, South Africa.Methods: We analysed retrospective aggregate data on viewership over time for the first year since launch of the dashboard and conducted a cross-sectional survey targeting adult users of the dashboard at one year post the initial launch. The self-administered, anonymous questionnaire with a total of 13 questions was made available via an online digital survey tool for a 2-week period.Results: After significant communication by senior provincial political leaders, adequate media coverage and two waves of COVID-19 the Western Cape public COVID-19 dashboard attracted a total of 2,248,456 views during its first year. The majority of these views came from Africa/South Africa with higher median daily views during COVID-19 wave periods.  A total of 794 participants responded to the survey questionnaire. Reported devices used to access the dashboard differed statistically between occupational status groups with students tending toward using mobile devices whilst employed and retired participants tending toward using desktop computers/laptops. Frequency of use increases with increasing age with 65.1% of those >70 years old viewing it daily. Overall, 76.4% of respondents reported that the dashboard influenced their personal planning and behaviour. High Likert score ratings were given for clarity, ease of use and overall end-user experience, with no differences seen across the various age groups surveyed. Conclusion: The study demonstrated that both the availability of data and an understanding of end-user need is critical when developing and delivering public health tools that may ultimately garner public trust and influence individual behaviour.

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time series analysis (preprint)

AimsIn March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. MethodsWe did an interrupted time series analysis using insurance claims from January 1, 2017, to June 1, 2020 of beneficiaries 18 years or older from a large private sector medical aid scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder, and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until June 1, 2020. Results710,367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% CI 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the lockdown and did not recover to pre-lockdown levels until June 1, 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). ConclusionsReduced mental health care contact rates during the COVID-19 lockdown likely reflect a substantial unmet need for mental health services with potential long-term consequences for mental health patients and their families. Steps to ensure access and continuity of mental health services during future lockdowns should be considered.

Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections – a survival analysis (preprint)

Background Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. Methods RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene Allplex™ 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the period of transition to Omicron was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex™ assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results 150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). Conclusion Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa (preprint)

Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained. Methods: In this cohort study, we included public sector patients aged [≥]20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all [≤]14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta.

Change in profile of COVID-19 deaths in the Western Cape during the fourth wave (preprint)

Fewer COVID-19 deaths have been reported in this fourth wave, with clinicians reporting less admissions due to severe COVID-19 pneumonia when compared to previous waves. We therefore aimed to rapidly compare the profile of deaths in wave 4 with wave 3 using routinely collected data on admissions to public sector hospitals in the Western Cape province of South Africa. Findings show that there have been fewer COVID-19 pneumonia deaths in the Omicron-driven fourth wave compared to the third wave, which confirms anecdotal reports and lower bulk oxygen consumption by hospitals in the province.

Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa (preprint)

ABSTRACT Background The SARS-CoV-2 Omicron variant of concern (VOC) almost completely replaced other variants in South Africa during November 2021, and was associated with a rapid increase in COVID-19 cases. We aimed to assess clinical severity of individuals infected with Omicron, using S Gene Target Failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We performed data linkages for (i) SARS-CoV-2 laboratory tests, (ii) COVID-19 case data, (iii) genome data, and (iv) the DATCOV national hospital surveillance system for the whole of South Africa. For cases identified using Thermo Fisher TaqPath COVID-19 PCR, infections were designated as SGTF or non-SGTF. Disease severity was assessed using multivariable logistic regression models comparing SGTF-infected individuals diagnosed between 1 October to 30 November to (i) non-SGTF in the same period, and (ii) Delta infections diagnosed between April and November 2021. Results From 1 October through 6 December 2021, 161,328 COVID-19 cases were reported nationally; 38,282 were tested using TaqPath PCR and 29,721 SGTF infections were identified. The proportion of SGTF infections increased from 3% in early October (week 39) to 98% in early December (week 48). On multivariable analysis, after controlling for factors associated with hospitalisation, individuals with SGTF infection had lower odds of being admitted to hospital compared to non-SGTF infections (adjusted odds ratio (aOR) 0.2, 95% confidence interval (CI) 0.1-0.3). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ between SGTF-infected individuals compared to non-SGTF individuals diagnosed during the same time period (aOR 0.7, 95% CI 0.3-1.4). Compared to earlier Delta infections, after controlling for factors associated with severe disease, SGTF-infected individuals had a lower odds of severe disease (aOR 0.3, 95% CI 0.2-0.5). Conclusion Early analyses suggest a reduced risk of hospitalisation among SGTF-infected individuals when compared to non-SGTF infected individuals in the same time period. Once hospitalised, risk of severe disease was similar for SGTF- and non-SGTF infected individuals, while SGTF-infected individuals had a reduced risk of severe disease when compared to earlier Delta-infected individuals. Some of this reducton is likely a result of high population immunity.

Severity and inpatient mortality of COVID-19 pneumonia from Beta variant infection: a clinical cohort study in Cape Town, South Africa (preprint)

ABSTRACT Background The SARS-CoV-2 Beta variant, associated with immune escape and higher transmissibility, drove a more severe second COVID-19 wave in South Africa. Individual patient level characteristics and outcomes with the Beta variant are not well characterized. Methods We performed a retrospective cohort study comparing disease severity and inpatient mortality of COVID-19 pneumonia between the first and second wave periods at a referral hospital in Cape Town, South Africa. Beta variant infection was confirmed by genomic sequencing. Outcomes were analyzed with logistic regression and accelerated failure time models. Results 1,182 patients were included: 571 during the first wave period and 611 from the second wave. Beta variant accounted for 97% of infections in the second wave. There was no difference in crude in-hospital mortality between wave periods (first wave 22.2%, second wave 22.1%; p = 0.9). Time to death was decreased with higher weekly hospital admissions (16%; 95% CI, 8 to 24 for every 50-patient increase), age (18%; 95% CI, 12 to 24 for every 10-year increase) and hypertension (31%; 95% CI, 12 to 46). Corticosteroid use delayed time to death by 2-fold (95% CI, 1.5 to 3.0). Admission during the second wave decreased time to death after adjustment for other predictors, but this did not reach statistical significance (24%; 95% CI, 47 to -2). There was no effect of HIV on survival. Conclusions There was a trend towards earlier mortality during the second COVID-19 wave driven by the Beta variant, suggesting a possible biological basis. Use of oral prednisone was strongly protective. Key points In Cape Town, South Africa, the second wave of COVID-19, dominated by the Beta variant, was associated with decreased time to inpatient death after adjustment for age, comorbidities, steroid use, and admission numbers. Use of oral prednisone was strongly protective.

Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy (preprint)

A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene Allplex™ 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95%CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective.

Reduced amplification efficiency of the RNA-dependent-RNA-polymerase (RdRp) target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests (preprint)

Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced PCR amplification efficiency of the RdRp gene target of the Seegene, Allplex 2019-nCoV diagnostic assay when detecting the Delta variant. We propose that this can be used as a surrogate for variant detection.

Increased mortality among individuals hospitalised with COVID-19 during the second wave in South Africa (preprint)

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

COVID-19 In-Hospital Mortality in South Africa: The Intersection of Communicable and Non-Communicable Chronic Diseases in a High HIV Prevalence Setting (preprint)

Background: The 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. We investigated this interaction using a nationally representative hospital surveillance system for laboratory-confirmed COVID-19 hospital admissions in South Africa.Methods: Using DATCOV data, we describe the demographic characteristics, clinical features, and in-hospital mortality among individuals admitted to public and private hospitals with COVID-19 during 5 March to 11 August 2020. Multivariable logistic regression models were used to assess the role of HIV-status and underlying comorbidities on in-hospital COVID-19 mortality.Findings: Hospital admissions peaked at 1,560 admissions per day, in late July. Among the 41,877 individuals admitted with laboratory-confirmed COVID-19, 7,662 (18.3%) died. Comorbidities were documented in 27,555 (65.8%) individuals, most commonly observed were hypertension (36.8%), diabetes (29.6%), obesity (19.7%), and HIV (8.7%); TB was reported in 0.7% of individuals. Increased risk of in-hospital mortality was associated with HIV and TB, as well as other described risk factors for COVID-19, such as increasing age, male sex, non-White race (Black, mixed and Indian race), chronic underlying conditions particularly hypertension, diabetes and obesity. In addition, HIV-infected individuals with immunosuppression had increased risk of mortality (adjusted odds ratio 2.2; 95% confidence interval 1.6-3.1). Among HIV-infected individuals, the prevalence of other comorbidities associated with severe COVID-19 outcomes was 39.9%. The effect of multiple comorbidities on mortality was similar in HIV-infected and -uninfected individuals.Interpretation: These data provide a better understanding of the interaction of non-communicable diseases, chronic infectious diseases like HIV and TB and COVID-19. Increasing age and presence of chronic underlying comorbidities (particularly hypertension and diabetes) are important additional factors associated with COVID-19 mortality in a middle-income African setting and are common among HIV-infected individuals. HIV- and TB-infected individuals, particularly those with additional comorbidities, would benefit from COVID-19 prevention programmes, as well as early referral and treatment.Funding Statement: DATCOV is funded by the National Institute for Communicable Diseases (NICD) and the South African National Government. No additional funding was obtained towards the completion of this analysis and the development of this manuscript.Declaration of Interests: The authors declare that there are no conflicts of interest.Ethics Approval Statement: The Human Research Ethics Committee (Medical), University of the Witwatersrand, approved the project protocol as part of a national surveillance program (M160667). This activity was reviewed by the U.S. Centers for Disease Control and Prevention (CDC) and was conducted consistent with applicable federal law and CDC policy. All personal identifying information was de-linked for our analysis and stored in a secure server.