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.

Association of close-range contact patterns with SARS-CoV-2: a household transmission study (preprint)

Background Households are an important location for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, especially during periods where travel and work was restricted to essential services. We aimed to assess the association of close-range contact patterns with SARS-CoV-2 transmission. Methods We deployed proximity sensors for two weeks to measure face-to-face interactions between household members after SARS-CoV-2 was identified in the household, in South Africa, 2020 - 2021. We calculated duration, frequency and average duration of close range proximity events with SARS-CoV-2 index cases. We assessed the association of contact parameters with SARS-CoV-2 transmission using mixed effects logistic regression accounting for index and household member characteristics. Results We included 340 individuals (88 SARS-CoV-2 index cases and 252 household members). On multivariable analysis, factors associated with SARS-CoV-2 acquisition were index cases with minimum Ct value <30 (aOR 10.2 95%CI 1.4-77.4) vs >35, contacts aged 13-17 years (aOR 7.7 95%CI 1.0-58.2) vs <5 years and female contacts (aOR 2.3 95%CI 1.1-4.8). No contact parameters were associated with acquisition (aOR 1.0 95%CI 1.0-1.0) for all three of duration, frequency and average duration. Conclusion We did not find an association between close-range proximity events and SARS-CoV-2 household transmission. It may be that droplet-mediated transmission during close-proximity contacts play a smaller role than airborne transmission of SARS-CoV-2 in the household, due to high contact rates in households or study limitations. Funding Wellcome Trust (Grant number 221003/Z/20/Z) in collaboration with the Foreign, Commonwealth and Development Office, United Kingdom.

TRENDS IN CASES, HOSPITALISATION AND MORTALITY RELATED TO THE OMICRON BA.4/BA.5 SUB-VARIANTS IN SOUTH AFRICA (preprint)

Introduction: The 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. Methods: Data from South Africa's 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. Results: In-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. Conclusion: Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's 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.

Risk factors for severe COVID-19 among HIV-infected and-uninfected individuals in South Africa, April 2020- March 2022:data from sentinel surveillance. (preprint)

Background Data on risk factors for COVID-19-associated hospitalisation and mortality in high HIV prevalence settings are limited. Methods Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalisation and mortality. Results From April 2020 through March 2022, SARS-CoV-2 was detected in 24.0% (660/2746) of outpatient and 32.5% (2282/7025) of inpatient cases. Factors associated with COVID-19-associated hospitalisation included: older age (25-44 [adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.1-2.9], 45-64 [aOR 6.8, 95%CI 4.2-11.0] and [≥]65 years [aOR 26.6, 95%CI 14.4-49.1] vs 15-24 years); black race (aOR 3.3, 95%CI 2.2-5.0); obesity (aOR 2.3, 95%CI 1.4-3.9); asthma (aOR 3.5, 95%CI 1.4-8.9); diabetes mellitus (aOR 5.3, 95%CI 3.1-9.3); HIV with CD4 [≥]200/mm3 (aOR 1.5, 95%CI 1.1-2.2) and CD4<200/mm3 (aOR 10.5, 95%CI 5.1-21.6) or tuberculosis (aOR 12.8, 95%CI 2.8-58.5). Infection with Beta (aOR 0.5, 95%CI 0.3-0.7) vs Delta variant and being fully vaccinated (aOR 0.1, 95%CI 0.1-0.3) were less associated with COVID-19 hospitalisation. In-hospital mortality was increased in older age (45-64 years [aOR 2.2, 95%CI 1.6-3.2] and [≥]65 years [aOR 4.0, 95%CI 2.8-5.8] vs 25-44 years) and male sex (aOR1.3, 95%CI 1.0-1.6) and was lower in Omicron -infected (aOR 0.3, 95%CI 0.2-0.6) vs Delta-infected individuals. Conclusion Active syndromic surveillance encompassing clinical, laboratory and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly, people with tuberculosis or people living with HIV, especially severely immunosuppressed should be prioritised for vaccination.

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.

Household transmission of SARS-CoV-2 from adult index cases living with and without HIV in South Africa, 2020-2021: a case-ascertained, prospective observational household transmission study (preprint)

Background In South Africa 19% of the adult population aged 15-49 years are living with HIV (LWH). Few data on the influence of HIV on SARS-CoV-2 household transmission are available. Methods We performed a case-ascertained, prospective household transmission study of symptomatic index SARS-CoV-2 cases LWH and HIV-uninfected adults and their contacts in South Africa. Households were followed up thrice weekly for 6 weeks to collect nasal swabs for SARS-CoV-2 testing. We estimated household cumulative infection risk (HCIR), duration of SARS-CoV-2 positivity (at cycle threshold value<30 as proxy for high viral load), and assessed associated factors. Results We recruited 131 index cases and 457 household contacts. HCIR was 59% (220/373); not differing by index HIV status (60% [50/83] in cases LWH vs 58% [173/293] in HIV-uninfected cases, OR 1.0, 95%CI 0.4-2.3). HCIR increased with index case age (35-59 years: aOR 3.4 95%CI 1.5-7.8 and 60 years or older: aOR 3.1, 95%CI 1.0-10.1) compared to 18-34 years, and contacts age, 13-17 years (aOR 7.1, 95%CI 1.5-33.9) and 18-34 years (aOR 4.4, 95%CI 1.0-18.4) compared to <5 years. Mean positivity duration at high viral load was 7 days (range 2-28), with longer positivity in cases LWH (aHR 0.3, 95%CI 0.1-0.7). Conclusions HIV-infection was not associated with higher HCIR, but cases LWH had longer positivity duration at high viral load. Adults aged >35 years were more likely to transmit, and individuals aged 13-34 to acquire SARS-CoV-2 in the household. Health services must maintain HIV testing with initiation of antiretroviral therapy for those HIV-infected.

The impact of COVID-19 non-pharmaceutical interventions on future respiratory syncytial virus transmission in South Africa (preprint)

In response to the COVID-19 pandemic, the South African government employed various nonpharmaceutical interventions (NPIs) in order to reduce the spread of SARS-CoV-2. In addition to mitigating transmission of SARS-CoV-2, these public health measures have also functioned in slowing the spread of other endemic respiratory pathogens. Surveillance data from South Africa indicates low circulation of respiratory syncytial virus (RSV) throughout the 2020-2021 Southern Hemisphere winter seasons. Here we fit age-structured epidemiological models to national surveillance data to predict the 2022 RSV outbreak following two suppressed seasons. We project a 32% increase in the peak number of monthly hospitalizations among infants < 2 years, with older infants (6-23 month olds) experiencing a larger portion of severe disease burden than typical. Our results suggest that hospital system readiness should be prepared for an intense RSV season in early 2022.

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.

Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa (preprint)

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and death was judged SARS-CoV-2 related by attending physician. Findings: 315,570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3,548,738 tests and 1.6% of all children in the country. Of children tested, 46,137 (14.6%) were positive. Children made up 2.9% (n=2,007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals (CI) 1.08 - 4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28 -18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01 -12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years and those with underlying conditions should be considered for increased testing and vaccination.

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

The Importation and Establishment of Community Transmission of SARS-CoV-2 During the First Eight Weeks of the South African COVID-19 Epidemic (preprint)

Background: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures.Methods: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt).Findings: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28-49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial Rt was 2.08 (95% confidence interval (CI): 1.71-2.51).Interpretation: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces.Funding Statement: South African National and provincial health departments.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: Surveillance activities for NMC including SARS-COV-2 infection are conducted by the NICD according to National Health Act Regulations. Publication of surveillance data in the peer-reviewed literature was approved by the University of the Witwatersrand Human Research Ethics Committee (Medical) protocol M160667.

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.

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa (preprint)

Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

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 (LMIC) in Africa. We investigated this interaction using a nationally representative hospital surveillance system in South Africa. Methods: A national surveillance system for laboratory-confirmed COVID-19 hospital admissions (DATCOV) was established. 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 compare individuals who were HIV-infected and HIV-uninfected and determine the factors associated with in-hospital 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 and treatment programmes.