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BackgroundBy August 2021, South Africa experienced three SARS-CoV-2 waves; the second and third associated with emergence of Beta and Delta variants respectively.MethodsWe conducted a prospective cohort study during July 2020-August 2021 in one rural and one urban community. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Serum was collected every two months and tested for anti-SARS-CoV-2 antibodies.ResultsAmong 115,759 nasal specimens from 1,200 members (follow-up rate 93%), 1976 (2%) were SARS-CoV-2-positive. By rRT-PCR and serology combined, 62% (749/1200) of individuals experienced ≥1 SARS-CoV-2 infection episode, and 12% (87/749) experienced reinfection. Of 662 PCR-confirmed episodes with available data, 15% (n=97) were associated with ≥1 symptom. Among 222 households, 200 (90%) had ≥1 SARS-CoV-2-positive individual. Household cumulative infection risk (HCIR) was 25% (213/856). On multivariable analysis, accounting for age and sex, index case lower cycle threshold value (OR 3.9, 95%CI 1.7-8.8), urban community (OR 2.0,95%CI 1.1-3.9), Beta (OR 4.2, 95%CI 1.7-10.1) and Delta (OR 14.6, 95%CI 5.7-37.5) variant infection were associated with increased HCIR. HCIR was similar for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index cases (p=0.165). Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection. People living with HIV who were not virally supressed were more likely to develop symptomatic illness, and shed SARS-CoV-2 for longer compared to HIV-uninfected individuals.ConclusionsIn this study, 85% of SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of Beta and Delta variants, likely contributed to successive waves, with >60% of individuals infected by the end of follow-up.Research in contextEvidence before this studyPrevious studies have generated wide-ranging estimates of the proportion of SARS-CoV-2 infections which are asymptomatic. A recent systematic review found that 20% (95% CI 3%-67%) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remained asymptomatic throughout infection and that transmission from asymptomatic individuals was reduced. A systematic review and meta-analysis of 87 household transmission studies of SARS-CoV-2 found an estimated secondary attack rate of 19% (95% CI 16-22). The review also found that household secondary attack rates were increased from symptomatic index cases and that adults were more likely to acquire infection. As of December 2021, South Africa experienced three waves of SARS-CoV-2 infections; the second and third waves were associated with circulation of Beta and Delta variants respectively. SARS-CoV-2 vaccines became available in February 2021, but uptake was low in study sites reaching 5% fully vaccinated at the end of follow up. Studies to quantify the burden of asymptomatic infections, symptomatic fraction, reinfection frequency, duration of shedding and household transmission of SARS-CoV-2 from asymptomatically infected individuals have mostly been conducted as part of outbreak investigations or in specific settings. Comprehensive systematic community studies of SARS-CoV-2 burden and transmission including for the Beta and Delta variants are lacking, especially in low vaccination settings.Added value of this studyWe conducted a unique detailed COVID-19 household cohort study over a 13 month period in South Africa, with real time reverse transcriptase polymerase chain reaction (rRT-PCR) testing twice a week irrespective of symptoms and bimonthly serology. By the end of the study in August 2021, 749 (62%) of 1200 individuals from 222 randomly sampled households in a rural and an urban community in South Africa had at least one confirmed SARS-CoV-2 infection, detected on rRT-PCR and/or serology, and 12% (87/749) experienced reinfection. Symptom data were analysed for 662 rRT-PCR-confirmed infection episodes that occurred >14 days after the start of follow-up (of a total of 718 rRT-PCR-confirmed episodes), of these, 15% (n=97) were associated with one or more symptoms. Among symptomatic indvidiausl, 9% (n=9) were hospitalised and 2% (n=2) died. Ninety percent (200/222) of included households, had one or more individual infected with SARS-CoV-2 on rRT-PCR and/or serology within the household. SARS-CoV-2 infected index cases transmitted the infection to 25% (213/856) of susceptible household contacts. Index case ribonucleic acid (RNA) viral load proxied by rRT-PCR cycle threshold value was strongly predictive of household transmission. Presence of symptoms in the index case was not associated with household transmission. Household transmission was four times greater from index cases infected with Beta variant and fifteen times greater from index cases infected with Delta variant compared to wild-type infection. Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection within households. People living with HIV (PLHIV) who were not virally supressed were more likely to develop symptomatic illness when infected with SARS-CoV-2, and shed SARS-CoV-2 for longer when compared to HIV-uninfected individuals.Implications of all the available evidenceWe found a high rate of SARS-CoV-2 infection in households in a rural community and an urban community in South Africa, with the majority of infections being asymptomatic in individuals of all ages. Asymptomatic individuals transmitted SARS-CoV-2 at similar levels to symptomatic individuals suggesting that interventions targeting symptomatic individuals such as symptom-based testing and contact tracing of individuals tested because they report symptoms may have a limited impact as control measures. Increased household transmission of Beta and Delta variants, likely contributed to recurrent waves of COVID-19, with >60% of individuals infected by the end of follow-up. Higher attack rates, reinfection and acquisition in adolescents and prolonged SARS-CoV-2 shedding in PLHIV who were not virally suppressed suggests that prioritised vaccination of individuals in these groups could impact community transmission.

BackgroundSARS-CoV-2 infections may be underestimated due to limited testing access, particularly in sub-Saharan Africa. South Africa experienced two SARS-CoV-2 waves, the second associated with emergence of variant 501Y.V2. In this study, we report longitudinal SARS-CoV-2 seroprevalence in cohorts in two communities in South Africa.MethodsWe measured SARS-CoV-2 seroprevalence two monthly in randomly selected household cohorts in a rural and an urban community (July 2020-March 2021). We compared seroprevalence to laboratory-confirmed infections, hospitalisations and deaths reported in the districts to calculate infection-case (ICR), infection-hospitalisation (IHR) and infection-fatality ratio (IFR) in the two waves of infection.FindingsSeroprevalence after the second wave ranged from 18% (95%CrI 10-26%) and 28% (95%CrI 17-41%) in children InterpretationThe second wave was associated with a shift in age distribution of cases from individuals aged to 35-59 to individuals at the extremes of age, higher attack rates in the rural community and a higher IFR in the urban community. Approximately 95% of SARS-CoV-2 infections in these two communities were not reported to the national surveillance system, which has implications for contact tracing and infection containment.FundingUS Centers for Disease Control and PreventionResearch in contextEvidence before this studySeroprevalence studies provide better estimates of SARS-CoV-2 burden than laboratory-confirmed cases because many infections may be missed due to restricted access to care and testing, or differences in disease severity and health-care seeking behaviour. This underestimation may be amplified in African countries, where testing access may be limited. Seroprevalence data from sub-Saharan Africa are limited, and comparing seroprevalence estimates between countries can be challenging because populations studied and timing of the study relative to country-specific epidemics differs. During the first wave of infections in each country, seroprevalence was estimated at 4% in Kenya and 11% in Zambia. Seroprevalence estimates in South African blood donors is estimated to range between 32% to 63%. South Africa has experienced two waves of infection, with the emergence of the B.1.351/501Y.V2 variant of concern after the first wave. Reported SARS-CoV-2 cases may not be a true reflection of SARS-CoV-2 burden and specifically the differential impact of the first and second waves of infection.Added value of this studyWe collected longitudinal blood samples from prospectively followed rural and urban communities, randomly selected, household cohorts in South Africa between July 2020 and March 2021. From 668 and 598 individuals included from the rural and urban communities, respectively, seroprevalence was found to be 7% (95%CrI 5-9%) and 27% (95%CrI 23-31%), after the first wave of infection, and 26% (95%CrI 22-29%) and 41% (95%CrI 37-45%) after the second wave, in rural and urban study districts, respectively. After standardising for age, we estimated that only 5% of SARS-CoV-2 infections were laboratory-confirmed and reported. Infection-hospitalisation ratios in the urban community were higher in the first (2.01%, 95%CI 1.57-2.57%) and second (2.29%, 95%CI 1.63-3.94%) wave than the rural community where there was a 0.75% (95%CI 0.49-1.41%) and 0.66% (95%CI 0.50-0.98%) infection-hospitalisation ratio in the first and second wave, respectively.When comparing the infection fatality ratios for the first and second SARS-CoV-2 waves, at the urban site, the ratios for both in-hospital and excess deaths to cases were significantly higher in the second wave (0.36%, 95%CI 0.28-0.57% in-hospital and 0.51%, 95%CI 0.34-0.93% excess deaths), compared to the first wave in-hospital (0.17%, 95%CI 0.15-0.20%) and excess (0.13%, 95%CI 0.10-0.17%) fatality ratios, pImplications of all the available evidenceIn South Africa, the overall prevalence of SARS-CoV-2 infections is substantially underestimated, resulting in many cases being undiagnosed and without the necessary public health action to isolate and trace contacts to prevent further transmission. There were more infections during the first wave in the urban community, and the second wave in the rural community. Although there were less infections during the second wave in the urban community, the infection-fatality ratios were significantly higher compared to the first wave. The lower infection-hospitalisation ratio and higher excess infection-fatality ratio in the rural community likely reflect differences in access to care or prevalence of risk factors for progression to severe disease in these two communities. In-hospital infection-fatality ratios for both communities during the first wave were comparable with what was experienced during the first wave in India (0.15%) for SARS-CoV-2 confirmed deaths. To our knowledge, these are the first longitudinal seroprevalence data from a sub-Saharan Africa cohort, and provide a more accurate understanding of the pandemic, allowing for serial comparisons of antibody responses in relation to reported laboratory-confirmed SARS-CoV-2 infections within diverse communities.