Our unique study design combining frequent rRT-PCR and serological screening allowed for more complete ascertainment of illness burden. Our study also had several limitations. and Rabacfosadine Delta (OR 14.6, 95%CI 5.7C37.5) variant illness were associated with improved HCIR. HCIR was related for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index instances (p=0.165). Assault rates were highest in individuals aged 13C18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 illness. 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. Conclusions In this study, 85% of SARS-CoV-2 infections were asymptomatic and index case sign status did not affect HCIR, suggesting a limited part for control steps targeting symptomatic individuals. Improved household transmission of Beta and Delta variants, likely contributed to successive waves, with 60% of individuals infected by the end of follow-up. strong class=”kwd-title” Keywords: SARS-CoV-2, burden, transmission, household, South Africa, HIV, rural, urban Intro Many low- and middle-income countries have experienced large numbers of hospitalisations and deaths related to COVID-19. However, reported levels of illness are not always proportional to the high levels of illness implied by serologic studies, suggesting reduced access to laboratory testing, or variations in transmission or susceptibility to developing SARS-CoV-2-related illness in these Rabacfosadine settings.1,2,3 Few detailed SARS-CoV-2 cohort studies are available from middle and low income settings, where vaccination rates remain suboptimal and immunity comes primarily from natural infections, as is the case in South Africa. South Africa has a relatively young populace with 5% of the population aged 65 Rabacfosadine years.4 In 2017, the national HIV prevalence among individuals of all ages was 14%, with 7,9 million people living with HIV.5 Following a initial detection of SARS-CoV-2 in South Africa in March 2020, a hard lockdown was implemented with restrictions on international travel, school closures, halting of non-essential business and confining people to their homes. Subsequent to this hard lockdown there was a progressive relaxation of restrictions, beginning on 1 May 2020.6 South Africa experienced three SARS-CoV-2 waves through August 2021; the first wave peaking in August 2020, the second, associated with the emergence of the Beta variant of SARS-CoV-2, peaking in January 2021 and the third associated with the Delta variant peaking in June 2021.7 SARS-CoV-2 restrictions were increased moderately including school closures round the maximum of the second and third waves and subsequently relaxed when case figures decreased. Both Beta and Delta variants have been shown to escape from immunity from earlier illness, be more transmissible and may be associated with more severe disease, even though epidemiological consequences of each of these guidelines remain debated.8,9,10,11 Studies to quantify the burden of asymptomatic infections, symptomatic fraction, duration of dropping and household transmission of SARS-CoV-2 from asymptomatically infected individuals have mostly been conducted as part of outbreak MMP17 investigations or in specific settings.12,13,14,15 Comprehensive community studies of asymptomatic infection and robust individual-level epidemiologic data about infection with Beta and Delta variants are limited. In randomly selected households from a rural and an urban community in South Africa, we estimated the cumulative incidence of SARS-CoV-2 illness using serial real-time reverse transcription PCR (rRT-PCR) and serology. We estimated the symptomatic portion of SARS-CoV-2 illness, the duration of viral RNA dropping and the household cumulative illness risk (HCIR) from symptomatic and asymptomatic index instances of different age groups. Methods The Prospective Household study of SARS-CoV-2, Rabacfosadine Influenza and Respiratory Syncytial computer virus community burden, Transmission dynamics and viral connection in South Africa (PHIRST-C) was based on a previously carried out study (PHIRST) at the same sites from 2016C2018.16,17 We implemented a prospective household cohort study inside a rural and an urban community of South Africa with twice weekly collection of mid-turbinate nasal swabs, sign, and health-seeking data and serum collection every two months to measure SARS-CoV-2 antibodies (Supplementary figure 1). The study included 58 weeks of follow-up in the rural site (16 July 2020 through 28 August 2021) and 56 weeks in the urban site (27 July 2020 through 28 August 2021) with seven serum selections at each site. Nasal swab collection began prior to.