Defining immunity to SARS-CoV-2 in key South African populations will provide much-needed insights into immune correlates of recovery and of protection. Such immune data will also enable the rapid development of locally relevant antibody-based interventions, key to mitigating the mid- to long-term public health impact of this pandemic in South Africa. 

The HIV Virology Section has re-purposed existing HIV platforms to define the kinetics, durability, and targets of SARS-CoV-2 neutralising and non-neutralising B cell responses, in order to isolate monoclonal antibodies for therapeutic utility.  The team will determine the titers, kinetics, durability of neutralising antibodies and Fc effector functions to SARS-CoV-2 in longitudinal samples from individuals with mild disease and severe disease, and with or without HIV infection.

They will also adapt their HIV epitope mapping approaches to map the targets of neutralising antibodies and isolate monoclonal antibodies from individuals with potent neutralisation activity and/or Fc activity. They will incorporate into assays SARS-CoV-2 spike protein sequences obtained from local viral surveillance efforts to tailor immune correlates and monoclonal antibodies to be locally useful.

Collaborators: Key aspects of the work are led by Drs Simone Richardson, Thandeka Moyo and Nono Mkhize, working very closely with Dr Jinal Bhiman of NICD CRDM and Prof Carolyn Williamson of UCT.

For collaborative studies please contact:

Prof Penny Moore – pennym@nicd.ac.za

Synopsis

In 2020 South Africa, like any other country, has had to manage the new public health threat, namely COVID-19 with all the available measures, including the non-pharmaceutical interventions. Critical to the future management of this health problem if the virus was to become endemic is to have as much detailed information on the epidemic. It was observed early on in the outbreak that there was a spectrum of how transmission occurs. Thus, it was not only individuals who presented with symptoms but also those who were infected and transmitted before developing symptoms.

Critical is the transmission of the virus by those who were infected but who never developed symptoms, i.e. were asymptomatic, as well as those who develop systems much later, i.e. were presymptomatic. The proportion of asymptomatic and presymptomatic infections varies depending on study and range from 20% to 40% and even higher (70%). Factors that can influence the way the virus is transmitted include spatial geography, population density, demographics, adherence to non-pharmaceutical interventions, immune or genetic factors. Essential information on how many South Africans acquired the infection is needed. Seroprevalence studies, i.e. how many people have produced antibodies against the new virus is how this information is collected.

The critical epidemiological questions include (1) what number of South Africans were infected with the virus, (2) the age distribution of the those infected and (3) the number of persons who had asymptomatic infections at the time of testing. Community acceptance and involvement will be essential factors for the success of the study. Two cross-sectional studies 6-8 weeks apart will be conducted across South Africa. The studies intend to enrol under 20,000 people from 6300 households. The numbers of participants in the study (sample size) will provide an accurate estimate of the numbers of South Africans who have been infected by the virus. A questionnaire will collect information on the risk factors for infection and questions on symptoms that are COVID-19 related. Also, a blood sample will be collected to measure antibodies to the virus. Various statistical analyses will be performed to answer the questions that the survey sets out to answer. Following data analysis feedback will be provided.

Background

Since the beginning of 2020, the majority of countries in the world have been facing the global public health pandemic of coronavirus disease (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, very little is known internationally and nationally about the magnitude and determinants of the epidemic, as prevalence is estimated mainly from confirmed cases based on polymerase chain reaction (PCR) testing for patients who have mild to severe symptoms. The proportion of asymptomatic and presymptomatic cases in the general population is unknown and marks an important goal of the present study. More specifically, the proposed study has two primary objectives:

1. To determine the extent of SARS CoV-2 virus infection in the general population with age-specific infection cumulative incidence, as determined by seropositivity; and
2. To determine the proportion of asymptomatic or subclinical COVID-19 infections. 

The secondary objectives of the study are:

1. To determine risk factors for COVID-19 virus infection
2. To estimate the prevalence of SARS-CoV-2 antibodies in age and sex sub-groups
3. To assess antibody levels quantitatively and neutralising antibody concentrations for future comparisons with correlates of protection for herd immunity estimations
4. To assess cytotoxic T-cell responses in a sub-group of participants who have and do not have antibody responses, in order to identify what proportion of individuals may have been infected with SARS-CoV-2 but do not have detectable antibodies

Methods

The proposed study will use two waves of cross-sectional population-based household seroprevalence surveys. The study will be implemented in all nine provinces in South Africa. The survey will target all the locality types (urban areas, rural formal and rural informal areas) within the selected geographic area (Small Area Layer, SAL).

A random sample of 6,390 households from 426 SALs will realise an estimated eligible sample of 19,170 respondents, based on the assumption of an average of three people per household. Considering the assumed response rate, it is estimated that 13,419 sero-tests will be completed nationally.

Overall, two survey waves are planned that will be initiated at the beginning of September 2020, and that will be repeated in mid-November 2020.

Each survey wave will be conducted for over 6-8 weeks and will consist of two distinct phases. In Phase 1, 18 junior researchers from the HSRC will undertake preliminary community entry visits and engage with community gatekeepers before the arrival of the data collection teams. During Phase 2, fieldworker teams, each consisting of a driver, a supervisor and six field workers, will be deployed into the selected SALs across all the nine provinces in the country. The fieldworkers will all be qualified phlebotomists who will conduct short interviews using tablets and also collect blood through venesection for serology testing.

The interviews will be based on a short questionnaire adapted from the World Health Organization (WHO) COVID-19 study questionnaire and will be used for obtaining information at the individual level on socio-demographic characteristics and various key risk factors for COVID-19 virus infection. Information includes the history of COVID-19 infection, history of exposure to contacts, co-morbidities, and behavioural prevention practices such as hand washing and social distancing.  Heads of households will be asked to complete an initial questionnaire that will be used for household enumeration. The data collected with the tablets will be sent to the central server at the HSRC’s main office in Pretoria for management and storage. 

Blood collected will be couriered under cold-chain conditions and within 24 hours, to the National Institute of Communicable Disease (NICD) for serology testing.

The prevalence of infection, taking into account the survey weights, stratification and clustering will be calculated and descriptive statistics used to illustrate the prevalence of COVID-19 antibodies (IgM and IgG) among the study population, differentiating between the population which exhibited symptoms and those who were asymptomatic. The risk factors associated with being exposed to the COVID-19 virus, and those who are not infected will be determined through multiple regression analysis. Furthermore, we shall also measure both T-cell responses to specific viral antigens and neutralising antibodies in a sub-study to better understand the immune responses and for future comparisons with correlates of protection for herd immunity estimations.

Intended feedback on the study

The study was requested by the COVID-19 Ministerial Advisory Committee (MAC) to inform both the modelling of the disease and other decisions that will be taken by the government of South Africa to mitigate the impact of the epidemic on the country. Results will be reported to the Minister of Health, the COVID-19 MAC, and the National Department of Health.  It will also be published in peer-reviewed journals and presented to both national and international conferences.

Principal investigators (PIs): Leickness Simbayi, Sizulu Moyo (Human Sciences Research Council)

Co-PIs: Khangelani Zuma, Nompumelelo Zungu, Edmore Marinda, Sean Jooste (Human Sciences Research Council), Adrian Puren (National Institute of Communicable Diseases), Lynn Morris (National Institute of Communicable Diseases)