Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05277298 |
| Other study ID # |
PHIRST-C |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
March 2022 |
| Source |
National Institute for Communicable Diseases, South Africa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The study aims to characterize the community burden (including the clinical features) and
transmissibility of SARS-CoV-2 within the context of a functional antibody response. In
addition,the study will assess the effect of the interaction of SARS-CoV-2 with influenza
virus and RSV on disease severity and transmission dynamics. A household-level prospective
cohort study will be conducted in one rural and one urban community located in Mpumalanga
Province and North West Province, respectively. The study will be conducted for 12 months of
intensive follow up (July 2020 to August 2021) with a post-intensive follow-up continuing for
a further 16 months (until December 2022). Two hundred households; 1,000 study participants
of all ages; will be randomly selected from a list of 327 hoseholds that participated and
successfully completed a 10-months follow-up period in a study similar to that currently
proposed, but directed at community burden and transmission dynamics of influenza,
respiratory syncytial virus and other respiratory pathogens. Each household and household
member will be enumerated and the HIV infection status and the level of immunosuppression of
HIV-infected individuals will be assessed. Each household member will be followed twice per
week during the intense follow-up period (12 months) of the study. During this period upper
respiratory tract samples will be collected irrespective of presence of symptoms and data on
key symptoms, healthcare seeking, hospitalization and death will be captured at each follow
up visit. Respiratory samples will be tested by reverse transcriptase real-time polymerase
chain reaction (rRT-PCR) for SARS-CoV-2, influenza and RSV, and selected samples will be
cultured and sequenced. An infection risk questionnaire will be administered to all study
participants at enrollment and every month thereafter. Sera will be collected at enrollment
and every 2 months during the 12-month intense follow-up period from all participants. In
addition, sera will be collected every 2 months for a further 6 months following the 12-month
intense follow-up period from study participants that tested positive for SARS-CoV-2 by
rRT-PCR on respiratory specimens at 14, 16 and 18 months and from all study participants at
18 months. Sera will be tested for the presence of SARS-CoV-2, influenza and RSV antibodies.
Wearable proximity sensors will be deployed for 8-12 days in each household over the 6-month
intense follow-up period.
Description:
Background and justification: On 31 December 2019, the World Health Organization (WHO) was
alerted to a cluster of pneumonia cases of unknown etiology in patients in Wuhan City, Hubei
Province of China, which, one week later, was attributed to a novel coronavirus (severe acute
respiratory syndrome coronavirus 2: SARS-CoV-2). Given its rapid spread globally, WHO
declared that the outbreak of SARS-CoV-2 met pandemic criteria on 11th March 2020. By
mid-April 2020 more than 2.5 million cases and more than 170,000 deaths have been
laboratory-confirmed in 210 countries and territories.
Influenza virus is responsible for elevated morbidity and mortality globally every year. In
South Africa annual seasonal influenza epidemics occur during the winter months (May-October,
with peak transmission in June-July) and result in an estimated 19 million symptomatic
infections, 128,000 severe cases and 11,000 deaths on average every year.
Human respiratory syncytial virus (RSV) is the commonest cause of childhood acute lower
respiratory tract infection, especially among infants <3 months of age. In South Africa RSV
circulates throughout the year with peak transmission occurring usually during
February-April. Nonetheless, from systematic virologic surveillance data delayed RSV
transmission is expected to occur in South Africa in 2020. This has the potential to result
in concomitant SARS-CoV-2, influenza and RSV peak transmission in the country.
HIV incidence remains high in South Africa. Similarly, rates of pulmonary tuberculosis (PTB),
with concomitant damage to lung tissue, remain persistently high despite concerted national
efforts. HIV and PTB infections have been associated with an increased risk of severe illness
(i.e., hospitalization and death) following infection with common respiratory pathogens,
including influenza and RSV, even among individuals on antiretroviral therapy.
Understanding the community burden, transmissibility potential and clinical features of
illness associated with SARS-CoV-2 infection is critical to inform the design and duration of
containment and mitigation measures, both locally and globally. An accurate estimation of
risk factors for community transmission, acquisition and duration of infectiousness is
crucial to inform guidance for public health measures to limit transmission as well as models
for epidemic forecasting for this and potential future epidemics. Moreover, factors specific
to South and sub-Saharan Africa (SSA) such as HIV, tuberculosis, high proportion of the
population who are children, malnutrition, and limited healthcare resources have the
potential to impact both the transmission dynamics, progression and prognosis of SARS-CoV-2
disease; as well as the burden on the healthcare system and society.
Whereas knowledge has been gained on the transmissibility and clinical features of SARS-CoV-2
since its emergence several key questions related to the natural history of the virus remain
poorly answered, notably in African context. In particular, the community attack rate by age,
the role of children in community and household transmission, the asymptomatic infected
fraction, the role of asymptomatic individuals in transmission, the interaction of SARS-CoV-2
with other common respiratory pathogens such as influenza and RSV, the risk of reinfection
with SARS-CoV-2 and the correlation between PCR-confirmed infection and serologic response
among others, remain poorly understood. Critically, the effect of HIV infection on
transmission and disease severity associated with SARS-CoV-2 infection is unknown. South
Africa has an HIV prevalence of approximately 15% in the general population, representing
over 7 million people of whom over 5 million are taking antiretroviral therapy.
Aim: In urban and rural South African environments, the study aims to characterize the
community burden (including the clinical features) and transmissibility of SARS-CoV-2 within
the context of a functional antibody response. In addition, the effect of the interaction of
SARS-CoV-2 with influenza virus and RSV on disease severity and transmission dynamics will be
assessed. This will be undertaken from an early stage throughout the epidemic in South
Africa.
Primary objectives:
1. To estimate the community burden of SARS-CoV-2, including:
1.1 the incidence of SARS-CoV-2 infection in the community as determined by polymerase
chain reaction (PCR) and serologic assays; 1.2 the correlation between individuals that
seroconverted for SARS-CoV-2 and tested positive by PCR; 1.3 the incubation period and
the symptomatic fraction associated with SARS-CoV-2 infection; 1.4 the spectrum of
severity associated with symptomatic infections; 1.5 the fraction of individuals with
symptomatic infection seeking medical care; and 1.6 the effect of the interaction of
SARS-CoV-2 with influenza and RSV on disease severity.
2. To assess the transmission dynamics of SARS-CoV-2 infections in the community,
including:
2.1 the estimation of the SARS-CoV-2 household secondary infection risk (SIR), generation
time and length of shedding; 2.2 the estimation of the probability of transmission of
SARS-CoV-2 infection between individuals (both symptomatic and asymptomatic/presymptomatic)
within the household and potentially the community; 2.3 the estimation of the SARS-CoV-2
effective reproduction number (Rt) and its variation over time in the community; and 2.4 the
effect of the interaction of SARS-CoV-2 with influenza and RSV on transmission dynamics.
Methods: A household-level prospective cohort study will be conducted in one rural and one
urban community located in Mpumalanga Province (the Agincourt demographic surveillance site)
and North West Province (Klerksdorp), respectively. The study will be conducted for 14 months
of intensive follow up (July 2020 to August 2021) with a post-intensive follow-up continuing
for a further 16 months (until December 2022).
Two hundred households; 100 per site with expected average number of household members of 5
resulting in 1,000 study participants of all ages; will be randomly selected from a list of
327 households that participated and successfully completed a 10-months follow-up period in a
study similar to that currently proposed, but directed at community burden and transmission
dynamics of influenza, respiratory syncytial virus and other respiratory pathogens (the
PHIRST study conducted during 2016-2018 in the same two communities). The approached
households will be re-assessed for study eligibility (i.e., a minimum of 3 household members
and at least 80% of household members consenting to participate). The households in the
2016-2018 PHIRST study were identified by randomly selected geo-coordinates within the two
communities. Baseline characteristics for this cohort are already available and will be
re-ascertained after obtaining consent. Consenting household members that have entered the
household since termination of the 2016-2018 PHIRST study will be also enrolled. Each
household and household member will be enumerated and the HIV infection status and the level
of immunosuppression of HIV-infected individuals will be assessed (if unknown) in consenting
individuals.
Each household member will be followed twice per week during the intense follow-up period (12
months) of the study. During this period upper respiratory tract samples will be collected
irrespective of presence of symptoms and data on key symptoms, healthcare seeking,
hospitalization and death will be captured at each follow up visit on a REDCap tablet-based
real-time database. Respiratory samples will be tested by reverse transcriptase real-time
polymerase chain reaction (rRT-PCR) for SARS-CoV-2, influenza and RSV, and selected samples
will be cultured and sequenced. An infection risk questionnaire will be administered to all
study participants at enrollment and every month thereafter. Sera will be collected at
enrollment and every 2 months during the 12-month intense follow-up period from all
participants. In addition, sera will be collected every 2 months for a further 6 months
following the 12-month intense follow-up period from study participants that tested positive
for SARS-CoV-2 by rRT-PCR on respiratory specimens at 14, 16 and 18 months and from all study
participants at 18 months. Sera will be tested for the presence of SARS-CoV-2, influenza and
RSV antibodies. Wearable proximity sensors will be deployed for 8-12 days in each household
over the 6-month intense follow-up period.
Impact: This study will provide essential information on the natural history of the virus
that will impact decisions on optimal strategies for the containment and mitigation of the
current and potential future epidemics of SARS-CoV-2 locally, regionally and globally.
