Transmission of COVID19 in Crowded Environments
Phase: NA
Conditions: Covid19, Sars-CoV-2 Infection
Sponsor: Desmond Tutu HIV Foundation

TRACE protocol version 2 06 October 2020 
 
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Protocol Title: TRAnsmission of Covid-19 in Crowded Environments 
Short Title: The TRACE Study. 
 
Study PI and co-PI  
Linda-Gail Bekker  
Philip John Smith 
The Desmond Tutu Health Foundation 
 
Study Co-Investigators:  
Desmond Tutu Health Foundation: 
Robin Wood 
Catherine Orrell 
Carey Pike 
 
School of Public Health: 
Mary-Ann Davies  
 
Department of Statistical Sciences: 
Francesca Little 
 
Knowledge Translation Unit: 
Lara Fairall  
Daniella Georgeu-Pepper 
Robyn Curran 
Audry Dube 
 
Provincial Dept of Health, Western Cape : 
Fatima Peters 
 
LSHTM: 
Nicky McCreesh 
Richard White 
 
AIGHD: 
Logan Stock 
Sabine Hermans 
Frank Cobelens 
 
 
 
 

TRACE protocol version 2 06 October 2020 
 
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TRaCE summary 
 
The overarching objective of this protocol is to understand and mitigate household transmission of 
SARs-CoV-2 infection in a low income, high density South African community setting. Data over an 8-
month period will be used to determine the Ro for SARS-CoV-2 infection, rate of symptomatic disease, 
and impact of a community healthcare worker (CHW) administered household infection mitigation 
intervention (STOPCOV intervention).  
 
•  Aim 1: To measure incidence and timing of transmission of SARS-CoV-2 to household contacts (HHC). 
SARS-CoV-2 transmission will be monitored using nasopharyngeal swabs for PCR and serology 
(IgM/IgG) assays in all Household Contacts (HHC) weekly for 1 month. Symptom checklists will be 
completed daily and collated weekly for each HHC. The proportion of patients and HHC who have 
symptoms vs asymptomatic disease will also be measured. 
•  Aim 2: To investigate the effect of an intensive infection mitigation intervention (STOPCOV) 
administered by lay health care workers on SARS-CoV-2 household transmission. The proportion of 
transmissions to HHC of COVID19 cases assigned to the infection mitigation intervention arm 
compared with the households in the Enhanced Usual Care (EUC) arm will be measured. In addition, 
we will evaluate the effectiveness of the STOPCOV intervention on uptake of infection mitigation 
strategies, loneliness, stigma and social impact among households.  
 
Setting and population: The Klipfontein sub-district is a resource-limited, densely populated, high HIV 
disease burden areas in Cape Town. Newly diagnosed COVID19 cases will be identified from two 
sources: screening conducted in DTHF mobile screening units and local public sector clinics. 
Consecutive cases (n=120 and households) will be invited to participate. After enrolment, the 
household will be randomised to the STOPCOV intervention or enhanced usual care messaging.  
 
Design: A cluster randomised controlled study with longitudinal follow up of SARS-CoV-2 infection in 
120 households which have newly diagnosed positive cases. The index cases and their HHC will be 
invited and enrolled after informed consent. Baseline surveys and SARs-CoV-2 screening (PCR and 
IgM/IgG serology) and then weekly SARs-CoV-2 screening (PCR and serology) of HHC will occur at 0, 1, 
2, 3 and 4 weeks. The households will be randomized to an intensified COVID19 infection mitigation 
intervention (n=60) administered by CHWs vs standard messaging currently being provided (n=60).  
 
Analysis: The proportion of SARS-CoV-2 transmission from index cases to HHC over 4-week period will 
be calculated. The proportion of symptomatic and asymptomatic SARS-CoV-2 infection in a high 
density, low resourced community will be described. The impact of the STOPCOV intervention by 
assessed by measuring transmission, and clinical outcomes, in households randomised to intervention 
vs standard of care. A process evaluation will explore the feasibility, acceptability and contextual 
factors impacting the STOPCOV intervention delivery.  
 
 

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TRaCE Schema 
Questions: 1 What is the transmission pattern (Ro number and timing of infection) of SARS-CoV-2 in 
a household in which a COVID-19 case has been identified in a low-income, high density community 
in Cape Town? 2 What is the burden of symptomatic versus asymptomatic SARS-CoV-2 cases in a high 
HIV/ TB disease burden setting in Cape Town, South Africa? 3 Can an intensified, infection mitigation 
intervention reduce the transmission in a household setting, improve clinical outcomes and reduce 
psychosocial impact of a COVID19 diagnosis? 
Objective: The overarching objective of this protocol is to understand and mitigate household 
transmission of SARs-CoV-2 infection in a low income, high density community setting.  
Aims: Specific Aim 1: To measure frequency and timing of transmission of SARS-CoV-2 to household 
contacts. The proportion of patients and household contacts who have symptoms vs asymptomatic 
disease will also be measured. Specific Aim 2: To investigate the effect of an intensive infection 
mitigation intervention (STOPCOV) administered by lay health care workers on the household 
transmission of SARS-CoV-2, clinical outcomes and psychosocial functioning.  
Design: The study design is a type 2 hybrid cluster (household) randomised controlled trial, with 
outcomes assessed on index patients and their household contacts (Fig 1). 120 consecutively newly 
diagnosed index patients (GeneXpert SARS-CoV-2 PCR) and up to 8 household contacts will be invited 
to participate in the trial as part of the prospective observational study evaluating transmission and 
symptoms. After completing consent, households will be randomised in a 1:1 ratio in blocks of 10 (60 
households per group; 360 patient and household contacts per group).  
Study setting and population: Klipfontein is a resource-limited, densely populated, high HIV/TB 
disease burden areas in Cape Town. Newly diagnosed COVID19 cases will be identified from two 
sources: screening conducted in DTHF mobile screening units and local public sector clinics working 
closely with DTHF. Consecutive cases (n=120 cases and households) will be invited to participate in 
the randomised trial and prospective longitudinal follow up of up to ~6 -8 household contacts. The 
contacts will be followed up after informed consent to SARS-CoV-2 screening, symptomatic 
questionnaires weekly up to 1 month.  
Study size: We will enrol n=120 SARS-CoV-2 positive and n=~6 their household contacts (n=~720). 
Process: Newly diagnosed SARS-CoV-2 index patients will be identified and recruited from a mobile 
clinic and local community clinics conducting SARS-CoV-2 testing. Index cases and their households 
will be invited to enroll. After enrolment, the household will be randomised to the infection mitigation 
intervention or enhanced usual care messaging. Baseline demographic, household characteristics 
questionnaire will be administered, and each household occupant invited to participate. Following 
consent procedures, household contacts (HHC) will be screened at baseline and weekly for 4 weeks 
for evidence of COVID infection. Specifically, the research team will conduct SARS-CoV-2 GeneXpert 
PCR testing and antibody serology. They will collate self- administered daily symptom checks on a 
weekly basis. Six months after a positive SARS-CoV-2 antibody, the study nurse will visit the participant 
household to conduct SARS-CoV-2 serology to assess for the presence of antibodies. 
Duration: We will recruit 120 households over 1-3 months. We will initiate a prospective longitudinal 
follow up of the household contacts of each case for 4 weeks in each case. 
Analysis: Calculate proportion of SARS-CoV-2 transmission from index cases in each household over 
4- week period. Describe the proportion of symptomatic and asymptomatic SARS-CoV-2 infection in a 
high density, low resourced community. Investigate the impact of the infection mitigation 
intervention by comparing Ro number in households randomised to intervention vs standard of care. 
Secondary outcomes for the trial will include clinical outcomes (hospitalisations, death), linkages to 
care for people, psychosocial functioning and stigma.  

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Background 
 
South Africa currently has the largest COVID19 epidemic in Africa, with >205,721 cases reported in all 
nine Provinces (COVID-19 South African Coronavirus News and Information Portal, n.d.). The South 
African Department of Health  has reported more than 3310 deaths of individuals infected with severe 
acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19) 
to date (Karim, 2020). As screening and testing is scaled up, South African healthcare facilities are 
preparing for the mitigation stage in the epidemic, wherein people with severe COVID-19, mostly 
adults, may require hospitalization, and intensive care (Karim, 2020).  
 
A large proportion of the 55 million people who make up the South African population live in low 
income, high density communities in peri-urban locations. These settlements may be formal or 
informal and often consist of crowded shack dwellings. Self-isolation and physical distancing may be 
impossible in these crowded environments (Davey et al., 2020). Many do not have water and need to 
stand in queues to get water or food. The major risk mitigation factors recommended by WHO and 
others – physical distancing and hygiene – are extremely difficult to implement in much of Africa 
(Joseph Davey et al., 2020; The Lancet, 2020).  
 
The Desmond Tutu Health Foundation mobile HIV counselling and testing (HCT) service was designed, 
built and launched in Cape Town in 2008. Previous studies using active case-finding with the Tutu 
Tester Mobile clinic services have successfully identified undiagnosed cases of HIV and TB and linked 
these patients to care (Govindasamy et al., 2013; Kranzer et al., 2012; Smith et al., 2014). The mobile 
clinic has provided accessible, community-based, rapid HCT services in high HIV and TB disease burden 
communities. The mobile clinic team sought to destigmatise HCT by embedding HIV testing in a 
wellness service for a range of chronic diseases, including diabetes and hypertension. In addition to 
HIV testing, the service included point of care (POC) STI screening, CD4 T cell testing and TB screening 
of HIV infected clients. After 90,000 client contacts in numerous communities with high rates of HIV 
and TB infection in the Cape Metro district we have established that this service is feasible, acceptable, 
effective, non-stigmatising and cost effective (Bassett et al., 2014; Govindasamy et al., 2013; Smith et 
al., 2019). Additionally, the mobile has enhanced linkage to care among HIV infected individuals, rapid 
ART initiation for pregnant women reduced PMTCT to <1% (Black et al., 2013) and POC diagnostics 
were in a mobile clinic setting (Kranzer et al., 2013). Mobile clinics provide an opportunity to actively 
identify communicable disease and link patients to care (Kranzer et al., 2012).  
 
With the advent of COVID19, the mobile services have added COVID testing to the suite of screening 
tests and has been conducting testing in partnership with the provincial health services since the 
beginning of April 2019. During the first three months of the pandemic the strategy had been to test 
all symptomatic individuals identified in a door to door community-based approach. Testing teams 
linked to the mobile and under armed police protection have been set up in “hotspots” in which a 
known COVID case has previously been identified. Community health care workers are trained to 
sweep through the immediate community administering a symptom questionnaire whilst community 
education via loud hailing is conducted. After completing a symptom questionnaire administered by 
community health workers, symptomatic individuals or people who have had known contact with a 
COVID case are screened by a clinician for symptoms and if confirmed, have been invited to undergo 
nasal swabbing in an outdoor gazebo linked to the mobile by a trained clinician.  This has been done 
safely and with a reasonable yield. To date, the case fatality rate (CFR) is 354 per million in the Western 
Cape, which is over 7 times higher than the national mortality rate of 49 per million 
(https://www.totalanalysis.com/187). The CFR is projected to be 700 per million in the Klipfontein 
region (Timeslive, 2 July 2020).  

TRACE protocol version 2 06 October 2020 
 
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These services have therefore already shown to be ideal for strategically identifying and following up 
cases and contacts of SARS-CoV-2 and triaging patients to quarantine, isolation, and hospital care as 
appropriate. The overall objective of this proposal is to understand and mitigate the transmission of 
SARS-CoV-2 in high density townships. We plan to do this by establishing the Ro number for SARS-
CoV-2 in low-income high-density households, and evaluating the effect of a lay health worker 
administered risk mitigation strategy on transmission, clinical outcomes and psychosocial functioning 
compared with enhanced usual care.  
 
Approach: 
 
Overall Objective: The overarching objective of this protocol is to understand and mitigate household 
transmission of SARs-CoV-2 infection in a low income, high-density community setting. Data over an 
8-month period will be used to determine the Ro for SARS-CoV-2 infection, the rate of symptomatic 
disease and the impact of a lay health care worker administered infection mitigation intervention 
(STOPCOV) in low income, high-density communities in South Africa.  
 
Specific Aim 1: To measure frequency and timing of transmission of SARS-CoV-2 to household 
contacts. The proportion of patients and household contacts who have symptoms vs asymptomatic 
disease will also be measured.  
Specific Aim 1 Endpoints: SARS-CoV-2 transmission will be monitored using nasopharyngeal swabs for 
SARS- CoV-2 PCR and serology (IgM/IgG) assays in all HHC weekly for 1 month. Symptom checklists 
will be completed daily and collated weekly for each HHC.  
 
Specific Aim 2: to investigate the effect of an intensive infection mitigation intervention known as 
STOPCOV administered by lay health care workers, compared with enhanced usual care, on SARS-CoV-
2 household transmission.  
Specific Aim 2 Primary Endpoint: The proportion of transmissions to HHC in the households of COVID 
cases assigned to the infection mitigation intervention arm compared with the households in the 
enhanced usual care (EUC) arm.  
 
Population and Sample: We will consecutively recruit n=120 SARS-CoV-2 positive index patients 12 
years and older. The index patients will be identified from referrals from associated public sector clinic 
screening in a high-density community in Cape Town. Each household is estimated to have 6-8 
occupants. We will invite HHC (n=~6-8) household contacts of each of the index patients (n=~720). 
 
Duration: The study will be conducted for eight months from June 2020 and last until Jan 2021. 
 
Setting: The study will be conducted in KMP. The community is a resource-limited, densely populated, 
high HIV/TB disease burden area in Cape Town. The DTHF Tutu Tester Mobile Clinics offer mobile HIV 
testing days in various locations in KMP. Specifically, there are four high HIV disease burden 
communities in the district; Philippi (population n=200,803), Crossroads (n=36,043), Gugulethu 
(n=98,468) and Nyanga (n=57,996). In addition to our well-established relationship with community 
organisations such as an independent advisory board, we have provided HIV testing services and 
linkage to treatment from the mobile clinic since 2008 and are currently partnering with the K/MP 
subdistrict health team in providing COVID screening and testing. Given our long-term relationship 
with and service in the community, our relationships with the Provincial Department of Health, and 
our experience with the research platforms, it is feasible for us to successfully execute the proposed 

TRACE protocol version 2 06 October 2020 
 
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research. The mobile clinic team will provide a screening service and SARS-CoV-2 polymerase chain 
reaction (PCR) testing with the GeneXpert or courier samples to accredited laboratories and rapid 
testing with the SARS-CoV-2 antibody COVID-19 lgG/lgM Rapid Test Device. Additionally, the mobile 
clinic team will offer screening for HIV, TB, STI and chronic diseases (e.g. diabetes, hypertension, and 
obesity).  
 
Design: A cluster randomised controlled study with longitudinal follow up of SARS-CoV-2 infection in 
120 households which have newly diagnosed SARS-CoV-2 positive cases. The index cases and their 
household contacts will be invited to participate in the study after informed consent. Baseline surveys 
and screening and then weekly screening of HHC will occur (Table 1). These household contacts will 
be tested at 0, 1, 2, 3 and 4 weeks.  
The study design is a type 2 hybrid cluster (household) randomised controlled trial, with outcomes 
assessed on index patients and their household contacts (Diag 1). 120 consecutively newly diagnosed 
index patients (GeneXpert SARS-CoV-2 PCR) and up to 8 household contacts will be invited to 
participate in the trial as part of the prospective observational study evaluating transmission and 
symptoms. After completing consent, households will be randomised in a 1:1 ratio in blocks of 10 (60 
households per group; 360 patient and household contacts per group).  
 
Diagram 1: Study flow 
 
 
 
 
Control group households will receive standard Western Cape Department of Health COVID-19 
recommendations for transmission mitigation at the time of diagnosis. Currently this includes advice 
on physical distancing, hand and respiratory hygiene and cleaning. Information has been distributed 
through dissemination of written pamphlets, WhatsApp messages, telephone hotlines and websites. 
Home care is only recommended if there is a separate room. Facility isolation and quarantine services 
are available for households without separate rooms, and are strongly advised should members of the 
household be considered at risk for severe COVID-19 (age ≥ 55 years and/or underlying chronic 
conditions especially diabetes). But uptake of such services has been lower than expected and beds 
are being decommissioned. Intervention group households will receive intensive support delivered by 
CHWs (See Table 1). This will comprise an initial household assessment to assess needs for facility 
isolation or quarantine referral, explain infection control measures and help the household adapt 

TRACE protocol version 2 06 October 2020 
 
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them to their homes, provision of basic supplies (masks, hand sanitiser and bleach) and written 
materials at appropriate literacy levels and in local language. The same CHWs will follow-up household 
members daily for the first two weeks and three times a week during weeks 2-4, as well as distribute 
pre-prepared twice daily text messages. Two CHWs will be assigned per household to sustain intensive 
support and prevent burnout.  
 
Table 1: Interventions 
 
Characteristic 
Usual care (outside 
study) 
Enhanced Usual Care 
StopCov intervention 
Testing of household 
contacts 
Not 
routinely 
available. Limited to 
symptomatic 
individuals at risk of 
severe COVID-19.* 
At baseline and weekly 
for up to 8 household 
contacts ≥ 12 years.  
At baseline and weekly 
for up to 8 household 
contacts ≥ 12 years. 
Facility based isolation 
and quarantine 
Available but uptake 
limited. 
Available but uptake 
limited. 
Counselled to take up 
service if isolation at 
home not possible and 
person in household at 
risk for severe COVID-
19. 
Hospital care 
Available 
through 
clinical 
services/ 
hotline 
Available 
through 
clinical 
services/ 
hotline 
Available 
through 
clinical 
services/ 
hotline 
Written material 
Extensive 
content 
available 
online. 
Limited 
content 
available as pamphlets 
and WhatsApps. No 
systematic distribution 
of 
WhatsApp 
messaging. 
Printed copies of PACK 
Home Volume 1 (Be 
coronavirus safe) and 
Volume 2 (COVID-19 
Caring at home). 
Printed copies of PACK 
Home Volume 1 and 2. 
WhatsApp optimised 
versions of content 
delivered daily.  
Community 
Health 
Worker visits 
Mainly 
alongside 
chronic 
medication 
delivery. 
Mainly 
alongside 
chronic 
medication 
delivery. 
Additional 
one 
off 
household assessment 
to 
establish 
relationship 
at 
baseline. 
Equipment 
Distributed 
through 
drives. 
Masks 
and 
hand 
sanitiser at enrolment. 
Masks, hand sanitiser, 
bleach, gloves (to wear 
when using bleach). 
Plus on demand during 
follow-up. 
Telephonic and text 
message support 
On demand hotline 
service. 
On demand hotline 
service 
Scheduled support: 
Active phase (until 14 
days after last person 
in 
household 
diagnosed): daily. 

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Follow-up phase: 3 
times a week for 7-14 
days. 
Close-out: 5 days (to 
facilitate 
full 
integration into usual 
services). 
 
* As of 06/07/2020 patients are considered at risk of severe COVID-19 if they are: 55 years or older or 
of any age with any one of the following: diabetes, on TB treatment, HIV, kidney disease, hypertension, 
previous TB, chronic clung disease, on cancer treatment.  
 
Outcomes will be independently assessed by research staff who are also collecting biological samples 
at 0, 1, 2, 3, and 4 weeks. Baseline surveys will collect information on demographics, COVID-19 
symptoms, household tracing information and home/ dwelling characteristics that impact 
transmission (size, rooms, ventilation, access to safe water, laundry facilities). Patient and household 
contact surveys will also include standardised measures to assess psychosocial functioning: General 
Health Questionnaire; UCLA Loneliness Scale and a version of the Brief AIDS-Related Stigma scale 
adapted for COVID-19. Research staff will complete a checklist documenting uptake of infection 
control measures at all follow-up contacts (1, 2, 3, 4 weeks). A sample size of 120 households (60 per 
group; 320 patient and household contacts per group) will provide 80-99% power to detect a 40% 
reduction in R0 (2.5 to 1.5) varying the intra-cluster correlation efficient from 0.90 (80%) to 0.05 (99%) 
(Table 3). Index patients and their contacts will be reimbursed with R150 for their time at the baseline 
and final study visits. 
  
A mixed methods process evaluation will explore acceptability, feasibility and contextual factors 
impacting intervention delivery guided by the Consolidated Framework for Implementation Research. 
Qualitative data collection during the first 4 weeks will be curtailed to minimise exposure of research 
staff completing qualitative interviews (high risk for COVID-19 transmission) and will be limited to 
observation of CHW training and up to 5 initial CHW household assessments. We will explore the 
feasibility of recording and analysing telephone interactions between CHWs and households. Once a 
household has been determined to be COVID-19 free (2 weeks after last symptoms in a diagnosed 
person) trained qualitative interviewers will conduct interviews with patients, household contacts and 
caregivers. These in-depth interviews will be limited to a purposive sample of 5 households per group. 
CHWs and community leaders will also be interviewed.  
 
Assessing SARS-CoV-2 transmission: The research team will conduct SARS-CoV-2 testing with 
household contacts at baseline and weekly for 1 month. SARS-CoV-2 transmission will be monitored 
using nasopharyngeal nostril swabs for SARS-CoV-2 GeneXpert PCR and antibody COVID-19 lgG/lgM 
Rapid serology assays. Nasopharyngeal samples will be collected in a well-ventilated sputum collection 
space and staff will have adequate protective equipment. Venepuncture will be used to obtain dried 
blood spots. The test results will be delivered telephonically to household contacts within 24 hours of 
the test. HHC will complete a daily symptom checklist and symptom data will be collated weekly by 
the research team. Six months after a positive SARS-CoV-2 antibody, the study nurse will visit the 
participant household to conduct SARS-CoV-2 serology to assess for the presence of antibodies. 
 
Eligibility of index case: 
Inclusion:  

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Individual >12 years  
Able to give assent if <18 years with parental/guardian consent  
Able to give consent> 18 years  
Self-isolating at home at the time of COVID diagnosis  
Exclusion: 
<12 years  
Unable to give consent  
 
Eligibility of HHC 
Inclusion:  
Living in the same household as index case  
Able to give assent if 12-17 years with parental/guardian consent  
Able to give consent≥ 18 years  
Exclusion:  
Unable to give consent 
 
Table 2: Study procedures 
 
  
  
  
  
  
  
Study participant  
Procedure  
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Index 
 
 
 
 
 
 
 
ICF  
x 
 
 
 
 
 
Demography survey  
x 
 
 
 
 
 
Symptom check  
x 
x 
x 
x 
x 
 
Follow up surveys  
x 
 
x 
 
x 
Household Contacts (HHC)  
 
 
 
 
 
 
 
ICF  
x 
 
 
 
 
 
Demography survey  
x 
 
 
 
 
 
Symptom check  
x 
x 
x 
x 
x 
 
COVID19 PCR  
x 
x 
x 
x 
x 
 
COVID serology  
x 
x 
x 
x 
x 
  
Follow up surveys  
x  
  
x  
  
x 
 
 
Data Collection and Management: Data will be collected by study staff on handheld devices. Data will 
be downloaded daily to a central database housed at the DTHF head office. Further details are 
available in Work Package 5 and the Data Management document.  
 
Statistical Analysis and sample size: We will describe and compare the characteristics and survey 
outcomes, isolation, and linkages of participants. We calculated the different effect sizes (Table 2). Based 
on exponential test for comparing hazards, assuming 120*6=720 subjects, different intraclass 
correlation coefficients (ICCs) and comparing R0=2.5 (with resulting incidence of 0.208 among 720 
subjects) to a reduced R0 of 0.9 (64% reduction, with resulting incidence of 0.075 among 720 subjects) 
or 1.25 (50% reduction) or 1.5 (40% reduction). 
 
Table 3: ICC calculations 

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ICC 
R0 2.5 to 0.9 
R0 2.5 to 1.25 
R0 2.5 to 1.5 
  
64% reduction 
50% reduction 
40% reduction 
0.05     
1.00000 
1.00000 
0.999944    
0.25     
1.00000 
0.999891 
0.991312 
0.50 
0.999993   
0.995042 
0.935880 
0.75     
0.999729         
0.972942  
0.846222    
0.90      
0.999033         
0.951485 
0.792745 
 
The analyses will be determined by the study analysis plan. These analyses include the calculation of 
the proportion of SARS-CoV-2 positive individuals screened over a 3-month period, the transmissibility 
of the virus by determining the proportion of SARS-CoV-2 transmitted to household contacts of the 
identified COVID19 cases over a 4-week period, the period of infectiousness by correlating the time 
to transmission and clinical symptoms of the index cases, and the symptomatic/asymptomatic ratio 
among transmitted SARS-CoV-2 in household contacts. The Ro will be determined by both looking at 
new cases among the population in contact with the index cases and the total population (both in our 
service and other clinics in the area) diagnosed over time. The main outcome relates to the incidence 
of new cases of COVID19. These will be analysed using mixed effect Poisson regression models and 
frailty models to take the clustering by household into account. Both these regression models take 
the duration of follow up into account. Scores (e.g., GHQ) will be baseline adjusted. Qualitative data 
will 
be 
transcribed, 
translated 
and 
inductively 
analysed 
for 
themes.  
 
Study Management: This project will be managed by a protocol team led by the overall PI, Prof Linda-
Gail Bekker. There will be a safety team made up of clinicians from the protocol team. This group will 
convene fortnightly. The protocol team, chaired by Prof Bekker, will constantly review study progress 
and outcomes.  
 
Ethical Review and Human Subjects Protection – The study will be reviewed and approved by the 
University of Cape Town Health Science Research Ethics Committee.  
 
Our research focuses on investigating transmission of SARS-CoV-2 in a crowded environment in the 
Klipfontein district in Cape Town, South Africa. In keeping with the urgency to understand the local 
COVID19 epidemic, we formally and respectfully request an expedited human subjects ethical review.  
The protocol meets the Common Rule criteria as the research study is expected to pose no more than 
minimal risk to subjects AND the procedures fall within “category 2” outlined the Human Research 
Protections (OHRP) and in compliance with 45 CFR 46.110(b)(1). According to the OHRP category 2, 
the proposed research poses no more than minimal risk with collection of blood samples through 
fingerprick, venepuncture and nasal swabs as per national standard operating procedures.  
 
Risk Mitigation: Staff will be given appropriate PPE and where possible all processes will be carried 
out in well ventilated spaces- outdoors where possible, whilst observing confidentiality. Cases and 
contacts will be invited to participate 24 hours before the mobile visit. Staff will invite contacts to 
attend the screening in small carefully controlled groups which will observe physical distancing. There 
are support services for participants at the site, including staff who are able to counsel participants, 
or telephonically, as well as established referral routes to external counselling resources. Participation 
in the study is voluntary. Participants may refuse participation, which will not affect further treatment. 
Participants will have the option to opt out of the study at any time. All information is anonymous and 
will be kept confidential. The name of investigators who are responsible for conducting the study and 

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direct contact details (telephone, address, e-mail) will be made available on the informed consent 
forms. The Site Investigator or designee will maintain, and store securely, complete, accurate, and 
current study records throughout the study, in accordance with local regulations. All records will be 
stored confidentially for five years from the beginning of the study.  
 
Overall Risk – The greatest risks here are exposure of staff or among potential participants to 
undiagnosed cases of COVID and or TB (which may mimic COVID symptoms). Every effort will be made 
to enhance and adequately implement infection control measures.  
 
Risks to participants: COVID-19 diagnosis has the potential to be stigmatized in communities. Although 
the study site will make every effort to protect participant privacy and confidentiality, including 
conducting testing and counselling in a private space, it is possible that participants’ involvement in 
the study could become known to others. Social harms will be monitored and documented throughout 
the duration of the study. Should additional support be required for some participants due to study- 
related harms, referrals will be made to community-based services as needed. DTHF has worked in 
the setting of HIV and TB for 20 years. The staff and policies are well developed to mitigate risk related 
to stigmatization. The DTHF mobiles for this reason conduct health screening that is multi-disease 
related with an emphasis on wellness. The mobile units, known as ‘Tutu Testers’ are a loved brand 
and well known in communities. Confidentiality is highly regarded and carefully maintained. Good 
participatory practices are also carefully followed by all. Risk and benefits will be carefully conveyed 
at the time of recruitment and enrolment. Cases and household contacts will participate voluntarily 
and can withdraw at any time. All data will be treated confidentially and after consent, participants 
will be assigned participant identifiers for all study related documents. Study related impacts and 
harms will be solicited weekly and where necessary participants will be referred for support.  
 
Risk to Staff: The risk of SARS-CoV-2 infection exists for research staff. All staff will be fully informed 
of risks. They will be provided with protective personal equipment to reduce infection risk including 
appropriate respirators, scrubs, aprons, goggles, gloves and sanitiser. The mobiles have running water 
for regular hand washing. The specimens will be collected in outdoor gazebos which allow adequate 
natural ventilation where possible. Where privacy is needed, the specimen collection will occur in the 
mobile clinic with only a single participant and adequate sanitisation and ventilation both before and 
after specimen collection. Staff providing the infection mitigation intervention will also be given 
appropriate counselling, training and equipment. Staff will be checked for symptoms daily and tested 
as needed. The mobile vehicle will be sanitised after each participant and decontaminated daily. 
 
Benefits: Participants will benefit from SARS-CoV-2 testing by knowing their status. Participants and 
others may benefit in the future from information learned from this study. Participants may 
appreciate the opportunity to collaboratively contribute to the field of SARS-CoV-2 research. 
Information learned in this study may lead to the development of interventions to prevent onward 
SARS-CoV-2 transmission in an HIV endemic community. Participants who test HIV/ TB positive will be 
referred to the nearest clinic for rapid ART and/ or TB treatment start.  
Data safety and monitoring: Information about study subjects will be kept confidential and all who 
choose to participate will complete an informed consent form. DTHF has standard operating 
procedures for data security and confidentiality procedures at collection, entry and storage levels, 
and will only release this information to study team members who have HREC/ IRB approval. All 
study data will remain securely stored by DTHF for the duration of the study. No participant 
identifiers will be included on any data forms; names and signatures will only be on the consent 

TRACE protocol version 2 06 October 2020 
 
12 
forms, which will be kept under lock and key by the DTHF study. At the end of the study, data will be 
kept for up to 5 years for electronic version, and up to 2 years for paper forms, including consent 
forms at the DTHF office. The TRACE study will not begin until all the relevant staff members have 
been trained on the study specific procedures (see Work Package E: Training and Capacity Building 
and Work Package D: Data Management). All staff who have contact with human subjects will have 
completed an acceptable Human Subjects Protection training. Enough is known about the 
procedures in this proposal to evaluate and determine anticipated risks and these will be explained 
to participants. In addition, the TRACE management team will routinely evaluate adverse events and 
assess for any social harms occurring during the study period. The site staff will intervene, at the 
participant’s request, to mitigate or resolve any social problems. Local phone numbers are provided 
on the consent form that participants can use to access resource persons for questions relating to 
social harms. The team will conduct HIV, TB, and SARS-CoV-2 risk reduction counselling to lower the 
chances of exposure for study participants.  
Trial registry. The TRACE study protocol team will register and post-trial information to the Pan 
African Clinical Trial registry, which is based in South Africa and can be found at: 
https://pactr.samrc.ac.za/  
Potential impact of the proposed research. The findings from this project have relevance to SARS- 
CoV-2 prevention and management in HIV and/ or TB co-infected patients. The findings will inform 
prevention methods to reduce SARS-CoV-19 infection acquisition and onward transmission in close 
crowded environments. Understanding the household and community transmission of SARS-CoV-2 
will contribute to policy for effective prevention measures. Research on scalable interventions is 
urgently required. The proposed study may influence large scale, community-based SARS-CoV-2 
testing and triage to circumvent COVID-19 patients overburdening hospital facilities. Understanding 
community viral transmission can facilitate decision making around prognosis and treatment.  
Additionally, COVID-19 treatment development is ongoing and mobile testing facilities would be ideal 
platforms for the targeted delivery of rapid-initiation treatment that does not require COVID-19 
patients to travel in public transport. DTHF is aware and committed to support the requirements of 
ensuring timely publications of results, that publications are placed in the public domain, and sharing 
of scientific results with scientists interested in SARS-CoV-2/ COVID-19 services that improve health 
outcomes. Materials generated under this project will be disseminated consistent with University 
policies regarding data sharing. Opportunities for secondary analyses will be available following 
completion of the project and publication of the main study findings. These findings will be available 
to the public through scientific meetings or peer-reviewed journals, as well as through a structured 
policy dissemination process.  
 
Management plan: timelines, milestones, and deliverables 
Activities 
Mo 1 
Mo 2 
Mo 3 
Mo 4 
Mo 5 
Mo 6 
Mo 7 
Mo 8 
Protocol development, Ethics Committee 
application, staff training (2 months) 
  
  
  
  
  
  
  
  
Aim 1 Accrual period (including first participant 
in and last participant in)  
  
  
  
  
  
  
  
  
Aim2: Randomised controlled trial intervention 
  
  
  
  
  
  
  
  
Aim 1: Household contact follow up 
  
  
  
  
  
  
  
  
End of data collection - last participant out  
  
  
  
  
  
  
  
  

TRACE protocol version 2 06 October 2020 
 
13 
Data lock 
 
 
 
 
 
 
 
 
Planned dissemination meetings and webinars  
 
 
 
 
 
 
 
 
Clinical study report: final report and primary 
manuscripts submitted for publication.  
  
  
  
  
  
  
  
  
 
 
 
 

TRACE protocol version 2 06 October 2020 
 
14 
References 
Bassett, I. V., Govindasamy, D., Erlwanger, A. S., Hyle, E. P., Kranzer, K., van Schaik, N., Noubary, F., 
Paltiel, A. D., Wood, R., Walensky, R. P., Losina, E., Bekker, L.-G., & Freedberg, K. A. (2014). 
Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-
Effectiveness. PLoS ONE, 9(1). https://doi.org/10.1371/journal.pone.0085197 
Black, S., Zulliger, R., Myer, L., Marcus, R., Jeneker, S., Taliep, R., Pienaar, D., Wood, R., & Bekker, L.-
G. (2013). Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot 
programme in Cape Town, South Africa. South African Medical Journal = Suid-Afrikaanse 
Tydskrif Vir Geneeskunde, 103(8), 557–562. 
COVID-19 South African coronavirus news and information portal. (n.d.). SA Corona Virus Online 
Portal. Retrieved April 17, 2020, from https://sacoronavirus.co.za/ 
Govindasamy, D., Kranzer, K., van Schaik, N., Noubary, F., Wood, R., Walensky, R. P., Freedberg, K. 
A., Bassett, I. V., & Bekker, L.-G. (2013). Linkage to HIV, TB and Non-Communicable Disease 
Care from a Mobile Testing Unit in Cape Town, South Africa. PLoS ONE, 8(11), e80017. 
https://doi.org/10.1371/journal.pone.0080017 
Joseph Davey, D., Bekker, L.-G., Coates, T. J., & Myer, L. (2020). Contracting HIV or Contracting SAR-
CoV-2 (COVID- 19) in Pregnancy? Balancing the Risks and Benefits. AIDS and Behavior, 1–3. 
https://doi.org/10.1007/s10461-020-02861-x 
Karim, S. S. A. (2020, April 13). SA’s COVID-19 epidemic: Trends & Next steps. SA Corona Virus Online 
Portal. https://sacoronavirus.co.za/2020/04/13/sas-covid-19-epidemic-trends-next-steps/ 
Kranzer, K., Lawn, S. D., Johnson, L. F., Bekker, L.-G., & Wood, R. (2013). Community Viral Load and 
CD4 Count Distribution Among People Living With HIV in a South African Township: 
Implications for Treatment as Prevention. JAIDS Journal of Acquired Immune Deficiency 
Syndromes, 63(4), 498–505. https://doi.org/10.1097/QAI.0b013e318293ae48 
Kranzer, K., Lawn, S. D., Meyer-Rath, G., Vassall, A., Raditlhalo, E., Govindasamy, D., van Schaik, N., 
Wood, R., & Bekker, L.-G. (2012). Feasibility, Yield, and Cost of Active Tuberculosis Case 

TRACE protocol version 2 06 October 2020 
 
15 
Finding Linked to a Mobile HIV Service in Cape Town, South Africa: A Cross-sectional Study. 
PLoS Med, 9(8), e1001281. https://doi.org/10.1371/journal.pmed.1001281 
Smith, P., Esch, A. van, Wallace, M., Wood, R., & Bekker, L. G. (2014). GeneXpert TB 8: A point-of-
care diagnostic pilot. South African Medical Journal, 104(8), 524. 
Smith, Philip, Tolla, T., Marcus, R., & Bekker, L.-G. (2019). Mobile sexual health services for 
adolescents: Investigating the acceptability of youth-directed mobile clinic services in Cape 
Town, South Africa. BMC Health Services Research, 19(1), 584. 
https://doi.org/10.1186/s12913-019-4423-4 
The Lancet,  null. (2020). Redefining vulnerability in the era of COVID-19. Lancet (London, England), 
395(10230), 1089. https://doi.org/10.1016/S0140-6736(20)30757-1 
 
 

VERSION 2 2020-10-06 
CLIENT SITE 
CODE:__________________ 
E.G. 
ABCD1234 or STICKER 
University of Cape Town - Department of Medicine 
Informed Consent Form – index patient 
 
Research Study: TRACE 
 
Invitation and Purpose: We are researchers from the Department of Medicine at the University of Cape Town. You are invited to take part 
in a research study where you will be asked questions about COVID-19 symptoms. We would like to understand SARS-CoV-2 transmission 
and the impact of improved information on preventing SARS-CoV-2 transmission. You may receive a standard message or an improved 
message about SARS-CoV-2 transmission prevention. Your participation will help us understand if people who receive enhanced messaging 
decreases SARS-CoV-2 transmission. 
Procedures: If you decide to take part in this study, we will ask you survey questions about your experience of symptoms, which will take 
15 minutes. As part of the usual clinic service, you will receive HIV and TB testing and counselling. If you test positive for TB or HIV, we will 
refer you for treatment at the nearest clinic. If you agree, we will follow up medical records to see if you access treatment at the facility. 
You will be reimbursed with a R150 voucher at this visit and at the last study visit (visit 5). Lastly, we will contact you six months after the 
study to test for COVID-19 antibodies. 
Risks, Discomforts & Inconveniences: There are no risks or discomforts over the standard survey, and HIV testing procedure. The fingerprick/ 
venepuncture blood draw may be painful. Additionally, it may be distressing to receive an HIV positive result. All information you give is 
confidential. We will not share your results with anyone.   
Benefits: This study will not benefit you directly. However, the knowledge we gain from it will be used to help develop improved messaging 
for SARS-CoV-2/ COVID-19 management.  
Alternatives (Other Options): You do not have to participate in this study—it is up to you. 
Privacy and Confidentiality: We will take strict precautions to safeguard your personal information throughout the study. Your information 
will be kept without your name or personal identifiers. Your information will be identified with a code on a password-protected computer. 
Study data will be kept on a password-protected, secure server in the Department of Medicine at the Desmond Tutu HIV Foundation. Only 
the researchers will be able to access your personal information. 
Questions: If you have questions, concerns, or complaints about the study, please contact Dr Philip Smith on 021 650 1895. If you have 
any questions about the rights you have while taking part in this study, call Prof. M Blockman, Chairperson for the University of Cape 
Town, Faculty of Health Sciences Human Research Ethics Committee, Old Main Building, Groote Schuur Hospital, Anzio Road, 
Observatory, Cape Town, 7925, South Africa, tel 021 406 6338; fax 021 406 6411) which is an independent committee established to 
help protect the rights of research participants. This is a group of scientific and non-scientific individuals who review research studies 
with the safety and welfare of research participants in mind and gave their positive opinion to this research study. 
Signatures: {Participant’s name}__________________________ has been informed of the nature and purpose of the procedures described 
above including any risks involved in its performance.  He or she has been given time to ask any questions and these questions have been 
answered to the best of the investigator's ability. A signed copy of this consent form will be made available to the participant. 
I have been informed about this research study and understand its purpose, possible benefits, risks, discomforts and that the researchers 
will follow up my medical records, including: 
- 
Fingerpick/ venepuncture blood draw (weekly) to test for SARS-CoV-2 antibodies 
- 
Nose and throat swabs (weekly) SARS-CoV-2 – to test for the virus 
- 
Access to medical records 
- 
Consent to samples and data to be stored and used in future research 
- 
Follow up visits (1 visit every week), additional visits if randomised to the StopCov arm 
I agree to take part in this research as a subject. I know that I am free to withdraw this consent and quit this project at any time, and 
that doing so will not cause me any penalty or loss of benefits that I would otherwise be entitled to enjoy.  
I consent (please check)   
 
 
 
I do not consent (please check)  
 
Participants name: _________________ 
Participants signature:  
_________________  
Date: _________________ 
 
 
Investigators name: ________________ 
Investigators signature:  
_________________ 
Date: _________________ 
 

VERSION 2 2020-10-06 
CLIENT SITE 
CODE:__________________ 
E.G. 
ABCD1234 or STICKER 
University of Cape Town - Department of Medicine 
Informed Consent Form – household contact 
 
Research Study: TRACE 
 
Invitation and Purpose: We are researchers from the Department of Medicine at the University of Cape Town. You are invited to take part 
in a research study where you will be asked questions about COVID-19 symptoms. We would like to understand SARS-CoV-2 transmission 
and the impact of improved information on preventing SARS-CoV-2 transmission. You may receive a standard message or an improved 
message about SARS-CoV-2 transmission prevention. Your participation will help us understand if people who receive enhanced messaging 
decreases SARS-CoV-2 transmission. 
Procedures: If you decide you to take part in this study, we will ask you survey questions about your experience of symptoms, which will 
take 15 minutes. As part of the usual clinic service, you will receive HIV, STI, blood pressure, blood glucose, and TB testing and counselling 
at baseline and SARS-CoV-2 testing at each visit. If you test positive for any of the tests, we will refer you for treatment at the nearest clinic. 
If you agree, we will follow up your medical records to see if you access treatment at the facility. You will be reimbursed with a R150 voucher 
at this visit and at the last study visit (visit 5). Lastly, we will contact you six months after the study to test for COVID-19 antibodies. 
Risks, Discomforts & Inconveniences: There are no risks or discomforts over the standard survey, nasopharangeal swabs, and HIV testing 
procedure. There is risk of discomfort and a mild nosebleed with nasopharyngeal swabs. The fingerprick/ venepuncture blood draw may 
be painful. Additionally, it may be distressing to receive a positive result for HIV/ COVID19/ TB and staff are trained to provide counselling. 
All information you give is confidential. We will not share your results with anyone.   
Benefits: This study will not benefit you directly. However, the knowledge we gain from it will be used to help develop improved messaging 
for SARS-CoV-2/ COVID-19 management.  
Alternatives (Other Options): You do not have to participate in this study—it is up to you. 
Privacy and Confidentiality: We will take strict precautions to safeguard your personal information throughout the study. Your information 
will be kept without your name or personal identifiers. Your information will be identified with a code on a password-protected computer. 
Study data will be kept on a password-protected, secure server in the Department of Medicine at the Desmond Tutu HIV Foundation. Only 
the researchers will be able to access your personal information. If you test positive for SARS-CoV-2, your result will be notified to the NICD.  
Questions: If you have questions, concerns, or complaints about the study, please contact Dr Philip Smith on 021 650 1895. If you have 
any questions about the rights you have while taking part in this study, call Prof. M Blockman, Chairperson for the University of Cape 
Town, Faculty of Health Sciences Human Research Ethics Committee, Old Main Building, Groote Schuur Hospital, Anzio Road, 
Observatory, Cape Town, 7925, South Africa, tel 021 406 6338; fax 021 406 6411) which is an independent committee established to 
help protect the rights of research participants. This is a group of scientific and non-scientific individuals who review research studies 
with the safety and welfare of research participants in mind and gave their positive opinion to this research study. 
Signatures: {Participant’s name}__________________________ has been informed of the nature and purpose of the procedures described 
above including any risks involved in its performance.  He or she has been given time to ask any questions and these questions have been 
answered to the best of the investigator's ability. A signed copy of this consent form will be made available to the participant. 
I have been informed about this research study and understand its purpose, possible benefits, risks, discomforts and that the researchers 
will follow up my medical records, including: 
- 
Fingerpick/ venepuncture blood draw (weekly) to test for SARS-CoV-2 antibodies 
- 
Nose and throat swabs (weekly) SARS-CoV-2 – to test for the virus 
- 
Access to medical records 
- 
Consent to samples and data to be stored and used in future research 
- 
Follow up visits (1 visit every week), additional visits if randomised to the StopCov arm 
I agree to take part in this research as a subject. I know that I am free to withdraw this consent and quit this project at any time, and 
that doing so will not cause me any penalty or loss of benefits that I would otherwise be entitled to enjoy.  
I consent (please check)   
 
 
 
I do not consent (please check)  
 
Participants name: _________________ 
Participants signature:  
_________________  
Date: _________________ 
 
 
Investigators name: ________________ 
Investigators signature:  
_________________ 
Date: _________________