Characterising Transmission of SARS-CoV-2 in a Peri-urban Population in Mozambique Using Population-based (Sero)Surveillance
Conditions: COVID-19
Sponsor: Institute of Tropical Medicine, Belgium

 
 
AfriCoVER population-based surveillance study amended protocol v3.1 14/04/2021 
p. 1 of 37 
 
 
ITM Clinical Trial  
Clinicaltrials.Gov. NCT04442165 
 
Characterising transmission of SARS-CoV-2 in 
a peri-urban population in Mozambique 
using population-based (sero) surveillance  
AfriCoVER 
 
Protocol  
Version 3.1, 14-Apr-2021 
 
 
 
 
 
 
Sponsor: 
Institute of Tropical Medicine 
Nationalestraat 155 
B-2000 Antwerpen - Belgium 
Coordinating 
Investigator: 
Dr Marc-Alain Widdowson 
 
 
 

 
 
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Version 3.1, dated 14-Apr-2020 
ClinicalTrials.Gov.: 
NCT04442165 
 
Study Title: 
Characterising transmission of SARS-CoV-2 in a peri-urban population 
in Mozambique using population-based (sero)surveillance  
Study Acronym 
AfriCoVER 
Version: 
v3.1 
Date: 
14/Apr/2021 
Previous version: 
V3.0, 09/Apr/2021 
Funder: 
EDCTP 
Sponsor: 
Institute of Tropical Medicine, Antwerp, Belgium 
 
Sponsor study team 
 
Institute of Tropical Medicine, Belgium 
Name 
Function 
Role 
Dr. Marc-Alain 
Widdowson 
Coordinating 
Investigator 
Leading the project, conceptual development of 
research questions and study design, revisions of the 
protocol and questionnaires 
Brecht Ingelbeen 
Investigator 
conceptual development of research questions and 
study design, written draft of the protocol and 
questionnaire, 
day-to-day 
study 
development 
(surveillance), data analysis (epidemiology) 
Marianne van der 
Sande 
Investigator 
conceptual development of research questions and 
study design, revisions of the protocol and 
questionnaires, epidemiology and public health 
expertise 
Anja De Weggheleire 
Investigator 
conceptual development of research questions and 
study design, written draft of the protocol and 
questionnaire, 
day-to-day 
study 
development 
(clinical), data analysis (clinical; predictors) 
Natacha Herssens 
Clinical 
Research 
Scientist 
Development of GCP compliant research protocol, ICF 
and other essential documents, clinical project 
management, (co-)monitoring, drafting of monitoring 
plan, regulatory follow-up and reporting. 
Jozefien Buyze 
Study 
Statistician 
Statistical input in study protocol, statistical data 
analysis for intermediate/final reporting 

 
 
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Version 3.1, dated 14-Apr-2020 
Harry Van Loen 
Data Manager 
Set-up and follow-up of study databases, advice on 
Good Data Management practices, data review, 
drafting of Data Management Plan 
Yven Van Herrewege 
Head of the CTU 
Development of GCP compliant research protocol, 
ICF and other essential documents, clinical project 
management, follow-up and coordination of study 
management performed by the Clinical Trials Unit 
Joachim Mariën 
Investigator 
conceptual development and validation of serology, 
revisions of the protocol and questionnaires, virology 
and 
modelling 
expertise, 
day-to-day 
study 
development (virology; serology), data analysis 
(serology; PCR) 
Kevin Arien 
Investigator 
conceptual development and validation of serology, 
virology expertise 
 
Site study team  
 
 Instituto Nacional de Saude (INS), Mozambique 
Name 
Function 
Role 
Dr. Ivalda Macicame  
Principal 
Investigator  
Revisions of the protocol and questionnaires, leading 
the project ensuring that the implementation of the 
study follows the plan described in the protocol and 
to high standards of scientific rigor, ensure that data 
analysis conforms to high standards of scientific rigor 
and ensure the write-up of the results for 
appropriate dissemination. 
Dr. Edna Viegas  
Investigator  
Contribute to the design and implementation of the 
project following high standards of scientific rigor. 
Participate in data analysis and report writing and 
dissemination. 
Dr. Sonia Enosse  
Investigator  
Contribute to the design and implementation of the 
project following high standards of scientific rigor. 
Participate in data analysis and report writing and 
dissemination. 
Paulino Da Costa  
Data Manager  
Set-up and follow-up of study databases, follow the 
Good Data Management practices, data review, 
revising Data Management Plan, ensure data 
cleaning and data analysis processes according to 
high standards of scientific rigor. 

 
 
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Version 3.1, dated 14-Apr-2020 
Ferao Mandlate  
Study 
Coordinator  
Implement the study in an ethical manner, including 
protecting the rights, welfare and privacy of human 
subjects who are participants in study. Participate in 
data analysis and report writing and dissemination. 
Dimpall Asmucrai  
Study 
Coordinator  
Ensure the implementation of the study in an ethical 
manner, including protecting the rights, welfare and 
privacy of human subjects who are participants in 
study. Ensure fair and equitable recruitment and 
retention practices while ensuring the maximum 
methodological rigor of the study.  
Dr. Nalia Ismael   
Laboratory 
Coordinator  
Implement the study according to the Good Clinical    
and Laboratory     l Practices, ensure sample 
collection, analyses and storage. 
 
 
External partners 
Institut de Recherche pour le Développement (IRD), France 
Name 
Function 
Role 
Dr Martine Peeters 
Investigator 
Developed jointly the SARS-CoV-2 serology Luminex 
set-up; analyses of serology results 
 
 
 
Utrecht University Medical Centre, Netherlands 
Name 
Function 
Role 
Dr. Mirjam Kretzschmar 
Investigator 
conceptual development of transmission models, 
data analysis (transmission parameters; epidemic 
modelling including population structure and social 
mixing patterns) 
 

 
 
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Version 3.1, dated 14-Apr-2020 
STATEMENT OF COMPLIANCE  
 
By signing this protocol, the Investigator(s) acknowledge(s) and agree(s): 
 
This protocol contains the necessary information for conducting this clinical study. The Principal 
Investigator will conduct this study as detailed herein and will make every reasonable effort to 
complete the study within the time designated. The Principal Investigator commits to carry out the 
study in compliance with the protocol, amendments, applicable procedures and other study-related 
documents provided by the Sponsor, and in compliance with the Declaration of Helsinki, Good Clinical 
[Laboratory] Practice (GC[L]P), the EU General Data Protection Regulation 2016/679 (GDPR), the 
ESF/ALLEA Code of Conduct for Research Integrity, and applicable regulatory requirements.  
The protocol and all relevant study information, which is provided by the Sponsor, will be made 
available to the physicians, nurses and other personnel who participate in conducting this study. The 
Investigator will use this material for their training so that they are fully informed regarding the drugs 
and the conduct of the study. 
The Sponsor of this study – the Institute of Tropical Medicine in Antwerp, Belgium (ITM) – can at any 
time have access to the source documents from which Case Report Form information may have been 
generated and will be permitted to perform trial-related monitoring and audits. All study material will 
be maintained according to regulatory requirements and until the Sponsor advises that retention is no 
longer necessary. 
 
COORDINATING INVESTIGATOR ITM AND DIRECTOR OF THE ITM: 
 
 
Title, Name: Dr. Marc-Alain Widdowson 
Date: 
 
 
Signed: 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR INS: 
 
 
Title, Name: Dr. Ivalda Macicame 
Date: 
 
 
Signed: 
 
 
 
 
 
 
 
Signing this document, I commit to carry out the trial in accordance with the protocol, Good Clinical 
Practice and applicable ethical and regulatory requirements. I also acknowledge the paragraph 
relevant to study confidentiality and authorize the Institute of Tropical Medicine, Antwerp, Belgium to 
record my data on a computerized system containing all the data pertinent to the study. 
 

 
 
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Table of Contents 
STATEMENT OF COMPLIANCE 
5 
Table of Contents 
6 
Synopsis 
8 
1. Introduction 
11 
1.1 Background 
11 
1.2 Rationale 
13 
2. Study Objectives 
13 
3. Study Design 
15 
4. Participants, Population & Selection 
16 
4.1 Setting 
16 
4.2 Selection and recruitment 
16 
4.3 Inclusion and exclusion criteria 
17 
4.4 Sample size 
18 
4.5 Withdrawal and termination of the study 
18 
Reasons for Withdrawal 
18 
Termination of Study 
18 
5. Study Procedures 
18 
5.1 Study/visit schedule 
18 
5.2 Obtaining informed consent 
24 
5.3 Specific procedures and activities 
24 
5.4. Laboratory procedures and analyses 
25 
5.4.1 Data Collection 
25 
5.4.2 Laboratory testing 
26 
5.4.3 Long-term storage and destruction of specimens 
26 
6. Safety Assessment 
27 
7. Statistical Analyses 
27 
7.1 Methods 
27 
7.2 Sample size and power 
28 
8. Monitoring And Quality Assurance 
29 
9. Data Management 
30 
10. Ethical Issues 
31 
10.1 Ethical and regulatory review 
31 
10.2 Patient and/or community involvement 
32 
10.3 Protocol amendments 
32 
10.4 Informed consent 
32 

 
 
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10.5 Confidentiality 
32 
10.6 Risks and benefits 
32 
10.7 Compensation for participation 
33 
10.8 Insurance 
33 
11. Dissemination of results, intellectual property 
33 
12. Archiving 
33 
13. References 
34 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Synopsis 
design 
Prospective cohort study (population-based surveillance and serial sero-
survey) 
study site & 
population  
 
Polana Caniço, peri-urban Maputo, Mozambique: a health- and demographic 
surveillance site (HDSS) covering a population of approximately 15,393, in the 
catchment area of the Polana Caniço General Hospital (PCGH). 
All      individuals residing in the 2108 HDSS households for at least 3 months 
(infants, children, adults, elderly) are included in bi-weekly surveillance 
rounds, regardless of age. 
An age-stratified random sample of that population (800 per age stratum) will 
be selected for the repeated sero- and social mixing survey. 
No exclusion criteria apply for participants able and willing to provide consent 
for participation in the study. 
duration 
December      2020-December      2021 (12 months) 
objectives and 
endpoints 
Primary objectives 
● Estimate the attack rate, serial interval, and reproduction number of 
SARS-CoV-2 infection in peri-urban Maputo. 
● Estimate the proportion of infections that are asymptomatic, and tease 
out the role these play in transmission. 
● Estimate the incidence rate of SARS-CoV-2 infection, COVID-19 disease 
(symptomatic infection), rate of severe COVID-19 disease, hospitalization 
for medical care and mortality, over a 12 month period in peri-urban 
Maputo 
● Identify risk factors for SARS-CoV-2 infection, for asymptomatic or clinical 
presentation, and for COVID-19-related death, which could include HIV 
status, nutritional status, blood group, underlying co-morbidities, 
household factors, pre-existing levels of anti-alphacoronavirus antibodies 
(CoV 229E, NL63) or anti-betacoronavirus antibodies (CoV OC43 and 
HKU1), and availability and adoption of measures aimed to reduce 
transmission. 
● Create social contact matrices that can be used to parametrize dynamic 
transmission models. 
● Estimate the household secondary infection rate 
Secondary objectives  
● Measure antibody titers over time and analyze the correlation between 
anti-coronavirus (endemic coronavirus or SARS-CoV-2) antibody titers 
and reinfection  
● Assess the individual uptake of measures aimed to reduce transmission 
(quarantine, physical distancing, hygiene, future vaccination) and assess 
barriers to uptake (absence soap/water, income loss, ability to self-
isolate, availability of masks, distrust, lack of understanding of the 
communication) 
● Derive and validate a clinical prediction rule for SARS-CoV-2 infection. 
● Geographical mapping of clusters, spread and identification of 
transmission hotspots 
● Sequence selected strains of SARS-CoV-2 

 
 
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● Understand non-SARS-CoV-2 etiologies of respiratory disease in the study 
population 
● Identify factors associated with household SARS-CoV-2 infection and with 
household infection resulting in Covid19 disease, including viral load and 
symptoms of household index case, household and individual 
characteristics and behaviour to prevent infection. 
● Estimate total (of vaccinees) and overall (including indirect protection of 
non-vaccinated) vaccine effectiveness among the study population, once 
one or more vaccines are introduced 
screening, 
recruitment & 
randomization 
 
All household members will be screened for symptoms during biweekly 
household visits. 
Individuals reporting any respiratory sign, or loss of smell or taste, with or 
without fever (either presenting at the COVID-19 care facility or identified 
through the biweekly household visits) will provide specimens that will 
undergo PCR testing. Symptoms, clinical outcome, vaccination status against 
COVID-19,  and potential exposure will be recorded.  
Three age-stratified subsets of the population (0-17 years; 18-50 years; >50 
years) will be recruited for a sero-survey at 0, 3, 6 and 12 months and a social 
mixing survey, repeated 4 times during the outbreak.  
Household contacts of household      cases testing positive for SARS-CoV-2 will 
be screened for virus and antibodies and for illness 1 day  after confirmation 
of the household index case and 28 days after index case symptom onset 
follow-up 
The clinical outcome of individuals with a confirmed SARS-CoV-2 infection 
(mild cases at home; hospitalised cases in the hospital or after discharge) will 
be recorded during the weekly visits and at 28 and 56 days post symptom 
onset. 
analytical 
methods 
 
* Description of transmission dynamics: rolling incidence rate of COVID-19 
disease throughout one year, adjusting for the sensitivity of SARS-CoV-2 RT-
PCR on nasal swabs by delay between symptom onset and testing; SARS-CoV-
2 infection incidence rate, SARS-CoV-2 annual attack rate, secondary infection 
rate, and infection fatality risk by age group, by adjusting for the proportion 
asymptomatics. 
* Risk factor analysis for SARS-CoV-2 infection and COVID-19 disease, and for 
severity (hospitalisation), overall and following household transmission in 
particular.      
* Model basic and effective reproductive numbers (R0 and Re), generation 
time distribution, ratio of transmissibility between symptomatic and 
asymptomatic cases, duration of the infectious period, household secondary 
infection rate. 
* Explore the correlation between R0 and Re, and the uptake of measures to 
reduce exposure/ transmission. 
* Case-cohort, case- control or similar      analysis to estimate vaccine 
effectiveness against confirmed COVID-19 in the population-based 
surveillance  and cohort analysis to estimate vaccine effectiveness against 
SARS-CoV-2 seroconversion (among sero-survey participants) 
safety 
The study does not involve an investigational product or intervention 

 
 
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statistical 
methods 
Descriptive (probabilistic) and inferential statistics 
Negative binomial regression for risk factor analysis 
Development of a compartmental mathematical model to describe the spread 
of SARS-CoV-2 on the population level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1. Introduction 
1.1 Background 
In sub-Saharan Africa, official Covid-19 case numbers are an underestimate because of limited 
surveillance and testing capacity, whereby testing, when it happens, is not systematic and focuses on 
high probability suspects, either severe, imported cases or their contacts. This provides a very limited 
and biased assessment of transmission and burden in the population and hence public health impact, 
also hampering implementation of targeted interventions (Ahmed A, 2020). Furthermore, co-
morbidities (such as HIV or TB) and malnutrition are more common in sub-Saharan Africa and are likely 
to affect disease dynamics and outcomes. Despite concerns of a possible pending catastrophic impact 
of Covid-19 on Africa, there is also still a pervasive hope that perhaps younger populations in warmer, 
humid tropical Africa, living mainly outdoors, might be less affected, which has been postulated as an 
explanation as to why months after the initial reported clusters of cases, so far still no or limited 
widespread transmission has been reported in many sub-Saharan African countries (Casanova et al 
2020; Notari A 2020). 
Nevertheless, experience from other enveloped respiratory RNA viruses such as influenza virus shows 
that respiratory transmission can occur throughout the year in tropical Africa with occasional usually 
erratic peaks (Gessner et al 2011). In Maputo, Mozambique, slightly south of the Tropic of Capricorn, 
influenza transmission is more seasonal once again, though in most years, two peaks can be observed 
(Nguenha et al 2018). Despite unclear seasonality in much of Africa, age-stratified estimates of 
mortality rate of the 2009 pandemic influenza were as high if not higher as elsewhere globally (Dawood 
et al 2011). Similarly, archival studies have estimated a huge societal impact of the 1918 influenza 
pandemic on the health of African populations (Andayi F 2019). Moreover, epidemiologic studies on 
endemic human coronaviruses in Kenya have shown substantial year-round circulation (Munywoki et 
al 2018). This suggests that SARS-CoV-2 could have a high impact in Africa, although SARS-CoV-2 is 
different in key ways to influenza virus and to other coronaviruses. Data from higher income country 
contexts is poorly applicable to African settings. Some lower resourced southern hemisphere settings 
have already seen large increases in cases in early April, such as Ecuador, but in the Southern 
temperate region, we only started to observe high intensity transmission from the end of May 
onwards. 
Several demographic, cultural and environmental factors may affect the transmission of SARS-CoV-2 
in communities and within households in Africa. These include population density, population age 
structure, poor-quality housing (including exposure to indoor smoke), climate, different intensity and 
pattern of contact (e.g. between the ages), different distribution of co-morbidities, different exposures 
to vaccines and infections, but also the ability to adhere to interventions aimed at interrupting 
transmission, such as physical distancing (including quarantine and isolation), use of masks and of 
water/soap for hand-washing. In addition, host factors may affect transmission. For instance, HIV-
infected persons with low CD4 counts may shed longer as is the case with influenza (von Mollendorf 
et al 2018), and there may be differences in ACE2 receptors (the binding receptor for SARS-CoV-2) 
densities across populations (Cao et al 2020) or other genetic factors (Ellinghaus et al preprint 2020). 
Host factors and co-morbidities more prevalent or specific to Africa could also affect to what extent 
an individual presents with asymptomatic or clinical illness, which may also affect transmissibility and 
infectiousness (Cohen et al 2015). 
Knowledge about transmission parameters will allow for the design of targeted, specific control 
measures to interrupt spread of SARS-CoV-2 through behaviour modification, social distancing and use 
of personal protective measures. In addition, intensity of transmission and prevalence of risk groups 
for infection and disease translates to population level burden of disease and the incidence rate of that 

 
 
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burden in communities. Understanding the number of events of relative severity, size of risk groups 
for severe disease and the current and projected rate of change of disease is critical to plan for current 
and future capacity for health care. 
The transmission potential of SARS-CoV-2 is determined in any particular context by the basic 
reproduction number (R0) when there is no protective immunity in the population. R0 will vary with 
time and context, such as population density, number of contacts and environmental conditions, and 
is dependent on the period of infectiousness, viral load, and the serial interval. Early data estimated 
the R0 for SARS-CoV-2 between 2.0 and 3.4 (Ferretti 2020; Li 2020), higher than that for seasonal 
influenza (Biggerstaff et al 2014). This is likely in part because of key divergent features from influenza 
such as pre and asymptomatic SARS-CoV-2 transmission (Ferretti 2020; Kimball 2020; He 2020), near 
absence of severe disease in young children (Wu et al 2020), and a longer estimated serial interval of 
3.96 days (Du Z Emerging Infect Dis 2020). The SARS-CoV-2 average R0 is also higher than estimated 
for previous novel viruses, such as influenza H1N1 in the 1918 (R0=1.8) and 2009 (R0=1.6) pandemics 
(Biggerstaff et al 2014) and SARS-CoV-1 (Ro=1-5) (Liu et al 2020). 
To date, evidence suggests that in temperate climates between 20 and 50% of infections could be 
asymptomatic (Mizumoto et al 2020; Bi et al 2020; Kimball et al 2020). Pre-symptomatic shedding is 
common, with comparable viral load in asymptomatic, pre-symptomatic and clinical cases (Kimball et 
al 2020). This complicates timely targeted application of interventions since people may not know they 
are infected and will not behave as if they were. The frequency of asymptomatic infection in sub-
Saharan African settings is as of yet unclear, and also may vary by setting. Understanding the 
proportion of asymptomatic infections and their contribution to the reproduction number is 
important. 
Immune factors may affect community transmission. Cross reactivity with existing endemic 
coronaviruses, (CoVs 229E, NL63, HKU1,OC43), two of which are related beta-coronaviruses 
(HKU1,OC43), could result in protection from infection and/or disease. Many models assume a person 
can no longer be infected once recovered (Fig 1). However, immunity to coronaviruses is unclear. 
Antibody titer to SARS-CoV-1 infection waned over a period of several months in recovered patients 
(Liu et al 2006), but unclear if this means waning protection. Additionally, endemic human 
coronaviruses existing neutralising antibodies may not sufficiently protect against reinfection (Callow 
et al 1985), while some reports of reinfection with SARS-CoV-2 have been reported, though none fully 
documented.  
 
Fig 1. Susceptible-Infected-Recovered Model 

 
 
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In the first few weeks of 2021, vaccines under WHO9s Emergency Use Listing have begun to be used in 
several countries and plans exist to roll out one or more vaccine types in Mozambique. Vaccine 
effectiveness studies are key to better understand how these vaccines perform in different settings, 
especially since the emergence of SARS-CoV-2 variants circulating in Mozambique against which 
several current vaccines may not protect. 
1.2 Rationale 
It is recognized that SARS-CoV-2 will transmit differently in African settings, and that risk factors for 
infection and mild or severe disease may be different to higher income settings. Understanding 
transmission and identifying at-risk populations is urgent for African countries, who need to target 
scarce resources as effectively as possible to interrupt transmission and protect vulnerable risk groups.  
Box. The epidemiological situation in Mozambique on 29/09/2020. 
The SARS-Cov-2 outbreak is still accelerating in Mozambique, as indicated by both the trend in the 
number of reported cases and the positivity rate. 7983 SARS-CoV-2 infected cases were reported, 
including 295 imported cases, and 58 deaths. Since the start of the outbreak, 134,011 suspected 
cases have been tested. In September 2020, consistently more than half of new cases were reported 
in Maputo City. In Maputo City a total of 3,427 cases and 38 deaths have been reported. The average 
number of new daily cases reported went from 47 in the first week of September, to 97 in the week 
up to 26/09. A sero-prevalence survey undertaken in the last two weeks of August 2020, found an 
overall seroprevalence of 3.8% in Mauto city, with only slight variation between age groups (range 
3.0% in 35-59 year olds to 4.5% in ≥60 year olds). Nevertheless, the latter age group accounts for the 
majority of hospitalisations. Of all cases reported in Mozambique, 56% were asymptomatic, 37% 
have a mild symptomatology, 6% moderate symptomatology and 1% a severe symptomatology. 42% 
of the infected individuals are female. 
We aim to determine robust transmission parameters of SARS-CoV-2 to understand infectiousness and 
epidemic spread. We will investigate risk factors for infection and severe disease, assess impact of 
vaccines / behavioral interventions on transmissibility and infectiousness, and explore the role of 
certain age groups, societal activities, pre- and asymptomatic infections in transmission in a peri-urban 
area of Maputo, Mozambique. By building on an existing health and demographic surveillance system 
(HDSS) it will be highly feasible to expand the existing population-based surveillance with biweekly 
home visits, viral RNA and serological testing. For serological testing, a newly validated SARS-CoV-2 
antibody assay will be added to the capacity at INS. This will provide high quality, timely, unbiased 
epidemiological data and indicators on the natural history and key SARS-CoV-2 transmission 
parameters, which can be rapidly collected and analysed, informing the country9s response, as well as 
that of other African countries.  
Since the number of cases started to accelerate in September 2020, we aim to have a first analysis 
point at 3 months after the implementation of the project in the HDSS, to estimate the progression of 
the pandemic in the community and help plan for effective and feasible control measures. 
2. Study Objectives 
Primary objectives 
● Estimate the attack rate, infection fatality, serial interval, and reproduction number of SARS-
CoV-2 infection in peri-urban Maputo. 
● Estimate the proportion of infections that are asymptomatic, and tease out the role these play 
in transmission. 

 
 
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● Estimate the incidence rate of SARS-CoV-2 infection, COVID-19 disease (symptomatic 
infection), rate of severe COVID-19 disease, hospitalization for medical care and mortality, 
over a 12 month period in peri-urban Maputo. 
● Identify risk factors for SARS-CoV-2 infection and for severe COVID-19 disease, which could 
include reported HIV status, nutritional status, blood group, underlying co-morbidities, 
household factors, pre-existing levels of anti-alphacoronavirus antibodies (CoV 229E, NL63) or 
anti-betacoronavirus antibodies (CoV OC43 and HKU1), and availability and adoption of 
measures aimed to reduced transmission. 
● Create social contact matrices that can be used to parametrize dynamic transmission models. 
● Estimate the household secondary infection rate 
Secondary objectives  
● Measure antibody titers over time and analyze the correlation between anti-coronavirus 
(endemic coronavirus or SARS-CoV-2) antibody titers and reinfection  
● Assess the individual uptake of measures aimed to reduce transmission and assess barriers to 
uptake (absence soap/water, income loss, ability to self-isolate, availability of masks, distrust, 
lack of understanding of the communication) 
● Derive and validate a clinical prediction rule for SARS-CoV2 infection 
● Geographical mapping of clusters, spread and identification of transmission hotspots. 
● Sequence selected strains of SARS-CoV-2 
● Understand non-SARS-CoV-2 etiologies of respiratory disease in the study population. 
● Identify factors associated with household SARS-CoV-2 infection and with household infection 
resulting in Covid19 disease, including viral load and symptoms of household index case, 
household and individual characteristics and behaviour to prevent infection. 
● Estimate total brand-specific vaccine effectiveness (among vaccinees) against PCR confirmed 
SARS-CoV-2 clinical infection. 
● Estimate total brand-specific vaccine effectiveness (among vaccinees) against SARS-CoV-2 
seroconversion 
● Estimate overall and brand-specific vaccine effectiveness (total among vaccinees and indirect 
among non-vaccinated) against PCR confirmed SARS-CoV-2 
 
Table 1. Study activities and outcome measures. Primary outcome measures in bold. 
Planned activities 
Sampling strategy and sample size 
Outcome measures 
Active syndromic population 
surveillance (biweekly) with 
PCR testing of symptomatic 
individuals – 12 months 
15393 individuals (2108 
households) 
Possible cases reporting any 
respiratory sign or loss of smell or 
taste, with or without fever, 
selected for PCR testing.  
Initially, before widespread 
community transmission, pooled 
testing of possible cases; when >50 
confirmed cases per week, switch 
to PCR testing of 1 in 10 possible 
cases (systematic selection - every 
10th possible case) 
● COVID-19 disease incidence rate 
(symptomatic infections per 
person-month) 
● COVID-19 related hospitalisation 
rate 
● Case (disease) fatality risk (%) 
● Risk factors for severe 
outcome/hospitalization  
● Basic reproduction number 
● Effective reproduction number 
● Serial interval 
● Proportion uptake of measures to 
prevent infection; barrier uptake  
● Effectiveness of interventions 

 
 
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● COVID-19 incidence density maps 
● COVID-19 likelihood ratios of 
clinical signs 
● Brand-     specific vaccine e     
ffectiveness against confirmed 
COVID-19 (disease) 
Age-stratified sero-survey at 0, 
3, 6, 12 months 
2400 individuals/dried blood spot 
samples per round (800 per age 
group <18yo, 18-50 yo, >50yo) 
An age stratified sample of 
individuals will be selected (simple 
random sample in each age group) 
● SARS-CoV-2 infection annual 
attack rate (%) 
● Infection fatality risk 
● Proportion asymptomatic 
infections, by age group 
● Risk factors for infection  
● Association between antibody 
titers and reinfection 
● Brand-specific total vaccine 
effectiveness against SARS-CoV-2 
seroconversion 
● Overall vaccine effectiveness 
against SARS-CoV-2 seroconversion 
Repeated social mixing survey  
the same 2400 individuals selected 
for the sero-survey (800 per age 
group <18yo, 18-50 yo, >50yo) 
● correlation between number of 
contacts, intensity of contacts and 
attack rate 
● correlation between uptake of 
control measures and attack rate 
● social contact matrices to be used 
to parametrize dynamic 
transmission models 
Household contact 
investigation at 1 day after 
confirmation of the household 
index case and 28 days after 
index case symptom onset 
First 100 households with ≥1 
confirmed case; median household 
size 7.3 => 100*6= 600 household 
contacts  
● Household secondary infection rate 
● Risk factors for household infection 
● Risk factors for household infection 
resulting in Covid19 disease 
● Total vaccine effectiveness against 
COVID-19 
3. Study Design 
Prospective cohort study (observational). We will use the established HDSS to set up population-based 
COVID-19 surveillance in a household cohort. From any individual in this population reporting any 
respiratory sign (symptom or lowered peripheral oxygen saturation) or loss of smell or taste, with or 
without fever, we will collect a respiratory specimen and test these for SARS-CoV-2 virus by PCR, during 
12 months. These cases will be identified through bi-weekly household visits, through an alert system 
involving community leaders and HDSS interviewers, or when presenting with symptoms at healthcare 
centres or at the referral hospital. Identified healthcare facilities will then alert the study team if a 
possible case from the HDSS population is consulted or admitted, if the patient agrees. Demographic, 
epidemiological and clinical data (comorbidities, medication, obesity, HIV, TB, smoking) of possible 
cases and of the source population will be recorded at baseline; recent illness, potential risk exposure 
of each household member (including duration and type) to SARS-CoV-2 positive individuals, uptake 
of measures to reduce exposure/transmission, and barriers to the uptake of such measures, will be 

 
 
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recorded/updated during every household visit. COVID-19      vaccination status           will be recorded 
from      possible cases and compared to that of a subset of the population, in a case-cohort design to 
determine vaccine effectiveness against symptomatic COVID-19          . 
An age-stratified serial sero-survey will be conducted at baseline in a subset of the population in the 
population-based COVID-19 surveillance, and at 3, 6 and 12 months, after confirmation of community 
transmission. Recording vaccination status of all sero-survey participants, we will determine vaccine 
effectiveness against SARS-CoV-2 seroconversion in a cohort design. 
Household transmission will be specifically investigated, by investigating contact history, vaccination 
status, and the presence of SARS-CoV-2 virus and serology among household members twice during 
the month after the symptom onset of a household index case.  
4. Participants, Population & Selection 
4.1 Setting 
Polana Caniço, peri-urban Maputo, Mozambique: a health- and demographic surveillance system 
(HDSS) covering a population of 15,393, in the catchment area of the Polana Caniço General Hospital 
(PCGH), one out of two COVID-19 referral facilities in Maputo.  
The population in peri-urban Polana Caniço is relatively representative of the increasingly urban 
population in Southern Africa, having young and mobile inhabitants. Moreover, the population suffers 
increasingly from non-communicable diseases, and prevalence of HIV and active tuberculosis is 
presumed to be important. Research gaps on COVID-19 transmission dynamics include whether the 
reproduction number could be different in such different (eg. younger) population. Also, the potential 
association between (uncontrolled) HIV infection or (active) tuberculosis and COVID-19 infection and 
severe disease, needs to be elucidated.  
The Polana Caniço-HDSS has been established since 2017. In total, as of time of writing, 2108 
households (defined as residents of the same building, sharing a cooking area) have been enrolled in 
the HDSS. All members residing in the household for at least 3 months (infants, children, adults, 
elderly) are enrolled in the HDSS. Surveillance rounds are currently carried out six-monthly. 
Demographic and health indicators collected in each surveillance round include but are not limited to: 
fertility/birth rate, mortality/cause of death, migration, disease cases, trauma and violence, 
socioeconomic status, water and sanitation facilities, risk factors for the acquisition of chronic diseases, 
women's health and family planning, immunization, risk behaviours and cultural practices related to 
the transmission of STI (including HIV and syphilis). Testing for HIV and syphilis is planned to be added 
as part of the surveillance rounds, from October 2020 onwards. Data on births, deaths, internal and 
external migration, pregnancies and their outcomes, and any other relevant events from a 
demographic perspective, are continuously reported by community key informants and confirmed 
through home visits. 
4.2 Selection and recruitment 
All households in the HDSS (2108 during the last round in 2019) consenting to participate in the study 
will be visited biweekly by a trained HDSS interviewer, following the same procedures as in routine 
HDSS rounds, specified in the HDSS protocol (Instituto Nacional de Saude, 2016). We assume the same 
number of households will consent to participate as in other HDSS rounds. Based on previous 
experience with the HDSS, we expect the HDSS interviewer to visit 6 households per working day on 
average.  

 
 
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Household heads, or an adult delegated by the household head, will be asked about COVID-19 
consistent symptoms among any consented household member, using a structured questionnaire. If a 
household member is identified by the household head as reporting any respiratory sign (symptom or 
lowered peripheral oxygen saturation) or loss of smell or taste, with or without fever, in the last week, 
i.e. a possible COVID-19 case, this household member will be asked to consent for participating, to 
respond to a structured questionnaire and to collect a nasal swab sample for SARS-CoV-2 testing. 
Specimens will be tested for SARS-CoV-2, using RT-PCR (at INS in Marracuene). Possible COVID-19 cases 
in the HDSS households will be detected through four entry points:  
○ 
Biweekly HH visits  
○ 
Phone call by patient (when symptoms occur) 
○ 
Phone call by study team (as currently done in HDSS) 
○ 
HDSS household members presenting as COVID-19 suspected case in healthcare 
facility 
If meeting the COVID-19 admission criteria as per national guidance, the possible COVID-19 case will 
be referred to the Polana Caniço General Hospital (PCGH), the closest healthcare facility and COVID-
19 patient management centre.  
An age-stratified random sample of that population will be selected for the repeated sero- and social 
mixing survey. By age stratum (0-17 years; 18-50 years; >50 years) we randomly select 800 individuals 
(simple random sample per age stratum; 2400 in total) from the Polana Caniço HDSS population 
(regardless of infection or disease status or history), from whom during home visits dried blood spots 
will repeatedly be collected at 0, 3, 6 and 12 months, vaccination status against COVID-19 will be 
recorded, and who will be asked to respond to a social mixing questionnaire. A HDSS sampling frame 
of all individual participants in the HDSS with socio-demographic data and unique identifiers, is 
available, and will be used to select a simple random sample of individuals by age group. 
When a member of a household with no prior widespread transmission (see exclusion criteria) tests 
SARS-CoV-2 positive, we will revisit the household twice for a household transmission investigation: 
as soon as possible after the result of the household index case (baseline), and once again one month 
after symptom onset of the household index case. An initial contact report form will be filled in as 
soon as possible, ideally within 24 hours, after laboratory confirmation of the primary case in the 
household. Respiratory and dried blood spot samples will be collected of everyone considered 
resident (as defined by the HDSS) in the household and who has been in contact with the SARS-CoV-
2 positive individual, regardless of age and presence or absence of symptoms. Respiratory samples 
will be analysed by RT-PCR for SARS-CoV-2 to assess presence of virus and viral load. The dried blood 
spots for serology on the Luminex assay. Data will be collected on household exposures of contacts 
and vaccine receipt. Symptomatic household contacts will be tested whenever symptoms appear, as 
part of the population-based surveillance. This is planned for upto 100 household index cases.  
4.3 Inclusion and exclusion criteria 
In order to be eligible, study participants must meet the following criteria: 
» Any individual enrolled in the Polana Caniço-HDSS: all members residing in the household for 
at least 3 months (infants, children, adults, elderly), regardless of age, underlying conditions, 
medical history, infection or disease status or history; 
» Able and willing to provide written informed consent: by the household head for the 
surveillance; by each selected participant for the sero-survey and household investigations. 
» For household investigations, over 50% of the eligible household members and index case 
should have provided consent for anyone in     the household to enrol. 

 
 
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Excluded from the household investigations: members of households in which more           than 3 
household members (including the index case) are known to have tested positive for SARS-CoV-2 in 
the past 7 days. 
 
4.4 Sample size 
See table 1, above, and justification for the sample size calculation in section 7.4 Sample size and 
power. 
 
4.5 Withdrawal and termination of the study 
Reasons for Withdrawal 
Participants may be withdrawn from the study if the participant or legally acceptable representative 
withdraws the consent. For participants who consented to participate, but who moved out of the study 
area during the study period, the months when residing in the study area will still be considered.  
 
Handling of Withdrawals 
When the investigator has no news of the participant, he/she must make every effort to contact 
him/her, to establish the reason for the discontinuation. If all these attempts to contact the participant 
fail, the investigator can then declare the participant <lost to follow-up=. The investigator should 
document all these attempts in the corresponding medical file. 
Termination of Study  
If the study is prematurely terminated or suspended, the Sponsor will promptly inform the 
investigators/institutions, and the regulatory authority(ies) of the termination or suspension and the 
reason(s) for the termination or suspension. The EC9s will also be informed promptly and provided the 
reason(s) for the termination or suspension by the Sponsor or by the investigator/institution, as 
specified by the applicable regulatory requirement(s). 
5. Study Procedures 
5.1 Study/visit schedule 
Table 2. Schedule of assessments for population-based surveillance. One row corresponds to two 
weeks. 
we
ek 
month 
Informed 
consent (1) 
Sero-
survey 
Household 
visit (2) 
Unscheduled 
visit for swab 
collection 
Case Follow-
up outcome 
(3) 
Social mixing 
& uptake (4) 
1 
Oct20 
x 
x 
x 
  
x 
  
3 
  
  
  
x 
x 
x 
  
5 
nov/20 
  
  
x 
x 
x 
x 
7 
  
  
  
x 
x 
x 
  
9 
  
  
  
x 
x 
x 
  

 
 
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11 
dec/20 
  
  
x 
x 
x 
  
13 
  
  
x 
x 
x 
x 
  
15 
jan/21 
  
  
x 
x 
x 
  
17 
  
  
  
x 
x 
x 
x 
19 
feb/21 
  
  
x 
x 
x 
  
21 
  
  
  
x 
x 
x 
  
23 
mar21 
  
  
x 
x 
x 
  
25 
  
  
x 
x 
x 
x 
x 
27 
apr/21 
  
  
x 
x 
x 
  
29 
  
  
  
x 
x 
x 
  
31 
may21 
  
  
x 
x 
x 
  
33 
  
  
  
x 
x 
x 
  
35 
  
  
  
x 
x 
x 
  
37 
jun/21 
  
  
x 
x 
x 
  
39 
  
  
  
x 
x 
x 
  
41 
jul/21 
  
  
x 
x 
x 
  
43 
  
  
  
x 
x 
x 
  
45 
aug/21 
  
  
x 
x 
x 
  
47 
  
  
  
x 
x 
x 
  
49 
sep/21 
  
  
x 
x 
x 
x 
51 
  
  
x 
x 
x 
x 
  
53 
  
  
  
  
  
x 
  
55 
  
  
  
  
  
x 
  
TOTAL  forms 
filled* 
2800 for 
  household 
surveillance,24
00 for sero-
survey,8000 for 
swab collection 
2400*4= 
9600 
2800*5= 
70000 
8000 
8000 
2400*4= 
9600 
TOTAL 
samples* 
  
2400*4= 
9600 
  
8000 
  
  

 
 
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Type of 
sample 
  
DBS for 
serology, 
collected 
at 
home**  
  
nasal swab 
for PCR,  
collected at 
home** 
  
  
 
DBS = dried blood spot 
1 Informed consent for household surveillance (by the household head) and sero-survey (by the selected individual or their caretaker) 
during baseline visit 
2 During baseline visit adapted questionnaire to update population characteristics  
3 Only of COVID-19 confirmed cases identified by the surveillance, at 28 and 56 days after symptom onset 
4 We plan the social mixing survey rounds each time one month after the sero-survey, to spread the workload. The same participants 
from the sero-survey are asked to complete the questionnaire 
* estimated, based on the available information at the start of the study; we anticipate 8000 respiratory episodes (possible cases), based 
on previous data from the HDSS, adjusted for increased frequency of reporting (previous data was recorded during three-monthly 
rounds) 
** both serology testing of DBS and PCR testing of nasal swabs will be carried out at INS Marracuene. DBS samples are collected during 
pre planned visits, PCR samples when a possible case is identified. Nasal swabs undergo PCR testing the day following sample collection 
and results are communicated back to the individual (or his/her caretaker) that same day.  
 
All HDSS households will be visited by a trained HDSS interviewer to present the study and ask for 
informed consent (i) by the household head for the population-based surveillance and (ii) by the 
individuals selected for the age-stratified serial sero-survey. During this same visit, if the household 
head consented, the demographics data (baseline household visit form) will be verified and updated. 
A study household card with unique IDs of each household member will be provided (code containing 
the housing block, household id and sequential household member number). Household members will 
be sensitized on symptoms related to COVID-19, are asked to keep track of possible symptoms they 
may develop, and inform the study team by phone if a household member has a respiratory symptom, 
loss of smell or taste, so that upon assessment he/she can be asked to be swabbed for virological 
testing.  In case a household member presents with symptoms which classify him/her as a possible 
case, a separate individual informed consent procedure for nasal swabbing will have to be performed 
prior to sampling.  This ICF covers sampling for the first episode and any subsequent episode during 
the study period when nasal sampling would be indicated. Also during the baseline household visit, if 
full informed consent was provided (both for surveillance by the household head and for the sero- and 
social mixing survey by the individual household member), individual household members selected for 
the sero-survey will be asked for a baseline dried blood spot sample on filter paper, by administering 
a few blood drops through a finger prick. 
Every two weeks a trained interviewer from the HDSS team will do calls to the head of the household 
or his representative, where during the call he will fill out a questionnaire (Household follow-up visit 
form) recording any respiratory symptoms, fever or other indicative sign of COVID-19 (at the time of 
the phone call, or in the last two weeks, if these symptoms go away), vaccination against COVID-19, 
and medical appointments that any family member has had. 
Meanwhile (if applicable), demographic changes or changes in the chronic medical conditions of family 
members will be recorded. If a family member reports a respiratory sign or loss of smell or taste, with 
or without fever (possible case), a trained interviewer will do a home visit to this household. 
In case that the head of the household or his representative is not available by phone (number 
disconnected or unreachable or without contact details), an interviewer will perform a visit for this 

 
 
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Version 3.1, dated 14-Apr-2020 
household. In addition to calls, home visits to households will be performed every three months to 
collect data in person. 
Any adolescent or adult able to self-administer a nasal swab will be asked to do so, at the participants 
home. For children or adults not capable of self-swabbing, the trained interviewer will put on personal 
protective equipment and collect a nasal swab. Preferentially, if confidentiality allows, the swab will 
be taken outside. Alternatively in a room without other household members. A 8Possible case report 
form9, based on the WHO case report form, will be completed, recording symptoms, recent risk 
exposure, and potential contact with COVID-19 cases. 
If in between household visits, a household member can inform the study team by phone when he/she 
develops any sign that could be indicative of COVID-19, so that a trained interviewer will be dispatched 
to assess whether the signs qualify for a possible case, complete the 8Possible case report form9, and 
collect a nasal swab (again by self-swabbing if possible) at the possible cases9 home.  
If during household visits or through phone call, the interviewer is notified that a participating 
household member has been admitted to a healthcare facility or presented to the COVID-19 clinical 
management centre at Polana Caniço General Hospital, the participant will be actively approached, 
and if applicable, a 8Possible case report form9 filled. If SARS-CoV-2 PCR testing has been done already, 
results will be requested and entered in a 8Possible case lab request and result form9. If no SARS-CoV-
2 PCR testing has been done yet, a nasal swab will be collected if indicated, following the same 
procedure as above. 
Household investigations will be held     , whenever a household index case ) is identified, excluding 
households in which more than 3 household members (including the index case) are known to have 
tested positive for SARS-CoV-2 in the past 7 days. During household transmission investigation visits, 
all eligible household members will be proposed to self-administer a nasal swab if adolescent or adult, 
or a nasal swab will be collected by the interviewer if the participant is a child or unable to administer 
a nasal swab. A Dried blood spot sample will be collected. The household head will be requested to 
keep track of any clinical sign or symptom of household members during the month following the 
baseline visit, in a diary, and if so, notify the study team. For symptomatic household participants, 
study procedures of a possible case report, as detailed above, will be followed. 28 days after symptom 
onset of the household index case, again a nasal swab and DBS sample will be collected for each 
household member. 
Table 3. Schedule of assessments and samples collected for household transmission investigations. 
 
Day0 
Onset of 
symptoms of 
index case 
Day X 
Diagnosis of 
index case 
Day X+1 
Sample collection 
from contacts 
Day 28  
28 days after 
onset of index 
Index case 
 
nasal swab 
DBS 
nasal swab + DBS 
Household 
contacts 
 
 
nasal swab + DBS 
nasal swab + DBS 
Collected swabs will be stored in viral transport media, kept on conditioned ice packs (0-8°C), then 
shipped twice a day to a fridge (2-8°C) in the CISPOC office, from where they will be dispatched for 
PCR-testing at INS in a cooled container (2-8°C) once a day. 

 
 
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Results of PCR testing will be reported once daily from the lab to the national COVID-19 surveillance 
(also coordinated by INS) and to the study team, who will within two hours inform the possible case 
on his/her (confirmed or negative) SARS-CoV-2 PCR result by phone and, if an infection is confirmed, 
provide instructions how to protect household members and when to seek specialized COVID-19 care 
at the Polana Caniço hospital (according to national guidance).  
Confirmed cases will be followed up by phone 28 days and 56 days after symptom onset, to record 
clinical outcome, using the 8Confirmed case follow-up form9. If not possible to connect by phone, this 
will be filled in during the subsequent household visit, or through follow-up with the COVID-19 clinical 
management centre at Polana Caniço General Hospital (if the patient died or is still hospitalised). 
The repeated sero-survey, collecting dried blood sports through a finger prick, will be added to the 
biweekly household visits at 3, 6 and 12 months after COVID-19 local transmission is confirmed. During 
four other biweekly household visits, the participants selected for the sero-survey will also be 
interviewed on contact and mobility patterns during the previous day, and uptake of COVID-19 control 
measures, using the 8Social mixing questionnaire9. Its timing will depend on the stage of the outbreak:  
1. shortly after the baseline interview (second visit),  
2. when local transmission is well established and the number of new cases is increasing,  
3. a month after an initial peak, when the number of new cases is decreasing, 
4. during the final study visit. 
Table 4     . Forms completed during each study activity 
Planned activities 
Sample size 
Research form 
Baseline household visit 
15393 individuals (2108 
households) 
· Informed consent form for 
population-based COVID-19 
surveillance (with household head) 
· Informed consent form for serial 
sero-survey (with selected individual) 
· Baseline household visit form 
Active syndromic population 
surveillance 
15393 individuals (2108 
households) visited every 2 weeks 
· Household follow-up visit form 
Swabbing & PCR testing of 
symptomatic individuals 
possible cases from the surveillance 
population; 
initially pooled testing of possible 
cases; when >50 confirmed cases 
per week, switch to PCR testing of 1 
in 10 suspected cases  
· Possible case report form 
· Possible case lab request and result 
form 
Follow-up of PCR confirmed 
cases at day 28 and day 56 
past symptom onset 
PCR confirmed cases from the 
surveillance population 
· Confirmed case follow-up form 
Age-stratified sero-survey at 
0, 3, 6, 12 months 
2400 individuals/serum samples per 
round (800 per age group <18yo, 
18-50 yo, >50yo NOTE: this is 
budget dependent, pending cost of 
· Sero-survey form 
· Sero-survey lab request and result 
form 

 
 
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Version 3.1, dated 14-Apr-2020 
assay, might be decreased to 1600, 
spread over two age strata) 
Social mixing survey 
the same 2400 individuals selected 
for the sero-survey; during different 
HH visits than sero-survey visits 
· Social mixing questionnaire 
Household transmission 
investigation 
100 household primary cases and 
their household members (who 
have been in contact with the index 
case  
· baseline household transmission 
form  
      
 
 
Table 5     . Samples collected during each surveillance and sero-survey study visit 
Study visit  
Baselin
e(M0) 
Biweekly 
visit  
M3 
Biweekl
y visit  
M6 
Biweekl
y visit  
M9 
Biwe
ekly 
visit  
M12 
possib
le case 
visit  
case 
follo
w-up 
visit 
(D28) 
case 
follo
w-up 
visi 
(D56) 
Tests to 
carry out 
NASAL SWAB 
RT-PCR  to 
detect 
SARS-Cov-2 
viral RNA 
* 
* 
* 
* 
* 
* 
* 
* 
* 
X 
  
  
DRIED BLOOD SPOT (DBS) 
Luminex 
(anti-SARS-
CoV-
2serology) 
X 
  
X 
  
X 
  
  
  
X 
  
  
  
Approx. 
volume of 
collected 
blood 
450ul 
  
450ul 
  
450ul 
  
  
  
450ul 
  
  
  
* A nasal swab will only be collected if an individual is identified as a possible COVID19 case (respiratory symptoms, loss 
of smell or taste, with or without fever). All tests will be carried out at the INS-Marracuene lab in Mapûto, Mozambique. 
 
 

 
 
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5.2 Obtaining informed consent 
The participation of each household in the health demographic surveillance system currently in place 
in Mozambique is strictly voluntary and is documented by signature of the head of the household or 
his/her designee (person aged no less than 18 years) on behalf of all household members on an 
informed consent form for the registration of each household in the system. During the baseline 
surveillance household visit, study specific written informed consent for the COVID-19 surveillance will 
be requested to the household head, as also requested for other sporadic studies integrated within 
the HDSS (Instituto Nacional de Saude, 2016). During the same visit, a separate informed consent will 
be requested of individuals (or their caretakers) selected for the sero-survey. For minors we will ask 
informed consent from parents or guardians, for minors of 12 years or older we will also have a written 
assent form. In case of illiteracy, a fingerprint from the illiterate study participant and a signature from 
a witness (person aged no less than 18 years that is not part of the HDSS team) will be obtained in all 
ICFs. 
At the first study visit that a household member reports symptoms that classify this person as a 
possible case we will ask to sign a separate informed consent form to collect nasal swabs. This informed 
consent will cover for this first nasal swab sampling, but also for future indicated nasal swabs up to the 
end of the last AfriCoVER COVID-19 household surveillance visit. For minors we will ask informed 
consent from parents or guardians, for minors of 12 years or older we will also have a written assent 
form. In case of illiteracy, a fingerprint from the illiterate study participant and a signature from a 
witness (person aged no less than 18 years that is not part of the HDSS team) will be obtained on all 
ICFs. 
For household transmission investigations, a separate individual informed consent will be requested 
to each participating household member. Only households participating and consenting to the 
population-based surveillance, and where at least 50% of household members enrol can be selected 
for household transmission investigations. 
A 10% refusal to participate will be anticipated when selecting the simple random sample of individuals 
for the sero-survey. 
After signing the informed consent the household and/or the individual participant is free to withdraw 
from participation in the study at any time. 
The informed consent procedure will describe the (legitimate) purpose of the study, the procedures 
to be followed, the risks and benefits of participation, etc. If a participant (or parent or guardian) is 
unable to read or write, a signature from a witness to the informed consent discussion will be obtained. 
Participants (or parents or guardians) will be informed that participation in the study is completely 
voluntary and that the participant can withdraw from the study at any time without any negative 
consequences. All Informed consent forms (ICFs) will be available in Portugese and the informed 
consent procedure will also take place in Portuguese.  
5.3 Specific procedures and activities 
Collection of a nasal swab for SARS-CoV-2 PCR testing 
Nasal swabs will be collected through self-swabbing under supervision of trained study staff (at >1.5m 
distance), or by the trained study staff member (in case of children or preference by participant). 
1. Write the unique HDSS household member identifier on the tube, adding: 8N_Afri_cover_day9 
and stick a ID label from the household participant card on the tube. 
2. (if the study staff is collecting the sample) Put on personal protective equipment 

 
 
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Version 3.1, dated 14-Apr-2020 
3. Insert the swab gently in a vertical position, 1-1.5 cm into the nostril, until there is gentle 
resistance 
4. Rotate against the inside of the nostril for 10-15 seconds, to absorb secretions, while applying 
pressure with a finger to the outside of the nostril  
5. Repeat the procedure in the other nostril with the same swab 
6. Submerge the nasal swab in 1-3ml sterile saline or 1.5ml of UTM medium (Capricorn Scientific) 
in an Eppendorf tube 
7. Keep in a cooled container with conditioned ice packs (0-8°C) 
8. Ship within 4 hours to the CISPOC office, where samples are refrigerated at 4°C before shipping 
The tubes with swabs will be stored at 2-8°C frigobox during transport to the INS lab and kept at this 
temperature if they can be tested within 72 hours. If a delay in testing or shipping is expected, 
specimens will be stored at -20°C or below. The samples can be stored at room temperature (15–30 
°C) for up to 8 hours and refrigerated (2– 8 °C) up to seven days until testing is performed (information 
from GeneXpert Instrument Systems). 
Dried blood spot for serology on Luminex 
Anti-SARS-COV-2 antibodies will be checked on DBS based on a fingerpick. DBS are easy-to-collect in 
the field and experience has shown that antibodies can be detected with similar sensitivity as serum 
(especially with Luminex which only requires a low input amount: 1µl per sample). Furthermore, the 
INS staff and residents of the HDSS are more experienced in taking blood samples with a finger prick 
procedure, as they used this approach during previous studies (e.g. on HIV and malaria).  
Blood spots will be collected through finger pricks by trained study staff.  
1. Write the unique HDSS household member code on each filter paper, write a number 0 to 4, 
representing the sequence of surveys on the filter paper and the zipped bag, and stick a ID 
label from the household participant card on the zipped bag 
2. Put on personal protective equipment, including gloves 
3. Use a finger prick device to finger- or heel-prick blood, until a large droplet of blood forms on 
the skin. Apply six blood spots (75µl each) on filter paper (903 whatman protein saver cards) 
4. Let the DBS sample air dry on a clean and dry surface, for 4 hours at ambient temperature 
5. Store in a separate zipped bag with desiccant to reduce humidity damage (one per participant)  
6. Store in a cool-box and ship at the end of the day to the central laboratory of INS or the CISPOC 
office, where they will be kept in a -20°C freezer. 
5.4. Laboratory procedures and analyses 
5.4.1 Data Collection 
All participants will have unique coded identifiers for the construction of a pseudonymized database 
for third parties. These identifiers will be made separately for the identification of the nasal swab and 
Dried Blood Spot (DBS) collections of each survey. All samples will be transported to the central 
laboratory of the INS for analysis with the Luminex platform (serology) or 7500 (RT-PCR). Pre-analytical, 
analytical and post-analytical work related to the study samples will be carried out in compliance with 
Good Clinical Laboratory Practice (GCLP). All samples will be stored at INS and, under this protocol, 
only be used for the detection of coronavirus viral RNA or antibodies. Both nasal swabs and DBS will 
be stored long-term (5 years) at the INS for future research. Subjects will have the option to agree for 
this long-term storage in the ICF. Additional ethical approval will be requested if the samples will be 
used for screening of other pathogens or antibodies or for future research in this scientific field. If it 

 
 
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would be needed to ship samples to other countries, this will first be requested in appropriate MTAs 
and in a protocol amendment or addendum. 
5.4.2 Laboratory testing 
Diagnostic testing of specimens (both swabs and DBS) will be handled at the INS laboratory facilities in 
Marracuene in a BSL-2 laboratory using Standard Precautions. Viral inactivation (addition of the lysis 
buffer) of swab material will be performed in a certified Class II Type A1 or A2 biosafety cabinet during 
which full personal protective equipment (PPE) will be worn, such as a surgical mask, a face shield or 
goggles, two-pairs of gloves and an impermeable gown.  
The total blood volume that will be collected for each individual participating in the serosurvey is 450µl 
by fingerprick and this will be repeated in each serosurvey round. This volume of blood will be collected 
on six circles of the DBS filter paper. Each of these circles takes approximately 75ul. 
A. RT-PCR for sars-Cov-2 viral RNA detection 
All collected nasal swabs will be checked for the presence of SARS-CoV-2 by real time reverse-
transcriptase PCR (as described in Corman et al 2020). Depending on the prevalence in the population, 
RNA will be extracted from individual or pooled swabs (max 5 swabs per pool) using the available RNA 
extraction kit. Real-time reverse-transcription PCR will be performed under the conditions described 
in Corman et al 2020.  
B. Luminex for anti-sars-CoV-2 antibody detection 
Blood spot filter papers will be prepared by punching two discs of 4-mm diameter, and eluted 
overnight in 160 μL of PBS-TBN (dilution 1:40, PBS-1 % BSA-0.15 % Tween, pH 7.4, Sigma-Aldrich). Just 
before use in the immunoassay, the eluted samples will be further diluted to 1:200 in PBS-BN. 
We will use an in-house developed multiplex antibody assay for the detection of anti-SARS-Cov-2 
antibodies, similar to the protocol described by Ayouba A et al, 2020. As a target for the detection of 
anti-CoV antibodies in our Luminex platform, we have selected the main immunodominant antigens 
of the CoV family members: the large spike glycoprotein (S) and the nucleocapsid (NC) protein. We 
therefore coupled recombinant NC- and S-proteins of all currently known human CoVs (all bought at 
Sino Biological including SARS-CoV-2, INTERCHIM, Montluçon, France) to SeroMAP microsphere beads. 
These beads are carboxylated polystyrene microparticles that have been colour coded into 100 
spectrally distinct sets or regions. Each of these regions can be quickly distinguished by an xMAP® 
Instrument, which allows the interrogation of up to 100 different analytes simultaneously from only a 
small volume of sample (<10μL). Biotinylated anti-human IgG, IgA and IgM will be used to determine 
positivity. A cut-off value will be estimated based on a panel of negative control samples also spotted 
on filter paper. 
Similar procedures will be conducted for testing for antibodies to other coronaviruses. 
Given that cross-reactivity with malaria can be expected (common in many serological assays), we will 
also test all field samples for malaria using a rapid diagnostic malaria test.  
5.4.3 Long-term storage and destruction of specimens 
INS will be the responsible entity for long term storage of samples. The temperatures of the freezer 
will be monitored by the INS9s central monitoring system. Participants will be asked orally and in 
writing on the informed consent form to consent for long term storage of samples pertaining to the 
study (max 5 years after final study report) for future testing. Explicit informed consent will be 
requested for storage of samples for future testing to objectives not covered in this protocol. Before 
samples will be used, approval from the sponsor and the concerned ethics committees will need to be 

 
 
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obtained. If a participant refused long-term storage, his/her samples will be destroyed after the 
submission of the final study report. Specimens stored for long-term will not be destroyed but will 
remain in storage at INS laboratory until instructed by the PI and laboratory coordinator. 
6. Safety Assessment 
No investigational medicinal product will be administered or evaluated in this study, nor will it include 
invasive diagnostic procedures apart from the dried blood spot (finger prick) sampling for the purpose 
of the sero-survey. For this sampling, following a finger prick, a capillary blood sample will be applied 
on filter paper, to generate a dried blood spot. The blood volumes required for the study are less than 
2% of the total blood volume of a healthy adult person and as such too small to affect the participants 
health. The participant might experience some discomfort from the finger prick: he/she may 
transiently feel dizzy or faint and could develop a bruise or swelling (and very rarely, a local infection) 
at the finger prick spot. 
Respiratory specimens will be collected for diagnosis of SARS-COV-2 infection by PCR during the 
biweekly visits as part of the surveillance. Taking these respiratory samples could feel uncomfortable 
but entail negligible risk to the participants health.  
Establishing a Data and Safety Monitoring board (DSMB) is not applicable for this study since no 
investigational product or intervention will be tested. 
7. Statistical Analyses 
7.1 Methods 
All estimated transmission or clinical outcome indicators will be adjusted for the design effect, related 
to the selection of HDSS enumeration areas (clusters) within the source populations. Intraclass 
correlation coefficients can be deducted from previous studies in the HDSS. The results of the sero-
survey and social mixing survey will additionally be adjusted for age-stratified sampling. 
We will calculate a incidence rate of COVID-19 disease throughout one year, adjusting for the 
sensitivity of SARS-CoV-2 RT-PCR on nasal swabs by delay between symptom onset and testing. Using 
the longitudinal sero-survey data, determining the proportion of asymptomatics, we will be able to 
adjust the clinical incidence rate to a SARS-CoV-2 infection incidence rate, and determine the SARS-
CoV-2 infection annual attack rate and the infection fatality risk by age group. 
We will undertake three risk factor analyses: of SARS-CoV-2 infection, of COVID-19 disease 
(symptomatic infection), and of COVID-19 hospitalisation and death (severe disease). Using negative 
binomial regression, we will investigate the association with socio-demographic factors, clinical 
characteristics such as underlying medical conditions, and uptake of preventive measures. We also 
investigate the association between SARS-CoV-2 infection (from the sero-survey) and recent exposure, 
contact and mobility patterns (from the social mixing questionnaire). 
We will assume everyone will be susceptible initially and basic and effective reproductive numbers (R0 
and Re) will be calculated by the rate of change of incidence over successive serial intervals (time 
between onset of infection of index and onset of infection of infected).  
We will use established methods (Cauchemez et al 2004; te Beest et al 2013) to estimate generation 
time distribution, ratio of transmissibility between symptomatic and asymptomatic cases, duration of 

 
 
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the infectious period, and the basic reproduction number, from the transmission data collected in 
households. 
We will include heterogeneity in these parameters as far as possible, e.g. focus on the difference in 
transmissibility between children and adults. How much heterogeneity can be included in the 
estimation procedure will depend on the quality of the collected data. The estimation procedure will 
provide an estimate of the basic reproduction number, possibly composed of within household 
transmission and between household transmission, depending on the observations. These parameter 
estimates will be used to inform a compartmental model that describes the spread of SARS-CoV-2 on 
the population level. We have developed such models for the situation in the Netherlands (Teslya et 
al 2020) and are currently extending this modelling approach to include age structure of the 
population. The model can be fitted and/or validated using reported numbers of cases on the national 
level and estimates of attack rates in the population obtained from the repeated sero-surveys. We will 
develop scenarios of possible interventions in collaboration with local partners from Mozambique and 
use our models to project the possible impact of such interventions when rolled out in the population. 
We have also developed a modelling approach that allows an assessment of the impact of social 
distancing and contact tracing on the doubling time of an outbreak (Kretzschmar et al 2020). This 
modelling approach was built on earlier work in modelling of outbreak response (see Kretzschmar et 
al 2004; Bonacic Marinovic et al 2014; 2015). In this work we have developed a framework to quantify 
timeliness of response based on disease specific parameters such as the generation time interval and 
proportion of secondary infections that are generated before symptom onset by an infectious case. 
We will explore whether data on contact tracing from Mozambique can be used to assess its impact 
on epidemic spread, and to derive guidance on how timely and complete tracing of contacts has to be 
so that it can be used as a tool to slow down or even contain the epidemic. 
We will derive brand-specific total vaccine effectiveness against infection and against disease, in 
respectively a case-cohort design and a cohort design. Total vaccine effectiveness is the protection of 
vaccinees due to direct effects and added protection of vaccinees owing to vaccination of their 
neighbors or contacts, while overall vaccine effectiveness considers protection of an entire population, 
irrespective of the vaccination status of its individual members, due to the combination of total 
protection and protection of non-vaccinees due to vaccination of their neighbors or contacts (Ali et al 
2015). To derive total vaccine effectiveness against infection, we will compare the proportion of sero-
survey participants who seroconverted in the past 3 months among vaccinated against the proportion 
in non-vaccinated, adjusting for age and sex and other confounders. To derive total vaccine 
effectiveness against disease, we will compare the odds of vaccination among symptomatic confirmed 
SARS-CoV-2 cases detected through the population-based surveillance with the odds of vaccination 
among sero-survey participants who did not seroconvert in the past 3 months, in a case-cohort design. 
We will also explore overall vaccine effectiveness against disease using regression models comparing 
housing blocks with different levels of vaccination coverage among sero-survey participants.      
We will estimate the conventional data-based secondary attack rate, which is the proportion of 
seroconversion among identified household contacts. However, these are not necessarily all secondary 
infections from the household index case, and could be tertiary. Therefore we will also derive a model-
based secondary attack rate, estimating the number of actual secondary infections of the household 
index case. To do so, we could use a chain-binomial statistical model, as described by Jing et al 
(doi:10.1016/S1473-3099(20)30471-0), with an expectation-maximisation algorithm to account for (a) 
uncertainty in the infection time of asymptomatic infections, for (b) an incubation and infectious 
period distribution, as described in literature, and consider (c) the timing of symptom onset in 

 
 
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symptomatic household contacts and (d) the age-specific proportion of asymptomatic infections as 
estimated from the active population-based surveillance and sero-survey.  
7.2 Sample size and power 
Assuming a 40% annual attack rate, 50% symptomatic infections (cases), 2% overall case fatality risk, 
of which 90% are identified by the active population surveillance, 2790 COVID-19 cases and 56 deaths 
will be identified through the study period. The average incidence rate of the HDSS population would 
then be 1.50 cases per 100 person months with lower and upper 95% confidence interval limits 1.45 
and 1.56. The overall case fatality risk would have as lower and upper 95% confidence interval limits 
at 1.53 and 2.58%. 
To determine the infection attack rate from a simple random population sample of three age strata 
(comparable in size), with +/-3% confidence limits, 95% confidence interval, assuming the attack rate 
may reach 40% towards the end of the study period, samples from 800 individuals per age stratum per 
round will need to be collected. 
Assuming the household secondary attack rate to be close to 17% (Fung et al, Clin Infect Dis, 2020) and 
a median household size of 7.3 (based on HDSS data), a 5% confidence limit and a design effect of 3, 
642 household members will need to be enrolled, or 100 households. The WHO also recommended to 
include 100 households in household transmission investigations. 
Assuming 20% vaccination coverage among the 2400 sero-survey participants, 5% of sero-conversion 
over 3 months and 10% of seroconversion over 6 months, a 95% two-sided confidence interval and an 
anticipated crude total vaccine effectiveness of 50%, there will be 66% power to observe this effect 
after 3 months and 97% power after 6 months. 
8. Monitoring And Quality Assurance 
Study monitoring and auditing will be performed in accordance with the sponsor9s procedures, GCP 
guidelines and any other applicable regulatory requirements. 
Upon approval of the protocol, the monitor will establish a monitoring plan. To ensure that the 
investigators and the study staff understand and accept their defined responsibilities, the monitor will 
maintain regular correspondence with the site and may be present during the course of the study to 
verify the acceptability of the facilities, compliance with the investigational plan and relevant 
regulations, and the maintenance of complete records. 
Investigators and/or their study staff will be trained on the study protocol and all applicable study 
procedures prior to study initiation.  
Study progress will be monitored by the CTU of the INS in collaboration with the CTU of the ITM as 
frequently as necessary to ensure the rights and well-being of study participants are protected; to 
verify adequate, accurate and complete data collection; protocol compliance and to determine that 
the study is being conducted in conformance with applicable regulatory requirements. Arrangements 
for monitoring visits will be made in advance in accordance with the monitoring plan, except in case 
of emergency. 
From the electronic data, a weekly data collection report will be generated (using a Rmarkdown script), 
which allows verifying the completeness and accuracy of the data (the number of non-responders, 
missing data, compare the interviewed population9s demographics with those of the source 
population, compare results from different interviewer teams). These reports will be used by the study 
monitor to strengthen the quality of data collection and entry. If the data quality of specific variables 

 
 
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or observations cannot be guaranteed, the epidemiologist with the support of a statistician could 
jointly decide to exclude specific observations and/or variables, with a justification for each exclusion 
(to be kept in the investigator9s file and to be described and justified in the study report). 
Beyond the qualifications of HDSS interviewers, HDSS data collection supervisors are expected to 
manage all team activities, deadline accomplishments, data quality control and assurance, retrain the 
other field staff and support them. 
The study may also be subject to inspection by regulatory authorities (national or foreign) as well as 
the International Ethics Committees/Institutional Review Boards to review compliance and regulatory 
requirements. 
9. Data Management 
Data Management will be performed by the data manager at the ITM in collaboration with the data 
manager at INS and with the study staff at the sites involved in collecting and handling the study data. 
A separate Data Management Plan will be prepared, with following essential data management 
aspects: 
Data collection, handling and retention 
Demographic, health and medical data from participants and households will be collected via 
electronic questionnaires on smartphones and/or tablets into the AfricoVER study database, by using 
Open Data Kit (ODK) and/or REDCap. The Open Data Kit is an open source software for collecting, 
managing, and using data in resource-constrained environments. Data collection will be done with 
ODK Collect, an open source Android app that replaces paper forms and is used in survey-based data 
gathering. REDCap (Research Electronic Data Capture) is a software widely used in the academic 
research community for building and managing surveys, databases and research studies. It is a secure 
web application as well as mobile application that can be used to collect, clean and manage subjects9 
information in accordance with various standards and applicable regulations (GCP, CFR 21 part 11, 
HIPAA). Furthermore, the software features amongst others a query management system and 
capabilities for importing and exporting data in various forms. 
Paper questionnaires might be used if deemed necessary (e.g. as a backup when having issues with 
the electronic device). Only data defined by the study protocol will be collected. Both ODK and REDCap 
allow for offline data collection at remote sites. When connecting to the internet or cellular networks, 
data from the mobile device can be synchronized with the study server where the study data will be 
retained.  
Edit checks and branching logic, programmed onto the electronic forms will validate at the point of 
data entry and support quality data. 
Questionnaires will be tested and validated before household visits start. The INS data collectors, data 
collection supervisors, the data manager and the QA/QC team will be trained on informed consent 
procedures, data collection and entry before the study start. 
Data security and confidentiality 
The data management/IT system that will be used includes a robust security architecture including 
encryption, firewalls, antivirus software and controlled user access (smartphone authentication, 

 
 
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username, personal password and authorized user role). A list with all users who have access to the 
system will be kept updated during the study. 
A backup of data will be provided at the server, computer, mobile device and/or database level where 
applicable or feasible. 
The ITM and INS will also see to it that the necessary measures are taken to ensure that all data 
management documents (The AfriCoVER Data Management Plan, procedures, completed 
questionnaires) and IT devices and equipment (smartphones, tablets, computers, server) are kept 
secure (closed cupboards, closed and/or badge controlled offices and/or rooms). 
Private data of the study participants will be handled confidential. Information such as the participant 
name or any other data which could lead to the identification of the participant will not be recorded 
in the study database(s) or on electronic transcripts, nor on any other paper documents (apart from 
the informed consent form) or electronic files. Household addresses, geographic coordinates of 
households, participant name and other contact data for each household or participant will be kept 
separate and limited to authorized staff at the study site(s) only. Instead, household addresses, 
participant names and contact data will be replaced by a specific study household and subject 
identification code (=pseudonym). These pseudonymized data will be used during the study. 
Data sharing 
AfricoVER will make its research data available for secondary research or to support the Mozambican 
COVID-19 response and by considering following essential aspects: 
- 
Ensuring data confidentiality by providing data anonymized and unlinkable (amongst others 
by replacing the study household and subject identification code with a new code; by 
generalizing and randomizing specific variables). 
- 
Making the AfriCoVER research data, which are in principal medical, personal and sensitive, 
available through a governed data access mechanism and along a transparent decision-making 
process, with: (i) Completion of a data request form, (ii) Evaluation by a data access committee, 
(iii) Data sharing Agreement, (iv) Secure transfer of anonymized data, and (v) Additional 
metadata which clarify the research data. Metadata will include the study protocol, 
questionnaire(s), and data dictionary. 
- 
Ensuring that ethical permissions have been obtained by ethical committees and by study 
participants. 
- 
Adhering to the FAIR data principles to ensure that research data are 8findable9, 8accessible9, 
8interoperable and 8re-usable9. 
- 
Providing data available through a repository for research datasets, which has sustainability 
planning in place to ensure long-term secure storage and availability. 
- 
Sharing of interim and final research data as soon as possible to essential stakeholders involved 
in response and research, including public health institutions and research communities. 
For data sharing between INS, the work package 2 (surveillance) lead, and ITM, the project coordinator, 
a Data Transfer Agreement has been signed by both parties. Transferred data will follow the same 
principles as mentioned above, but will be pseudonymized (personal information that could allow 
identifying a participant will be removed) instead of anonymized, which is essential for the data 
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10. Ethical Issues 
10.1 Ethical and regulatory review 
The study will be carried out according to the principles stated in the World Medical Association9s 
Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects) as amended 
in 2013, all applicable regulations and according to established international scientific standards. 
The study protocol will first be submitted simultaneously to the Institutional Review Board (IRB) of the 
Instituto Nacional de Saude (INS), to the IRB of the Institute of Tropical Medicine and to the Ethical 
Committee (EC) of the University Hospital Antwerp. Once approved it will be submitted to the National 
Committee for Bioethics in Health of Mozambique (CNBS; Comité Nacional De Bioética para Saúde). 
No participants will be enrolled in the study, nor will any study specific and subject related activities 
be performed before written approval is obtained from the IRB of ITM and INS and the national ethics 
committees in Mozambique and Belgium, the sponsor's resident countries. 
Any subsequent study analysing the data or samples collected during AfriCoVER, will need to have a 
separate study protocol approved from by the ethics committee of the study principal investigator or 
sponsor, and from the CNBS in Mozambique. As mentioned in the section 8data sharing9, this is also a 
requirement for sharing the research data collected during AfriCoVER. 
10.2 Patient and/or community involvement 
The HDSS community advisory board is being consulted on study procedures (eg. how and where to 
organise specimen collection), which has been successful and beneficial during previous studies 
integrated within the HDSS. Before the study starts, the HDSS staff will present the study to community 
leaders. 
As soon as data are available and analysed after 3, 6 and 12 months, preliminary findings (COVID-19 
incidence rate; case fatality; evolution of the reproduction number) will be presented to the HDSS 
community advisory board, health authorities and the national COVID-19 response team. Three 
months after evidence of local transmission, a larger preliminary analysis, including a first estimate of 
the infection attack rate and risk factor analysis will be presented to the same stakeholders, but also 
to community leaders. 
10.3 Protocol amendments 
Once the final clinical study protocol has been issued and signed by the authorized signatories, it 
cannot be informally altered. Protocol amendments have the same legal status and must pass through 
the appropriate steps before being implemented. Any substantial change must be approved by all the 
bodies and EC9s that have approved the initial protocol, prior to being implemented, unless it is due to 
participant9s safety concerns (in which case the immediate implementation can be necessary for the 
sake of participant9s protection. In case modifications to the protocol or amendment are requested by 
any local EC during the review process, these must be discussed and agreed upon with the Sponsor 
prior to any resubmission incorporating those changes. 
10.4 Informed consent 
No participant may be admitted into the study until the Investigator or designee has obtained the 
written informed consent form. 
10.5 Confidentiality 
See <Data security and confidentiality= in section <9. Data Management= 

 
 
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The Data Protection Officer at the ITM will review the data protection measures taken within this 
study.  
10.6 Risks and benefits 
The minimal risks related to participating in this study are those related to blood and respiratory 
sample taking for laboratory testing: the discomfort of a finger prick and a nasal swab. The volume of 
blood removed will be too small to affect the participants health. Having biweekly household visits 
may be experienced as cumbersome. We do not know yet whether there may be potentially some risk 
of stigma if home testing in PPE will be done, even though consultations and sensitization with the 
community advisory board has already started before protocol development. A regular feedback loop 
with the community advisory board will be used as safeguard. 
No antiviral drugs or any other treatment will be provided as part of this study and this study will not 
have direct influence on clinical outcome nor treatment. However, by participating in this study the 
participants health status will be closely monitored and the study participant will be referred to clinical 
care if needed. Participants are encouraged to inform the study team by phone if a household member 
develops clinical signs indicative of COVID-19. Those phone calls can be reimbursed, providing airtime 
allowing a 10 minute phone call, when a study staff member subsequently visits the household. 
The risk of breaches of privacy and confidentiality breach will be kept at an ultimate minimum by not 
mentioning the participants name from processed samples nor in the study databases.  
10.7 Compensation for participation 
There will be no compensation for participation in this study.  
10.8 Insurance 
As required by the Belgian law on experiments on the human person of May 7th 2004, the sponsor has 
obtained a no-fault liability insurance with Amlin Corporate Insurance covering any harm, injury or 
(material) damage which may occur to study participants and which may be directly or indirectly 
caused by their participation in the trial. The insurance provisions will also be mentioned during the 
informed consent discussion. 
11. Dissemination of results, intellectual property 
All study documents are provided by the Sponsor to the Investigators and his/her appointed staff in 
confidence. None of this material may be disclosed to any party not directly involved with the study, 
without written permission from the Sponsor.  
The study will be registered in ClnicalTrials.gov before recruitment of the first study subject. At the end 
of the study, a comprehensive study report will be prepared by the ITM in collaboration with the INS. 
This to serve the demands of funder, regulatory and ethical bodies when needed. Outcome data of 
this study will be entered in ClnicalTrials.gov and for access to other researchers. 
Reporting and publication will be done in accordance with the CONSORT statement 
(http://www.consort-statement.org/consort-statement/). Results of this research (either positive or 
negative) will be rapidly communicated and the publication will be submitted for revision in open-
access peer-reviewed journals. In addition, data will be made available as soon as possible for 
secondary research or to support the COVID-19 response. More details on data sharing are to be found 
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12. Archiving 
The sponsor and Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented and the study data to be verified. The relevant (essential) documents 
are those documents which individually and collectively permit to assess the conduct of the trial, the 
quality of the data produced and the compliance with GCP standards and applicable regulatory 
requirements. The Investigator9s File should at least contain all the (essential) documents as listed in 
the procedure <Set up and maintenance of the Investigator Trial File=. A copy of all source data and 
Case Report Forms must always be kept on site. 
 
All the relevant study documentation present at all partners involved should be retained (in binders 
both at the site and at the ITM, except for the CRF that will be archived digitally at the ITM and on a 
USB at the site) for a minimum of twenty (20) and according to applicable local regulations. The 
Sponsor should be informed prior to destruction of the files. 
After completion of the study, the IF will remain available for internal audits and/or inspections of 
regulatory authorities for a period of twenty years, unless differently requested by national 
authorities. 
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