Prevalence of SARS-CoV-2 antibodies among Belgian nursing home residents and staff during the primary COVID-19 vaccination campaign

Abstract Background Nursing home residents (NHR) and staff have been disproportionally affected by the COVID-19 pandemic and were therefore prioritised in the COVID-19 vaccination strategy. However, frail older adults, like NHR, are known to have decreased antibody responses upon vaccination targeting other viral antigens. Objectives As real-world data on vaccine responsiveness, we assessed the prevalence of SARS-CoV-2 antibodies among Belgian NHR and staff during the primary COVID-19 vaccination campaign. Methods In total, we tested 1629 NHR and 1356 staff across 69 Belgian NHs for the presence of SARS-CoV-2 IgM/IgG antibodies using rapid tests. We collected socio-demographic and COVID-19-related medical data through questionnaires. Sampling occurred between 1 February and 24 March 2021, in a randomly sampled population that received none, one or two BNT162b2 vaccine doses. Results We found that during the primary vaccination campaign with 59% of the study population fully vaccinated, 74% had SARS-CoV-2 antibodies. Among fully vaccinated individuals only, fewer residents tested positive for SARS-CoV-2 antibodies (77%) than staff (98%), suggesting an impaired vaccine-induced antibody response in the elderly, with lowest seroprevalences observed among infection naïve residents. COVID-19 vaccination status and previous SARS-CoV-2 infection were predictors for SARS-CoV-2 seropositivity. Alternatively, age ≥ 80 years old, the presence of comorbidities and high care dependency predicted SARS-CoV-2 seronegativity in NHR. Conclusion These findings highlight the need for further monitoring of SARS-CoV-2 immunity upon vaccination in the elderly population, as their impaired humoral responses could imply insufficient protection against COVID-19. Trial registration This study was retrospectively registered on ClinicalTrials.gov (NCT04738695).


Secondary objectives
This study was designed late 2020, when COVID-19 vaccines were still in research development. However, on January 5 th , 2021, the vaccination campaign in Belgian NH started. The implementation of vaccines directly impacts the seroprevalence, meaning that some of the secondary objectives were no longer accurate (e.g., assessment of risk factors for infection). Therefore, adjustments were made to the secondary objectives, and tertiary objectives concerning the proportion in the sample that is not vaccinated were added.

Objectives 3. Data analysis
Additional questions concerning vaccine hesitancy In the first test round we observed that 15% of staff in the sample were not vaccinated against COVID- 19. Therefore, we aim to explore the reason behind vaccine hesitancy by adding additional questions in the followup questionnaire of the following sampling point concerning if and why they hesitated/are hesitating to get vaccinated as a part of the follow-up questionnaire (one-off). 2.7.2 Demographic and medical data 6.3 Appendix: questionnaires

Statistical analysis
The statistical analysis plan was adjusted to the changes made in the secondary objectives and addition of tertiary objectives. 3. Data analysis

Background and objectives
Statistics on reverse-transcriptase polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 cases and deaths aid in monitoring the dynamics of disease propagation. However, diagnostic RT-PCR testing is far from ideal when trying to estimate the proportion of the population infected, a key indicator for public health decision making in the ongoing COVID-19 pandemic (Roda et al., 2020) 1 . For example, mildly affected or asymptomatic individuals are often not screened. Furthermore, RT-PCR-based testing yields only an epidemiological snapshot, because it fails to detect persons that already cleared SARS-CoV-2, making it difficult to infer the true proportion of the population that has been infected. Also, during the first months of the pandemic, most countries, including Belgium, did not have an adequate RT-PCR testing capacity for screening of anyone suspected or at risk of infection with SARS-CoV-2. As a result, the number of confirmed SARS-CoV-2 infections is largely underestimated (Verity et al., 2020) 2 .
In this context, seroprevalence surveys are of utmost importance. These studies can assess the proportion of the population that has already developed SARS-CoV-2 antigen-specific antibodies () and might potentially be protected against subsequent infection (Lipsitch et al., 2020) 3 . As recommended by WHO, monitoring changes of seroprevalence over time is also crucial to anticipate the dynamics of the pandemic and plan an adequate public health response (WHO, 2020) 4,5 . So far, seroprevalence data are available in Belgium for the general population (4.3%; blood donors) (Rode Kruis, 2020) 6 , ITG (8.4) (MAY 2020) and hospital staff (6.4%) (Steensels et al., 2020) 7 . Additionally, a national study among health care workers in Belgian hospitals showed an anti-SARS-CoV-2 IgG seroprevalence of 7.7% (Mortgat et al., 2020) 8 .
Few data are available concerning the SARS-CoV-2 seroprevalence among nursing home (NH) residents and staff in Belgium, although these populations suffered from severe local SARS-CoV-2 outbreaks. Elderly are at high risk to develop severe cases of COVID-19, as 27% of the Version 6.2 dd 23/06/2021 total of the 9878 COVID-19 fatal cases in Belgium (between March 8 th and June 2 nd 2020) were reported from nursing homes (Sciensano, 2020) 9 . In May 2020, a pilot baseline seroprevalence study was conducted in NHs among Flanders, which showed that 24,5% and 19,1% of respectively NH residents and staff developed SARS-CoV-2 antigen-specific antibodies.
Among the nine different nursing homes included in this study, a large variation in seroprevalence was seen ranging from 0,0% to 38,4% and 5,2% to 31,0% for residents and staff respectively (unpublished data). However, the degree of seroprevalence and sero-incidence for NHs in Brussels and Wallonia remains unknown. Furthermore, the pilot study conducted in May 2020 assessed the seroprevalence 4 to 6 weeks after the peak incidence of the first epidemic wave. Additionally, when a COVID-19 vaccination will be implemented, it will be of crucial importance to monitor the seroprevalence in Belgian nursing homes and assess the degree of persistance of this vaccine-induced immune response.
Therefore, our major study goals are to assess the current seroprevalence of SARS-CoV-2 in NH residents and staff in Belgium with subsequent 2-monthly follow-up of the sero-incidence over a period of 10 months. Furthermore, many questions remain unsolved about the proportion of asymptomatic cases of SARS-CoV-2 antibody positive NH residents and staff (and about their individual risk factors). Our secondary study goal is to gain additional insights on the association between seropositivity, clinical manifestation and COVID-19 disease outcome. 5 Version 6.2 dd 23/06/2021

Objectives
Primary objectives 1. Assess the seroprevalence of SARS-CoV-2 among NH residents and staff in Belgium at month 0 and at every follow-up visit in the cohort at month 2, 4, 6, 8 and 10.. 2. Assess the sero-incidence of SARS-CoV-2 among NH residents and staff in Belgium over five two month time frames and summarised over a ten month time period. 1. To assess the seroprevalence according to vaccination status among NH residents and staff in Belgium at month 0 and at every follow-up visit in the cohort at month 2, 4, 6, 8 and 10.

To assess the risk of getting a SARS-CoV-2 infection since vaccination between:
o Residents and staff o Seropositive and seronegative participants at all timepoints o Individuals with or without previous self-reported SARS-CoV-2 infections o Adjusted for the updated vaccination degree of NH at all timepoints 3. To assess the proportion of confirmed COVID-19 deaths and non-COVID-19 related deaths and the time until death since vaccination (within the study timeframe) between sero-positive and -negative participants for NH residents 4. To assess the duration of SARS-CoV-2 specific antibody responses (seroreversion/no antibody response) since vaccination among NH residents and staff in Belgium. 1. To assess the risk of getting SARS-CoV-2 infected between vaccinated and nonvaccinated (at last visit) residents/staff. Version 6.2 dd 23/06/2021 2. To assess the proportion of confirmed COVID-19 deaths and non-COVID-19 related deaths and the time until death (within the study timeframe) between vaccinated and non-vaccinated residents. 3. To assess the duration of SARS-CoV-2 specific antibody responses (seroreversion/no antibody response) since self-reported infection in a non-vaccinated residents/staff.

Project planning
We plan the current proposal into four work packages (WPs) outlined below (Table 1). WP1 will focus on obtaining ethical clearance. In WP2 we will take a random sample of NHs, recruit the NHs willing to participate, and subsequently randomly sample all participants. In WP3, capillary blood samples and COVID-19 related medical data will be collected over a period of 10 months. Analysis and reporting will be performed in WP4. However, given the rapid changes of the epidemic evolution and dynamics, the foreseen timeline is subjected to reevaluation. If necessary, the foreseen timeline for testing will be re-considered, depending on the epidemiological situation (see special considerations and circumstances). Participants can be included if they are ≥ 18 years old, have been informed (orally and by means of a written information form) on the goal of the study and the procedures of the study and have agreed to participate in the study by means of a signature on the informed consent form. In some cases, NH residents can give oral consent to their legal representative or caregiver, who will confirm this oral consent by their signature. Service flat residents are not considered as target population in this study and are therefore excluded. Temporary staff, employed for a period of less than 1 year starting from baseline collection, will also be excluded. Participants who are unable to provide a capillary blood sample for the point-of-care (POC) test will also be excluded.

Sample size
To assess the cumulative incidence after 10 months of follow-up in residential care centers in Belgium a sample of 381 participants (residents & staff) is required to estimate a proportion of 0.5 with a half-width of 5%, using a 95% Wilson score CI. As residents/staff are clustered within care facilities, the sample size will be augmented by the design effect. Assuming, 15 participants (7 residents and 8 staff) per institution after 10 months of follow-up, and an ICC of 0.12, the design effect is 2.68 = (1+0.12 x ( 15-1)). The total sample size required is 1022=381 x 2.68. At least 69 institutions, each including 15 participants, need to be included in this study, which brings the total sample size to 1035 after 10 months follow-up.
In order to obtain at least 15 participants, in 69 institutions after 10 months of follow-up, assuming a drop-out rate of 0. 2 A final sample size calculation will be performed to check whether the sample size obtained for   the second research question will be sufficient for the analysis of the first research question. To assess the seroprevalence in residential care centers in Belgium a sample of 381 participants (residents & staff) is required to estimate a seroprevalence of 0.5 with a half-width of 5%, using a 95% Wilson score CI.
As residents/staff are clustered within care facilities, the sample size will be augmented by the design effect. Based on the previous calculation, 44 participants (24 residents and 20 staff) will be sampled per institution. Assuming an ICC of 0.12, the design effect is 6.16 = (1+0.12 x ( 44-1)). The total sample size required is 2347=381 x 6. 16. At least 54 institutions, each including 44 participants, need to be included in this study, which brings the total sample size to 2376 participants.
Therefore, to assess both the first (seroprevalence) and second (cumulative sero-incidence) research question, the sample size will include 69 NHs, each including 44 participants (20 staff, 24 residents). This brings the total sample size up to 3036 participants.

Sampling procedure
Stratified random sampling of nursing homes.
A stratified random sample of 69 nursing homes from NHs in Belgium will be selected. NHrelated features that will be necessary for this method of sampling will be extracted from the existing Sciensano database. The RIZIV number will be necessary to identify the selected nursing homes. The nursing homes will be equally spread over Belgium and randomly sampled within the strata defined by region and province, and in proportion to the population. Random samples from the stratified province will be taken in proportional to the number of beds. The selected NHs will be contacted for agreement to participate in this study by Ghent University. Version 6.2 dd 23/06/2021 If a NH refuses to participate, a substitute NH with a comparable profile according to the strata will be contacted. The reason of refusal will be documented to assess possible selection bias.

Stratified random sampling of participants
Nursing homes that have agreed to participate will be asked to make an alphabetic list of the current staff/residents separately (service flat residents and temporary staff excluded) and to send the number of residents and staff to the Ghent University. Staff/residents will be sampled in a 5:6 ratio in each nursing home. Online statistical computing web programming will be used to generate the random sampling schedule out of the staff and resident numbers. The list of randomly selected numbers, including a list with substitute numbers, will be sent back to the NH. The NH's have to sample 20 staff and 24 residents out of their alphabetic list according to delivered random generated numbers.
When a participant refuses (after asking for oral consent) to join the study the subject according to the first following numeric list will be asked to participate. The participants will be assigned to a unique identification code of the following format: CX(X)SXXY or CX(X)RXXY for staff and residents respectively ( C, nursing home (centre); S, staff; R, resident). In this way, test results and medical data are pseudonymized for the involved researchers. The link between the identification code and personal data will be safeguarded by the principal investigator. The oral consenting will be confirmed by a means of a signature before or on the day of the first data collection.

Collection of capillary blood samples and point-of-care test procedures
The capillary blood samples will be obtained using a lancet to finger prick the middle finger and collect a 1-10 drops of capillary blood. A capillary blood drop will be transferred to the Version 6    For the study any positive result of IgM or IgG will be considered as a positive result. In case of an invalid test, the test is repeated. When it is still invalid it will be noted as such.
Additionally, a few drops of capillary blood will be collected on Dried Blood Spot (DBS) collection cards for (semi-)quantitative analysis of vaccine-inudced/infection-induced anti-SARS-CoV-2-specific antibodies as a part of the sub-study performed by Ghent University (details are provided in appendix 6.4 At the NH level, the management will be asked, at baseline, about the proportion of care grade Individual medical data, comprising medical history and if participants have experienced an episode of COVID-19 symptoms or underwent a COVID-19 (PCR/antigen) test (with mention of date and result) or if COVID-19 was confirmed by a CT-scan, reason of missing data of drop outs (death, hospitalisation, sick leave, leaving the job), and whether they received a COVID-19 vaccination (date, type of vaccine, number of doses) in both NH residents and staff will be collected through an online questionnaire at both baseline and follow-up sampling timepoints (LimeSurvey) (See Appendix 6.3 for questionnaires). The CRC will fill out the questionnaire concerning the resident participants during the week of the sampling timepoint. Therefore the head of the nursing staff or the representative of the resident can be asked to provide the data.
In this questionnaire, the surveyed medical data will be linked to the participant identification code. Concerning the medical history, the participants (NH staff and residents) will be asked

Data collection: organisation
Before start of the study, each study center will be assigned to a selection of NHs that agreed to participate (recruited by Ghent University). Bimonthly, rapid SARS-CoV-2 antibody-testing by means of a point-of-care (POC) test and DBS collection as part of the sub-study conducted by Ghent University (see appendix 6.4) will be organized in each participating NH. The study centers organize the SARS-CoV-2 antibody testing and the data collection in their specifically Version 6.2 dd 23/06/2021 assigned NHs. A standard operational procedure (SOP) will be developed to ensure that each study center performs the antibody testing and the data collection in the same standardized way.
Additionally, the person(s) from the study centers that will conduct the antibody testing and the data collection in the NH will receive a brief training organized by Ghent University on how to conduct these tasks (this is possible in an online training). Additionally, in each NH, a contact person (local NH staff) will be assigned for communication between the study centers and NHs for study-related inquiries. The interpreted test result of the POC test will be documented by the researchers/CRC with mention of the participant identification code and collection date. If a test was not performed, the reason will be documented (e.g. hospitalisation, sick leave,…).
Concerning the reporting of the results of the POC test to individual NH staff members, the test result will be interpreted by the CRC and communicated directly to the individual staff member participant accompanied by a written explanation form about the clinical meaning of the result.
Concerning the NH residents, the CRC will communicate the result directly, write it down on a written form explaining the clinical meaning of the result. One copy of this form will be left by the resident, the other copy is meant for the head of the nursing staff, and can be send/forwarded to the Coordinating and advising physician (CRA) , the family or legal representative of the resident and the general practitioner of the resident.
When test results are missing, for instance when a staff member was absent on the sampling day, the study center contacts the NH in order to obtain the test result within 2 days after the sampling day for that NH. At Ghent University, the individual medical data from all participants will be extracted from the LimeSurvey database for statistical analysis. The test results and the questionnaires will both be linked to the unique participant identification number. Version 6.2 dd 23/06/2021

Expected outcome
The benefits to get out of the achievement of this study would be the following*: -Assessment of seroprevalence at baseline and follow-up in the cohort at month 2, 4, 6, 8, 10 and follow-up of sero-incidence over 5 two month time periods among nursing home staff and residents in NH's in Belgium.
* For every participant, it will be registered whether a COVID-19 vaccine was administered to differentiate between vaccinated and non-vaccinated participants.

Statistical analysis
Primary objectives 1. To assess the seroprevalence of SARS-CoV-2 among NH residents and staff in Belgium at month 0 and at every follow-up visit in the cohort at month 2, 4, 6, 8 and 10.
The seroprevalence of SARS-CoV-2 among NH residents and staff in Belgium at month 0, and follow-up in the cohort at month 2, month 4, month 6, month 8 and month 10, will be reported stratified for staff and residents, as well as a total seroprevalence with the 95% confidence interval (CI), assessed by a generalized equation estimation (GEE) analysis with independence covariance structure. The average seroprevalence in Belgian NH will be estimated via a generalized equation estimation (GEE) analysis with exchangeable covariance structure. All characteristics will also be displayed for the Belgian regions separately. Version 6.2 dd 23/06/2021 2. To assess the sero-incidence of SARS-CoV-2 among NH residents and staff in Belgium over five two month time frames and summarised over a ten month time period.
The sero-incidence of SARS-CoV-2 among NH residents and staff in Belgium over 5 two month time periods, as well as summarized over a period of 10 months, will be estimated as a total sero-incidence, as well as for NH residents staff separately, via a clustered Poisson (or binomial) regression, taking the clustered nature of participants within nursing homes into account.  6. To assess the proportion of confirmed COVID-19 deaths and non-COVID-19 related deaths since vaccination and the time until death (within the study timeframe) between sero-positive and -negative participants for NH residents For vaccinated NH residents only, a survival analysis will be performed to investigate the proportion of deaths within the study follow-up and the time (in days) to a confirmed COVID-19 death since 14 days after being fully vaccinated (full dose regimen). The survival or censoring time (in days) is registered since14 days after being fully vaccinated until first event (or censoring moment). A non-COVID-19 related death will be considered as a competing risk in the analysis. If the proportional hazard assumption holds, a stratified (by NH) Cox proportional hazards regression model will be used to model the cause-specific hazards between seropositive and seronegative residents. The latter will be included as a time-varying covariate.

Secondary objectives
A history of self-reported SARS-COV-2 infections, a time-varying NH vaccination degree, province, age, gender, care profile, and presence of COVID-specific comorbidities will be Version 6.2 dd 23/06/2021 considered for model adjustment. 7. To assess the duration of SARS-CoV-2 specific antibody response (seroreversion/no antibody response) since 14 days after being fully vaccinated among NH residents and staff in Belgium.
The duration of SARS-CoV-2 specific antibody responses among NH residents and staff in Belgium will be modelled by means of an interval-censored survival analysis. Seroreversion will be defined as a negative rapid test result after at least one positive rapid test result or as two succeeding negative test results (implying the participant did not seroconvert after vaccination within two to four months). The time interval to seroreversion/no response is the time interval between 14 days after the (second) vaccination date (full dose regimen) and the first test moment of a negative test result after at least one positive rapid test or of the two succeeding negative rapid test results. As a sensitivity analysis, the event will also be defined as two succeeding negative rapid test results (whether or not after at least one positive rapid test result), if the rapid test result would turn out to be unstable.

Tertiary objectives
Although this study was not designed to assess vaccine effectiveness, end points will be compared between vaccinated and non-vaccinated participants, applying propensity score methods, if sufficient non-vaccinated participants occur in the random selected sample. 8. To assess the risk of getting SARS-CoV-2 infected between vaccinated and non- Propensity score methods will be applied to reduce the effects of confounding. If insufficient non-vaccinated residents would be available in the cohort, the analysis will be performed for staff only. 9. To assess the proportion of confirmed COVID-19 deaths and non-COVID-19 related deaths and the time until death (within the study timeframe) between vaccinated and non-vaccinated residents.
If sufficient non-vaccinated residents would be available, a survival analysis will be performed to investigate the time (in days) to a confirmed COVID-19 death since 14 days after vaccination (or since 14 days after main (second) vaccination date in corresponding NH in case of non-vaccinated participants). A non-COVID-19 related death will be considered as a competing risk in the analysis.
If the proportional hazard assumption holds, a stratified (by NH) Cox proportional hazards regression model will be used to model the cause-specific hazards between vaccinated and Version 6.2 dd 23/06/2021 non-vaccinated residents, adjusting for history of self-reported SARS-COV-2 infections, and a time-varying NH vaccination degree. Propensity score methods will be applied to reduce the effects of confounding. 10. To assess the duration of SARS-CoV-2 specific antibody responses (seroreversion/no antibody response) since self-reported infection in a non-vaccinated residents/staff.
If sufficient non-vaccinated participants with self-reported infection would be available in the random selected sample, a survival analysis for interval censored data will be performed to investigate the time (in days) to a SARS-CoV-2 specific seroreversion/no antibody response since self-reported, natural SARS-CoV-2 infection. A participant is considered to have an event (seroreversion/no antibody response) during the interval between a positive and a negative rapid test result during the follow-up visits, or between the between the positive test date and the first visit date in case of a negative rapid test at the first test date.
If the rapid test results would turn out to be unstable, a sensitivity analysis will be performed and an event is considered after two succeeding negative rapid test results during the followup study visits. The survival or censoring time will be expressed as an interval in days between the positive test date until the visit date with first event (or censoring moment).
A Cox proportional hazards regression model for interval censored data will be used to

Quality assurance
As for the questionnaire, this protocol will be reviewed by other researchers and experts in the field. The informed consent and the questionnaire will be available in two languages (French and Dutch). The sample collection and interpretation of the test result will be performed by trained researchers/CRC's. Data analysis will be done by the researchers of Ghent University.

Bias and limitations
-Loss of follow-up or missing data is possible, for instance, when a NH staff-member is not present at the moment of sample collection or a sample was not collected due to heavy workload. In this case, effort will be made to contact the NH and collect the sample within two days after the sampling day. In case of, for instance hospitalization of NH resident or selfisolation of NH staff, missing test result data is inevitable. In order to prevent missing data in the online questionnaires, results will be monitored and effort will be made to remind participants to fill in the survey (by e-mail/telephonic contact or at the moment of testing). Version  -Data collection, however, researchers/CRC's in charge of collecting the samples will be trained to ensure correct use of the COVID-19 IgG/IgM Rapid Test Cassette and interpretation of the results to minimize reporting bias.
-Due to practical limitations, seroprevalence data cannot be collected at the same point in time in all participants in this study. Seroprevalence, however, is subjected to fluctuations of the infection rate in the current SARS-CoV-2 pandemic and is therefore also time-dependent.
Therefore, the maximal difference between the first and last samples collected within the baseline collection round is set at ± 4 weeks days.

Distribution of results
The study protocol will be registered at Clinicaltrials.gov (NCT04738695).
Anonymous study results should be made accessible and available as soon as possible after every testing point and at the end of the study to public health authorities involved in management of the COVID-19 epidemic in Belgium. This can be done through a policy brief or presentation. Sciensano will coordinate the distribution of results. These results will be also published on the relevant websites of these institutions. The general public will also be informed regarding these anonymous results through press communications. This will be done by the communication departments of Sciensano and of the study partners. Version 6.2 dd 23/06/2021 Scientific peer-reviewed publications (possible short publication, regular paper) will be prepared to add to the body of evidence and availability for the global scientific community and public health decision makers.

Special considerations and circumstances
Given the uncertainty about the future development of the COVID-19 epidemic, adaptation of testing periods (more frequent, or adding additional testing period(s)and extension of the study might be considered and needed. Additionally, in case of implementation of a SARS-CoV-2 vaccine, it could be appropriate to sample more frequently to estimate the vaccine related seroincidence.

Risks
The risks for participants are minimal as the capillary blood sampling (fingerprick) is minimally invasive.

Benefits
Participants will be informed about their test result. In this way, participants will know whether they have developed SARS-CoV-2 specific antibodies, which are possibly protective against new SARS-CoV-2 infections (Lipsitch et al., 2020)³.

Confidentiality
Although tests results will be communicated to each participant, at the researchers level, sample results and questionnaires will be pseudonymized via a unique identification code attributed to each participant.
Participant confidentiality will be maintained throughout the investigation. Two different databases will be created. One will contain identifying data such as names, surnames, NH linked Version 6.2 dd 23/06/2021 to the participant and a unique registration code assigned to each participant. The other database will contain the study data (POC test results and questionnaire information) and will have as identifier the unique registration code. These 2 databases will be kept separately and will be protected by a password. If the investigator entrusts the data for statistical processing, only the second database will be entrusted to this third person. As such, data in the database for analysis will be pseudonymized. Only the principal investigator will keep the database containing personal information and the unique identification number assigned to each participant.

Informed consent
Information on the study will be provided by the NH or the CRC/researcher sampling team and informed consent will be obtained from all participants, in their working language. The informed consent (Dutch and French) is attached in respectively Appendix 6.1 and 6.2.

Ethical committee clearance
The study will be submitted to the Ethical Committee of Ghent University Hospital.

Study insurance
We have an insurance for this study with Ethias. Insurance reference is: 45.439.317

Data processing and protection (GDPR)
Data processing and protection for this study complies with the provisions of the regulations Beste, U wordt uitgenodigd om deel te nemen aan een studie. Neem, voor u beslist deel te nemen aan deze studie, voldoende tijd om deze informatiebrief aandachtig te lezen en dit te bespreken met de arts of zijn/haar vertegenwoordiger. Neem ook de tijd om vragen te stellen indien er onduidelijkheden zijn of indien u bijkomende informatie wenst. Dit proces wordt 'informed consent' of 'geïnformeerde toestemming' genoemd. Eens u beslist heeft om deel te nemen aan de studie zal men u vragen om het toestemmingsformulier achteraan te ondertekenen.
Uw deelname aan deze studie zal beëindigd worden als de arts meent dat dit in uw belang is. U kan ook voortijdig uit de studie teruggetrokken worden door de onderzoeker als u de in deze informatiebrief beschreven procedures niet goed opvolgt of u de beschreven items niet respecteert. Indien u uit de studie gehaald wordt, zullen de reeds verzamelde gepseudonimiseerde gegevens in de databank blijven voor analyse, maar er zal geen nieuwe data toegevoegd worden.
Ook is het mogelijk dat zich andere risico's en ongemakken voordoen die op dit moment nog onbekend zijn. Het is daarom van groot belang om elke nieuwe gezondheidsklacht zo snel mogelijk aan de arts-onderzoeker te melden, ongeacht of de klacht volgens u te maken heeft met de studie of niet.

TOT WIE KUNT U ZICH RICHTEN IN HET GEVAL VAN PROBLEMEN OF INDIEN U VRAGEN HEEFT?
Als er een letsel optreedt ten gevolge van de studie, of als u aanvullende informatie wenst over de studie of over uw rechten en plichten, kunt u in de loop van de studie op elk ogenblik contact opnemen met de arts-onderzoeker of de hoofdonderzoeker: Ik stem in om deel te nemen aan de volgende delen van de studie: 1) Ik stem ermee in om volledig samen te werken met de arts-onderzoeker. Ik zal hem/haar op de hoogte brengen als ik onverwachte of ongebruikelijke symptomen ervaar.
3) Ik stem in met de verzameling van een Dry Blood Spot en dit maximaal 10-maal gespreid over een periode van

Sub-study on (semi-)quantitative assessment of anti-SARS-CoV-2 specific antibodies upon COVID-19 vaccination
As part of the study on SARS-CoV-2 seroprevalence and seroconversion among residents and staff members of nursing homes in Belgium, a sub-study will be performed by Ghent University.

Objectives
(Semi)-quantitative follow-up of vaccine-induced and infection-induced anti-SARS-CoV-2 specific antibodies for assessment of COVID-19 vaccine effectiveness.

Study population
The study population will be the NH residents/ staff members tested for the purpose of the main seroprevalence study.

Study design
This sub-study follows the same time scheduling as the seroprevalence study. For each participant, in addition to every POC rapid antibody test, a few drops of capillary blood will be collected on a Dry Blood Spot saver card (4 saturated spots).

Data collection and analysis
Only biological specimens will be collected. No additional questionnaire will be needed. The collected dry blood spots will be send back to Ghent University and saved in a study-specific biobank. The collected samples will be analyzed using an Enzyme-Linked Immuno Sorbent Assay (ELISA) for (semi)-quantitative detection of anti-SARS-CoV-2 specific antibodies (anti-S1/anti-NCP). The Dry Blood Spot samples will be pseudonymized.

Risks
No additional risks. By longitudinal follow-up of the immune response in this study population, additional knowledge on COVID-19 vaccine effectiveness will be gained.

Informed consent and ethics
Permission for collection of the Dry Blood Spot will be asked in the informed consent form and ethical approval will be obtained for this sub-study by the ethical committee of University Hospital Ghent as part of the seroprevalence study.