Keywords
SeMaCo study protocol, COVID-19, SARS-CoV-2 antibodies, seroprevalence, repeat blood donors, COVID-vaccination, epidemiology
-
Views
-
Downloads
How to cite this article
Pohl R, Krämer SW, Stallmann C et al. Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.12688/f1000research.53845.1)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Export Citation
Sciwheel
EndNote
Ref. Manager
Bibtex
ProCite
Sente
▬
✚
Study Protocol
Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors
[version 1; peer review: 2 approved with reservations]
PUBLISHED 29 Sep 2021
OPEN PEER REVIEW
REVIEWER STATUS
Abstract
Corresponding author:
Robert Pohl
Competing interests:
No competing interests were disclosed.
Grant information:
The study is funded by the Ministry of Science, Economics and Digitization of the Federal State of Saxony-Anhalt (funding codes I 122 and I 129).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:
© 2021 Pohl R et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Pohl R, Krämer SW, Stallmann C et al. Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.12688/f1000research.53845.1)
First published: 29 Sep 2021, 10:982 (https://doi.org/10.12688/f1000research.53845.1)
Latest published: 29 Sep 2021, 10:982 (https://doi.org/10.12688/f1000research.53845.1)
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Introduction
The SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2) has been circulating since December 2019. It is the causative agent for COVID-19 (coronavirus disease 2019). Transmission is facilitated through infectivity in pre- and asymptomatic disease (Robert Koch-Institut – SARS-CoV-2 virus – profile). In Germany, more than 3.5 million people have contracted COVID-19 and more than 84,000 people have died as of 8th May 2021 (Robert Koch-Institut – SARS-CoV-2 virus – report).
At the beginning of the pandemic, the federal state of Saxony-Anhalt (FSA) was considered a COVID-19 low prevalence area within Germany (Robert Koch-Institut SARS-CoV-2 virus – report). Meanwhile, the FSA has a seven day incidence of COVID-19 in 103 per 100,000 inhabitants, which is in line with the nationwide average (as of 14th May 2021) (Robert Koch-Institut – SARS-CoV-2 virus – case numbers). Data from Japan and Italy show that approximately 18–23 % of all individuals infected with SARS-CoV-2 are asymptomatic.1,2 Therefore, the number of COVID-19 infections in the FSA may still be substantially underestimated.
Patients suffering from COVID-19 develop a cellular and humoral immune response. Detailed data on the long-term kinetics of the immune response are currently not available. Neutralizing antibodies3 and memory T-cells4 have been shown to persist for at least several months. By vaccination, high neutralizing antibody titers can be induced with vaccine efficacies of up to 95% in clinical studies.5 However, reports show that reinfections occur6 and vaccines do not offer 100% protection.7 During the course of the pandemic, new variants of the virus may lead to immune escape.
Epidemics become self-limiting when herd immunity is reached through natural infection or mass vaccination. The threshold when herd immunity can be expected is influenced by various factors such as the basic reproduction number, occurrence of immune escape variants, and waning immunity. Monitoring seroprevalence and circulating variants can help to understand these mechanisms.
Due to the temporary successful containment of SARS-CoV-2 in summer 2020 and despite the current exponential viral spread only a small proportion of the German population has experienced a SARS-CoV-2 infection. In March 2021, the seroprevalence of specific SARS-CoV-2 antibodies in a German population sample (93,000 blood donors) was reported to be a small proportion 7–8% (Robert Koch-Institut – Project RKI/SeBluCo Report) The use of safe and effective vaccines should protect individuals and the population from SARS-CoV-2 infection and/or COVID-19 disease. The vaccination start date in Germany was 27th December 2020. Several effective vaccines are currently available. However, a third wave with exponential growth, with variants of SARS-CoV-2, is currently being observed in Germany.
The detection of SARS-CoV-2-specific IgG antibodies in serum is a relatively reliable indicator of infection. About 90 % of patients with mild symptoms develop SARS-CoV-2 –specific IgG antibodies in serum whereas IgG is formed by all patients with severe symptoms.8 IgM and IgG antibodies are formed approximately simultaneously, 7–14 days after infection.9
Most commercially available serological tests detect SARS-CoV-2 antibodies against either the spike protein or the nucleocapsid protein. The spike protein is essential for binding to and fusion of the virus with the target cell. It can elicit a protective immune response and is also used as an antigen in vaccines.
The detection of specific antibodies to SARS-CoV-2 in a representative group will provide a better estimate of the true extent of the COVID-19 epidemic in the FSA. The SeMaCo study (Serologische Untersuchungen bei Blutspendern des Großraums Magdeburg auf Antikörper gegen SARS-CoV-2) will observe blood donors in the city of Magdeburg (capital of the FSA with 240,000 inhabitants) and surrounding areas.
Objectives
The primary objective of the study is to determine the dynamics of the antibody response to the spike protein of SARS-CoV-2 on a population level. Important secondary objectives are:
1. To investigate the influence of age, gender, occupational activities, domestic conditions, and the frequency of family and other social contacts, on the incidence of SARS-CoV2 antibodies.
2. To analyse differences between participants with symptomatic and asymptomatic COVID19 disease courses.
3. To assess vaccination preparedness and the effect of a vaccination campaign on vaccination preparedness.
4. If a new vaccine becomes available, to analyse the influence of vaccination on the antibody detection rate.
5. To determine test characteristics of other serological tests for antibodies against SARS-CoV-2 spike and nucleocapsid antigens, other coronaviruses like SARS, MERS, 229E NL63, and HKU1, as well as influenza A and B antigen subtypes.
Protocol
Study design and setting
This prospective, longitudinal cohort study will recruit donors at the blood donation service of the University Hospital Magdeburg in the FSA. Donors of blood, plasma, and thrombocytes will be asked to participate during four survey periods. Existing blood samples from 2019 will also be tested (negative controls):
BS-0: ca. 2,000 existing samples from 2019 (Q3/Q4, 2019)
BS-1: ca. 2,000 donors, January–April 2021
BS-2: ca. 2,000 donors, July–October 2021
BS-3: ca. 2,000 donors, January–April 2022
BS-4: ca. 2,000 donors, July–October 2022
We aim to test the same participants during all four survey periods. Donors who do not attend subsequent survey periods will be replaced by new donors until the sample size of 2,000 donors for each planned collection period has been reached. The first survey period (BS-1) is three and a half months (20th January 2021 – 30th April 2021).
The study will be conducted for 21 months so that vaccination effects can be reliably assessed (e.g., first approval for vaccine in the EU was on 27th December 2020).
Prior to the start of the SeMaCo study, we assessed demographic factors of the blood donors at the University Hospital Magdeburg. In addition to blood sampling, the study participants will be asked to fill out two questionnaires (Q1–2) and, from the start of the second survey period, a follow-up questionnaire (Q3): Q1 for possible contacts and contact frequencies in their educational, professional and private contexts, Q2 for their attitude towards vaccination (in general and towards COVID-19) as well as recording the timing, vaccine and undesired effects of vaccination. Different questionnaires will be used at the initial and the follow-up examinations. At follow-up, the answers regarding current educational, professional, and private contact frequencies (Q3) and the current vaccination status will be updated. To ensure compatibility with other studies in Germany, questions were adapted from other COVID studies and vaccination surveys with permission of the authors10–11 (https://hzi-c19-antikoerperstudie.de/ and https://methodcov.de/). One aim was to be able to compare the results of our study with other COVID studies in Germany. The questions we used were therefore taken from other COVID and vaccination surveys conducted in Germany. Questions on socio-demographics are based on the demographic standards of the Federal Statistical Office. In addition, some questions from questionnaire 2 (vaccination attitudes) were developed by ourselves.12 All questionnaires were pretested and slightly revised for final use.
Study population
The study population are blood donors at the University Hospital Magdeburg. In 2019, 4,724 donors attended, 2,317 (49.0%) of whom were women. A total of 3,931 (83.2%) were multiple donors. The multiple donors all age groups, from 18 years upward, were rather equally represented with an increase of donors in the higher age groups older than 45 years. This resembles the general age distribution of the FSA where the average age was 47.9 years and the majority of inhabitants were older than 40 years in 2019 (https://de.statista.com/). Residents of Magdeburg represent 68% of the Magdeburg University Hospital blood donors and 32% are residents of the surrounding area. Overall, the blood donors essentially represent a cross-section of the healthy working population. It is expected that a high proportion of the blood donors will participate in the study due to their intrinsic motivation.
Criteria for patient inclusion
Participants must be a minimum of 18 years old and must provide written informed consent. Consent can be given stepwise for each study module: testing of blood samples, sociodemographic/contact survey, and the attitude towards vaccination survey.
Criteria for patient exclusion
The exclusion criteria are based on the donor exclusion criteria of the German Medical Association. There are numerous reasons that can lead to temporary or even permanent exclusion from blood donation. Typical reasons for temporary deferral are medical interventions, taking medication or travelling abroad, especially to areas in which mosquitoes can transmit malaria or viruses (e.g., Chikungunya virus, Zika virus). Reasons for temporal deferral do not result in exclusion from this study. Serious diseases are the most common reasons for a permanent ban and do result in an exclusion from this study.
Sample size calculation
Sample size was calculated using the G*Power program (version 3.1.9.7, Heinrich- Heine-University Düsseldorf, Düsseldorf, Germany) (G*Power, RRID:SCR_013726).13 Based on interim results of a similar study (Robert Koch-Institut – Project RKI/SeBluCo Report), there was an assumption that 1% of our study population was undetected infected. The sample calculation resulted in a sample size of n = 1,719 (α = 0.05, beta = 0.80, with a power of 80%). Therefore, our goal was to recruit at least 1,719 subjects.
Based on the donor numbers from the blood bank, we assumed 2,000 participants during the planning. We aim to test the same participants during survey periods. Donors who do not attend subsequent survey periods will be replaced by new donors until the sample size of 2,000 donors for each planned collection period has been reached.
Laboratory processing
Sample collection and transport
Blood samples (serum tubes, 8.5 ml) are collected during blood donation. Samples are pseudonymized in the Institute for Transfusion Medicine and Immunohematology with blood bank (ITIB). A label with the ITIB blood donation identification number (INR) is printed and attached to the serum tube. The samples are then registered using the laboratory information and management system (LIMS) of the Institute of Medical Microbiology and Hospital Hygiene (IMMB) and assigned an order number for every sample. The samples are transported from the ITIB to the IMMB with a pneumatic tube system.
Serological testing
Specifically, IgG antibodies are serially measured in first time and repeat blood donors over a period of 21 months. Upon arrival at the laboratory (IMMB), the serum tube is centrifuged and stored at 4°C for a maximum of 72 hours before being analysed. The test system ensures comparability of IgG values over all four survey periods by internal quality control procedures and assay calibration as prescribed in the analysers instruction manual and the IMMB Standard Operating Procedure. IgG antibody testing is performed according to the IMMB Standard Operating Procedure using an automated, CE-marked, accredited procedure. A uniform test system will be used throughout the study (LIAISON® SARS-CoV-2 TrimericS IgG, Diasorin).
Several retention samples are frozen at −80°C. These samples serve for retesting, neutralization tests, and testing in case new test methods become available.
The test results are stored in the IMMB’s laboratory information and management system (LIMS) and are accessible through the order number. The test results can be accessed by the ITIB. The pseudonymized results will be stored for 30 years in the LIMS. If a test result is positive for antibodies, the participant will be informed by the ITIB.
Neutralizing antibodies
Neutralizing antibodies will be determined for a random portion of the samples at the IMMB. Additionally, samples from individuals who reported a COVID-19 infection or vaccination but do not exhibit IgG-antibodies in the serological test will be tested for neutralizing antibodies. A sample from the time prior to the infection is included in the analysis for comparison.
Data management and data protection
The study participant’s survey will be pseudonymized during the participant’s blood donation using five-digit participant pseudonyms (ID-P) by the ITIB. Ideally, the questionnaires will be completed online using the Otto-von-Guericke University’s survey system, LimeSurvey (version 3.23.1+200825, LimeSurvey GmbH/LimeSurvey: An open-source survey tool. LimeSurvey GmbH, Hamburg, Germany). A paper version of the questionnaire will be available to participants who do not wish to complete it online. The subsequent electronic recording of the paper questionnaires will be done by the Institute of Social Medicine and Health Systems Research (ISMHSR). The ISMHSR and the IMMB will not have access to the study participants’ personal data at any time.
The data processing (collection, storage, use) in the SeMaCo study is based on the University Hospital Magdeburg’s and the ISMHSR’s data protection concepts. The data collection in the context of the (online) survey is carried out using the LimeSurvey server at the OvGU University Computing Center (UCC). The data protection concepts are in accordance with the EU General Data Protection Regulation (EU-GDPR) and the Federal Data Protection Act.
Data flow
1. The participant management at the ITIB uses five-digit participant pseudonyms (ID-P) for each of the study participants, which remain unchanged for each participant for the duration of the study. In addition, an eight-digit identification number (INR) is generated for each blood donation.
2. The online questionnaires are generated by the ISMHSR on OvGU's LimeSurvey server and made available to the study participants for completion.
3. The study participants fill in the online questionnaires, indicating their ID-P. Alternatively, a paper version of the questionnaire will be provided to participants who do not wish to complete the questionnaire online, or in the event that the survey system has a malfunction. The ID-P is also recorded on the paper version.
4. The survey data is stored pseudonymously in the LimeSurvey survey system in the OvGU Computing Centre for the duration of the respective collection period (BS-1 to BS-4).
5. At the end of the respective sampling period (BS-1 to BS-4), the survey data will be exported from the survey system to the ISMHSR. Intermediate data backups will also be made.
6. The survey data will be stored, long-term, pseudonymously in the ISMHSR.
7. Blood samples are taken from the study participants. The sample tubes are marked with the specific INR of the ITIB, assigned an order number for every sample in the IMMB’s LIMS by ITIB and sent to the IMMB.
8. The IMMB performs the blood analysis and stores the results, together with the corresponding INR.
9. The antibody test-result is sent to the ITIB, together with the INR in the IMMB’s LIMS.
10. The serological test results will be exported into a Microsoft Excel (version 2016) (RRID:SCR_016137) spreadsheet (An open-access alternative that can provide an equivalent function is Google sheets (RRID:SCR_017679)) in the ITIB computer system (Excel spreadsheet) and stored there for the long-term. The Excel file will contain the INR, the ID-P and the antibody result.
11. The antibody findings are assigned to the corresponding ID-P in the ITIB.
12. A positive antibody status (test result) is extracted from the antibody findings and stored separately, together with the INR.
13. The antibody status is transmitted to the ISMHSR together with the corresponding ID-P.
14. The antibody status and ID-P are stored, long-term, in the ISMHSR.
15. The survey data is linked to the antibody status data via the ID-P at the ISMHSR. The dataset is stored as an analysis dataset.
16. This is followed by the analysis of the data by the SeMaCo researchers.
Data storage locations
• Person identifying data: ITIB Donor Information System, Excel Data Sheet ITIB
• Pseudonymized blood analysis results: LIMS of the University Hospital Magdeburg
• Pseudonymized survey results: Temporary storage on the LimeSurvey server of the UCC; permanent storage in the ISMHSR
• Pseudonymized antibody status: permanent storage in the ITIB and ISMHSR
Data analysis and statistical plan
The main analyses will be descriptive using e.g., counts and percentages. Missing values will be excluded. We will compare groups (for example: vaccinated and non-vaccinated subjects) with the Wilcoxon test (for continuous parameters). Analyses of covariance (ANCOVA) are also included. P-values of 0.05 or less are deemed significant. All statistical analyses will be performed using Statistical Package for the Social Sciences (SPSS, version 26.0, Armonk, NY: IBM Corp (IBM SPSS Statistics, RRID:SCR_019096)) An open-access alternative that can provide an equivalent function is the R stats package (R Project for Statistical Computing, RRID:SCR_001905).
Patient confidentiality
Participants can revoke consent for each module of the study in writing. If the participant revokes consent to participate in the study, the questionnaire survey data will be deleted, and the results of the antibody tests will be anonymized. The study participants will be informed of the deletion and anonymization.
Ethics and dissemination
The written informed consent includes information about the study objectives and content, the measuring instruments, the type and content of data collection and storage, the voluntary nature of their participation, and the option to revoke consent at any time. The blood donors also have the option not to participate in individual study modules (partial consent) and are not disadvantaged by non-participation. The blood donors will have sufficient time to consider their decision before giving their consent/refusal. The blood donation staff will be always available to answer questions. The study has been approved by the Otto-von-Guericke University Magdeburg ethics committee (No. 163/20). The study is registered in the DRKS (German Clinical Trials Register): DRKS00023263.
The results of the study will be published in peer-reviewed journals and presented to the public at a press event. In addition, social media (e.g., Instagram, Facebook, Twitter, LinkedIn) will be used to inform the public about news from the study.
Conclusions
Seroepidemiological studies can be an important component for better estimation and classification of the prevalence of infection during the COVID-19 pandemic.10 The SeMaCo study expands the spectrum of German sero-epidemiological studies by investigating the prevalence of antibodies to SARS-CoV-2 in blood donors from Magdeburg and the surrounding areas of the capital of Saxony-Anhalt in a prospective manner. Both genders equally contribute to blood donation and the donors’ age distribution reflects the age distribution in the general population of the FSA. Moreover, older donors (60–72 years of age) are also included. For donors over 60 years of age, this is possible in accordance with criteria of the German Medical Association after an individual medical decision. Therefore, we consider blood donors as a suitable surrogate from the healthy working age until pension age population of the FSA.
Longitudinal sampling in repeat donors will allow for an estimate of how the virus spreads in the general population and/or the success of a vaccination campaign during the study period of 21 months (January 2021 to October 2022). In addition to the serological examination, information about daily individual face-to-face contacts in the context of the donors’ normal professional and social activities are collected and correlated with a future COVID infection.
Furthermore, the SeMaCo study assesses blood donors’ attitude towards vaccination and their COVID-19 vaccination status. A special feature of the study is that both the antibody tests and the questionnaires are conducted among repeat donors at four different time periods. This allows a more accurate view on the dynamics and course of SARS-CoV-2 antibody prevalence, contact intensities and patterns and attitudes towards vaccination over time in northern Saxony-Anhalt. Depending on the further course of the epidemic, the efficacy of containment measures and the vaccination frequency within the study population, COVID-19 antibody levels are expected to increase significantly in the three subsequent survey periods. Moreover, SeMaCo will deliver data on the persistence of the SARS-CoV-2 antibody response in a large group of healthy individuals over a study period of 21 months. We expect that the results of the SeMaCo study can influence policy decisions and prevention efforts.
Data availability
Extended data
Figshare: Extended data for ‘Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors’.
https://doi.org/10.6084/m9.figshare.16546215.v2.12
This project contains the following extended data:
(Questionnaire 1 (Contact Information) and Questionnaire 3 (Follow-up):
Questions about sociodemographic data (Information about the person, school degree, occupational activities); Questions about contacts with COVID-19 infected persons and (occupational and private) contacts; questions about nursing activities; questions about participation in events (during pandemic); questions about commuting to work, housing conditions, household, family and travel used with permission from Robert Koch-Institute.10
Questions about testing for COVID-19 and physician diagnosis of COVID-19 and symptoms if test/diagnosis is positive used with permission from Robert Koch-Institute10 and Helmholz Center for Infection Research (https://hzi-c19-antikoerperstudie.de/). Questions about marital status based on MethodCOV project (https://methodcov.de/).
Questionnaire 2 (Attitude towards vaccination): Questions about attitudes toward vaccination for COVID-19 used with permission from KUNO Kids Health Study. University of Regensburg.11)
Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).
Download
Export To
metrics
| Views | Downloads | |
|---|---|---|
| F1000Research | - | - |
|
PubMed Central
Data from PMC are received and updated monthly.
|
- | - |
Citations
CITE
how to cite this article
Pohl R, Krämer SW, Stallmann C et al. Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations] F1000Research 2021, 10:982 (https://doi.org/10.12688/f1000research.53845.1)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
track
receive updates on this article
Track an article to receive email alerts on any updates to this article.
Open Peer Review
Current Reviewer Status:
Key to Reviewer Statuses
VIEW
HIDE
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations
A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 29 Sep 2021
Views
44
How to cite this report:
Mak GCK. Reviewer Report For: Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.5256/f1000research.57268.r140445)
The direct URL for this report is:
https://f1000research.com/articles/10-982/v1#referee-response-140445
https://f1000research.com/articles/10-982/v1#referee-response-140445
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 01 Jul 2022
Approved with Reservations
VIEWS 44
The study protocol written by Pohl et al. described the plan to investigate SARS-CoV-2 seroprevalence in the city of Magdeburg and surrounding areas. Overall, the study protocol was clear and well written. It covered different aspects, (1) objectives, (2) study
... Continue reading
CITE
HOW TO CITE THIS REPORT
Mak GCK. Reviewer Report For: Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.5256/f1000research.57268.r140445)
The direct URL for this report is:
https://f1000research.com/articles/10-982/v1#referee-response-140445
https://f1000research.com/articles/10-982/v1#referee-response-140445
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Views
31
How to cite this report:
Spinetti T. Reviewer Report For: Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.5256/f1000research.57268.r140446)
The direct URL for this report is:
https://f1000research.com/articles/10-982/v1#referee-response-140446
https://f1000research.com/articles/10-982/v1#referee-response-140446
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 29 Jun 2022
Approved with Reservations
VIEWS 31
In the present study protocol, the authors aim to address the seroprevalence of SARS-CoV2 or/and SARS-CoV2 vaccination in the Saxony-Anhalt area population in Germany. In addition, the authors will also assess social behaviors and the subject's attitude towards vaccination via
... Continue reading
CITE
HOW TO CITE THIS REPORT
Spinetti T. Reviewer Report For: Study protocol for the SeMaCo study: A longitudinal regional cohort study to assess COVID-19 seroprevalence in blood donors [version 1; peer review: 2 approved with reservations]. F1000Research 2021, 10:982 (https://doi.org/10.5256/f1000research.57268.r140446)
The direct URL for this report is:
https://f1000research.com/articles/10-982/v1#referee-response-140446
https://f1000research.com/articles/10-982/v1#referee-response-140446
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Comments on this article Comments (0)