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The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.


The aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.


We developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.


We demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.


Implementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.


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  1. Milne G, Hames T, Scotton C, Gent N, Johnsen A, Anderson RM, et al. Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity? Lancet Respir Med. 2021;9(12):1450-66.  https://doi.org/10.1016/S2213-2600(21)00407-0  PMID: 34688434 
  2. Altarawneh HN, Chemaitelly H, Hasan MR, Ayoub HH, Qassim S, AlMukdad S, et al. Protection against the Omicron variant from previous SARS-CoV-2 infection. N Engl J Med. 2022;386(13):1288-90.  https://doi.org/10.1056/NEJMc2200133  PMID: 35139269 
  3. Folkhälsomyndigheten (FoHM). Teststrategi för covid-19 under 2021. [Testing strategy för covid-19 during 2021]. Stockholm: FoHM. [Accessed: 9 Feb 2023]. Swedish. Available from: https://www.folkhalsomyndigheten.se/contentassets/a1c9634c15dd487e8a8575ff10a53319/teststrategi-for-covid-19-under-2021.pdf
  4. Michlmayr D, Hansen CH, Gubbels SM, Valentiner-Branth P, Bager P, Obel N, et al. Observed protection against SARS-CoV-2 reinfection following a primary infection: A Danish cohort study among unvaccinated using two years of nationwide PCR-test data. Lancet Reg Health Eur. 2022;20:100452.  https://doi.org/10.1016/j.lanepe.2022.100452  PMID: 35791335 
  5. Hansen CH, Friis NU, Bager P, Stegger M, Fonager J, Fomsgaard A, et al. Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark. Lancet Infect Dis. 2023;23(2):167-76.  https://doi.org/10.1016/S1473-3099(22)00595-3  PMID: 36270311 
  6. Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman LS, Ash N, et al. Protection and waning of natural and hybrid immunity to SARS-CoV-2. N Engl J Med. 2022;386(23):2201-12.  https://doi.org/10.1056/NEJMoa2118946  PMID: 35613036 
  7. The Lancet Infectious Diseases. Why hybrid immunity is so triggering. Lancet Infect Dis. 2022;22(12):1649.  https://doi.org/10.1016/S1473-3099(22)00746-0  PMID: 36372089 
  8. Krammer F, Simon V. Serology assays to manage COVID-19. Science. 2020;368(6495):1060-1.  https://doi.org/10.1126/science.abc1227  PMID: 32414781 
  9. Lopman BA, Shioda K, Nguyen Q, Beckett SJ, Siegler AJ, Sullivan PS, et al. A framework for monitoring population immunity to SARS-CoV-2. Ann Epidemiol. 2021;63:75-8.  https://doi.org/10.1016/j.annepidem.2021.08.013  PMID: 34425208 
  10. Shioda K, Lau MSY, Kraay ANM, Nelson KN, Siegler AJ, Sullivan PS, et al. Estimating the cumulative incidence of SARS-CoV-2 infection and the infection fatality ratio in light of waning antibodies. Epidemiology. 2021;32(4):518-24.  https://doi.org/10.1097/EDE.0000000000001361  PMID: 33935138 
  11. To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020;20(5):565-74.  https://doi.org/10.1016/S1473-3099(20)30196-1  PMID: 32213337 
  12. Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845-8.  https://doi.org/10.1038/s41591-020-0897-1  PMID: 32350462 
  13. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020;92(6):568-76.  https://doi.org/10.1002/jmv.25748  PMID: 32134116 
  14. Ing AJ, Cocks C, Green JP. COVID-19: in the footsteps of Ernest Shackleton. Thorax. 2020;75(8):693-4.  https://doi.org/10.1136/thoraxjnl-2020-215091  PMID: 32461231 
  15. Beyerl J, Rubio-Acero R, Castelletti N, Paunovic I, Kroidl I, Khan ZN, et al. A dried blood spot protocol for high throughput analysis of SARS-CoV-2 serology based on the Roche Elecsys anti-N assay. EBioMedicine. 2021;70:103502.  https://doi.org/10.1016/j.ebiom.2021.103502  PMID: 34333234 
  16. Swedish Ministry of Social Affairs. Ökad nationell testning för covid-19, 2020 - Överenskommelse mellan staten och Sveriges Kommuner och Regioner. DNR: S2020/05276. [Increased national testing for covid-19, 2020 - Agreement between the state and The Swedish Association of Local Authorities and Regions]. Stockholm: Swedish Government; 2020. Swedish. Available from: https://www.regeringen.se/overenskommelser-och-avtal/2020/06/okad-nationell-testning-for-covid-19-2020---overenskommelse-mellan-staten-och-sveriges-kommuner-och-regioner
  17. Folkhälsomyndigheten (FoHM). Nationell plan för vaccination mot covid-19. [National plan for vaccination against COVID-19]. Stockholm: FoHM; 2020. Swedish. Available from: https://www.folkhalsomyndigheten.se/contentassets/d4c81c0ca7814f79a61bb457d4baab49/nationell-plan-vaccination-covid-19-rekommendation-prioritering.pdf
  18. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-3.  https://doi.org/10.1126/science.abb2507  PMID: 32075877 
  19. Hober S, Hellström C, Olofsson J, Andersson E, Bergström S, Jernbom Falk A, et al. Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay. Clin Transl Immunology. 2021;10(7):e1312.  https://doi.org/10.1002/cti2.1312  PMID: 34295471 
  20. United States Food and Drug Administration. (US FDA). Policy for Coronavirus Disease-2019 Tests - Guidance for Developers and Food and Drug Administration Staff. 4th edition. Silver Spring, Maryland, US: USFDA; 2020. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised
  21. Amanat F, Stadlbauer D, Strohmeier S, Nguyen THO, Chromikova V, McMahon M, et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020;26(7):1033-6.  https://doi.org/10.1038/s41591-020-0913-5  PMID: 32398876 
  22. Okuya K, Hattori T, Saito T, Takadate Y, Sasaki M, Furuyama W, et al. Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection. Microbiol Spectr. 2022;10(2):e0155321.  https://doi.org/10.1128/spectrum.01553-21  PMID: 35319248 
  23. Lagerqvist N, Maleki KT, Verner-Carlsson J, Olausson M, Dillner J, Wigren Byström J, et al. Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers. Sci Rep. 2021;11(1):7614.  https://doi.org/10.1038/s41598-021-87289-6  PMID: 33828214 
  24. Castro Dopico X, Muschiol S, Grinberg NF, Aleman S, Sheward DJ, Hanke L, et al. Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates. Clin Transl Immunology. 2022;11(3):e1379.  https://doi.org/10.1002/cti2.1379  PMID: 35284072 
  25. Meyers E, Coen A, De Sutter A, Padalko E, Callens S, Vandekerckhove L, et al. Diagnostic performance of the SARS-CoV-2 S1RBD IgG ELISA (ImmunoDiagnostics) for the quantitative detection of SARS-CoV-2 antibodies on dried blood spots. J Clin Virol. 2022;155:105270.  https://doi.org/10.1016/j.jcv.2022.105270  PMID: 36027822 
  26. Wong MP, Meas MA, Adams C, Hernandez S, Green V, Montoya M, et al. Development and implementation of dried blood spot-based COVID-19 serological assays for epidemiologic studies. Microbiol Spectr. 2022;10(3):e0247121.  https://doi.org/10.1128/spectrum.02471-21  PMID: 35612315 
  27. Klumpp-Thomas C, Kalish H, Drew M, Hunsberger S, Snead K, Fay MP, et al. Standardization of ELISA protocols for serosurveys of the SARS-CoV-2 pandemic using clinical and at-home blood sampling. Nat Commun. 2021;12(1):113.  https://doi.org/10.1038/s41467-020-20383-x  PMID: 33397956 
  28. Toh ZQ, Higgins RA, Anderson J, Mazarakis N, Do LAH, Rautenbacher K, et al. The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies. J Public Health (Oxf). 2022;44(2):e260-3.  https://doi.org/10.1093/pubmed/fdab011  PMID: 33611565 
  29. Roxhed N, Bendes A, Dale M, Mattsson C, Hanke L, Dodig-Crnković T, et al. Multianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2. Nat Commun. 2021;12(1):3695.  https://doi.org/10.1038/s41467-021-23893-4  PMID: 34140485 
  30. Beser J, Galanis I, Enkirch T, Kühlmann Berenzon S, van Straten E, Duracz J, et al. Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021. Sci Rep. 2022;12(1):10816.  https://doi.org/10.1038/s41598-022-15183-w  PMID: 35752708 
  31. Folkhälsomyndigheten (FoHM). Undersökningar av förekomsten av antikroppar mot SARS-CoV-2. [Investigations of the presence of antibodies against SARS-CoV-2]. Stockholm: FoHM. [Accessed: 1 May 2022]. Swedish. Available from: https://www.folkhalsomyndigheten.se/smittskydd-beredskap/utbrott/aktuella-utbrott/covid-19/statistik-och-analyser/undersokningar-och-datainsamlingar/forekomst-av-antikroppar
  32. Hergott DEB, Owalla TJ, Balkus JE, Apio B, Lema J, Cemeri B, et al. Feasibility of community at-home dried blood spot collection combined with pooled reverse transcription PCR as a viable and convenient method for malaria epidemiology studies. Malar J. 2022;21(1):221.  https://doi.org/10.1186/s12936-022-04239-x  PMID: 35836179 
  33. Barquín D, Ndarabu A, Carlos S, Fernández-Alonso M, Rubio-Garrido M, Makonda B, et al. HIV-1 diagnosis using dried blood spots from patients in Kinshasa, DRC: a tool to detect misdiagnosis and achieve World Health Organization 2030 targets. Int J Infect Dis. 2021;111:253-60.  https://doi.org/10.1016/j.ijid.2021.08.035  PMID: 34419584 
  34. Øverbø J, Aziz A, Zaman K, Julin CH, Qadri F, Stene-Johansen K, et al. Stability and feasibility of dried blood spots for hepatitis E virus serology in a rural setting. Viruses. 2022;14(11):2525.  https://doi.org/10.3390/v14112525  PMID: 36423134 
  35. Region Västerbotten. Aktuellt läge – följ statistik för covid 19. [Current situation – follow statistics for covid-19]. Umeå: Region Västerbotten. [Accessed: 7 Jun 2021]. Swedish. Available from: https://www.regionvasterbotten.se/coronavirus/aktuellt-vardlage-i-region-vasterbotten-covid-19
  36. Cox RJ, Brokstad KA. Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol. 2020;20(10):581-2.  https://doi.org/10.1038/s41577-020-00436-4  PMID: 32839569 
  37. Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020;181(7):1489-1501.e15.  https://doi.org/10.1016/j.cell.2020.05.015  PMID: 32473127 
  38. GeurtsvanKessel CH, Okba NMA, Igloi Z, Bogers S, Embregts CWE, Laksono BM, et al. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat Commun. 2020;11(1):3436.  https://doi.org/10.1038/s41467-020-17317-y  PMID: 32632160 
  39. Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients. Emerg Infect Dis. 2020;26(7):1478-88.  https://doi.org/10.3201/eid2607.200841  PMID: 32267220 
  40. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8.  https://doi.org/10.1016/j.cell.2020.02.052  PMID: 32142651 
  41. Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol. 2020;41(5):355-9.  https://doi.org/10.1016/j.it.2020.03.007  PMID: 32249063 

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