181
Views
0
CrossRef citations to date
0
Altmetric
Invited Reviews

Applications of SARS-CoV-2 serological testing: impact of test performance, sample matrices, and patient characteristics

, , & ORCID Icon
Pages 70-88 | Received 01 Jun 2023, Accepted 29 Aug 2023, Published online: 06 Oct 2023

References

  • Winter AK, Hegde ST. The important role of serology for COVID-19 control. Lancet Infect Dis. 2020;20(7):758–759. doi: 10.1016/S1473-3099(20)30322-4.
  • Wu X, Fu B, Chen L, et al. Serological tests facilitate identification of asymptomatic SARS‐CoV‐2 infection in Wuhan, China. J Med Virol. 2020;92(10):1795–1796. doi: 10.1002/jmv.25904.
  • Fox T, Geppert J, Dinnes J, et al. Antibody tests for identification of current and past infection with SARS‐CoV‐2. Cochrane Database Syst Rev. 2022;11(11):CD013652. doi: 10.1002/14651858.CD013652.pub2.
  • Australian Government Department of Health and Aged Care. Australian National Disease Surveillance Plan for COVID-19 [Internet]. Australian Government Department of Health and Aged Care; 2020 [cited 2022 Dec 27]. Available from: https://www.health.gov.au/resources/publications/australian-national-disease-surveillance-plan-for-covid-19?language=en.
  • Ong DSY, Fragkou PC, Schweitzer VA, et al. How to interpret and use COVID-19 serology and immunology tests. Clin Microbiol Infect. 2021;27(7):981–986. doi: 10.1016/j.cmi.2021.05.001.
  • Janeway CA, Jr, Travers P, Walport M, et al. The distribution and functions of immunoglobulin isotypes. In chapter 9: the humoral immune response. In Lawrence E, Austin P, editors. Immunobiology: the immune system in health and disease. 5th edition. New York: Garland Science; 2001.
  • Moulds JM. Introduction to antibodies and complement. Transfus Apher Sci. 2009;40(3):185–188. doi: 10.1016/j.transci.2009.03.010.
  • Klimpel GR. Immune defenses. Chapter 50. In: Baron S, editor. Medical microbiology. 4th ed. Galveston TX: University of Texas Medical Branch at Galveston; 1996 [cited 2022 Nov 18]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK8423/.
  • Van Caeseele P, Bailey D, Forgie SE, et al. SARS-CoV-2 (COVID-19) serology: implications for clinical practice, laboratory medicine and public health. CMAJ. 2020;192(34):E973–E979. doi: 10.1503/cmaj.201588.
  • Suhandynata RT, Hoffman MA, Kelner MJ, et al. Longitudinal monitoring of SARS-CoV-2 IgM and IgG seropositivity to detect COVID-19. J Appl Lab Med. 2020;5(5):908–920. doi: 10.1093/jalm/jfaa079.
  • Tang MS, Case JB, Franks CE, et al. Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays. Clin Chem. 2020;66(12):1538–1547. doi: 10.1093/clinchem/hvaa211.
  • EUA authorized serology test performance. FDA [Internet]; 2022 [cited 2022 Nov 19]; Available from: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance.
  • Ebell MH, Barry HC. Beware of false-positive results with SARS-CoV-2 antibody tests. Am Fam Physician. 2020;102:5–6.
  • Chen Y-H, Fang C-T. A simple rule for interpreting COVID-19 antibody test results, by seroprevalence and vaccination status. J Microbiol Immunol Infect. 2022;55(2):341–343. doi: 10.1016/j.jmii.2021.02.008.
  • Brownstein NC, Chen YA. Predictive values, uncertainty, and interpretation of serology tests for the novel coronavirus. Sci Rep. 2021;11(1):5491. doi: 10.1038/s41598-021-84173-1.
  • Bailey D, Konforte D, Barakauskas VE, et al. Canadian Society of Clinical Chemists (CSCC) interim consensus guidance for testing and reporting of SARS-CoV-2 serology. Clin Biochem. 2020;86:1–7. doi: 10.1016/j.clinbiochem.2020.09.005.
  • Kalou MB. Application of enzyme immunoassay methods using dried blood spot specimens, Chapter 5. In: Li W. Lee MS, editors. Dried blood spots. Hoboken (NJ): John Wiley & Sons, Ltd; 2014. p. 40–52.
  • Nikiforuk AM, McMillan B, Bartlett SR, et al. Performance of immunoglobulin G serology on finger prick capillary dried blood spot samples to detect a SARS-CoV-2 antibody response. Microbiol Spectr. 2022;10(2):e0140521. doi: 10.1128/spectrum.01405-21.
  • Grüner N, Stambouli O, Ross RS. Dried blood spots - Preparing and processing for use in immunoassays and in molecular techniques. J Vis Exp. 2015;(97):52619. doi: 10.3791/52619.
  • Morshed M, Sekirov I, McLennan M, et al. Comparative analysis of capillary vs venous blood for serologic detection of SARS-CoV-2 antibodies by RPOC lateral flow tests. Open Forum Infect Dis. 2021;8(3):ofab043. doi: 10.1093/ofid/ofab043.
  • Dhingra N, Diepart M, Dziekan G, et al. Capillary sampling, Chapter 7. In: Cadman H, editor. WHO guidelines on drawing blood: best practices in phlebotomy. Geneva: World Health Organization; 2010. https://www.who.int/publications/i/item/9789241599221
  • Villar LM, de Oliveira JC, Cruz HM, et al. Assessment of dried blood spot samples as a simple method for detection of hepatitis B virus markers. J Med Virol. 2011;83(9):1522–1529. doi: 10.1002/jmv.22138.
  • Itell HL, Weight H, Fish CS, et al. SARS-CoV-2 antibody binding and neutralization in dried blood spot eluates and paired plasma. Microbiol Spectr. 2021;9(2):e0129821. doi: 10.1128/Spectrum.01298-21.
  • Crimmins EM, Zhang YS, Kim JK, et al. Dried blood spots: effects of less than optimal collection, shipping time, heat, and humidity. Am J Hum Biol. 2020;32(5):e23390. doi: 10.1002/ajhb.23390.
  • Toh ZQ, Higgins RA, Anderson J, et al. The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies. J Public Health. 2022;44(2):e260–e263. doi: 10.1093/pubmed/fdab011.
  • Mulchandani R, Brown B, Brooks T, et al. Use of dried blood spot samples for SARS-CoV-2 antibody detection using the Roche Elecsys ® high throughput immunoassay. J Clin Virol. 2021;136:104739. doi: 10.1016/j.jcv.2021.104739.
  • Omosule CL, Conklin J, Seck S, et al. Qualitative and quantitative detection of SARS-CoV-2 antibodies from dried blood spots. Clin Biochem. 2023;117:16–22. doi: 10.1016/j.clinbiochem.2021.12.012.
  • Cholette F, Mesa C, Harris A, et al. Dried blood spot specimens for SARS-CoV-2 antibody testing: a multi-site, multi-assay comparison. PLOS One. 2021;16(12):e0261003. doi: 10.1371/journal.pone.0261003.
  • Jorgensen SCJ, Burry L, Tabbara N. Role of maternal COVID-19 vaccination in providing immunological protection to the newborn. Pharmacotherapy. 2022;42(1):58–70. doi: 10.1002/phar.2649.
  • Collier A-RY, McMahan K, Yu J, et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA. 2021;325(23):2370–2380. doi: 10.1001/jama.2021.7563.
  • Larcade R, DeShea L, Lang GA, et al. Maternal-fetal immunologic response to SARS-CoV-2 infection in a symptomatic vulnerable population: a prospective cohort. J Infect Dis. 2022;225(5):800–809. doi: 10.1093/infdis/jiab591.
  • Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. doi: 10.1136/bmj.m3320.
  • Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133–146. doi: 10.1038/s41579-022-00846-2.
  • Edlow AG, Castro VM, Shook LL, et al. Neurodevelopmental outcomes at 1 year in infants of mothers who tested positive for SARS-CoV-2 during pregnancy. JAMA Netw Open. 2022;5(6):e2215787. doi: 10.1001/jamanetworkopen.2022.15787.
  • Bender JM, Lee Y, Cheng WA, et al. Coronavirus disease 2019 vaccine booster effects are seen in human milk antibody response. Front Nutr. 2022;9:898849. doi: 10.3389/fnut.2022.898849.
  • Ibrahimi N, Delaunay-Moisan A, Hill C, et al. Screening for SARS-CoV-2 by RT-PCR: saliva or nasopharyngeal swab? Rapid review and meta-analysis. PLOS One. 2021;16(6):e0253007. doi: 10.1371/journal.pone.0253007.
  • Campbell C, Roblin D, Padmanabhan N, et al. Saliva-based SARS-CoV-2 serology using at-home collection kits returned via mail. Sci Rep. 2022;12(1):14061. doi: 10.1038/s41598-022-17057-7.
  • Thomas AC, Oliver E, Baum HE, et al. Evaluation of isotype specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults [Internet]. medRxiv; 2022 [cited 2022 Oct 23]. doi: 10.1101/2022.04.11.22273690.
  • Thomas AC, Oliver E, Baum HE, et al. Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults. Commun Med. 2023;3(1):14. doi: 10.1038/s43856-023-00264-2.
  • Pang NY-L, Pang AS-R, Chow VT, et al. Understanding neutralising antibodies against SARS-CoV-2 and their implications in clinical practice. Mil Med Res. 2021;8(1):47. doi: 10.1186/s40779-021-00342-3.
  • Sterlin D, Mathian A, Miyara M, et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med. 2021;13(577):eabd2223. doi: 10.1126/scitranslmed.abd2223.
  • Tate JR, Myers GL. Harmonization of clinical laboratory test results. EJIFCC. 2016;27:5–14.
  • Testing devices for COVID-19: serological testing devices [Internet]; 2020 [cited 2022 Dec 14]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/medical-devices/testing/serological.html.
  • Considerations for the use of antibody tests for SARS-CoV-2 – first update [Internet]. European Centre for Disease Prevention and Control; 2022 [cited 2022 Dec 14]. Available from: https://www.ecdc.europa.eu/en/publications-data/use-antibody-tests-sars-cov-2.
  • Infantino M, Pieri M, Nuccetelli M, et al. The WHO international standard for COVID-19 serological tests: towards harmonization of anti-spike assays. Int Immunopharmacol. 2021;100:108095. doi: 10.1016/j.intimp.2021.108095.
  • Nkuba Ndaye A, Hoxha A, Madinga J, et al. Challenges in interpreting SARS-CoV-2 serological results in African countries. Lancet Glob Health. 2021;9(5):e588–e589. doi: 10.1016/S2214-109X(21)00060-7.
  • Kristiansen PA, Page M, Bernasconi V, et al. WHO international standard for anti-SARS-CoV-2 immunoglobulin. Lancet. 2021;397(10282):1347–1348. doi: 10.1016/S0140-6736(21)00527-4.
  • Karger AB, Brien JD, Christen JM, et al. The serological sciences network (SeroNet) for COVID-19: depth and breadth of serology assays and plans for assay harmonization. mSphere. 2022;7(4):e0019322. doi: 10.1128/msphere.00193-22.
  • Theel ES, Slev P, Wheeler S, et al. The role of antibody testing for SARS-CoV-2: is there one? J Clin Microbiol. 2020;58(8):e00797-20. doi: 10.1128/JCM.00797-20.
  • Sharma S, Shrivastava S, Kausley SB, et al. Coronavirus: a comparative analysis of detection technologies in the wake of emerging variants. Infection. 2023;51(1):1–19. doi: 10.1007/s15010-022-01819-6.
  • Brehm J, Spaeth A, Dreßler L, et al. SARS-CoV-2 antibody progression and neutralizing potential in mild symptomatic COVID-19 patients – a comparative long term post-infection study. Front Immunol. 2022;13:915338. doi: 10.3389/fimmu.2022.915338.
  • SARS-CoV-2 Viral mutations: impact on COVID-19 tests. FDA [Internet]; 2023 [cited 2023 Mar 17]. Available from: https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/sars-cov-2-viral-mutations-impact-covid-19-tests.
  • Rodgers MA, Olivo A, Harris BJ, et al. Detection of SARS-CoV-2 variants by Abbott molecular, antigen, and serological tests. J Clin Virol. 2022;147:105080. doi: 10.1016/j.jcv.2022.105080.
  • Li X, Wang J, Geng J, et al. Emerging landscape of SARS-CoV-2 variants and detection technologies. Mol Diagn Ther. 2023;27(2):159–177. doi: 10.1007/s40291-022-00631-0.
  • Teunis PFM, van Eijkeren JCH. Estimation of seroconversion rates for infectious diseases: effects of age and noise. Stat Med. 2020;39(21):2799–2814. doi: 10.1002/sim.8578.
  • Liu W, Russell RM, Bibollet-Ruche F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis. 2021;27(9):2454–2458. doi: 10.3201/eid2709.211042.
  • Long Q-X, Liu B-Z, Deng H-J, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845–848. doi: 10.1038/s41591-020-0897-1.
  • Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med. 2020;1(3):100040. doi: 10.1016/j.xcrm.2020.100040.
  • Premkumar L, Segovia-Chumbez B, Jadi R, et al. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48):eabc8413. doi: 10.1126/sciimmunol.abc8413.
  • Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371(6529):eabf4063. doi: 10.1126/science.abf4063.
  • Isho B, Abe KT, Zuo M, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020;5(52):eabe5511. doi: 10.1126/sciimmunol.abe5511.
  • Štěpánek L, Janošíková M, Štěpánek L, et al. The kinetics and predictors of anti‐SARS‐CoV‐2 antibodies up to 8 months after symptomatic COVID‐19: a Czech cross‐sectional study. J Med Virol. 2022;94(8):3731–3738. doi: 10.1126/sciimmunol.abe5511.
  • Zhang S, Xu K, Li C, et al. Long-term kinetics of SARS-CoV-2 antibodies and impact of inactivated vaccine on SARS-CoV-2 antibodies based on a COVID-19 patients cohort. Front Immunol. 2022;13:829665. doi: 10.3389/fimmu.2022.829665.
  • Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205–1211. doi: 10.1038/s41591-021-01377-8.
  • Wei J, Matthews PC, Stoesser N, et al. Anti-spike antibody response to natural SARS-CoV-2 infection in the general population. Nat Commun. 2021;12(1):6250. doi: 10.1038/s41467-021-26479-2.
  • Toh ZQ, Mazarakis N, Nguyen J, et al. Comparison of antibody responses to SARS-CoV-2 variants in Australian children. Nat Commun. 2022;13(1):7185. doi: 10.1038/s41467-022-34983-2.
  • Rijkers G, Murk J-L, Wintermans B, et al. Differences in antibody kinetics and functionality between severe and mild severe acute respiratory syndrome coronavirus 2 infections. J Infect Dis. 2020;222(8):1265–1269. doi: 10.1093/infdis/jiaa463.
  • Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020;584(7821):437–442. doi: 10.1038/s41586-020-2456-9.
  • Huang AT, Garcia-Carreras B, Hitchings MDT, et al. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun. 2020;11(1):4704. doi: 10.1038/s41467-020-18450-4.
  • Seow J, Graham C, Merrick B, et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. Nat Microbiol. 2020;5(12):1598–1607. doi: 10.1038/s41564-020-00813-8.
  • Röltgen K, Powell AE, Wirz OF, et al. Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci Immunol. 2020;5(54):eabe0240. doi: 10.1126/sciimmunol.abe0240.
  • Ren L, Zhang L, Chang D, et al. The kinetics of humoral response and its relationship with the disease severity in COVID-19. Commun Biol. 2020;3(1):780. doi: 10.1038/s42003-020-01526-8.
  • Oved K, Olmer L, Shemer-Avni Y, et al. Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation. EClinicalMedicine. 2020;29:100651. doi: 10.1016/j.eclinm.2020.100651.
  • Marklund E, Leach S, Axelsson H, et al. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders. PLOS One. 2020;15(10):e0241104. doi: 10.1371/journal.pone.0241104.
  • Bhatt M, Zemek RL, Tang K, et al. Antibody seronegativity in COVID-19 RT-PCR–positive children. Pediatr Infect Dis J. 2022;41(8):e318–e320. doi: 10.1097/INF.0000000000003573.
  • Talaei M, Faustini S, Holt H, et al. Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK). BMC Med. 2022;20(1):87. doi: 10.1186/s12916-022-02286-4.
  • Ozgocer T, Dagli ŞN, Ceylan MR, et al. Analysis of long‐term antibody response in COVID‐19 patients by symptoms grade, gender, age, BMI, and medication. J Med Virol. 2022;94(4):1412–1418. doi: 10.1002/jmv.27452.
  • Klein SL, Pekosz A, Park H-S, et al. Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population. J Clin Invest. 2020;130(11):6141–6150. doi: 10.1172/JCI142004.
  • Yang HS, Costa V, Racine-Brzostek SE, et al. Association of age with SARS-CoV-2 antibody response. JAMA Netw Open. 2021;4(3):e214302. doi: 10.1001/jamanetworkopen.2021.4302.
  • Delgado JF, Berenguer-Llergo A, Julià G, et al. Antibody response induced by BNT162b2 and mRNA-1273 vaccines against the SARS-CoV-2 in a cohort of healthcare workers. Viruses. 2022;14(6):1235. doi: 10.3390/v14061235.
  • De Greef J, Scohy A, Zech F, et al. Determinants of IgG antibodies kinetics after severe and critical COVID‐19. J Med Virol. 2021;93(9):5416–5424. doi: 10.1002/jmv.27059.
  • Johannesen CK, Rezahosseini O, Gybel-Brask M, et al. Risk factors for being seronegative following SARS-CoV-2 infection in a large cohort of health care workers in Denmark. Microbiol Spectr. 2021;9(2):e0090421. doi: 10.1128/Spectrum.00904-21.
  • Frasca D, Reidy L, Cray C, et al. Influence of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients. PLOS One. 2021;16(3):e0245424. doi: 10.1371/journal.pone.0245424.
  • Yamamoto S, Mizoue T, Tanaka A, et al. Sex‐associated differences between BMI and SARS‐CoV‐2 antibody titers following the BNT162b2 vaccine. Obesity. 2022;30(5):999–1003. doi: 10.1002/oby.23417.
  • Mendizabal M, Ducasa N, Benencio P, et al. Heterologous adenovirus‐vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients. Hepatol Commun. 2022;6(10):2850–2859. doi: 10.1002/hep4.2034.
  • Gallian P, Pastorino B, Morel P, et al. Lower prevalence of antibodies neutralizing SARS-CoV-2 in group O french blood donors. Antiviral Res. 2020;181:104880. doi: 10.1016/j.antiviral.2020.104880.
  • Peckham H, de Gruijter NM, Raine C, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020;11(1):6317. doi: 10.1038/s41467-020-19741-6.
  • Jin J-M, Bai P, He W, et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health. 2020;8:152. doi: 10.3389/fpubh.2020.00152.
  • Arnold CG, Libby A, Vest A, et al. Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes. Biol Sex Differ. 2022;13(1):7. doi: 10.1186/s13293-022-00417-3.
  • Huang B, Cai Y, Li N, et al. Sex-based clinical and immunological differences in COVID-19. BMC Infect Dis. 2021;21(1):647. doi: 10.1186/s12879-021-06313-2.
  • Markmann AJ, Giallourou N, Bhowmik DR, et al. Sex disparities and neutralizing-antibody durability to SARS-CoV-2 infection in convalescent individuals. mSphere. 2021;6(4):e0027521. doi: 10.1128/mSphere.00275-21.
  • Jolliffe DA, Faustini SE, Holt H, et al. Determinants of antibody responses to SARS-CoV-2 vaccines: population-based longitudinal study (COVIDENCE UK). Vaccines. 2022;10(10):1601. doi: 10.3390/vaccines10101601.
  • Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS‐CoV‐2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021;21(8):2719–2726. doi: 10.1111/ajt.16615.
  • Rozen-Zvi B, Yahav D, Agur T, et al. Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study. Clin Microbiol Infect. 2021;27(8):1173.e1–1173–e4. doi: 10.1016/j.cmi.2021.04.028.
  • Regele F, Heinzel A, Hu K, et al. Stopping of mycophenolic acid in kidney transplant recipients for 2 weeks peri-vaccination does not increase response to SARS-CoV-2 vaccination—a non-randomized, controlled pilot study. Front Med. 2022;9:914424. doi: 10.3389/fmed.2022.914424.
  • Kuczborska K, Krzemińska E, Buda P, et al. Immune response to SARS-CoV-2 infections in children with secondary immunodeficiencies. J Clin Immunol. 2023;43(1):57-64. doi: 10.1007/s10875-022-01365-8.
  • Subbarao S, Warrener LA, Hoschler K, et al. Robust antibody responses in 70–80-year-olds 3 weeks after the first or second doses of pfizer/BioNTech COVID-19 vaccine, United Kingdom, january to february 2021. Eurosurveillance. 2021;26(12):2100329. doi: 10.2807/1560-7917.ES.2021.26.12.2100329.
  • Amirthalingam G, Bernal JL, Andrews NJ, et al. Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England. Nat Commun. 2021;12(1):7217. doi: 10.1038/s41467-021-27410-5.
  • Azak E, Karadenizli A, Uzuner H, et al. Comparison of an inactivated Covid19 vaccine-induced antibody response with concurrent natural Covid19 infection. Int J Infect Dis. 2021;113:58–64. doi: 10.1016/j.ijid.2021.09.060.
  • Rai P, Kumar BK, Deekshit VK, et al. Detection technologies and recent developments in the diagnosis of COVID-19 infection. Appl Microbiol Biotechnol. 2021;105(2):441–455. doi: 10.1007/s00253-020-11061-5.
  • Parmar H, Montovano M, Banada P, et al. RT-PCR negative COVID-19. BMC Infect Dis. 2022;22(1):149. doi: 10.1186/s12879-022-07095-x.
  • Yong SEF, Anderson DE, Wei WE, et al. Connecting clusters of COVID-19: an epidemiological and serological investigation. Lancet Infect Dis. 2020;20(7):809–815. doi: 10.1016/S1473-3099(20)30273-5.
  • Perez-Toledo M, Faustini SE, Jossi SE, et al. Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with paediatric inflammatory multi-system syndrome. medRxiv. 2020;2020(06.05.20123117) doi: 10.1101/2020.06.05.20123117.
  • Beneš J, Džupová O, Poláková A, et al. Repeatedly negative PCR results in patients with COVID-19 symptoms: do they have SARS-CoV-2 infection or not? Epidemiol Mikrobiol Imunol. 2021;70(1):3–9.
  • Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: an overview. Diabetes Metab Syndr. 2021;15(3):869–875. doi: 10.1016/j.dsx.2021.04.007.
  • Coronavirus disease 2019 (COVID-19) – serology [Internet]. Public Health Ontario; 2023 [cited 2023 Apr 2]. Available from: https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/COVID-19-Serology.
  • Mejias A, Schuchard J, Rao S, et al. Leveraging serologic testing to identify children at risk for post-acute sequelae of SARS-CoV-2 infection: an electronic health record–based cohort study from the RECOVER program. J Pediatr. 2023;257:113358. doi: 10.1016/j.jpeds.2023.02.00.
  • Iyer AS, Jones FK, Nodoushani A, et al. Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients. Sci Immunol. 2020;5(52):eabe0367. doi: 10.1126/sciimmunol.abe0367.
  • Lumley SF, Wei J, O'Donnell D, et al. The duration, dynamics, and determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in individual healthcare workers. Clin Infect Dis. 2021;73(3):e699–e709. doi: 10.1093/cid/ciab004.
  • Wang P. Significance of IgA antibody testing for early detection of SARS‐CoV‐2. J Med Virol. 2021;93(4):1888–1889. doi: 10.1002/jmv.26703.
  • Boyton RJ, Altmann DM. The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions? Nat Rev Immunol. 2021;21(12):762–768. doi: 10.1038/s41577-021-00631-x.
  • Gong F, Wei H, Li Q, et al. Evaluation and comparison of serological methods for COVID-19 diagnosis. Front Mol Biosci. 2021;8:682405. doi: 10.3389/fmolb.2021.682405.
  • Kurano M, Morita Y, Nakano Y, et al. Response kinetics of different classes of antibodies to SARS-CoV2 infection in the Japanese population: the IgA and IgG titers increased earlier than the IgM titers. Int Immunopharmacol. 2022;103:108491. doi: 10.1016/j.intimp.2021.108491.
  • Beck EJ, Hsieh Y-H, Fernandez RE, et al. Differentiation of individuals previously infected with and vaccinated for SARS-CoV-2 in an inner-city emergency department. J Clin Microbiol. 2022;60(3):e02390-21. doi: 10.1128/jcm.02390-21.
  • Garbuglia AR, Minosse C, Del Porto P. mRNA- and adenovirus-based vaccines against SARS-CoV-2 in HIV-positive people. Viruses. 2022;14(4):748. doi: 10.3390/v14040748.
  • Suhandynata RT, Bevins NJ, Tran JT, et al. SARS-CoV-2 serology status detected by commercialized platforms distinguishes previous infection and vaccination adaptive immune responses. J Appl Lab Med. 2021;6(5):1109–1122. doi: 10.1093/jalm/jfab080.
  • Bates TA, McBride SK, Leier HC, et al. Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants. Sci Immunol. 2022;7(68):eabn8014. doi: 10.1126/sciimmunol.abn8014.
  • Hedges JF, Thompson MA, Snyder DT, et al. Titers, prevalence, and duration of SARS-CoV-2 antibodies in a local COVID-19 outbreak and following vaccination. Vaccines. 2021;9(6):587. doi: 10.3390/vaccines9060587.
  • Sariol CA, Pantoja P, Serrano-Collazo C, et al. Function is more reliable than quantity to follow up the humoral response to the receptor binding domain of SARS-CoV-2 spike protein after natural infection or COVID-19 vaccination. Viruses. 2021;13(10):1972. doi: 10.3390/v13101972.
  • Ibarrondo FJ, Hofmann C, Fulcher JA, et al. Primary, recall, and decay kinetics of SARS-CoV-2 vaccine antibody responses. ACS Nano. 2021;15(7):11180–11191. doi: 10.1021/acsnano.1c03972.
  • Anka AU, Tahir MI, Abubakar SD, et al. Coronavirus disease 2019 (COVID-19): an overview of the immunopathology, serological diagnosis and management. Scand J Immunol. 2021;93(4):e12998. doi: 10.1111/sji.12998.
  • Krsak M, Henao-Martínez AF, Franco-Paredes C. COVID-19: way forward with serosurveillance without overemphasizing neutralizing antibodies. Viral Immunol. 2021;34(3):130–133. doi: 10.1089/vim.2020.0246.
  • Ward S, Lindsley A, Courter J, et al. Clinical testing for COVID-19. J Allergy Clin Immunol. 2020;146(1):23–34. doi: 10.1016/j.jaci.2020.05.012.
  • Saeed S, Drews SJ, Pambrun C, et al. SARS‐CoV‐2 seroprevalence among blood donors after the first COVID‐19 wave in Canada. Transfusion. 2021;61(3):862–872. doi: 10.1111/trf.16296.
  • Labonne S. Helping to guide Canada’s epidemic response [Internet]. COVID-19 Immune. Task Force; 2023 [cited 2023 Mar 28]. Available from: https://www.covid19immunitytaskforce.ca/.
  • Clarke KEN. Seroprevalence of infection-induced SARS-CoV-2 antibodies—United States, September 2021–February 2022. MMWR Morbidity and Mortal Weekly Report [Internet]; 2022 [cited 2023 Mar 28]. Available from: https://www.cdc.gov/mmwr/volumes/71/wr/mm7117e3.htm.
  • Woon YL, Lee YL, Chong YM, et al. Serology surveillance of SARS-CoV-2 antibodies among healthcare workers in COVID-19 designated facilities in Malaysia. Lancet Reg Health West Pac. 2021;9:100123. doi: 10.1016/j.lanwpc.2021.100123.
  • Chua PEY, Gwee SXW, Wang MX, et al. Severe acute respiratory syndrome coronavirus 2 diagnostic tests for border screening during the very early phase of coronavirus disease 2019 pandemic: a systematic review and meta-analysis. Front Med. 2022;9:748522. doi: 10.3389/fmed.2022.748522.
  • Papst I, Li M, Champredon D, et al. Age-dependence of healthcare interventions for COVID-19 in Ontario, Canada. BMC Public Health. 2021;21(1):706. doi: 10.1186/s12889-021-10611-4.
  • Dimcheff DE, Schildhouse RJ, Hausman MS, et al. Seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection among veterans affairs healthcare system employees suggests higher risk of infection when exposed to SARS-CoV-2 outside the work environment. Infect Control Hosp Epidemiol. 2021;42(4):392–398. doi: 10.1017/ice.2020.1220.
  • Bobrovitz N, Arora RK, Cao C, et al. Global seroprevalence of SARS-CoV-2 antibodies: a systematic review and meta-analysis. PLOS One. 2021;16(6):e0252617. doi: 10.1371/journal.pone.0252617.
  • Coelho LE, Luz PM, Pires DC, et al. Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: a population-based serosurvey. Lancet Regional Health – Americas [Internet]; 2022 [cited 2023 Mar 27]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337985/.
  • Nicholson S, Karapanagiotidis T, Khvorov A, et al. Evaluation of 6 commercial SARS-CoV-2 serology assays detecting different antibodies for clinical testing and serosurveillance. Open Forum Infect Dis. 2021;8(7):ofab239. doi: 10.1093/ofid/ofab239.
  • Galipeau Y, Greig M, Liu G, et al. Humoral responses and serological assays in SARS-CoV-2 infections. Front Immunol. 2020;11:610688. doi: 10.3389/fimmu.2020.610688.
  • Cromer D, Steain M, Reynaldi A, et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2022;3(1):e52–e61. doi: 10.1016/S2666-5247(21)00267-6.
  • Considerations for the 2023 COVID-19 vaccine program in Ontario; 2023. Available from: https://www.publichealthontario.ca/-/media/Documents/nCoV/Vaccines/2023/02/oiac-considerations-2023-covid-19-vaccine-program-ontario.pdf?rev=a9acb37632a04d8880c74dc925fef690&sc_lang=en.
  • Recommendations: COVID-19 vaccine booster doses for adolescents. Available from: https://www.publichealthontario.ca/-/media/Documents/nCoV/Vaccines/2022/03/covid-19-booster-doses-adolescents-oiac.pdf?rev=2e7a1fbfc65f4b85960830219a61447b&sc_lang=en.
  • Updated recommendation: Co-administration of COVID-19 vaccines. Available from: https://www.publichealthontario.ca/-/media/Documents/nCoV/Vaccines/2023/02/oiac-updated-recommendations-co-covid-19-vaccines-children.pdf?rev=e22ba9b7c7f24635943b217ebcf29f8c&sc_lang=en.
  • Government of Canada invests new funding for post COVID-19 condition, in line with recommendations from the Chief Science Advisor’s report – Canada.ca [Internet]; 2023 [cited 2023 Mar 28]. Available from: https://www.canada.ca/en/public-health/news/2023/03/government-of-canada-invests-new-funding-for-post-covid-19-condition-in-line-with-recommendations-from-the-chief-science-advisors-report.html.
  • Nam M, Yun SG, Kim S-W, et al. Humoral and cellular immune responses to vector, mix-and-match, or mRNA vaccines against SARS-CoV-2 and the relationship between the two immune responses. Microbiol Spectr. 2022;10(4):e0249521. doi: 10.1128/spectrum.02495-21.
  • Bayarri-Olmos R, Idorn M, Rosbjerg A, et al. SARS-CoV-2 neutralizing antibody responses towards full-length spike protein and the receptor-binding domain. J Immunol. 2021;207(3):878–887. doi: 10.4049/jimmunol.2100272.
  • Moore JP, Offit PA. SARS-CoV-2 vaccines and the growing threat of viral variants. JAMA. 2021;325(9):821–822. doi: 10.1001/jama.2021.1114.
  • Noval MG, Kaczmarek ME, Koide A, et al. Antibody isotype diversity against SARS-CoV-2 is associated with differential serum neutralization capacities. Sci Rep. 2021;11(1):5538. doi: 10.1038/s41598-021-84913-3.
  • Harrington WE, Trakhimets O, Andrade DV, et al. Rapid decline of neutralizing antibodies is associated with decay of IgM in adults recovered from mild COVID-19. Cell Rep Med. 2021;2(4):100253. doi: 10.1016/j.xcrm.2021.100253.
  • Zhu F, Althaus T, Tan CW, et al. WHO international standard for SARS-CoV-2 antibodies to determine markers of protection. Lancet Microbe. 2022;3(2):e81–e82. doi: 10.1016/S2666-5247(21)00307-4.
  • Wajnberg A, Amanat F, Firpo A, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;370(6521):1227–1230. doi: 10.1126/science.abd7728.
  • Lau EH, Hui DS, Tsang OT, et al. Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection. eClinicalMedicine. 2021;41:101174. doi: 10.1016/j.eclinm.2021.101174.
  • Liu L, To KK-W, Chan K-H, et al. High neutralizing antibody titer in intensive care unit patients with COVID-19. Emerg Microbes Infect. 2020;9(1):1664–1670. doi: 10.1080/22221751.2020.1791738.
  • Hendriks J, Schasfoort R, Koerselman M, et al. High titers of low affinity antibodies in COVID-19 patients are associated with disease severity. Front Immunol. 2022;13:867716. doi: 10.3389/fimmu.2022.867716.
  • Bonelli F, Sarasini A, Zierold C, et al. Clinical and analytical performance of an automated serological test that identifies S1/S2-neutralizing IgG in COVID-19 patients semiquantitatively. J Clin Microbiol. 2020;58(9):e01224-20. doi: 10.1128/JCM.01224-20.
  • Lee WT, Girardin RC, Dupuis AP, et al. Neutralizing antibody responses in COVID-19 convalescent sera. J Infect Dis. 2021;223(1):47–55. doi: 10.1093/infdis/jiaa673.
  • Błaszczuk A, Michalski A, Sikora D, et al. Antibody response after SARS-CoV-2 infection with the Delta and omicron variant. Vaccines. 2022;10(10):1728. doi: 10.3390/vaccines10101728.
  • Sheward DJ, Kim C, Fischbach J, et al. Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies. Lancet Infect Dis. 2022;22(11):1538–1540. doi: 10.1016/S1473-3099(22)00663-6.
  • Cao Y, Yisimayi A, Jian F, et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by omicron infection. Nature. 2022;608(7923):593–602. doi: 10.1038/s41586-022-04980-y.
  • Wang Q, Guo Y, Iketani S, et al. Antibody evasion by SARS-CoV-2 omicron subvariants BA.2.12.1, BA.4 and BA.5. Nature. 2022;608(7923):603–608. doi: 10.1038/s41586-022-05053-w.
  • Röltgen K, Boyd SD. Antibody and B cell responses to SARS-CoV-2 infection and vaccination. Cell Host Microbe. 2021;29(7):1063–1075. doi: 10.1016/j.chom.2021.06.009.
  • Su Y, Yuan D, Chen DG, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185(5):881–895.e20. doi: 10.1016/j.cell.2022.01.014.
  • Measles – serology [Internet]. Public Health Ontario; 2023 [cited 2023 Apr 13]. Available from: https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Measles-Diagnostic-Serology.
  • Prenatal – Serology [Internet]. Public Health Ontario; 2023 [cited 2023 Apr 13]. Available from: https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Prenatal-Serology.
  • Hepatitis C – diagnostic serology [Internet]. Public Health Ontario; 2023 [cited 2023 Apr 13]. Available from: https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Hepatitis-C-Diagnostic-Serology.
  • Westendorf K, Žentelis S, Wang L, et al. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Rep. 2022;39(7):110812. doi: 10.1016/j.celrep.2022.110812.
  • Anti-SARS-CoV-2 monoclonal antibodies [Internet]. NIH COVID-19 treatment guidelines’; 2022 [cited 2022 Dec 2]. Available from: https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals-including-antibody-products/anti-sars-cov-2-monoclonal-antibodies/.
  • Bierle DM, Ganesh R, Tulledge-Scheitel S, et al. Monoclonal antibody treatment of breakthrough COVID-19 in fully vaccinated individuals with high-risk comorbidities. J Infect Dis. 2022;225(4):598–602. doi: 10.1093/infdis/jiab570.
  • Bailey JJ, Morris AM, Bean S, et al. Evidence-based recommendations on the use of anti-SARS-CoV-2 monoclonal antibodies (casirivimab + imdevimab, and sotrovimab) for adults in Ontario [Internet]. Ontario COVID-19 Science Advisory Table; 2021 [cited 2022 Dec 28]. Available from: https://covid19-sciencetable.ca/sciencebrief/evidence-based-recommendations-on-the-use-of-anti-sars-cov-2-monoclonal-antibodies-casirivimab-imdevimab-and-sotrovimab-for-adults-in-ontario/.
  • Dougan M, Azizad M, Mocherla B, et al. A randomized, placebo-controlled clinical trial of bamlanivimab and etesevimab together in high-risk ambulatory patients with COVID-19 and validation of the prognostic value of persistently high viral load. Clin Infect Dis. 2022;75(1):e440–e449. doi: 10.1093/cid/ciab912.
  • Brobst B, Borger J. Benefits and risks of administering monoclonal antibody therapy for coronavirus (COVID-19). StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Nov 16]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK574507/.
  • Cohen MS. Monoclonal antibodies to disrupt progression of early covid-19 infection. N Engl J Med. 2021;384(3):289–291. doi: 10.1056/NEJMe2034495.
  • Yamasoba D, Kosugi Y, Kimura I, et al. Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies. Lancet Infect Dis. 2022;22(7):942–943. doi: 10.1016/S1473-3099(22)00365-6.
  • Lundgren JD, Grund B, Barkauskas CE, et al. Responses to a neutralizing monoclonal antibody for hospitalized patients with COVID-19 according to baseline antibody and antigen levels: a randomized controlled trial. Ann Intern Med. 2022;175(2):234–243. doi: 10.7326/M21-3507.
  • Post-COVID conditions: information for healthcare providers. Centers for Disease Control and Prevention; 2020 [cited 2023 May 19). Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html.
  • Castanares-Zapatero D, Chalon P, Kohn L, et al. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022;54(1):1473–1487. doi: 10.1080/07853890.2022.2076901.
  • Matta J, Wiernik E, Robineau O, et al. Association of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms among French adults during the COVID-19 pandemic. JAMA Intern Med. 2022;182(1):19–25. doi: 10.1001/jamainternmed.2021.6454.
  • Fogh K, Larsen TG, Hansen CB, et al. Self-reported long COVID and its association with the presence of SARS-CoV-2 antibodies in a Danish cohort up to 12 months after infection. Microbiol Spectr. 2022;10(6):e0253722. doi: 10.1128/spectrum.02537-22.
  • Klein J, Wood J, Jaycox J, et al. Distinguishing features of long COVID identified through immune profiling. medRxiv. 2022 Aug 10;2022.08.09.22278592. doi: 10.1101/2022.08.09.22278592.
  • García-Abellán J, Padilla S, Fernández-González M, et al. Antibody response to SARS-CoV-2 is associated with long-term clinical outcome in patients with COVID-19: a longitudinal study. J Clin Immunol. 2021;41(7):1490–1501. doi: 10.1007/s10875-021-01083-7.
  • Augustin M, Schommers P, Stecher M, et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. Lancet Reg Health Eur. 2021;6:100122. doi: 10.1016/j.lanepe.2021.100122.
  • Talla A, Vasaikar SV, Lemos MP, et al. Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence [internet]. bioRxiv2021; 2023 [cited May 19]. doi: 10.1101/2021.05.26.442666.
  • Horn MP, Jonsdottir HR, Brigger D, et al. Serological testing for SARS‐CoV‐2 antibodies in clinical practice: a comparative diagnostic accuracy study. Allergy. 2022;77(7):2090–2103. doi: 10.1111/all.15206.
  • Alefishat E, Jelinek HF, Mousa M, et al. Immune response to SARS-CoV-2 variants: a focus on severity, susceptibility, and preexisting immunity. J Infect Public Health. 2022;15(2):277–288. doi: 10.1016/j.jiph.2022.01.007.
  • Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: Current state of the science. Immunity. 2020;52(6):910–941. doi: 10.1016/j.immuni.2020.05.002.
  • Ni L, Ye F, Cheng M-L, et al. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity. 2020;52(6):971–977.e3. doi: 10.1016/j.immuni.2020.04.023.
  • Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383(25):2427–2438. doi: 10.1056/NEJMoa2028436.
  • Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396(10249):467–478. doi: 10.1016/S0140-6736(20)31604-4.
  • Galson JD, Schaetzle S, Bashford-Rogers RJM, et al. Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures. Frontiers in Immunology [Internet]; 2020 [cited 2022 Dec 21]. doi: 10.3389/fimmu.2020.605170.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.