Şiddetli akut solunum sendromu koronavirüs-2'nin (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) etiyolojik etkeni olduğu koronavirüs hastalığı 2019 (coronavirus disease 2019; COVID-19) pandemisi, mevcut ve olası sonuçları açısından tüm dünyayı etkisi altına almıştır. COVID-19 oldukça özgün virolojik, klinik ve immünolojik karakteristik özelliklere sahiptir. COVID-19 tanılı hastalarda SARS-CoV-2'ye karşı antikor yanıtlarının karakterize edilmesi ve tanımlanması, salgının dinamiklerinin anlaşılması ve daha etkin mücadele stratejilerinin geliştirmesi için kritik önem taşımaktadır. SARSCoV-2'ye karşı humoral immün yanıtlara ilişkin bazı belirsizlikler mevcuttur. Bunlardan ilki SARS-CoV-2 enfeksiyonuna karşı oluşan B hücre bellek yanıtlarının süresi ile ilgilidir. Bir virüse yönelik uygun B hücre yanıtlarının, reenfeksiyonlara karşı koruyucu olması beklenir. Buna karşın mevcut veriler, COVID-19 enfeksiyonu sonrası antikor aracılı bağışıklığın, reenfeksiyona karşı koruyucu etkinliğinin sınırlı olduğuna işaret etmektedir. Bir diğer sorun ise serokonversiyonu belirlemek ve antikor yanıtlarını ölçmek amacıyla kullanılan serolojik deneylerin özgüllüğü ve validasyonu ile ilişkilidir. COVID-19'da hastaların bir kısmında antikor yanıtlarının zayıf olması ve diğer CoV'ler ile ilişkili çapraz reaktivitenin varlığı, serolojik deneylerin güvenirliliğini sınırlandırabilmektedir. Bu nedenle anti-SARS-CoV-2 antikorlarının kinetiği, antikor ilişkili immünitenin etkinliği ve immünopatogenezinin anlaşılması ile spesifik ve valide serolojik testlerin geliştirilmesi hususunda yoğun bir araştırma çabası mevcuttur. Bu derlemede anti-SARSCoV-2 antikorlarının kinetiği, antikor aracılı immünitenin etkinliği ve serolojik tanıya yönelik gelişmelerin irdelenmesi amaçlamıştır.
Anahtar Kelimeler: SARS-CoV-2; COVID-19; antikor yanıtları; B hücre bellek yanıtları; reenfeksiyon; nötralzan antikorlar; serolojik deneyler; bağışıklık belgesi
Coronavirus disease-2019 (COVID-19) pandemic which is the etiological agent of severe acute respiratory syndrome-associated a coronavirus (SARS-CoV-2) has influenced the whole world with the current and possible results. COVID-19 has very unique characteristic of virological, clinical and immunological. Characterization and identification of antibody responses against SARS-CoV-2 in patients with COVID-19 is critical for understanding the dynamics of the outbreak and to developed more effective interventions strategies. Some of gaps about humoral immune responses to SARS-CoV-2. The first of these is about life-span of B cell memory responses to SARS-CoV-2 infection. It is expected that eligible B cell response to a virus prevents reinfection. However, current evidence is pointed that effectiveness of prevent against reinfection to antibody-mediated immunity after COVID-19 infection is limited. Second else challenge is about to specificity and validation of serological assay used to determine seroconversion and measure antibody responses. In COVID-19, weak antibody responses in some patients and the presence of cross-reactivity associated with other CoVs may limit the reliability of serological experiments. Therefore, there is an intense research effort to reveal kinetics, effectiveness of antibody-mediated immunity and immunopathogenesis of antiSARS-CoV-2 antibodies with to develop specific and validated serological tests. In this review, it is aimed to examination about kinetics of anti-SARS-CoV-2 antibodies, effectiveness of antibody-mediated immunity with also advances in serological diagnosis.
Keywords: SARS-CoV-2; COVID-19; antibody responses; B cell memory responses; reinfection; neutralizing antibodies; serological assays; immunity passports
- Lee N, Chan PKS, Ip M, Wong E, Ho J, Ho C, et al. Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome. J Clin Virol. 2006;35(2):179-84. [Crossref] [PubMed] [PMC]
- Huang AT, Garcia-Carreras B, Hitchings MDT, Yang B, Katzelnick LC, et al. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv. 2020;2020.04.14.20065771. [Crossref] [PubMed]
- Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020;ciaa344. [Crossref] [PubMed]
- Wajnberg A, Mansour M, Leven E, Bouvier NM, Patel G, Firpo A, et al. Humoral immune response and prolonged PCR positivity in a cohort of 1343 2 SARS-CoV 2 patients in the New York City region. medRxiv. 2020. [Crossref] [PMC] :
- Cao WC, Liu W, Zhang, PH, Zhang F, Richardus JH. Disappearance of antibodies to SARS-associated coronavirus after recovery. N Engl J Med. 2007;357(11):1162-3. [Crossref] [PubMed]
- Zhou W, Wang W, Wang H, Lu R, Tan W. First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood. BMC Infect Dis. 2013;13:433. [Crossref] [PubMed] [PMC]
- Schmidt OW, Allan ID, Cooney MK, Foy HM, Fox JP. Rises in titers of antibody to human coronaviruses OC43 and 229E in Seattle families during 1975-1979. Am J Epidemiol. 1986;123(5):862-8. [Crossref] [PubMed] [PMC]
- Gorse GJ, Donovan MM, Patel GB. Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnesses. J Med Virol. 2020;92(5):512-7. [Crossref] [PubMed] [PMC]
- Gaunt ER, Hardie A, Claas ECJ, Simmonds P, Templeton KE. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol. 2010;48(8):2940-7. [Crossref] [PubMed] [PMC]
- Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020;26(4):453-5. [Crossref] [PubMed] [PMC]
- 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 2019 patients. Emerg Infect Dis. 2020;26(7):1478-88. [Crossref] [PubMed] [PMC]
- Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105(2):435-46. [Crossref] [PubMed] [PMC]
- Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020;368(6493)860-8. [Crossref] [PubMed] [PMC]
- Eyal N, Lipsitch M, Smith PG. Human challenge studies to accelerate coronavirus vaccine licensure. J Infect Dis. 2020;221(11)1752-6. [Crossref] [PubMed] [PMC]
- Chan KH, Chan JFW, Tse H, Chen H, Lau CCY, Cai JP, et al. Cross-reactive antibodies in convalescent SARS patients' sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests. J Infect. 2013;67(2):130-40. [Crossref] [PubMed] [PMC]
- Yu Y, Jin H, Chen Z, Yu QL, Ma YJ, Sun XL, et al. Children's vaccines do not induce cross reactivity against SARS-CoV. J Clin Pathol. 2007;60(2):208-11. [Crossref] [PubMed] [PMC]
- Wu F, Wang A, Liu M, Wang Q, Chen J, Xia S, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv. [Crossref]
- 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. medRxiv. 2020;2020.03.17.20037713. [Crossref] [PubMed]
- Stadlbauer D, Amanat F, Chromikova V, Jiang K, Strohmeier S, Arunkumar GA, et al. SARS-CoV-2 seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup. Curr Protoc Microbiol. 2020;57(1):e100. [Crossref] [PubMed] [PMC]
- Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. SARS-CoV-2 specific antibody responses in COVID-19 patients. medRxiv. [Crossref]
- Stadlbauer D, Amanat F, Chromikova V, Jiang K, Strohmeier S, Arunkumar GA, et al. SARS-CoV-2 seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup. Curr Protoc Microbiol. 2020;57(1):e100. [Crossref] [PubMed] [PMC]
- Tan CW, Chia WN, Qin X, Liu P, Chen MIC, Tiu C, et al. A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nature Biotechnology. 2020; [Crossref] [PubMed]
- Meyer B, Drosten C, Müller MA. Serological assays for emerging coronaviruses: challenges and pitfalls. Virus Res. 2014;194:175-83. [Crossref] [PubMed] [PMC]
- Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181(2):281-92.e6. [Crossref] [PubMed] [PMC]
- Paules CI, Marston HD, Fauci AS. Coronavirus infections-more than just the common cold. JAMA. 2020. [Crossref] [PubMed]
- Tortorici MA, Walls AC, Lang Y, Wang C, Li Z, Koerhuis D, et.al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol. 2019;26(6):481-9. [Crossref] [PubMed] [PMC]
- Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol. 2016;3(1):237-61. [Crossref] [PubMed] [PMC]
- Lv H, Wu NC, Tsang OTY, Yuan M, Perera RAPM, Leung WS, et al. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. bioRxiv. 2020;2020.03.15.993097. [Crossref] [PubMed]
- Petherick A. Developing antibody tests for SARS-CoV-2. Lancet. 2020;395(10230):1101-2. [Crossref] [PubMed]
- Ju B, Zhang Q, Ge X, Wang R, Yu J, Shan S, et al. Potent human neutralizing antibodies elicited by SARS-CoV-2 infection. bioRxiv. 2020. [Crossref]
- Hachim A, Kavian N, Cohen CA, Chin AWH, Chu DKW, Mok CKP, et al. Beyond the spike: identification of viral targets of the antibody responses to SARS-CoV-2 in COVID-19 patients. medRxiv. 2020. [Crossref]
- Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265-9. [Crossref] [PubMed] [PMC]
- 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. [PubMed]
- World Health Organization. "Immunity passports" in the context of COVID-19. www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19
.: Process List