Harika Öykü DİNÇ, Mehmet DEMİRCİ, Yusuf Emre ÖZDEMİR, Serhat SİREKBASAN, Ayse Nur AKTAŞ, Yeşim Tuyji TOK, Doğukan ÖZBEY, Rüveyda AKÇİN, Nesrin GAREAYAGHİ, Mert Ahmet KUŞKUCU, Kenan MİDİLLİ, Gökhan AYGÜN, Suat SARIBAŞ, Bekir KOCAZEYBEK

Anti-SARS-CoV-2 IgG and Neutralizing Antibody Levels in Patients with Past COVID-19 Infection: A Longitudinal Study

Background: Monitoring the longevity of immunoglobulin G (IgG) responses following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is vital to understanding the role of antibodies in preventing infection. Aims: To determine the quantitative IgG responses specific to the Spike-S1 (S1) receptor-binding domain (S1/RBD) region of the virus in serum samples taken between 4 weeks and 7 months after polymerase chain reaction (PCR) positivity in patients who are diagnosed with coronavirus disease-2019 (COVID-19). Study Design: A longitudinal study. Methods: This study included 113 patients with a clinical and molecular diagnosis of COVID-19. The first and second serum samples were taken 1 and 7 months, respectively, after the PCR positivity. S1/ RBD-specific IgG antibody response was assayed using anti-SARS- CoV-2 QuantiVac ELISA (IgG) kit (Euroimmun, Lübeck, Germany). The neutralizing antibodies were investigated in 57 patients whose IgG test results were above the cut-off value. Results: In 57 patients with SARS-CoV-2 IgG, the anti-SARS-CoV-2 IgG quantitative antibody levels significantly decreased after 7 months (Z = −2.197, p = 0.028). A correlation was detected between the anti- SARS-CoV-2 IgG and nAb percent inhibition (IH%) levels detected in 1 month (rs = 0.496, p < 0.001), but without significant correlation in serum samples taken on 7 months. The nAb IH% levels of the first and second were compared for COVID-19 severity and revealed no statistical difference (p = 0.256). In the second serum sample, the nAb IH%s of patients with moderate COVID-19 showed a statistically significant difference from patients with mild COVID-19 (p = 0.018), but without significant differences between severe and moderate or mild COVID-19. Conclusion: SARS-CoV-2 quantitative IgG antibody titers are significantly reduced at long-term follow-up (> 6 months). Due to the limited information on seroconversion, comprehensive studies should be conducted for long-term follow-up of the immune response against SARS-CoV-2.

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1. Word Health Organization (WHO). Coronavirus disease (COVID-2019) situation reports. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/ situation-reports [CrossRef]
2. Zhu N, Zhang D, Wang W, et al. A novel Coronavirus from Patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733. [CrossRef]
3. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020;71:2027-2034. [CrossRef]
4. Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584:450-456. [CrossRef]
5. Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020;ciaa478. doi: 10.1093/cid/ciaa478. Online ahead of print. [CrossRef]
6. Muecksch F, Wise H, Batchelor B, et al. Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients. J Infect Dis. 2021;223:389-398. [CrossRef]
7. Legros V, Denolly S, Vogrig M, et al. A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity. Cell Mol Immunol. 2021;18:318-327. [CrossRef]
8. McKeigue PM, Weir A, Bishop J, et al. Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT- SCOT): A population-based case-control study. PLoS Med. 2020;17:e1003374. [CrossRef]
9. Romero Starke K, Petereit-Haack G, Schubert M, et al. The Age-Related Risk of Severe Outcomes Due to COVID-19 Infection: A Rapid Review, Meta-Analysis, and Meta-Regression. Int J Environ Res Public Health. 2020;17:5974. [CrossRef]
10. Ali N. Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID-19. J Med Virol. 2020;92:2409-2411. [CrossRef]
11. Lu C, Liu Y, Chen B, et al. Prognostic value of lymphocyte count in severe COVID-19 patients with corticosteroid treatment. Signal Transduct Target Ther. 2021;6:106. [CrossRef]
12. Yamasaki Y, Ooka S, Tsuchida T, et al. The peripheral lymphocyte count as a predictor of severe COVID-19 and the effect of treatment with ciclesonide. Virus Res. 2020;290:198089. [CrossRef]
13. Wang Y, Zhang L, Sang L, et al. Kinetics of viral load and antibody response in relation to COVID-19 severity. J Clin Invest. 2020;130:5235-5244. [CrossRef]
14. Zhang J, Lin H, Ye B, et al. One-year sustained cellular and humoral immunities of COVID-19 convalescents. Clin Infect Dis. 2021;iab884. [CrossRef]
15. Gillot C, Favresse J, Maloteau V, Dogné JM, Douxfils J. Dynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2 Infection and Correlation with Commercial Serologic Tests. A Reappraisal and Indirect Comparison with Vaccinated Subjects. Viruses. 2021;13:2329. [CrossRef]
16. Hou H, Wang T, Zhang B, et al. Detection of IgM and IgG antibodies in patients with coronavirus disease 2019. Clin Transl Immunology. 2020;9:e01136. [CrossRef]
17. Ren L, Fan G, Wu W, et al. Antibody Responses and Clinical Outcomes in Adults Hospitalized With Severe Coronavirus Disease 2019 (COVID-19): A Post hoc Analysis of LOTUS China Trial. Clin Infect Dis. 2021;72:e545-e551. [CrossRef]
18. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581:465-469. [CrossRef]