key: cord-0711776-ciyp02yv authors: Ivanov, Andrei; Semenova, Elena title: Long‐term monitoring of the development and extinction of IgA and IgG responses to SARS‐CoV‐2 infection date: 2021-07-06 journal: J Med Virol DOI: 10.1002/jmv.27166 sha: 1cddc8c3a6f48a1e2c71846309931045ac755c80 doc_id: 711776 cord_uid: ciyp02yv Despite the great interest of the scientific community in the behavior of the human body after contact with the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), long‐term (more than 6 months) monitoring of the immunological status of patients with coronavirus disease 2019 (COVID‐19) having varying severity degrees and of the people with a low SARS‐CoV‐2 viral load is practically absent. The aim of this study is a 9‐month monitoring of SARS‐CoV‐2 infection immune response development and extinction using quantitative assessment of IgA and IgG levels in the blood of healthy donors living in the context of the coronavirus pandemic and of the patients who have undergone COVID‐19. The project involved 180 volunteers, of whom 51 persons (28.33%) fell ill with COVID‐19 during the observation period. All people who underwent COVID‐19 developed a stable humoral immune response but their individual immune status had a number of features. Approximately 39.22% (20 of 51 people) of project participants diagnosed with COVID‐19 showed an unusual change in plasma anti‐SARS‐CoV‐2 IgA levels. Relatively high levels of IgA (ratio ~ 3) after recovery persisted for a long time (more than 6 months). In one‐third (17 of 51 people) of patients with COVID‐19, the IgA level exceeded the IgG level. IgA antibodies appeared earlier and showed a stronger and more robust response to the SARS‐CoV‐2 virus than IgG. Increased levels of anti‐SARS‐CoV‐2 IgA (ratio from 0.8 to 2.36) throughout the observation period were recorded in 28 of 180 project participants (15.56%) of whom only one person fell ill with COVID‐19. At the initial stage, COVID-19 was diagnosed with a positive PCR test. Subsequently, the disease severity was assessed based on the project participants' testimony. In all patients with COVID-19 (51 people) the disease was asymptomatic or relatively mild. No serious or critical conditions were recorded. No one was hospitalized. In most cases of mild COVID-19, symptoms of a mild respiratory illness were observed: malaise, accompanied by a slight increase in temperature for several days, headache, and runny cough. In 14 project participants, a short-term loss of smell was noted. The authors declare that the use of human biological material (blood and flushes from the mucous membranes of the nose and throat) was The presence of SARS-CoV-2 virus RNA was tested with RT-PCR using the swabs from nose and throat mucous membranes. A fully automatic Cobas 6800 platform and reagents manufactured by Roche (Switzerland) were used. All reactions were performed in accordance with the manufacturer's instructions. Immunoassay for anti-SARS-CoV-2 IgA and IgG semiquantitative determination in serum was carried out using Euroimmun (Lubeck) reagent kits. The S1 domain of the SARS-CoV-2 thorn glycoprotein was used as an antigen. Venous blood was collected on an empty stomach using vacuum tubes Lind-Vac with a coagulation activator and gel. HydroFlex automatic microplate washer, Infinite F50 reader, and Magellan V.7.2. software (all by Tecan) were used. Euroimmun recommends interpreting results as follows: ratio less than 0.8-negative for both IgA and IgG. Calculate the ratio according to the following formula: Extinction of the control or patient sample/Extinction of calibrator. were diagnosed with COVID-19 using PCR analysis during the observation period. Consequently, there is no significant difference in the number of men and women with COVID-19. The peak incidence occurred in November 2020-January 2021 but there were several cases in June-July 2020. The mean age of non-COVID-19 patients in both groups (men and women) was 34.11 ± 6.23 years and the average age of study participants who had COVID-19 during the observation period is 34.01 ± 5.73 years. Thus, no relationship was found between the age of the study participants and the susceptibility to SARS-CoV-2. Analysis of the COVID-19 patients' plasma samples interaction with antibodies against the S-protein from SARS-CoV-2 and SARS-CoV also reveals cross-reactivity. 21 About 3% of a fairly large group of healthy volunteers without COVID-19 gave a positive response to the presence of SARS-CoV-2 specific IgA. 22 In 7% of blood samples from patients with COVID-19, borderline cross-reactivity of IgA and IgG antibodies with human coronaviruses NL63 and OC43 is found. 23 However, in the present study, the percentage of people with elevated IgA levels was higher. In addition, there was a slight increase in the mean anti-SARS-CoV-2 IgA level (ratio 0.8-1.2) over time in this group ( Figure 3A) . Apparently, this phenomenon was not the result of the cross-reactivity alone. It is possible that SARS-CoV-2-specific IgA plays an independent role in providing protective immunity at low viral loads. However, elevated IgA levels were not absolute protection against COVID-19 disease: one of the project participants who demonstrated elevated plasma IgA values for a long period was diagnosed with COVID-19 after 4 months of observation ( Figure 1D ). 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