key: cord-0722507-mmnv0bln authors: Lin‐Wang, Hui T.; Lemes, Rogerio C.; da Silva Farias, Eduardo; Bajgelman, Marcio C.; Franchini, Kleber G.; Viana, Renata; Gun, Carlos title: Sequential IgG antibody monitoring for virus‐inactivated and adenovirus‐vectored COVID‐19 vaccine in Brazilian healthcare workers date: 2022-04-27 journal: J Med Virol DOI: 10.1002/jmv.27782 sha: d6a7f970e13d79e5f592e1a9c229ed31b091bec9 doc_id: 722507 cord_uid: mmnv0bln Vaccination certainly is the best way to fight against the COVID‐19 pandemic. In this study, the seroconversion effectiveness of two vaccines against severe acute respiratory syndrome coronavirus 2 was assessed in healthcare workers: virus‐inactivated CoronaVac (CV, n = 303), and adenovirus‐vectored Oxford–AstraZeneca (AZ, n = 447). The immunoglobulin G (IgG) antibodies anti‐spike glycoprotein and anti‐nucleocapsid protein were assessed by enzyme‐linked immunosorbent assay at the time before vaccination (T1), before the second dose (T2), and 30 days after the second dose (T3). Of all individuals vaccinated with AZ, 100% (n = 447) exhibited seroconversion, compared to 91% (n = 276) that were given CV vaccine. Among individuals who did not respond to the CV, only three individuals showed a significant increase in the antibody level 4 months later the booster dose. A lower seroconversion rate was observed in elders immunized with the CV vaccine probably due to the natural immune senescence, or peculiarity of this vaccine. The AZ vaccine induced a higher humoral response; however, more common side effects were also observed. Nonvaccinated convalescent individuals revealed a similar rate of anti‐spike IgG to individuals that were given two doses of CV vaccine, which suggests that only a one‐shot COVID‐19 vaccine could produce an effective immune response in convalescents. SARS-CoV-2 were assessed in this study. The first one is CoronaVac (CV), which was developed by Sinovac Life Sciences in partnership with the Butantan Institute (São Paulo, Brazil), using a classical inactivated virus approach. 14 Data showed that after two consecutive doses, the humoral response induced by CV was detected in around 99.0% of individuals, 15, 16 and the efficacy to avoid severe symptoms and death was 50.38%. 17 Other vaccine, ChAdOx1 nCoV-19 (AZD1222), was developed by the University of Oxford and the AstraZeneca company (AZ) in collaboration with Fiocruz (Rio de Janeiro, Brazil). This is a vector-based vaccine using a recombinant nonreplicating chimpanzee adenovirus as a vector, 14 the efficacy observed was 90.0%. 18 All vaccines follow the same final pathway, basically, a major histocompatibility complex (MHC) Class I or Class II on the professional antigen-presenting cells display the virus fragment (peptides) to antigen-specific CD8+ cytotoxic T-cell or CD4+ T-helper cell, respectively, and trigger B cells for the antibody production. 13 MHC I and MHC II molecules are extremely polymorphic; above 10 000 different alleles of MHC I molecules have been identified, 19 suggesting that the same vaccine could induce a different immune response due to genetic diversity. This prospective longitudinal study aimed to assess the seroconversion effectiveness of two vaccines used in Brazil at the beginning of the COVID-19 pandemic and contribute to a better understanding of anti-SARS-CoV-2 protective immunity. All healthcare workers, administrative and support staff working at our hospital, and those who agreed to receive anti-SARS-CoV-2 vaccines were eligible for this study. Vaccination was performed with a dose of 0.5 ml, respecting the recommended interval between the first and second doses, 28 days for CV and 90 days for AZ vaccine. A total of 1362 individuals were vaccinated between January and February of 2021, 470 (34.5%) immunized with CV, and 892 (65.5%) with AZ vaccine. However, only 303 in the CV group and 447 in the AZ group completed the planned blood collection scheme for this study. Those without three samples collected were withdrawn from the study. Three sequential blood samples were obtained via antecubital venipuncture by using BD Vacutainer serum collection tubes on the vaccination day, before the first dose (T1), before the second dose (T2), and 30 days after the second dose (T3). All samples were collected between January to July 2021. All serum samples were stored at −30°C in single-use aliquots. The protocol to assess the anti-SARS-CoV-2 antibody was based on our previous publication. 20, 21 Ten COVID-19 negative serums and another 10 positive serums were pooled and rerun on every assay plate as interassay control. Results higher than the cutoff value of 0.300 optical density (OD) were reported as positive for the anti-SARS-CoV-2 antibody. Numeric variables with a normal distribution were presented as mean ± standard deviation and compared by the t-test, whereas those without a normal distribution were presented as median and interquartile range and compared by using the Mann-Whitney U test or Kruskal-Wallis test. Categorical variables were presented in percentage and were compared by using the Pearson χ 2 test or Fisher's exact test, when appropriate. Statistical significance p < 0.05. The research subjects were categorized into three groups, according to the vaccine-induced immune response: no responder, responder, and previous sensitized (Table 1) . Although there was no significance in gender between the groups, the massive participation of women in this study was observed (n = 543; 72.4%). The group of nonresponders immunized with CV was significantly older (57.8 vs. 48.6 and 45 years; p < 0.05). There were no differences in the race or ethnicity variable. The number of individuals previously infected by SARS-CoV-2 was higher between nurses or nursing assistants than in other staff groups in both vaccines, CV (p < 0.05) and AZ (p = 0.029). Similar results were also observed in professionals who were exposed to SARS-CoV-2 at work, CV (p = 0.014), and AZ (p = 0.025). The percentage of individuals with hypertension and diabetes is significantly higher in the nonresponders group immunized with CV, this is probably associated with the elderly people in this group. However, individuals that were immunized with the AZ vaccine exhibited higher rates of anti-spike IgG, which were even potentiated when individuals were previously exposed to SARS-CoV-2 ( Figure 2 ). The CV vaccine is produced with the whole virus-inactivated particles, then antibody anti-nucleocapsid was assessed to confirm the specificity of the enzyme-linked immunosorbent assay (ELISA). The statistics analyzed by the Pearson test showed a good correlation between the level of antibodies against spike proteins and nucleocapsid protein (Figure 4 ). With only one dose of vaccine, 2 (0.7%) in the group immunized by In this study, the number of participants who reported any side effects, such as headache, myalgia, fatigue, and fiver was significantly higher in the AZ group than in the CV. Additionally, the percentage of individuals who reported any side effects following the first and second dose of the AZ vaccine was 55.8% and 42.2%, respectively, which is in line with 50.15% and 52.6% of other studies. 18, 25 The data in the literature suggests that adenovirus-vectored vaccines usually induce more side effects. [24] [25] [26] The serological analysis of samples harvested before the vaccination allowed to discriminate those who had been previously exposed to SARS-CoV-2, and allowed to observe the profile of immune response to the vaccine. Before vaccination, 251 out of 750 (33.5%) of our hospital staff enrolled in this study already had antibodies against SARS-CoV-2 spike protein. Our result is slightly higher than the research reported by University Hospitals Birmingham NHS Foundation Trust, the UK in April 2020, which revealed an overall seroprevalence of 24.4% (n = 126/516). 27 However, these data are noticeably higher than another Brazilian study reported by Oliveira et al., 28 which observed 5.5% of seroprevalence among individuals enrolled between March and July 2020. These conflicting results are probably because the study was performed more than 1 year before ours, and also before the worst COVID-19 pandemic peak in our country. In both vaccines assessed in this study, the previous sensitized group presented a similar level of antibody anti-spike protein in T2 (before the second dose) and T3 (30 days after the second dose). These results suggest that only a single dose may produce efficient antiviral immune responses in COVID-19 convalescents. Some studies are exploring the association between vaccination and autoimmune disease, including GBS. 29, 30 The attributable risk was estimated at one additional case of GBS for every 100 000 doses of influenza vaccine administered. 31 Although the individual risk for autoimmune complications is likely to be small, it raises concerns to better explore adverse effects associated with the use of new technologies, such as adenovirus-vectored or mRNA for mass vaccination. In Brazil, the COVID-19 vaccination has been well accepted, and it is associated with a daily decrease in the death rate caused by COVID-19. 32 However, SARS-CoV-2 mutants that emerged recently (omicron) contain more than 30 changes to spike proteins 33 which may result in loss of antibody neutralization to SARS-CoV-2 in the present vaccinated population and an additional booster shot is now recommended by health authorities. The seroconversion rate was lower among elders immunized with the virus-inactivated vaccine, probably due to the natural immune senescence or peculiarity of this vaccine. The adenovirus-vectored vaccine induced a higher humoral response; however, more common side effects were also observed. The individuals previously exposed to SARS-CoV-2 could receive only one dose of the vaccine, which will be enough to boost an effective immune response. Study design: Hui T. Lin-Wang, Renata Viana, and Carlos Gun. Experiments: Hui T. Lin-Wang. Statistical analysis: Rogerio C. F I G U R E 4 CoronaVac vaccine-induced antibody production against SARS-CoV-2 spike and nucleoprotein at the same level. The serum from 303 individuals immunized by CoronaVac on the day of the (A) second dose (T2) and 30 days after the (B) second dose (T3) was assessed by enzyme-linked immunosorbent assay to detect antibodies anti-spike protein and nucleoprotein. The results showed absorbance (optical density). Statistical analysis was performed by Pearson's two-tailed test (α = 0.05). IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Lemes and Eduardo da Silva Farias. Manuscript preparation: Hui T. Lin-Wang, Marcio C. Bajgelman, and Kleber G. Franchini. The authors would like to thank their colleagues from the Pazzanese de Cardiologia, and LNBio facilities for their technical support. They would also like to thank Marcia F. Maluf for proofreading support, and Dr. Leda Castilho of the Federal University of Rio de Janeiro for providing the spike protein used in the enzymelinked immunosorbent assay. The authors declare no conflicts of interest. The data supporting the findings of this study are available with the corresponding author upon reasonable request. The epidemiology and clinical information about COVID-19 COVID-19: insight into the asymptomatic SARS-CoV-2 infection and transmission Asymptomatic patients as a source of COVID-19 infections: a systematic review and meta-analysis Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical features of patients infected with 2019 novel coronavirus in Wuhan COVID-19 pathophysiology: a review Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19? A Review of coronavirus disease-2019 (COVID-19) Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19 Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 patients SARS-CoV-2/COVID-19: viral genomics, epidemiology, vaccines, and therapeutic interventions COVID-19 vaccines: the status and perspectives in delivery points of view A Review of the progress and challenges of developing a vaccine for COVID-19 Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial Quantitation of antibodies against SARS-CoV-2 spike protein after two doses of CoronaVac in healthcare workers Eficácia global da Coronavac é de 50,38%, anuncia governo paulista Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK Present yourself! By MHC Class I and MHC Class II molecules Serological testing for COVID-19, immunological surveillance, and exploration of protective antibodies Development of low-cost serological immunoassay to detect antiviral antibodies to SARSars-Cov-2 Spike protein Relation between COVID-19 and Guillain-Barré syndrome in adults. Systematic review Guillain-Barré syndrome associated with SARS-CoV-2 The effectiveness of inactivated SARS-CoV-2 vaccine (CoronaVac) on antibody response in participants aged 65 years and older COVID-19 vaccine: side effects after the first dose of the Oxford AstraZeneca vaccine among health professionals in low-income country: Ethiopia Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID symptom study app in the UK: a prospective observational study SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study SARS-CoV-2 seroprevalence and risk factors among health care workers: estimating the risk of COVID-19 dedicated units Vaccination and induction of autoimmune diseases Immunemediated adverse reactions to vaccines Guillain-Barre syndrome, influenza, and influenza vaccination: the epidemiologic evidence Sequential IgG antibody monitoring for virusinactivated and adenovirus-vectored COVID-19 vaccine in Brazilian healthcare workers