Humoral immune response to SARS-CoV-2 in five different groups of individuals at different environmental and occupational risks of infection
In this study, we detected quite a different seroconversion rate against SARS-CoV-2 among the five groups considered, being higher in subjects who were diagnosed with SARS-CoV-2 infection with a virus test. Previously positive RT-PCR on the nasopharynx or oropharynx. swab. Interestingly, the serological test also gave positive results in 61% of hospitalized patients with a clinical diagnosis of COVID-19 disease based on suggestive clinical and laboratory results, but tested negative on two consecutive naso- or oropharyngeal swabs. performed within a week of admission to hospital. .
We have also shown that humoral immunity against SARS-CoV-2 is maintained for at least 6 months and we have identified factors associated with seroconversion.
The present results confirm that a population-based serological test can provide a more accurate estimate of the rate of infection in individuals who have not been diagnosed by the RT-PCR test, and is particularly relevant for detecting asymptomatic subjects. and pauci-symptomatic.ten. In our series, subjects included in group 3 who have had contact or exposure with confirmed cases of SARS-CoV-2 infection could be comparable to asymptomatic individuals. In these subjects, the seroconversion rate was 40%, a figure which, with all the limitations linked to the limited number of subjects considered, is in line with the data in the literature.ten.
Although serological tests are potentially simple and effective as a screening method, they have shown limitations in the diagnosis of acute infections due to the time required to acquire an adaptive immune response.11. However, detection of SARS-CoV-2 antibodies offers the possibility of confirming past exposure, which may be of particular interest in the case of asymptomatic or subclinical transmissions. In addition, these epidemiological studies can help identify the extent of the spread of the virus in specific households, communities and environments, which could help guide control measures.4.12.
A review of 54 studies found that antibody tests done a week after a patient first developed symptoms detected only 30% of patients with COVID-19. Accuracy increased to 72% at two weeks and 94% at week three8. Our study was initiated when the first wave of the pandemic was already weakening and the interval between clinical recovery from COVID-19 disease and serological testing exceeded 4 weeks and, therefore, the performance of the test. are comparable to previously available data.
Studies assessing the epidemiology of SARS-CoV-2 among healthcare workers in different countries have reported wide variation in HIV prevalence data ranging from 1.6 to 31.6%13. Such huge variation likely depended on varying work parameters, types of exposure, rates of transmission of infections in the community, use of personal protective equipment, and methodological differences between studies. In our study, the prevalence rate among physicians working in non-COVID-19 departments or consulting rooms was 28%, no different from those working in dedicated COVID-19 departments. Notably, two Italian studies of healthcare workers in geographic areas with a low incidence of SARS-CoV-2 indicated lower seroconversion rates on the order of 3 to 5%.14.15.
Our study established that HIV status was associated with advanced age, male sex, previous COVID-19 illness, and contact with people infected with SARS-CoV-2. The number of symptoms was linearly increased with the risk of seropositivity, while smoking was inversely associated. These results are consistent with previous observations on population-based studies, reporting that the profession as healthcare workers16 and disease severity were associated with the presence of antibodies, while female gender and smoking were associated with lower antibody levels.17. The correlation between anti-SARS-CoV-2 antibody titer and disease severity, however, is not always consistent between different studies.18.
The negative association between a history of smoking and serological positivity should be viewed with caution. Plausible biological mechanisms while smoking might protect against COVID-19 include an anti-inflammatory effect of nicotine, a blunt immune response in smokers, and an increase in nitric oxide in the respiratory tract in addition to the potential protective role of squamous cell metaplasia, which is usually associated with smoking. At present, however, claims of a protective effect should be viewed with extreme caution and some studies suggest that the effect of smoking should not be interpreted causally given the presence of factors which may have an effect. mediating influence.19.20.
A relevant question concerns whether the seropositive results obtained with the IgM / IgG immunoassays available for SARS-CoV-2 indicate the presence of neutralizing antibodies. In a previously published study, neutralizing antibodies increased in line with immunoglobulin titers after symptom onset21, and the results were confirmed in other studies22.23. One of these studies showed that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have varying degrees of accuracy in predicting the activity of neutralizing antibodies.23. Taken together, these results provide immediate clinical relevance to serological findings which can be equated with the activity of neutralizing antibodies and could serve as a valuable “road map” to guide the choice and interpretation of serological tests for SARS. -CoV-2. However, in a Chinese study, the titers of neutralizing antibodies against SARS-CoV-2 appeared to vary widely, and in 117 patients available for a two-week follow-up appointment, the levels of neutralizing antibodies were significantly reduced compared to at the levels at the exit.24. More recently, a prospective and longitudinal serological survey of a large cohort of healthcare workers revealed the presence of anti-peak antibodies associated with a minimal risk of further infection with SARS-CoV-2 during the 31 weeks. monitoring.25. These laboratory observations require long-term serial testing to confirm or rule out whether long-term immunity to SARS-CoV-2 confers protection against reinfection.
Our data indicate that at the 6-month follow-up, the level of humoral immunity was maintained and in some groups the median level of SARS-CoV-2 antibodies was even increased. Our results extend our current understanding of whether the immune response to SARS-CoV-2 infection decreases over time. Studies have shown that anti-SARS-CoV-2 antibody levels remain stable for several months after infection, but there are also conflicting reports, suggesting that the antibody titer decreases rapidly, especially in people. with milder disease.26. The rate of degradation appears to depend on the type of antigen, and anti-S antibodies are believed to be stable for at least 3 months26. In a study of> 30,000 individuals with anti-SARS-CoV-2 antibodies, neutralization titers correlated with anti-peak binding titers and most individuals who recovered from mild illness showed moderate to high titers. Longitudinal assessment was performed in a subset of 121 who were tested at different times observing stable levels for at least 3 months followed by a reduction limited to 5 months27. In another study, samples were collected at multiple times after severe COVID and only 3 in 70 people showed anti-RBD IgG seroreversion at 3 months28. In a surveillance study of> 3,000 health workers followed for a median of 4 months, 16% tested positive for IgG antibodies. While a decrease in titer was observed for anti-core antibodies at 3 months, 94% of individuals with anti-spike antibodies maintained a detectable titer at 6 months, although a quantitative analysis was not. carried out.25. Also Thangaraj et al.30 observed a marked decrease in anti-core and anti-spike antibodies, but the persistence of neutralizing anti-receptor-binding domain antibodies in 86.2% of participants more than 6 months after diagnosis and Epaulard et al.30 confirmed this result with longer follow-up. In their report, neutralizing antibodies of the anti-receptor binding domain remained detectable 7 months after infection in 65 of 67 patients, and antibody levels remained stable between 6 months and 1 year.
This kind of knowledge about specific serological tests and long-term serial blood tests will allow scientists to better understand how long these antibodies persist and whether they determine protection against reinfection and transmission. This information can also help public health officials understand the extent of the outbreak and could help support the development of COVID-19 treatments and vaccines. In times of limited vaccine dose availability, assessing SARS-CoV-2 seropositivity in different samples of the population can help define a priority scale for immunization access that may be postponed in individuals. having high antibody levels. Additionally, assessing the antibody response to SARS-CoV-2 can help support a reliable disease surveillance system and assess community risk.
The strengths of the study are the contemporary assessment of different groups of individuals living in the same area and workplace (a teaching hospital) during the pandemic, thus giving a comprehensive assessment of the spread of infection. by SARS-CoV-2 by individuals with a range of occupational and environmental risks, and its prospective assessment of humoral immunity. Limitations of the study include the limited sample size, the fact that the 3-month PCR test was only performed in 88% of those enrolled, and the six-month serological assessment was not performed. than in positive people at 3 months. In addition, recall and social desirability biases in symptom reporting cannot be ruled out.
In conclusion, the present study shows that humoral immunity against the SARS-CoV-2 virus is not transient; conversely, it can last several months. Among the most relevant factors influencing antibody titer are age, gender, contact with infected individuals, history of disease, clinical severity, and smoking status.