Home Immunity Study examines factors that influence immune responses more than 15 months after SARS-CoV-2 infection

Study examines factors that influence immune responses more than 15 months after SARS-CoV-2 infection

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed more than 6.4 million lives worldwide. Research on COVID-19 has highlighted various clinical manifestations, from asymptomatic symptoms to severe symptoms.

Several studies have reported the development and persistence of antibodies following SARS-CoV-2 infection.

Study: Factors influencing immune response more than 15 months after SARS-CoV-2 infection: A population-wide longitudinal study in the Faroe Islands. Image Credit: Corona Borealis Studio/Shutterstock

However, as antibodies wane over time, it is important to assess their durability to determine the period of protection against COVID-19.

Background

Data on the long-term durability of anti-SARS-CoV-2 antibodies after symptomatic infection are scarce. It is also important to understand the extent of the protective capacity of these antibodies against COVID-19 reinfection. Although several studies indicated the development of neutralizing antibodies post-COVID-19, the limited duration of the follow-up period posed a challenge in determining the period of protection against subsequent infection. Nevertheless, this information is essential for effective management of the pandemic in the future.

Several studies have indicated that anti-SARS-CoV-2 antibodies persist for at least 12 months. An Italian study observed the persistence of anti-Spike (S) receptor-binding domain (RBD) IgG in most participants for 14 months after COVID-19. A varied level of immune responses has been reported from individual to individual.

In the Faroe Islands, until the emergence of the SARS-CoV-2 Omicron variant, the reinfection rate was relatively rare. To determine the durability of immune responses against SARS-CoV-2, a longitudinal analysis, considering two waves of COVID-19 that occurred in the Faroe Islands, was conducted. The first wave started in March 2020 and ended in April 2020, while the second wave occurred between August 2020 and December 2020.

About the study

Long-term humoral immunity against SARS-CoV-2 was investigated in this study. The antibody response was determined by analyzing 1063 blood samples, from 411 patients (aged 0-93 years), from two waves of infections. Blood samples were taken multiple times from each patient for fifteen months after the onset of COVID-19.

Total anti-SARS-CoV-2 RBD IgM, IgA and IgG antibodies were determined using a qualitative RBD sandwich ELISA. Additionally, neutralizing antibodies (NAb) were assessed using an ELISA-based pseudo-neutralizing assay. The ELISA-based test was used to determine IgG subclasses in a subset of samples. The durability of SARS-CoV-2 antibody responses was analyzed via nonlinear models.

Results

The study cohort exhibited a wide range of COVID-19 symptoms, such as asymptomatic, mild, moderate, and severe illness. In this national longitudinal study, antibodies specific for SARS-CoV-2, up to fifteen months after infection with SARS-CoV-2, were evaluated.

In 94% of participants, a detectable level of SARS-CoV-2 antibodies, particularly IgG, was found. Antibody levels varied differently over time in COVID-19 patients. A characteristic decrease in IgG levels has been observed from the onset of COVID-19. In both waves, the researchers observed that after the initial drop in the IgG level, it stabilized and remained stable for almost seven months. This pattern is known as the biphasic pattern.

The biphasic pattern is consistent with the hypothesis that part of the plasma cells in an acute immune reaction are transformed into memory plasma cells. This result suggests a shift from antibody production by short-lived plasma cells to antibody production by memory plasma cells.

Although a reduction in IgG levels occurred, the neutralizing capacity of circulating antibodies remained significantly elevated. This finding suggests the high efficiency of neutralizing antibodies induced by natural infection. A strong relationship between IgG levels and neutralizing antibodies has been established, suggesting the existence of immunity acquired by infection for about fifteen months.

Interestingly, only one Faroese resident experienced reinfection with COVID-19 among 4477 people diagnosed with COVID-19 as of December 17, 2021. The finding of this study is consistent with previous studies that reported that IgG1 and IgG3 were the most common subclasses, where IgG1 was primarily responsible for the IgG response. After the first sampling, among the total antibody composition, 83% were found to be neutralizing antibodies, which increased to 94% in the second sampling.

Only 19% of participants had persistent IgA and 3% had IgM 15 months after infection. Positive IgA responses varied significantly over time. A characteristic decrease in IgA has been observed since the onset of the infection. As with IgG, higher IgA levels have been observed in men and the elderly.

Importantly, the current study indicated that BMI, hospitalization and smoking affected IgG antibody synthesis. A low level of IgG was found in smokers, high levels in hospitalized people, and a faster decline in antibodies was seen in people with a high BMI. These factors may influence the risk of reinfection and the duration of protection against the SARS-CoV-2 virus. In younger participants, the magnitude and durability of immune responses post-COVID-19 were lower than in older participants who required hospitalization.

conclusion

Taken together, the majority of participants revealed a robust and durable immune response after SARS-CoV-2 infection, which lasted fifteen months after an initial decline for the first seven months. This study found that gender, smoking status, age, and hospitalization influence initial levels of SARS-CoV-2 antibodies. The rate of antibody decay was found to be primarily related to age, gender, and BMI.