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 shed light on various clinical manifestations, from asymptomatic to severe symptoms.
Several studies have reported the development and persistence of antibodies after SARS-CoV-2 infection.
Study: Factors influencing the immune response during 15 months after SARS-CoV-2 infection: a longitudinal study of the whole population in the Faroe Islands. Image credit: Corona Borealis Studio/Shutterstock
However, as antibodies decline 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 reinfection with COVID-19. Although several studies have indicated the development of neutralizing antibodies post-COVID-19, the limited duration of the follow-up period has posed a challenge in determining the period of protection against subsequent infections. However, this information is essential for effective pandemic management in the future.
Several studies have indicated that anti-SARS-CoV-2 antibodies persist for at least 12 months. An Italian study observed persistence of the anti-Spike (S) receptor-binding domain (RBD) in most participants 14 months after COVID-19. A varying level of immune responses was reported between individuals.
In the Faroe Islands, until the emergence of the Omicron SARS-CoV-2 variant, the reinfection rate was relatively rare. To determine the durability of immune responses against SARS-CoV-2, a longitudinal analysis was performed, taking into account two waves of COVID-19 that occurred in the Faroe Islands. The first wave started in March 2020 and ended in April 2020, while the second wave took place between August 2020 and December 2020.
About the study
In this study, long-term humoral immunity to SARS-CoV-2 was investigated. The antibody response was determined by analyzing 1063 blood samples, from 411 patients (0-93 years), from two waves of infections. Blood samples were obtained multiple times from each patient over fifteen months after the onset of COVID-19.
Total anti-SARS-CoV-2 RBD IgM, IgA, and IgG antibody was determined using a qualitative RBD sandwich ELISA. In addition, neutralizing antibodies (NAb) were assessed using an ELISA-based pseudo-neutralization assay. The ELISA-based assay was used to determine IgG subclasses in a subset of samples. The durability of SARS-CoV-2 antibody responses was analyzed using non-linear models.
discoveries
The study cohort presented with a wide range of symptoms of COVID-19, including asymptomatic, mild, moderate, and severe disease. In this nationwide longitudinal study, SARS-CoV-2-specific antibodies were assessed up to fifteen months after SARS-CoV-2 infection.
In 94% of the participants, a detectable level of SARS-CoV-2 antibodies, especially IgG, was found. Antibody levels varied differently over time in patients with COVID-19. A characteristic decline in IgG levels was observed since the onset of COVID-19. In both waves, the researchers observed that after the initial decline in the IgG level, it leveled off and remained stable for nearly seven months. This trend is known as a biphasic pattern.
The biphasic pattern is consistent with the assumption that a portion of plasma cells in an acute immune reaction are transformed into memory plasma cells. This result suggests the shift from antibody production by short-lived plasma cells to antibody production by memory plasma cells.
Although there was a reduction in IgG levels, the neutralizing capacity of circulating antibodies remained significantly high. This finding suggests the high efficacy of neutralizing antibodies induced by natural infection. A strong relationship was established between IgG levels and neutralizing antibodies, suggesting the existence of acquired immunity to infection for about fifteen months.
Interestingly, only one resident of the Faroe Islands presented a reinfection with COVID-19 among 4477 people diagnosed with COVID-19 on 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% during the second sampling.
Only 19% of participants had persistent IgA and 3% had IgM after 15 months from infection. Positive IgA responses varied significantly over time. A characteristic decrease in IgA was observed from the onset of infection. Similar to IgG, a higher level of IgA was 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 those 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 following COVID-19 were lower compared to older participants who required hospitalization.
Conclusions
Overall, the majority of participants revealed a robust and long-lasting immune response after SARS-CoV-2 infection, lasting fifteen months after an initial decline during the first seven months. This study found that sex, smoking status, age, and hospitalization influence baseline levels of SARS-CoV-2 antibodies. The rate of antibody decay was found to depend mainly on age, sex, and BMI.