Antibody response of COVID-19 patients to SARS-CoV-2 and seasonal coronaviruses

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Coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in 2019. It is the causative agent of the 2019 coronavirus (COVID-19) pandemic. In addition to SARS-CoV-2, there are six other known coronaviruses, among which four are human coronaviruses that are seasonal and cause mild, self-limiting upper respiratory infections.

Study: Humoral response to SARS-CoV-2 and seasonal coronaviruses in COVID-19 patients. Image Credit: Kateryna Kon / Shutterstock

In a new study published in Journal of Medical VirologyIn a cohort study, scientists measured the prevalence and levels of nucleocapsid (N) antibody responses to SARS-CoV-2 and four seasonal human coronaviruses.

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Scientists have described the protective effect of previous human coronavirus infection against SARS-CoV-2 infection and the less severe disease COVID-19. The description of the former was mainly based on putative infections, while in the latter, PCR-confirmed infections were associated with less severe disease manifestations. However, more research is needed to determine the effect of previous infection on disease severity. In the current study, scientists used ELISA-based immunoassays to detect antibodies against five human coronaviruses. They also tested sera from convalescent plasma donors for SARS-CoV-2 and the control group (SARS-CoV-2 not exposed).

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The current study was approved by the local ethics committee of the Heinrich Heine University in Düsseldorf, and informed consent was obtained from 115 donated SARS-CoV-2 plasma. The control group (N = 114) were excluded patients with known underlying chronic diseases or immunosuppression. The basic demographics were similar for both groups.

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Disease severity was rated as 0 for patients without any symptoms (n = 5), 1 for patients with only mild symptoms and no activity restriction (n = 28), 2 for patients with restricted activities (n = 44), and 3 for patients with more severe symptoms (n = 16). No classification information was available for the 20 patients, and none of them were hospitalized.

All blood samples were collected between March 2020 and July 2020, and for 10 patients, sera could be collected up to six months after symptoms appeared. The researchers used a two-step ELISA protocol to capture the analysis, in which the antigens used were SARS-CoV-2, HCoV-HKU1, HCoV-OC43 HCoV-229E and HCoV-NL63-Nucleocapsid (N), expressed as GST fusion proteins in E cells coli BL21 was in situ on glutathione-coated ELISA plates.

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Scientists have found a relationship between the level of SARS-CoV-2 antibodies and the severity of the disease. However, they found no association between the severity and level of antibodies to seasonal coronaviruses. The reason for the recent discovery may be that in some viral infections, non-neutralizing antibodies may promote infection and not protect against reinfection. Based on the available data, the researchers concluded that there is insufficient evidence to demonstrate that previous seasonal MERS infections had an effect on the severity of COVID-19 disease.

In the 10 donors who received consecutive serum, the researchers noted that in most cases, antibody levels against seasonal coronaviruses were elevated in the initial serum and decreased in subsequent follow-ups, which could be due to cross-stimulation of B cells. Since this has been observed in many cases with antibodies against more than one coronavirus, it is unlikely to be caused by a pure cross-antibody reaction.

Diminishing antibodies have been documented in previous studies, but in the current study, scientists have shown that this decrease also affects antibodies against seasonal coronaviruses. However, the scientists reported that they had no information on whether this cross-stimulation of antibodies also occurs against epitopes of other viral proteins.

The study’s most significant finding was the extremely significant association between antibody levels among all coronaviruses. The relationship with SARS-CoV-2 was slightly lower, possibly because COVID-19 patients were still in the post-infection period when factors, such as time of blood collection and severity of illness, could influence antibody levels.

Consistent with previous studies, researchers note that in the post-COVID serum, individual differences in antibody level were significant. It was not clear whether the decrease in antibodies also translates to a loss of protection against reinfection with SARS-CoV-2. Based on the results of this paper, the scientists argued that there could be an individually adaptive humoral immune response against the entire family of human coronaviruses. This observation could be useful in evaluating the protection induced by the SARS-CoV-2 vaccine by the humoral immune system.

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An alternative interpretation of the data could refer to “trained immunity”. Some evidence suggests that the flu vaccine can lead to protection from COVID-19 by stimulating trained immunity. It may therefore be reasonable to determine pre-existing immunity to seasonal coronaviruses before vaccinating individuals against the emerging coronavirus. This will help researchers and policy makers understand whether the low response to the vaccine is simply because the individual is responsive to the coronavirus.

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