Abstract
Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
Discussion
[...]
In reflecting on the association of the identified Ig signature correlating with increased risk of PACS, the following aspects are worth considering. IgM and, particularly, IgG3 secretion by B cells is induced by interferons and antagonized by IL-4 signals19,20,21. Thus, reduced production of type I interferons, as proposed to occur in poorly controlled SARS-CoV-2 infection22,23, or a predisposition to secreting increased IL-4 concentrations, as present in asthma bronchiale24, may contribute to a failure to efficiently induce Ig isotype switching to IgG3. This hypothesis is consistent with our finding of low IgG3 in asthma bronchiale patients. Conversely, immune responses dominated by IgG3 can occur with similar temporal dynamics as IgM responses and have been associated with viral infections at mucosal tissues25,26. Thus, the reduced IgG3 concentrations in patients with PACS might support a role for IgG3 in Fc receptor-dependent viral control. Low IgG3 levels have also been linked to chronic fatigue syndrome, a debilitating condition resembling certain symptoms of PACS, as well as an increased rate of respiratory infections18,27.
PACS has been proposed to result from tissue damage due to direct effects of the virus, excessive inflammation, or thrombotic events; alternatively, PACS could be the consequence of bystander or virus-mediated activation of autoreactive T and B cells28. Recent observations of PACS resolution after SARS-CoV-2 vaccination might hint at the depletion of persisting viral reservoirs29. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which in turn is crucial for understanding the pathomechanisms of PACS and identification of preventive measures for treatment and care.
The study: https://www.nature.com/articles/s41467-021-27797-1
The central findings here are that people that on beforehand have low IgM and IgG3 are at higher risk of LC. When you get infected IgM is supposed to increase rapidly while IgG3 will increase later to provide longer term protection.
Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which – combined with age, history of asthma bronchiale, and five symptoms during primary infection – is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.
Discussion
[...]
In reflecting on the association of the identified Ig signature correlating with increased risk of PACS, the following aspects are worth considering. IgM and, particularly, IgG3 secretion by B cells is induced by interferons and antagonized by IL-4 signals19,20,21. Thus, reduced production of type I interferons, as proposed to occur in poorly controlled SARS-CoV-2 infection22,23, or a predisposition to secreting increased IL-4 concentrations, as present in asthma bronchiale24, may contribute to a failure to efficiently induce Ig isotype switching to IgG3. This hypothesis is consistent with our finding of low IgG3 in asthma bronchiale patients. Conversely, immune responses dominated by IgG3 can occur with similar temporal dynamics as IgM responses and have been associated with viral infections at mucosal tissues25,26. Thus, the reduced IgG3 concentrations in patients with PACS might support a role for IgG3 in Fc receptor-dependent viral control. Low IgG3 levels have also been linked to chronic fatigue syndrome, a debilitating condition resembling certain symptoms of PACS, as well as an increased rate of respiratory infections18,27.
PACS has been proposed to result from tissue damage due to direct effects of the virus, excessive inflammation, or thrombotic events; alternatively, PACS could be the consequence of bystander or virus-mediated activation of autoreactive T and B cells28. Recent observations of PACS resolution after SARS-CoV-2 vaccination might hint at the depletion of persisting viral reservoirs29. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which in turn is crucial for understanding the pathomechanisms of PACS and identification of preventive measures for treatment and care.
The study: https://www.nature.com/articles/s41467-021-27797-1
The central findings here are that people that on beforehand have low IgM and IgG3 are at higher risk of LC. When you get infected IgM is supposed to increase rapidly while IgG3 will increase later to provide longer term protection.