CRP and IgA antibodies to activin-A are also important predictors.
Following “recovery” from acute COVID-19, a fraction of patients remain ill with various symptoms, a condition called Long COVID or post-COVID condition. Many past studies of Long COVID have found evidence of persisting inflammation and oxidative stress. Many also have found evidence of residual SARS-CoV-2 nucleic acid and/or antigen, and even of residual replicating virus, in people with Long COVID, compared to post-COVID patients who have returned to health. Several past studies also have found evidence of reactivation of latent herpesvirus infection, as evidenced by elevated antibodies to HHV-6 and Epstein-Barr, especially antibodies to EBV early antigen (EA) (Postolou 2022, Gold 2021, Peluso 2023).
A new study, using some different assays as well as neural network computational techniques to analyze the large dataset, comes to similar conclusions. Altogether, 90 patients with at least two persisting symptoms for at least 4 months after acute COVID-19 (documented by PCR) were compared to 90 people deemed currently healthy (past COVID status unclear).
As shown in Table 1, levels of IgG and IgM (but not IgA) to both HHV-6 and HHV-6-dUTPase were strong and statistically significant predictors of Long COVID. In addition (not shown in Table 1), IgM antibodies to SARS-CoV-2 spike protein also were elevated in people with Long COVID, and were predictors of the condition. Interestingly, antibody levels against EBV EBNA2 and EBV dUTPase, were not predictors of lingering illness. For unclear reasons, antibodies to EBV-EA, markers of active or recent reactivation, were not tested.
Table 1 – Results of binary logistic regression analysis with the diagnosis long COVID as dependent variable (healthy controls as reference group).
Figure 1 shows the relative importance of each of the several statistically significant predictors, as determined by neural network computational techniques. As can be seen, antibodies to HHV-6 and HHV-6-dUTPase were among the most important predictors. In addition, autoantibodies (IgA, IgM, IgG) to activin-A, all were predictors (positively or inversely) of Long COVID. Activin-A is a member of the TGF-ß family. Its production is stimulated by inflammatory cytokines, Toll-like receptor ligands, and oxidative stress, and it helps regulate the growth and differentiation of various immune cell types.
Figure 1 – Importance chart of a neural network analysis with long COVID patients versus controls.
This study is consistent with several others in finding that reactivation of HHV-6 is often found in people with Long COVID. Unanswered is the question of whether this reactivation contributes to producing the symptoms of the illness, or is simply an epiphenomenon of the immune dysregulation seen in Long COVID.
Read the full article: Vojdani 2024