SARS-CoV-2 infection can trigger an exacerbated inflammatory response, whose effects may persist beyond the acute phase of COVID-19, resulting in long COVID. This intense response is related to the so-called cytokine storm, characteristic of severe disease. Cytokines such as IFN-α and TNF-α have been found at higher concentrations in patients with severe COVID-19. On the other hand, the bacillus Calmette–Guérin (BCG) vaccine is known for its immunomodulatory effects and nonspecific action against viral infections, and may represent a possible therapeutic intervention for COVID-19 and, potentially, for long COVID symptoms. To analyze TNF-α and IFN-α cytokine levels in COVID-19 convalescent individuals randomized to BCG vaccine or placebo over time. Fifty-eight convalescent individuals participated; 29 received a BCG booster (BCG group) and 29 received 0.9% saline solution (placebo group). Samples were collected at three time points: T0 (study enrollment and vaccination day), T45D (45 days after vaccination), and T6M (6 months after vaccination). Plasma cytokine levels were measured by ELISA and flow cytometry. Statistical analyses used the Mann–Whitney and Friedman tests. The BCG group showed statistically significant differences in IFN-α (p < 0.0001) and TNF-α (p = 0.0086) levels over time. IFN-α levels were higher at T6M than at T0 (p < 0.001), whereas TNF-α levels were lower at T6M than at T0 (p = 0.0122). In the placebo group, there were also differences in IFN-α (p = 0.0360) and TNF-α (p = 0.0347) across the three time points. IFN-α concentration decreased from T0 to T45D (p = 0.0454), and TNF-α increased from T45D to T6M (p = 0.0334). When comparing groups at each time point, IFN-α levels were higher in the BCG group than in placebo at T0 (p = 0.0116), T45D (p < 0.0001), and T6M (p < 0.0001). TNF-α was higher in the BCG group compared with placebo at T45D (p = 0.0097), with no difference at the other times. It is likely that BCG modulated the cytokine profile analyzed in COVID-19 convalescent patients, leading to a sustained increase in IFN-α and a reduction in TNF-α levels six months after vaccination. This may impact disease progression and subsequent development of post-COVID symptoms.
Brito et al. (Sun,) studied this question.