BCG Vaccine Is Protective Against Long COVID

If administered within the COVID-19 convalescence period, the intradermal Bacillus Calmette-Guérin (BCG) vaccine is protective against long COVID development among adults with mild COVID-19, according to study findings published in the Journal of Internal Medicine.

Researchers conducted a double-blind, placebo-controlled, phase 3, randomized clinical trial (Therapeutic BCG Vaccine in COVID-19 Convalescence [BATTLE]; ClinicalTrials.gov Identifier: NCT04369794) to assess whether BCG vaccination interferes with long COVID symptoms if administered during active infection.

Adults who tested positive for SARS-CoV-2 were randomly assigned 1:1 to receive either 0.1 mL of BCG or placebo within 2 weeks of symptom initiation. Changes in comorbidities and long COVID symptoms were assessed at 6- and 12-month follow-up visits. Generalized linear mixed models were used in statistical analysis.

A total of 393 adults were included in the study, of whom 202 were randomly assigned to receive placebo and 191 were randomly assigned to receive the BCG vaccine. At the 6-month follow-up, 157 BCG recipients and 142 placebo recipients participated. At the 12-month follow-up, 97 BCG recipients and 95 placebo recipients participated.

At 6 months, patients who received BCG vs placebo were less likely to report ear nose and throat (ENT) symptoms (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P =.044).

Sleeping (OR, 0.45; P =.027), concentration (OR, 0.36; P =.009), memory (OR, 0.38; P =.009), and vision problems (OR, 0.36; P =.022) were also less common in the BCG vs placebo group at 12 months.

Overall, the median long COVID score was significantly lower among BCG vs placebo recipients (median score, 1 vs 2; P =.002). Similarly, the ENT (P =.024) and cognitive dysfunction (P <.001) scores were also lower in the BCG vs placebo group.

While BCG reduced hair loss in men (OR, 0.18; P =.031), the vaccine slightly increased hair loss in women (OR, 1.7; P =.086) at 6 months.

Sensitivity analyses confirmed the benefits of BCG at 6 (β, -0.23; P =.010) and 12 (β, -0.28; P =.031) months.

BCG immunomodulation was found to be most likely mediated via the inhibition of FAS ligand expression in blood, as well as increased induction of interleukin (IL) 6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.

Study limitations include loss to follow-up and the inability to test for prior mycobacterial exposure.

“Further studies are necessary, and we strongly recommend including sex-based crossover interactions and complex feedforward loops in both the design and analysis,” the researchers concluded.