The intersection of SARS-CoV-2 with TB: It's complicated
A new animal study found mice infected with Mycobacterium tuberculosis and SARS-CoV-2 had an interesting synergism, according to a poster presented at ASM Microbe 2022 (abstract 3696), in Washington, D.C.
The data suggest that latent M. tuberculosis prevents high SARS-CoV-2 viral load but does not affect weight loss or deaths related to SARS-CoV-2. This is likely due to the activity of immune cells already in the lung environment from another infection preventing SARS-CoV-2 from replicating as quickly, according to lead author Rachel Hildebrand, a graduate student at the Talaat Laboratory, University of Wisconsin, in Madison.
The effect of SARS-CoV-2 on the immune system, however, may include the containment of M. tuberculosis, resulting in higher bacterial burden especially in organs other than the lungs.
Bacille Calmette-Guérin (BCG) vaccination against tuberculosis (TB) had no impact on the parameters looked at for SARS-CoV-2. However, SARS-CoV-2 did affect levels of usually protective immune molecules associated with BCG.
The researchers infected mice with M. tuberculosis and then at early and late time points infected them with SARS-CoV-2. They found SARS-CoV-2 infection after M. tuberculosis infection did not result in worsening of weight loss or mortality than when mice were only infected with SARS-CoV-2.
They also found bacterial levels were higher in mice coinfected with both pathogens, especially in the spleen. Supporting this finding were the slight changes observed in the immune environment showing a decrease of cytokines associated with controlling M. tuberculosis and an increase of those associated with reactivation.
In addition, the lungs displayed damage typical of M. tuberculosis infection, but mice that were coinfected with both organisms exhibited less damage.
Overall, these data were collected over a very short window of time for M. tuberculosis infections, and these changes were surprising given that there are usually changes for M. tuberculosis over weeks to months instead of days, according to Ms. Hildebrand. Finally, the investigators also looked at BCG-vaccinated mice to see whether BCG vaccination would affect SARS-CoV-2. Using the same setup and experimental outputs, they found BCG had no relationship to weight loss, mortality or viral load of SARS-CoV-2. Interestingly, SARS-CoV-2 infection modified some cytokines induced by vaccination. In particular, interleuken-17, usually associated with protection from M. tuberculosis, decreased in mice infected with SARS-CoV-2.
Before COVID-19, M. tuberculosis—the organism that causes TB—was the deadliest infectious organism, resulting in between 1.3 million and 1.7 million deaths annually. M. tuberculosis is estimated to infect about one-third of the world’s population. Based on the massive case numbers of both TB and the COVID-19 pandemic, many people will become coinfected with both SARS-CoV-2 and tuberculosis, the researchers surmised.
Therefore, it is critical to understand how these two diseases interact, according to Ms. Hildebrand.
