Superinfection with SARS-CoV-2 Has Deleterious Effects on Mycobacterium bovis BCG Immunity and Promotes Dissemination of Mycobacterium tuberculosis

• Published in: Microbiology spectrum 2022-10, Vol.10 (5), p.e0307522-e0307522
• Main Authors: Hildebrand, Rachel E, Chandrasekar, Shaswath Sekar, Riel, Mariah, Touray, Bubacarr J B, Aschenbroich, Sophie A, Talaat, Adel M
• Format: Article
• Language: English
• Subjects: Animals; BCG; BCG Vaccine; COVID-19; Cytokines; Interleukin-17; Mice; Microbial Pathogenesis; Mycobacterium bovis; Mycobacterium tuberculosis; pathogenesis; Research Article; SARS-CoV-2; Superinfection; Tuberculosis, Lymph Node; virulence
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.03075-22

An estimated one-third of the world's population is infected with Mycobacterium tuberculosis, with the majority being vaccinated with Mycobacterium bovis BCG. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a threat, and we must understand how SARS-CoV-2 can modulate both BCG immunity and tuberculosis pathogenesis. Interestingly, neither BCG vaccination nor tuberculosis infection resulted in differences in clinical outcomes associated with SARS-CoV-2 in transgenic mice. Surprisingly, earlier M. tuberculosis infection resulted in lower SARS-CoV-2 viral loads, mediated by the heightened immune microenvironment of the murine lungs, unlike vaccination with BCG, which had no impact. In contrast, M. tuberculosis-infected tissues had increased bacterial loads and decreased histiocytic inflammation in the lungs following SARS-CoV-2 superinfection. SARS-CoV-2 modulated BCG-induced type 17 responses while decreasing type 1 and increasing type 2 cytokines in M. tuberculosis-infected mice. These findings challenge initial findings of BCG's positive impact on SARS-CoV-2 infection and suggest potential ramifications for M. tuberculosis reactivation upon SARS-CoV-2 superinfection. Prior to SARS-CoV-2, M. tuberculosis was the leading infectious disease killer, with an estimated one-third of the world's population infected and 1.7 million deaths a year. Here, we show that SARS-CoV-2 superinfection caused increased bacterial dissemination in M. tuberculosis-infected mice along with immune and pathological changes. SARS-CoV-2 also impacted the immunity of BCG-vaccinated mice, resulting in decreased interleukin-17 (IL-17) levels, while offering no protective effect against SARS-CoV-2. These results demonstrate that SARS-CoV-2 may have a deleterious effect on the ongoing M. tuberculosis pandemic and potentially limit BCG's efficacy.