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Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination
Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger
Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger
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Research Article Immunology Infectious disease

Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination

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Abstract

Secondary infections are frequent complications of viral respiratory infections, but the potential consequence of SARS-CoV-2 coinfection with common pulmonary pathogens is poorly understood. We report that coinfection of human ACE2–transgenic mice with sublethal doses of SARS-CoV-2 and Streptococcus pneumoniae results in synergistic lung inflammation and lethality. Mortality was observed regardless of whether SARS-CoV-2 challenge occurred before or after establishment of sublethal pneumococcal infection. Increased bacterial levels following coinfection were associated with alveolar macrophage depletion, and treatment with murine GM-CSF reduced numbers of lung bacteria and pathology and partially protected from death. However, therapeutic targeting of IFNs, an approach that is effective against influenza coinfections, failed to increase survival. Combined vaccination against both SARS-CoV-2 and pneumococci resulted in 100% protection against subsequent coinfection. The results indicate that when seasonal respiratory infections return to prepandemic levels, they could lead to an increased incidence of lethal COVID-19 superinfections, especially among the unvaccinated population.

Authors

Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger

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Figure 5

Efficacy of vaccination for protection against SARS-CoV-2/S.

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Efficacy of vaccination for protection against SARS-CoV-2/S.

pneumoniae...
pneumoniaecoinfection. (A) Experimental design. (B) Anti-spike serum antibody titers induced by the Pfizer-BioNtech COVID-19 vaccine, and (C) anti-pneumococcal polysaccharide serotype 3 serum antibody titers induced by the Pfizer Prevnar13 vaccine. Serum antibody titers from individual mice were determined by ELISA using 50% maximal binding as the titer endpoint. n = 11–22 mice per group pooled from 2 independent experiments. Protection in terms of (D) survival and (E) weight loss of hACE2 mice following SARS-CoV-2/S. pneumoniae coinfection by Prevnar13 pneumococcal conjugate vaccine, Pfizer mRNA vaccine, or dual Prevnar13 and Pfizer mRNA vaccines. n = 5–8 mice per group per experiment; data pooled from 2 independent experiments. Statistical analyses for survival were performed by the log-rank Mantel-Cox test. *P < 0.05, ****P < 0.0001. Spn, S. pneumoniae. DPI, days post immunization.

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