Time-Dependent Increase in Susceptibility and Severity of Secondary Bacterial Infections During SARS-CoV-2

Abstract

Secondary bacterial infections can exacerbate SARS-CoV-2 infection, but their prevalence and impact remain poorly understood. Here, we established that a mild to moderate infection with the SARS-CoV-2 USA-WA1/2020 strain increased the risk of pneumococcal (type 2 strain D39) coinfection in a time-dependent, but sex-independent, manner in the transgenic K18-hACE2 mouse model of COVID-19. Bacterial coinfection increased lethality when the bacteria was initiated at 5 or 7 d post-virus infection (pvi) but not at 3 d pvi. Bacterial outgrowth was accompanied by neutrophilia in the groups coinfected at 7 d pvi and reductions in B cells, T cells, IL-6, IL-15, IL-18, and LIF were present in groups coinfected at 5 d pvi. However, viral burden, lung pathology, cytokines, chemokines, and immune cell activation were largely unchanged after bacterial coinfection. Examining surviving animals more than a week after infection resolution suggested that immune cell activation remained high and was exacerbated in the lungs of coinfected animals compared with SARS-CoV-2 infection alone. These data suggest that SARS-CoV-2 increases susceptibility and pathogenicity to bacterial coinfection, and further studies are needed to understand and combat disease associated with bacterial pneumonia in COVID-19 patients.

Complementary Sets of Autoantibodies Induced by SARS-CoV-2, Adenovirus and Bacterial Antigens Cross-React with Human Blood Protein Antigens in COVID-19 Coagulopathies

“…Thus, a substantial body of evidence beyond the current study also points towards COVID-19 coagulopathies being due to bacterial, and possibly adenoviral, infections complicating SARS-CoV-2 and activating synergistic sets of Toll-like receptors resulting in a hyperinflammation. This effect has been demonstrated for a combination of SARS-CoV-2 with Streptococci in mouse models of coinfection [ 129 , 130 ]. Notably, this hyperinflammatory state could be prevented by vaccination against either SARS-CoV-2 or pneumococci.…”

“…Other implications of our data can be tested in animal models. For example, SARS-CoV-2-susceptible species (such as golden hamsters or some strains of mice) might be co-infected with the virus and with bacteria such as group A Streptococci, Staphylococci, Klebsiella, Acinetobacter or Haemophilus , or with viruses such as adenovirus type 5 (e.g., [ 129 , 130 ]). The effect of such bacterial coinfections on vaccination with SARS-CoV-2 vaccines could be tested in a similar manner.…”

Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice

“…As presented in the study timeline (Figure 1A), mice were inoculated with PBS or infected with a low dose (500 PFU) of the A lineage strain, WA1. The dose was chosen to enable infection but allow at least two-thirds of the cohort to survive for the subsequent challenge reported previously [18]. Of the low-dose WA1-infected cohort, 44/64 (68.75%) survived infection (Figure 1B).…”

The Human Superorganism: Using Microbes for Freedom vs. Fear

“…Early during the COVID-19 pandemic, Di Stadio et al [32] argued that the nasal microbiome was important for immunomodulatory protection against the COVID-19 infection. Smith et al [33] and Jochems et al [34] reported that carriage of specific nasal bacteria was important in the host response and resistance/vulnerability to COVID-19 infection. Specific nasal bacteria were directly connected with specific cytokine production and, thereby, affected whether airway-damaging mucosal inflammation occurred during the response to COVID-19.…”

“…Considering that it is (1) more than a century since an influenza pandemic produced high levels of death by bacterial pneumonia, and (2) we know that prominent animal respiratory coronaviruses often produce death via bacterial pneumonia, it is not surprising that bacterial and/or fungal infections increased COVID-19 case severity and often resulted in death [47]. Using the K18-hACE2 mouse model of COVID-19, Smith et al [33] performed a study examining the time-sensitive immunological mechanisms through which the SARS-CoV-2 virus increases the susceptibility and pathogenicity of bacterial co-infection. Immunologically, Peng et al [48] found that coronavirus impairs the host's ability to clear bacterial pathogens by interfering with lysosomal function.…”