Viral infections complicated by a bacterial infection are typically referred to as coinfections or superinfections. Streptococcus pyogenes, the group A streptococcus (GAS), is not the most common bacteria associated with influenza A virus (IAV) superinfections but did cause significant mortality during the 2009 influenza pandemic even though all isolates are susceptible to penicillin. One approach to improve the outcome of these infections is to use passive immunization targeting GAS. To test this idea, we assessed the efficacy of passive immunotherapy using antisera against either the streptococcal M protein or streptolysin O (SLO) in a murine model of IAV-GAS superinfection. Prophylactic treatment of mice with antiserum to either SLO or the M protein decreased morbidity compared to mice treated with non-immune sera; however, neither significantly decreased mortality. Therapeutic use of antisera to SLO decreased morbidity compared to mice treated with non-immune sera but neither antisera significantly reduced mortality. Overall, the results suggest that further development of antibodies targeting the M protein or SLO may be a useful adjunct in the treatment of invasive GAS diseases, including IAV-GAS superinfections, which may be particularly important during influenza pandemics.
Background: Venous thromboembolism (VTE) is a known complication of coronavirus disease (COVID-19) in patients requiring hospitalization and intensive care. We examined the association between extended pharmacological VTE prophylaxis and outcomes among patients hospitalized with COVID-19. Methods: This was a retrospective cohort study of patients with an index positive SARS-CoV-2 polymerase chain reaction (PCR) test at the time of, or during hospitalization. Patients who were prescribed extended pharmacological VTE prophylaxis were compared against patients who were not. Multivariable logistic regression was used to produce odds ratio (OR) estimates and Cox proportional hazard models for hazard ratios (HR) with 95% CI to examine the association between pharmacological VTE prophylaxis and outcomes of interest. Primary outcomes were 30- and 90-day VTE events. Secondary outcomes included 30- and 90-day mortality, 30-day superficial venous thrombosis (SVT), acute myocardial infarction (MI), acute ischemic stroke, critical limb ischemia, clinically significant bleeding, and inpatient readmissions. Results: A total of 1936 patients were included in the study. Among them, 731 (38%) were discharged on extended pharmacological VTE prophylaxis. No significant difference was found in 30- and 90-day VTE events among groups. Patients discharged on extended VTE prophylaxis showed improved survival at 30 (HR: 0.35; 95% CI: 0.21–0.59) and 90 days (HR: 0.36; 95% CI: 0.23–0.55) and reduced inpatient readmission at 30 days (OR: 0.12; 95% CI: 0.04–0.33) when compared to those without. Conclusion: Patients discharged on extended VTE prophylaxis after hospitalization due to COVID-19 had similar thrombotic events on follow-up. However, use of extended VTE prophylaxis was associated with improved 30- and 90-day survival and reduced risk of 30-day inpatient readmission.
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