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

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.

Modified Bain's Circuit as an Alternate to Non-invasive Ventilation in COVID 19.

Introduction COVID-19 is a pandemic that severely affects the lungs. Symptomatically affected individuals often become severely hypoxic, requiring non-invasive ventilation. The scarcity of resources in resource-compromised countries like India led to the adoption of novel strategies like using Bain's circuit for assisting spontaneous ventilation. This study compares the outcome when a standard circuit is replaced with a shortened Bain's circuit. Aims and objectives To compare shortened Bain's circuit and bilevel positive airway pressure (BiPAP) in spontaneously ventilated COVID 19 patients with regards to effects on hemodynamic stability and efficacy of ventilation using blood gas analysis. Methodology Twenty-four COVID patients aged between 35-70 years, requiring non-invasive ventilation but not tolerating BiPAP or not improving on BiPAP were enrolled in the study. Baseline heart rate and arterial blood gases (ABG) were recorded. Patients were then ventilated using shortened Bain's circuit. Heart rate and ABG were then recorded two hours after ventilation. Results Hemodynamic and blood gas parameters were comparable between the two groups at baseline and on BiPAP. Group A showed better hemodynamic and blood gas profiles compared to group B, but the difference was not statistically significant because of small sample size. Conclusion Shortened Bain's circuit may be a viable alternative to non-invasive ventilation in spontaneously breathing hypoxic patients with efficacy comparable to a standard Bain's circuit and reduced chances of carbon dioxide retention. Studies with a larger sample size are needed to further validate the conclusion.

Lack of active SARS-CoV-2 virus in a subset of PCR-positive COVID-19 congregate care patients.

Highly sensitive nucleic acid amplification tests (NAATs) designed to detect SARS-CoV-2 RNA are the standard of care for the diagnosis of COVID-19. However, the accuracy of these methods for the quantitation of active virus rather than non-infectious RNA fragments that can persist for extended periods of time has been unclear. This issue is particularly relevant for congregate care patients who are unable to return to their home residence until fully negative by NAATs. We tested paired samples from individual patients for the presence of virus at both early and later stages of disease. Culture of nasopharyngeal swab samples for 10 days in Vero E6 cells revealed active virus in only 4 out of 14 (28.6%) patients. The ability to isolate viral plaque-forming units (PFU) correlated with viral RNA loads of >6.79 log genomic copies/ml and only occurred in samples collected from patients early after symptom onset and before development of antibody. Culture in Vero E6 cells lacking the STAT1-dependent interferon signaling pathway increased the numbers of viral PFU detected but did not affect the incidence of positive cultures. We conclude that culturable virus is correlated with SARS-CoV-2 NAATs detection only during early symptom onset and with high viral titers/low antibody titers in non-immunosuppressed patients.