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American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277664


Objective: Viral pneumonias cause significant morbidity and mortality worldwide. The emergence of novel SARSCoV- 2 emphasizes the need for novel antiviral therapies. Dexamethasone (DXM) is one therapy that has recently been reported to confer benefit in severe SARS-CoV-2 infection. Our lab has recently reported that CD8+ T cells were associated with fatal immunopathology causing mortality in a mouse model of severe Sendai paramyxovirus (SeV) pneumonia, and this fatal immunopathology could be prevented either by eliciting a robust, early antiviral response via inhalational treatment with Toll-like receptor agonists (Pam2-ODN) or by depletion of CD8+ T cells during late stage SeV pneumonia. Given the lympholytic effects of DXM, we tested our hypothesis that the reported survival advantage of DXM in severe viral pneumonia derives from CD8+ T cell- mediated immunopathology. Methods: Mice were intrapharyngeally infected with SeV with or without Pam2-ODN pretreatment, then observed for 14 days. Some mice were intraperitoneally injected with DXM (5mg/kg) every day starting day 0 or day 8 after infection. CD8+ T cells were assessed on day 10 after infection by flow cytometry of digested mouse lungs. Results: Treatment with DXM starting on day 8 enhanced mouse survival of SeV pneumonia, whereas mice treated with DXM from day -1 onward demonstrated increased susceptibility to SeV pneumonia. Mice treated with CD8+ T cell depleting antibody on day 8 displayed 100% survival. DXM treated mice displayed reduced CD8+ T cells in comparison to PBS treated SeV challenged mice, supporting our hypothesis. Consistent with our recent report, mice aerosolized with Pam2-ODN displayed 100% survival of SeV pneumonia with reduced CD8+ T cell lung influx on day 10. Conclusion: These data suggest that the survival benefit of DXM in severe viral pneumonia results from reduced CD8+ T cell-mediated immunopathology. Improved outcomes appear likely to be achieved by either use of broad immunosuppressive agents such as DXM or a targeted approach to deplete CD8+ T cells during late-stage pneumonia such as COVID19. These data also provide a preclinical model to test other immunosuppressive agents and optimize timing and dosing of such agents.

J Hosp Infect ; 110: 60-66, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1087052


BACKGROUND: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence. AIM: To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8). METHODS: All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured. FINDINGS: In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0-16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 [0.66%, 95% confidence interval (CI) 0.18-2.4] HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14-4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23-7.0) HCWs tested positive in Greece. CONCLUSION: Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.

Antibodies, Viral/blood , COVID-19/epidemiology , Health Personnel/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Occupational Diseases/epidemiology , Risk Assessment/statistics & numerical data , Adult , Aged , Cross-Sectional Studies , Europe/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Seroepidemiologic Studies , South Africa/epidemiology , Young Adult