Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series

Andrew P Platt; Benjamin T Bradley; Nadia Nasir; Sydney R Stein; Sabrina C Ramelli; Marcos J Ramos-Benitez; James M Dickey; Madeleine Purcell; Shreya Singireddy; Nicole Hays; Jocelyn Wu; Katherine Raja; Ryan Curto; Stephen J Salipante; Claire Chisholm; Stephanie Carnes; Desiree A Marshall; Brad T Cookson; Kevin M Vannella; Ronson J Madathil; Shahabuddin Soherwardi; Michael T McCurdy; Kapil K Saharia; Joseph Rabin; Nih Covid-Autopsy Consortium; Alison Grazioli; David E Kleiner; Stephen M Hewitt; Joshua A Lieberman; Daniel S Chertow

doi:10.3390/pathogens12070932

Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series

Pathogens. 2023 Jul 12;12(7):932. doi: 10.3390/pathogens12070932.

Authors

Andrew P Platt^{1

2}, Benjamin T Bradley³, Nadia Nasir⁴, Sydney R Stein^{1

2}, Sabrina C Ramelli⁴, Marcos J Ramos-Benitez^{1

2

5}, James M Dickey^{1

2}, Madeleine Purcell⁶, Shreya Singireddy⁶, Nicole Hays⁶, Jocelyn Wu⁶, Katherine Raja⁶, Ryan Curto⁶, Stephen J Salipante⁷, Claire Chisholm⁷, Stephanie Carnes⁸, Desiree A Marshall⁷, Brad T Cookson⁷, Kevin M Vannella^{1

2}, Ronson J Madathil⁹, Shahabuddin Soherwardi¹⁰, Michael T McCurdy^{6

11}, Kapil K Saharia¹², Joseph Rabin¹³, Nih Covid-Autopsy Consortium, Alison Grazioli¹⁴, David E Kleiner⁴, Stephen M Hewitt⁴, Joshua A Lieberman⁷, Daniel S Chertow^{1

2}

Affiliations

¹ Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
² Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
³ Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
⁴ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Department of Basic Sciences, Division of Microbiology, Ponce Research Institute, School of Medicine, Ponce Health Sciences University, Ponce, PR 00716, USA.
⁶ University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁷ Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USA.
⁸ American Esoteric Laboratories, Memphis, TN 38134, USA.
⁹ Department of Surgery, Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹⁰ Hospitalist Department, TidalHealth Peninsula Regional, Salisbury, MD 21801, USA.
¹¹ Department of Medicine, University of Maryland St. Joseph Medical Center, Towson, MD 21204, USA.
¹² Institute of Human Virology, Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹³ R Adams Cowley Shock Trauma Center, Department of Surgery and Program in Trauma, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
¹⁴ R Adams Cowley Shock Trauma Center, Department of Medicine and Program in Trauma, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

Keywords: COVID-19; autopsy; co-infection; invasive fungal infections; nosocomial infections; pneumonia.

Grants and funding

n/a/CA/NCI NIH HHS/United States