The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective
- Division of Experimental Medicine, University of California, San Francisco, United States
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute; Division of Critical Care Medicine, Nationwide Children’s Hospital, United States
- Department of Pediatrics, The Ohio State University College of Medicine, United States
- Pacific Biosciences Research Center, University of Hawaiʻi at Mānoa, United States
- Department of Pathology, University of Illinois at Chicago, United States
- Division of Infectious Diseases, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, United States
- Emory Vaccine Center, Department of Pediatrics, Emory University School of Medicine, United States
- Howard University Pathology Department, United States
- Department of Molecular Biology and Microbiology, Tufts University, United States
- PHRI, Rutgers New Jersey Medical School, United States
- Pathogen and Microbiome Institute, Northern Arizona University, United States
- Department of Microbiology, Immunology and Molecular Genetics, University Texas Health, United States
- NIH RECOVER Research Initiative: Patient representative, United States
- Department of Microbiology, Global Health and Emerging Pathogens Institute, Department of Medicine, The Tisch Cancer Institute, The Icahn Genomics Institute, and Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, United States
- Department of Medicine, Rutgers New Jersey Medical School, United States
Figures
Figure 1
Potential mechanisms implicated in post-COVID-19 surge of non-SARS-CoV-2 infections.
Some of the mechanisms and underlying causes that can explain the increased incidence of various non-SARS-CoV-2-driven infectious diseases following the COVID-19 pandemic are shown.
Figure 2
Potential temporal relationships between SARS-CoV-2 and co-infections.
Various co-infections occurring at various times relative to the acute SARS-CoV-2 infection may predispose to post-acute sequelae of SARS-CoV-2 infection (PASC) or modulate the course of PASC.
Figure 3
How co-infections may result in post-acute sequelae of SARS-CoV-2 (PASC) development in an organ system: the example of the lung.
Pre-existing fungal, bacterial, and viral infections may result in acute and chronic inflammation, parenchymal damage, immune activation, and impaired lung function. For example, latent Mycobacterium tuberculosis infection may be reactivated during acute COVID-19, worsen COVID-19 clinical outcome, and/or lead to the development of PASC. Other pathogens such as those causing bacterial or fungal pneumonia during acute SARS-CoV-2 infection or early convalescence may also exacerbate lung tissue damage, cardiopulmonary function, systemic inflammation, and immune dysregulation, and favor development of PASC.
Figure 4
How co-infections may result in post-acute sequelae of SARS-CoV-2 (PASC) development systemically.
The etiology of PASC is heterogeneous and involves multiple pathophysiological mechanisms. (A) shows how SARS-CoV-2 along with other viral and bacterial infections may compromise mucosal barriers (in this example, the intestinal lining) or change microbiome homeostasis leading to dysregulation of tight junctions, microbial translocation, immune activation, and systemic inflammation. (B) shows the potential impact of Epstein-Barr virus (EBV) reactivation during or following acute COVID-19. Viral shedding from lytic EBV-infected epithelial or B cells may lead to direct tissue damage, molecular mimicry, autoreactivity from host-cell expression of viral proteins, or pathogenic transformation of B cells that may traffic to various anatomical regions outside the areas of initial viral reactivation. All these mechanisms may lead to immune dysregulation and systemic tissue damage (C). LMP = latent membrane protein; EBNA = EBV nuclear antigen.
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The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective
eLife 14:e106308.
https://doi.org/10.7554/eLife.106308
