The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective
Henrich, TJ; Montgomery, CP; Graf, J; et al., eLife, November 2025
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Short Summary
This RECOVER paper combined research findings, patient experiences, and possible explanations about how the body works to understand how different germs and health factors might play a role in Long COVID. Researchers looked at how having a viral, bacterial, or fungal infection before, during, or after COVID-19 might make someone more likely to develop Long COVID. The combined information suggests that these infections can confuse the immune system, making it attack healthy cells or cause problems to the body’s organs. For example, the stress of fighting SARS-CoV-2, the virus that causes COVID-19, might “wake up” old viruses that were dormant (asleep or inactive) in the body, which can make a person sicker or more likely to develop Long COVID. This paper is important because it shows that Long COVID is complex and may involve different germs that change the body’s responses to infection. By learning more about these connections, researchers hope to find better ways to test for and treat Long COVID in everyone.
This summary was prepared by the RECOVER Initiative.
Publication Details
DOI: 10.7554/eLife.106308
Abstract
A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or Long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairments that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent Long COVID.
Authors
Timothy J Henrich, Christopher P Montgomery, Joerg Graf, Nahed Ismail, Sindhu Mohandas, Mehul S Suthar, Hassan Brim, John M Coffin, Aayush Pagaria, Jeisac Guzmán Rivera, Urmila Vudali, Paul Keim, Guangming Zhong, Rebecca McGrath, Belinda Edwards, Adolfo García-Sastre, Maria Laura Gennaro
Keywords
PASC; SARS-CoV-2; co-infection; immunology; infectious disease; inflammation; long COVID; microbiology