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 publication summarizes what scientists know so far about how having different infections other than COVID-19 (called co-infections) may affect the development of Long COVID. These co-infections include those that a person may have had before COVID-19, infections that became active again during or after COVID-19, and new infections that may happen after having COVID. After reviewing existing studies, researchers found that differences in the type and timing of these co-infections make it difficult to fully understand their role in Long COVID. They note that co-infections could make Long COVID more severe, or COVID could cause other infections to worsen, depending on the infection, timing, and many other factors. The publication highlights the need for continued, coordinated research efforts, including longitudinal studies like RECOVER, to understand how co-infections may impact the development of Long COVID and the mechanisms leading to those impacts.
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