{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:09:53Z","timestamp":1770829793623,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,9]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":17,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,9]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n This study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1\u20132%), it rises markedly in the setting of chronic viral co-infections, particularly HIV (15\u201340%). Given its immunologic effects and persistence, HPgV represents a biologically plausible but unexplored viral co-factor SARS-CoV-2 infection.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed four cohorts: SARS-CoV-2\u2013positive individuals, ICU patients with respiratory symptoms but SARS-CoV-2\u2013negative, HIV-positive individuals as a positive control for HPgV detection, and uninfected controls.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n HPgV prevalence in COVID-19 patients was low (2.1%) and comparable to population estimates. As expected, HPgV prevalence was substantially higher in the HIV cohort (34%), validating assay performance and cohort stratification. Among HPgV-positive COVID-19 cases, most experienced mild disease, with directional trends toward reduced severity despite high baseline risk factors. Healthcare workers in the control group showed unexpectedly elevated HPgV prevalence (9.6%).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n HPgV is an unmonitored but widely circulating viral co-infection in humans that may influence host responses to SARS-CoV-2. Although limited by small numbers, our findings support further investigation of HPgV and other immunomodulatory viral co-infections in COVID-19. This study suggests that HPgV co-infection may influence COVID-19 outcomes, warranting further investigation.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n Systematic screening of human pegivirus (HPgV), an unmonitored viral co-infection, in COVID-19 (n = 634).<\/jats:p>\n <\/jats:list-item>\n \n HPgV prevalence in COVID-19 mirrored population estimates but was markedly enriched in HIV (positive control).<\/jats:p>\n <\/jats:list-item>\n \n HPgV-positive COVID-19 cases showed trends toward milder clinical outcomes.<\/jats:p>\n <\/jats:list-item>\n \n Findings highlight the potential relevance of immunomodulatory viral co-infections in SARS-CoV-2 infection.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>\n \n Executive Summary<\/jats:title>\n This study evaluated the prevalence of human pegivirus (HPgV) co-infection among SARS-CoV-2\u2013positive patients as part of a broader effort to understand how concurrent viral infections may influence COVID-19 severity. HPgV is a largely unmonitored, persistent human virus with well-described immunomodulatory effects in other viral infections, yet it has not been systematically evaluated in COVID-19. We therefore screened HPgV prevalence across COVID-19 cases, comparator cohorts, and an HIV-positive cohort as a positive control due to the well-established high prevalence of HPgV in HIV infection. Our findings indicate that HPgV prevalence in SARS-CoV-2\u2013positive and \u2013negative hospitalized individuals are consistent with the general U.S. population range (approximately 1\u20135%). Healthcare professionals exhibited a higher HPgV prevalence (\u223c10%), suggesting that repeated occupational viral exposures may influence infection rates. While limited by small numbers, HPgV co-infection in COVID-19 cases was associated with directional trends toward reduced disease severity, warranting further longitudinal and mechanistic investigation.<\/jats:p>\n <\/jats:sec>\n \n Editor\u2019s summary<\/jats:title>\n This study identifies human pegivirus as a widely circulating, unmonitored viral co-infection in COVID-19 with potential relevance to disease severity.<\/jats:p>\n <\/jats:sec>","DOI":"10.64898\/2026.02.06.26344215","type":"posted-content","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:55:42Z","timestamp":1770688542000},"source":"Crossref","is-referenced-by-count":0,"title":["Viral Co-infection in COVID-19: Prevalence and Clinical Associations of Human Pegivirus"],"prefix":"10.64898","author":[{"given":"Mathieu","family":"Garand","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching Ching","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranav","family":"Kirti","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack T.","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Microbiology & Immunology, University of Iowa and Iowa City Veterans Affairs Healthcare System, Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pirooz","family":"Eghtesady","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"5","key":"2026021108150781000_2026.02.06.26344215v1.1","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.3390\/biomedicines11051402","article-title":"Viral Coinfection of Children Hospitalized with Severe Acute Respiratory Infections during COVID-19 Pandemic","volume":"11","year":"2023","journal-title":"Biomedicines"},{"issue":"3","key":"2026021108150781000_2026.02.06.26344215v1.2","doi-asserted-by":"crossref","first-page":"e13107","DOI":"10.1111\/irv.13107","article-title":"Bacterial and viral infections among adults hospitalized with COVID-19, COVID-NET, 14 states, March 2020\u2013April 2022","volume":"17","year":"2023","journal-title":"Influenza Other Respir Viruses"},{"key":"2026021108150781000_2026.02.06.26344215v1.3","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.027490-0"},{"key":"2026021108150781000_2026.02.06.26344215v1.4","first-page":"17","article-title":"Human Pegivirus Type 1: A common human virus that is beneficial in immune-mediated disease","volume":"13","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"19","key":"2026021108150781000_2026.02.06.26344215v1.5","doi-asserted-by":"crossref","first-page":"5553","DOI":"10.1158\/0008-5472.CAN-14-0209","article-title":"GBV-C INFECTION AND RISK OF NHL AMONG U.S","volume":"74","year":"2014","journal-title":"ADULTS. 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