Journal Article

Chronic viral coinfections differentially affect the likelihood of developing long COVID

Munter, Sadie E., Goldberg, Sarah A., Peluso, Michael J., Hsue, Priscilla Y., Chan, Fay, Hellmuth, Joanna, Durstenfeld, Matthew S., Chenna, Ahmed, Kelly, J. Daniel, Tai, Viva, Chen, Jessica Y., Hunt, Peter W., Henrich, Timothy J., Ryder, Dylan, Buck, Amanda, Rodriguez, Antonio, Petropoulos, Christos J., Deeks, Steven G., Yee, Brandon C., Lu, Scott, Deswal, Monika, Torres, Leonel, Deitchman, Amelia N., Beck-Engeser, Gabriele, Ngo, Lynn H., Martin, Jeffrey N., Deveau, Tyler-Marie, Hoh, Rebecca, Buitrago, Melissa, Spinelli, Matthew A., Iyer, Nikita S., Winslow, John W.

2023

Overview

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).

• Publisher: American Society for Clinical Investigation
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / Analysis / Antibodies, Viral / Antigens / Biological products industry / Biomedical research / Chronic diseases / Clinical Medicine / Cognition / Coinfection - epidemiology / Complications and side effects / Coronaviruses / COVID-19 / COVID-19 - epidemiology / Cytomegalovirus / Cytomegalovirus Infections / Demographics / Fatigue / Fatigue - epidemiology / Fatigue - etiology / Health aspects / HIV / HIV infection / HIV Infections - complications / HIV Infections - epidemiology / Hospitalization / Human immunodeficiency virus / Humans / Immunoglobulin G / Infection / Infections / Infectious diseases / Long COVID / Medical research / Medicine, Experimental / Post-Acute COVID-19 Syndrome / Regression analysis / SARS-CoV-2 / Serology / Severe acute respiratory syndrome coronavirus 2 / T cell receptors / Viral infections / Viremia / Virus diseases