Dealing with a COVID-19 infection is an unpleasant experience. Persistent cough, debilitating headaches, and an overwhelming lack of energy take its toll on the body after the usual couple weeks of infection. For one man in the U.S., that experience lasted more than 750 days.
A new case study, published in The Lancet, has shed light on this longest documented case of COVID-19. The paper discusses how persistent infections in immunocompromised individuals can act as incubators for viral evolution, providing crucial insights into how new variants may emerge.
“This report emphasizes that SARS-CoV-2 can establish a chronic, non-lethal infection in individuals with compromised immune function that leads to considerable viral evolution,” said the authors in their paper.
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The Longest Documented Case of COVID-19
The patient, a 41-year-old man living with HIV/AIDS since 2002, was not consistently taking antiretroviral therapy (ART) to manage his HIV. In May 2020, he was exposed to COVID-19 via close contact and developed the usual suite of unpleasant symptoms. The symptoms persisted, and he continued to have positive PCR tests until his death over two years later.
During these two years, eight clinical samples were taken from the patient by the team at the Medical University of South Carolina. By sequencing these samples, the team was able to reveal some significant findings — including the fact that there had been significant viral evolution taking place inside the patient’s body.
The Link Between Long-Term Infection and Viral Evolution
Since the pandemic began, the global genome sequencing efforts have documented the rapid emergence of many new variants. Omicron, a variant that swept the globe starting in late 2021, quickly displaced earlier variants in severity and contagiousness. Its success is partly due to mutations that made it both highly transmissible and better able to evade immunity.
Long-term infections in immunocompromised people create a unique environment for viral adaptations like omicron. Unlike in the general population where repeated transmission create genetic bottlenecks, the virus inside a single compromised host can evolve continuously without interruption. Over more than two years of infection, the virus in this particular patient accumulated spike protein mutations that allowed it to evade antibodies and enhance its binding to host cells.
The study found striking parallels between the mutations observed in this patient and those later identified in omicron, suggesting that prolonged infections may act as breeding grounds for dangerous new variants.
“The virus population that developed over this long-term infection appears to have been well adapted for successful replication within this specific host,” said the research team in the paper. “There was no evidence for superinfection or displacement by alpha, delta, or omicron variants despite these viruses sweeping through the USA over the course of infection. Such adaptation to one individual could have resulted in trade-offs that limited onward transmission.”
What Are the Implications for Public Health?
This case highlights the urgent need to ensure access to effective HIV treatment and consistent ART, both to protect immunocompromised individuals and to limit opportunities for viral evolution. Previous studies have already shown that uncontrolled HIV can make beating COVID-19 infections far more difficult.
The research team hopes their study will increase public health focus on immunocompromised individuals, especially those who have difficulty accessing treatment for chronic disease and COVID-19 infections, and avoid the emergence of deadlier variants created inside the human body.
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