Prolonged inflammation in patients hospitalized for coronavirus disease 2019 (COVID‐19) resolves 2 years after infection

• Published in: Journal of medical virology 2023-05, Vol.95 (5), p.e28774-n/a
• Main Authors: Fong, Siew‐Wai, Goh, Yun Shan, Torres‐Ruesta, Anthony, Chang, Zi Wei, Chan, Yi‐Hao, Neo, Vanessa Kexin, Lee, Bernett, Duan, Kaibo, Amrun, Siti Naqiah, Yeo, Nicholas Kim‐Wah, Chen, Hsiuyi V., Tay, Matthew Zirui, Carissimo, Guillaume, Tan, Seow Yen, Leo, Yee‐Sin, Lye, David C., Renia, Laurent, Young, Barnaby Edward, Ng, Lisa F. P.
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood; Cell differentiation; Complications; Coronaviruses; COVID vaccine; COVID-19; Cytokines; Hospitalization; Humans; Immune system; Immunological memory; Infections; Inflammation; long COVID; Longitudinal Studies; Lymphocytes; Lymphocytes T; Memory cells; mRNA; Prospective Studies; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; subclinical signs; Vaccines; Viral diseases; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.28774

Long‐term complications from coronavirus disease 2019 (COVID‐19) are concerning, as survivors can develop subclinical multiorgan dysfunction. It is unknown if such complications are due to prolonged inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination may reduce sequela. We conducted a prospective longitudinal study on hospitalized patients over 24 months. Clinical symptoms were collected by self‐reporting during follow‐up, along with blood samples for quantification of inflammatory markers and immune cell frequencies. All patients were given one dose of mRNA vaccine at 12−16 months. Their immune profiles at 12 and 24 months were compared. Approximately 37% and 39% of our patients reported post‐COVID‐19 symptoms at 12 and 24 months, respectively. The proportion of symptomatic patients with more than one symptom decreased from 69% at 12 months to 56% at 24 months. Longitudinal cytokine profiling revealed a cluster of individuals with persistently high inflammatory cytokine levels 12 months after infection. Patients with prolonged inflammation showed elevated terminally differentiated memory T cells in their blood; 54% had symptoms at 12 months. The majority of inflammatory markers and dysregulated immune cells in vaccinated patients recovered to a healthy baseline at 24 months, even though symptoms persisted. Post‐COVID‐19 symptoms can linger for 2 years after the initial infection and are associated with prolonged inflammation. Prolonged inflammation in hospitalized patients resolves after 2 years. We define a set of analytes associated with persistent inflammation and presence of symptoms, which could be useful biomarkers for identifying and monitoring high‐risk survivors.