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Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

ABSTRACT: Two years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.

SUBMITTER: Thompson RC

PROVIDER: S-EPMC8509101 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

Thompson Ryan C RC Simons Nicole W NW Wilkins Lillian L Cheng Esther E Del Valle Diane Marie DM Hoffman Gabriel E GE Fennessy Brian B Mouskas Konstantinos K Francoeur Nancy J NJ Johnson Jessica S JS Lepow Lauren L Le Berichel Jessica J Chang Christie C Beckmann Aviva G AG Wang Ying-Chih YC Nie Kai K Zaki Nicholas N Tuballes Kevin K Barcessat Vanessa V Cedillo Mario A MA Huckins Laura L Roussos Panagiotis P Marron Thomas U TU Glicksberg Benjamin S BS Nadkarni Girish G Gonzalez-Kozlova Edgar E Kim-Schulze Seunghee S Sebra Robert R Merad Miriam M Gnjatic Sacha S Schadt Eric E EE Charney Alexander W AW Beckmann Noam D ND

medRxiv : the preprint server for health sciences 20211005

Two years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase o ...[more]

PMID: 34642700

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Project description:BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic has progressed, there has been a growing awareness of the long-term impacts of the COVID-19 infection. However, until recently, there was no published study that investigated COVID-19-related sequelae and related factors for greater than six months from the onset of COVID-19 symptoms or the time of COVID-19 diagnosis in Korea.Materials and methodsOnline survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020. Responders aged between 16 and 70 years were included. Long-term sequelae were defined as persistent symptoms or signs ≥ 6 months after acute COVID-19 infection. The survey was conducted from September 8, 2020 to September 10, 2020. Clinical characteristics and self-reported clinical sequelae of the responders were analyzed to investigate the prevalence and factors associated with sequelae using descriptive and multivariate logistic regression analysis.ResultsThe median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 195 (interquartile range [IQR] 191 - 200) days. The response rate was 17.1% (900 out of 5,252). The median age was 31 (IQR 24.0 - 47.0) years old, and 627 responders were female (69.7%). Regarding the disease severity, 29 (3.2%) were asymptomatic, 763 (84.8%) mild, 86 (9.6%) moderate, 17 (1.9%) severe, and 5 (0.6%) critical. In total, 591 (65.7%) responders suffered from COVID-19-related long-term sequelae and 78 (8.6%) responders were receiving outpatient treatment for COVID-19-related long-term sequelae. The most common symptoms identified during the isolation period were anosmia and ageusia at 44.5% and 43.5%, respectively. Fatigue was the most common long-term sequelae, accounting for 253 (26.2%) responders, followed by concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression, which accounted for over 20%. Female gender was identified as the factor associated with mental and psychological long-term sequelae (P <0.05).ConclusionThe results showed that the rate of COVID-19-related long-term sequelae was 65.7%. The most common long-term sequela was fatigue. The risk factor identified was female gender. It was found that the long-term sequelae had various manifestations, including mental and psychological aspects. To improve the care of COVID-19 recovered patients with COVID-19-related long-term sequelae, the participation of a comprehensive and an interdisciplinary group of researchers is required.

Dataset Information

Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

Publications

Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

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