Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection
Chen Chen, Sairam Parthasarathy, Jacqueline M Leung, Michelle J Wu, Katherine A Drake, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Bellur S Prabhakar, Mujeeb Basit, Mirella Salvatore, Jerry A Krishnan, Charles C Kim
Frontiers in Medicine, doi:10.3389/fmed.2023.1227883
Background: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.
Methods: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection. Results: We identified three phenotypic clusters associated with PASC that could be characterized as remittent, persistent, or incident based on the 3-month change in symptom number compared to study entry: remittent (median; min, max: -4; -17, 3), persistent (-2; -14, 7), or incident (4.5; -5, 17) (p = 0.041 remittent vs. persistent, p < 0.001 remittent vs. incident, p < 0.001 persistent vs. incident). Despite younger age and lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, 24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, 4.36)].
Conclusion: An incident disease phenotype characterized by symptoms that were absent during acute illness and the observed association with high dose steroids during acute illness have potential critical implications for preventing PASC.
Ethics statement The studies involving humans were approved by the Study Protocol # 20201016 WCG Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.
Author contributions HZ, WC, and CK conceptualized the study. CC, KD, HZ, WC, VR, MB, and JK were involved in the study design. SP, VT, JM, CRd, IR, MB, MS, and JK recruited patients and collected the samples. CC, SP, JL, MW, and MS analyzed the data. CC, SP, JL, MW, MS, JK, and CK wrote the manuscript. CC, SP, JL, MW, KD, VR, HZ, WC, VT, JM, CRd, IR, BP, MB, MS, JK, and CK reviewed the manuscript. All authors contributed to the article and approved the submitted version.
Conflict of interest CC, JL, MW, KD, and CK maintain equity ownership and employment at Verily Life Sciences. SP reports personal fees from Jazz Pharmaceuticals, Inc., and UpToDate, Inc., and grants from Philips, Inc., Sommetrics, Inc., and Regeneron. CRd serves on advisory boards for Abbott Diagnostics, Ortho/Quidel Diagnostics, and Roche Diagnostics. JK receives research funding from Regeneron. JK has also provided consulting for GlaxoSmithKline, AstraZeneca, CereVu Medical, Propeller/ResMed, and BData, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The..
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'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>The understanding of Post-acute sequelae '
'of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms '
'encompassing the acute illness period. To gain insight into the various disease trajectories '
'of PASC, we assessed symptom evolution and clinical factors associated with the development '
'of PASC over 3 months, starting with the acute illness '
'period.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a '
'prospective cohort study to identify parameters associated with PASC. We performed cluster '
'and case control analyses of clinical data, including symptomatology collected over 3 months '
'following infection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We '
'identified three phenotypic clusters associated with PASC that could be characterized as '
'remittent, persistent, or incident based on the 3-month change in symptom number compared to '
'study entry: remittent (median; min, max: −4; −17, 3), persistent (−2; −14, 7), or incident '
'(4.5; −5, 17) (<jats:italic>p</jats:italic> = 0.041 remittent vs. persistent, '
'<jats:italic>p</jats:italic> &lt; 0.001 remittent vs. incident, '
'<jats:italic>p</jats:italic> &lt; 0.001 persistent vs. incident). Despite younger age and '
'lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, '
'24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 '
'and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration '
'during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, '
'4.36)].</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>An incident '
'disease phenotype characterized by symptoms that were absent during acute illness and the '
'observed association with high dose steroids during acute illness have potential critical '
'implications for preventing PASC.</jats:p></jats:sec>',
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