Abstract
BACKGROUNDIndividuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.METHODSWe performed a prospective cohort study of individuals with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.RESULTSSixty-one participants were enrolled across 2 academic medical centers at a median of 9 weeks (interquartile range, 6–10 weeks) after COVID-19 illness: n = 13 participants (21%) had mild COVID-19 and were not hospitalized, n = 30 participants (49%) were hospitalized but were considered noncritical, and n = 18 participants (30%) were hospitalized and in the intensive care unit (ICU). Fifty-three participants (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P < 0.05) but these values did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered participants by past COVID-19 severity. Lipocalin-2 (LCN2), MMP-7, and HGF identified by our analysis were significantly higher in the ICU group (P < 0.05), inversely correlated with FVC and DLCO (P < 0.05), and were confirmed in a separate validation cohort (n = 53).CONCLUSIONSubjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.FundingNational Heart, Lung, and Blood Institute (K08HL130557 and R01HL142818), American Heart Association (Transformational Project Award), the DeLuca Foundation Award, a donation from Jack Levin to the Benign Hematology Program at Yale University, and Duke University.
Highlights
Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function
As the number of patients who recover from acute coronavirus disease 2019 (COVID-19) rises, it is increasingly apparent that a substantial subset displays persistent subjective and objective respiratory ailments
Little is known about the biological drivers of long-term respiratory disease after COVID-19 and how acute COVID illness severity affects the emerging COVID-19 long-hauler syndrome or postacute sequelae of SARS-CoV-2 infection (PASC)
Summary
As the number of patients who recover from acute coronavirus disease 2019 (COVID-19) rises, it is increasingly apparent that a substantial subset displays persistent subjective and objective respiratory ailments. Little is known about the biological drivers of long-term respiratory disease after COVID-19 and how acute COVID illness severity affects the emerging COVID-19 long-hauler syndrome or postacute sequelae of SARS-CoV-2 infection (PASC). To better understand the relationship between subjective and objective respiratory abnormalities and underlying biological drivers, we measured symptom burden, pulmonary function tests, and plasma biomarkers in individuals that have recovered from COVID-19 infection. Individuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity
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