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The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.

ABSTRACT: Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.

SUBMITTER: Schultheiß C

PROVIDER: S-EPMC9214726 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.

Schultheiß Christoph C Willscher Edith E Paschold Lisa L Gottschick Cornelia C Klee Bianca B Henkes Svenja-Sibylla SS Bosurgi Lidia L Dutzmann Jochen J Sedding Daniel D Frese Thomas T Girndt Matthias M Höll Jessica I JI Gekle Michael M Mikolajczyk Rafael R Binder Mascha M

Cell reports. Medicine 20220601 6

Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentr ...[more]

PMID: 35732153

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Project description:BackgroundData on the post-acute and post-infectious complications of patients who have recovered from severe coronavirus disease 2019 (COVID-19) are limited. While studies report that approximately 5-15% of COVID-19 hospitalized patients require intensive care and mechanical ventilation, a substantially higher number need non-invasive ventilation and are subject to prolonged hospitalizations, with long periods of immobility and isolation. The purpose of this study is to describe the post-infectious sequelae of severe viral illness and the post-acute complications of intensive care treatments in critically ill patients who have recovered from severe COVID-19 infection.MethodsWe performed a retrospective chart review of adult patients initially hospitalized with confirmed COVID-19 infection, who recovered and were transferred to a general medical ward or discharged home between March 15, 2020 and May 15, 2020, dates inclusive, after an intensive care unit (ICU) or high dependency unit (HDU) admission in a designated COVID-19 hospital in the United Arab Emirates. Demographic data, underlying comorbidities, treatment, complications, and outcomes were collected. Descriptive statistical analyses were performed.ResultsOf 71 patients transferred out of ICU (n = 38, 54%) and HDU (n = 33, 46%), mean age was 48 years (SD, 9.95); 96% men; 54% under age 50. Mean ICU stay was 12.4 days (SD, 5.29), HDU stay was 13.4 days (SD, 4.53). Pre-existing conditions were not significantly associated with developing post-acute complications (Odds Ratio [OR] 1.1, 95% confidence interval [CI] 0.41, 2.93, p = 1.00). Fifty nine percent of patients had complications; myopathy, swallowing impairments, and pressure ulcers were most common. Delirium and confusion were diagnosed in 18% (n = 13); all were admitted to the ICU and required mechanical ventilation. Of note, of all patients studied, 59.2% (n = 42/71) had at least 1 complication, 32.4% (n = 23) had at least 2 complications, and 19.7% (n = 14) suffered 3 or more sequelae. Complications were significantly more common in ICU patients (n = 33/38, 87%), compared to HDU patients (n = 9/33, 27%) (OR 17.6, 95% CI 5.23, 59.21, p <0.05).ConclusionIn a subset of critically ill patients who recovered from severe COVID-19 infection, there was considerable short-term post-infectious and post-acute disability. Long-term follow-up of COVID-19 survivors is warranted.

Dataset Information

The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.

Publications

The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.

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