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. 2024 Jan-Dec:15:21501319241254751.
doi: 10.1177/21501319241254751.

Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs

Ravindra Ganesh  1 , Siddhant Yadav  1 , Ryan T Hurt  1 , Michael R Mueller  1 , Christopher A Aakre  1 , Elizabeth A Gilman  1 , Stephanie L Grach  1 , Joshua Overgaard  1 , Melissa R Snyder  1 , Nerissa M Collins  1 , Ivana T Croghan  1 , Andrew D Badley  1 , Raymund R Razonable  1 , Bradley R Salonen  1
Affiliations

Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs

Ravindra Ganesh et al. J Prim Care Community Health. 2024 Jan-Dec.

Abstract

Background: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs.

Methods: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants.

Results: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α (P < .001) and interleukin 1β (P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs.

Discussion: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.

Keywords: PASC; SARS-CoV-2; cytokines; long COVID; variants.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RG is a consultant for Alpaca Health; RTH is a consultant for Nestle; RG and RTH have received research funding from the GHR Foundation (Minneapolis, MN) and have received research support from electroCore Inc., InteraXon Inc., and Reulay Inc.; ADB is supported by grants from NIAID (grants AI110173 and AI120698), Amfar (#109593), and Mayo Clinic (HH Shieck Khalifa Bib Zayed Al-Nahyan Named Professorship of Infectious Diseases). ADB is a paid consultant for Abbvie, Gilead, Freedom Tunnel, Pinetree therapeutics Primmune, Immunome, MarPam, Rion, Symbiosis, NexImmune and Flambeau Diagnostics, is a paid member of the DSMB for Corvus Pharmaceuticals, Equilium, CSL Behring, and Excision Biotherapeutics. Raymund R. Razonable has received grants from Regeneron, Roche, and Gilead for research not directly related to this study. All authors are employees of the Mayo Clinic. All other authors report no potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Scatter plots of selected cytokine levels by SARS-CoV-2 variant.
See this image and copyright information in PMC

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