From Online Data Collection to Identification of Disease Mechanisms: The IL-1ß, IL-6 and TNF-α Cytokine Triad Is Associated With Post-Acute Sequelae of COVID-19 in a Digital Research Cohort

Willscher, Edith; Paschold, Lisa; Gottschick, Cornelia; Klee, Bianca; Glasauer, Saskia; Henkes, Svenja-Sibylla; Bosurgi, Lidia; Dutzmann, Jochen; Sedding, Daniel; Frese, Thomas; Girndt, Matthias; Höll, Jessica I.; Gekle, Michael; Mikolajczyk, Rafael; Binder, Mascha

doi:10.2139/ssrn.3963839

Cited by 14 publications

(14 citation statements)

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“…In association with clinical observations, the kinetic measurement of IL-6 during SARS-CoV-2 infection is a crucial tool to predict the prognosis and outcome of patients with COVID-19 [ 30 ]. While inflammatory cytokines such as IL-6 could underpin some of the long-term neuropsychiatric features of COVID-19 [ 31 ], persistently elevated levels of IL-6 and other cytokines may be a hallmark of post-acute sequelae of COVID-19 [ 32 ]. However, these biomarkers are not routinely available for every inpatient, and several other inflammatory biomarkers might offer reliable information.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory and Cardiac Biomarkers in Relation with Post-Acute COVID-19 and Mortality: What We Know after Successive Pandemic Waves

et al. 2022

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Background: Biomarkers were correlated with mortality in critically ill COVID-19 patients. No prediction tools exist for noncritically ill COVID-19 patients. We aimed to compare the independent prognostic value of inflammation and cardiac biomarkers for post-acute COVID-19 patients and the 30-day mortality rate in noncritically ill COVID-19 patients, as well as the relation with the virus variant involved. Methods: This observational cohort study was conducted at an emergency clinical hospital between 1 October 2020 and 31 December 2021. We included consecutive patients with biomarkers determined within 24 h of presentation, followed up at least 30 days postdischarge. Results: Post-acute COVID-19 was diagnosed in 20.3% of the cases and the all-cause 30-day mortality rate was 35.1% among 978 patients infected with variants of concern. Neutrophil-to-lymphocyte ratio (1.06 [95%CI, 1.01–1.11], p = 0.015) and NT-pro BNP were correlated with 30-daymortality, while the monocyte-to-lymphocyte ratio (2.77 [95%CI, 1.10–6.94], p = 0.03) and NT-pro BNP (1.68 [95%CI, 1.00–2.84], p = 0.05) were correlated with post-acute COVID-19. High-sensitivity to troponin was associated with 30-day mortality (1.55 [95%CI, 1.00–2.42], p = 0.05). A Cox proportional-hazards model confirmed that NT-pro BNP was independently associated with mortality. NT-pro BNP remained independently associated with 30-day mortality during follow-up (1.29 [95%CI, 1.07–1.56], p = 0.007) after adjustment for confounders. Conclusion: Inflammation and cardiac biomarkers, determined upon admission and predischarge, in a cohort of hospitalized noncritically ill COVID-19 patients throughout successive pandemic waves, showed a predictive value for post-acute COVID-19 and 30-day mortality.

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Section: Discussionmentioning

confidence: 99%

Inflammatory and Cardiac Biomarkers in Relation with Post-Acute COVID-19 and Mortality: What We Know after Successive Pandemic Waves

et al. 2022

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“…Notably, the DEGs for pneumonia were almost entirely downregulated (Fig. 3b), not simply recapitulating the association between pneumonia and higher plasma outcomes through elements of the immune response to SARS-CoV-2 infection [7][8][9][10][11][12][13][14][15] . However, examined sample sizes have often been small and the scope of molecular profiling generally limited.…”

Section: Pasc Symptoms Associate With Distinct Cts Gene Expressionmentioning

confidence: 99%

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Thompson

Simons

Wilkins

et al. 2022

Nat Med

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Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.

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“…47,48 A further study demonstrated that TNF-a levels in serum can serve as a prognostic marker of post-acute sequelae in COVID-19 patients (long covid). 49 In addition, the kynurenine/tryptophan ratio positively correlates with patient severity. 50,51 In this context, our data suggest that a KD may improve patient health with reduced risk of hospitalization and long covid.…”

Section: Discussionmentioning

confidence: 99%

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Palermo¹,

Shen²,

Hoeve

et al. 2022

Preprint

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The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.

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From Online Data Collection to Identification of Disease Mechanisms: The IL-1ß, IL-6 and TNF-α Cytokine Triad Is Associated With Post-Acute Sequelae of COVID-19 in a Digital Research Cohort

Cited by 14 publications

References 0 publications

Inflammatory and Cardiac Biomarkers in Relation with Post-Acute COVID-19 and Mortality: What We Know after Successive Pandemic Waves

Inflammatory and Cardiac Biomarkers in Relation with Post-Acute COVID-19 and Mortality: What We Know after Successive Pandemic Waves

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

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