Findings From Mayo Clinic’s Post-COVID Clinic: PASC Phenotypes Vary by Sex and Degree of IL-6 Elevation

Durstenfeld, Matthew S; Hsue, Priscilla Y.; Peluso, Michael J.; Deeks, Steven G.

doi:10.1016/j.mayocp.2022.01.020

Cited by 9 publications

(9 citation statements)

References 24 publications

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“…Other work indicates a trend towards elevated IL-6 and TNF-⍺ in PASC patients, although fold-changes compared to controls are small. 30,31 In a different study, the combination of inflammatory mediators, including IL-6, IFN-γ, IFN-β, PTX3, and IFN-λ2/3, was found to be a more informative predictor of PASC. 32 Therefore, even though we do not observe cytokine levels to be elevated above the normal range in most cases, monitoring cytokines over time in a larger cohort warrants further investigation.…”

Section: Discussionmentioning

confidence: 97%

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Swank

Senussi

Alter

et al. 2022

Preprint

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The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC.

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Section: Discussionmentioning

confidence: 97%

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Swank

Senussi

Alter

et al. 2022

Preprint

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“…We found more women than men presenting with Long COVID across all age groups, consistent with literature and anecdotes from Long COVID clinic providers. [46] When evaluating the U09.9 cohort across age groups and socioeconomic status, Long COVID presentation was more heterogeneous. While our findings do not present a clear socio-demographic trend (see Table 1), the role of access to providers and the economic means to afford Long COVID care should continue to be studied for their role as confounders.…”

Section: Discussionmentioning

confidence: 99%

Coding Long COVID: Characterizing a new disease through an ICD-10 lens

Pfaff

Madlock‐Brown

Baratta

et al. 2022

Preprint

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Naming a newly discovered disease is always challenging; in the context of the COVID-19 pandemic and the existence of post-acute sequelae of SARS-CoV-2 infection (PASC), which includes Long COVID, it has proven especially challenging. Disease definitions and assignment of a diagnosis code are often asynchronous and iterative. The clinical definition and our understanding of the underlying mechanisms of Long COVID are still in flux. The deployment of an ICD-10-CM code for Long COVID in the US took nearly two years after patients had begun to describe their condition. Here we leverage the largest publicly available HIPAA-limited dataset about patients with COVID-19 in the US to examine the heterogeneity of adoption and use of U09.9, the ICD-10-CM code for “Post COVID-19 condition, unspecified.”Our results include a characterization of common diagnostics, treatment-oriented procedures, and medications associated with U09.9-coded patients, which give us insight into current practice patterns around Long COVID. We also established the diagnoses most commonly co-occurring with U09.9, and algorithmically clustered them into three major categories: cardiopulmonary, neurological, and metabolic. We aim to apply the patterns gleaned from this analysis to flag probable Long COVID cases occurring prior to the existence of U09.9, thus establishing a mechanism to ensure patients with earlier cases of Long-COVID are no less ascertainable for current and future research and treatment opportunities.

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“…For example, fatigue predominates among women with PASC and has been associated with elevated IL-6, while dyspnea is prevalent among men with PASC and did not correlate with IL-6 levels ( 68 ). Sex-related differences in the innate immune system may also be involved, including the fact that the gene encoding TLR7, which activates the IFN-I antiviral response, a key defense against SARS-CoV-2 ( 39 , 50 ), is on the X chromosome, and women predominate in most autoimmune phenomena ( 69 ).…”

Section: Formulating Hypotheses For Pasc Pathogenesismentioning

confidence: 99%

“…Correlation with microthrombus and SARS-CoV-2 persistence in peripheral nerve tissues should be pursued. SARS-CoV-2 does infect the CNS, including those regions responsible for autonomic regulation, with defects leading to dysautonomia and postural orthostatic tachycardia syndrome, additional neurologic features of PASC, particularly among women ( 69 ).…”

Section: Formulating Hypotheses For Pasc Pathogenesismentioning

confidence: 99%

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

Ahamed¹,

Laurence²

2022

Journal of Clinical Investigation

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SARS-CoV-2–infected individuals may suffer a multi–organ system disorder known as “long COVID” or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology. Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.

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Findings From Mayo Clinic’s Post-COVID Clinic: PASC Phenotypes Vary by Sex and Degree of IL-6 Elevation

Cited by 9 publications

References 24 publications

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Coding Long COVID: Characterizing a new disease through an ICD-10 lens

Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches

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