Tag: mild vs severe covid infection

Inflammatory and neuroinjury blood biomarkers across COVID-19 severity groups in individuals with persistent neurological symptoms

Abstract:

Persistent neurological symptoms such as cognitive impairment, fatigue, and neuropsychiatric disturbances are increasingly reported in patients with long COVID, with chronic neuroinflammation and neuronal injury proposed as potential contributors. To characterize inflammatory and neuroinjury-related biomarker patterns, we conducted a case-control study including 325 participants recruited at King Chulalongkorn Memorial Hospital between January 2022 and December 2023, comprising 265 individuals with persistent neurological symptoms following COVID-19 infection and 60 asymptomatic COVID-19 participants who did not develop long COVID symptoms.

Blood samples were analysed for inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IFN-α, IL-4) using multiplex immunoassays, and for neuroinflammatory and neurodegenerative biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, and beta-amyloid peptides (Aβ40, Aβ42) using SIMOA and ELISA platforms. Among 265 participants with complete data (critical = 7, severe = 22, moderate = 79, mild = 157), patients with severe and critical COVID-19 exhibited significantly higher concentrations of IL-6, IL-1β, TNF-α, and IL-8, together with elevated NfL, GFAP, and phosphorylated tau181 levels, and reduced Aβ42/40 ratios.

Strong positive correlations between neurodegenerative biomarkers and pro-inflammatory cytokines were observed in critically ill patients, whereas these associations were weak or absent in mild and moderate cases. Older age was also associated with greater disease severity and increased risk of persistent neurological complications.

These findings indicate that individuals with persistent neurological symptoms following COVID-19, particularly those with a history of severe or critical disease, exhibited higher inflammatory and neuroinjury-related biomarker levels, while blood-based biomarkers such as NfL, GFAP, and phosphorylated tau181 may serve as minimally invasive tools for characterizing neurological involvement and identifying patients at risk of long-term neurological sequelae.

Source: Ruchisrisarod C, Kaewpom T, Wanthong P, Luechaipanit W, Bunprakob S, Ampoot W, Yomrat S, Hemachudha P, Supharatpariyakorn T, Thanapornsangsuth P, Tammachote R, Saraya AW. Inflammatory and neuroinjury blood biomarkers across COVID-19 severity groups in individuals with persistent neurological symptoms. Int J Immunopathol Pharmacol. 2026 Jan-Dec;40:3946320261465568. doi: 10.1177/03946320261465568. Epub 2026 Jul 16. PMID: 42460883; PMCID: PMC13376473. https://pmc.ncbi.nlm.nih.gov/articles/PMC13376473/ (Full text)

The metabolic and physiologic impairments underlying long COVID associated exercise intolerance

Abstract:

Data from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO2), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO2 and exercise capacity (VO2) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). ‘

In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO2 with reduced peak VO2 (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO2 [88% predicted (IQR 81% – 108%) vs. 70% predicted (IQR 64% – 89%); p = 0.02] and EO2 [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection.

In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO2 was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO2 and consequently peak VO2 impact long COVID patients in a severity dependent manner.

Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.

Source: Leitner BP, Joseph P, Quast AF, Ramirez MA, Heerdt PM, Villalobos JG, Singh I. The metabolic and physiologic impairments underlying long COVID associated exercise intolerance. Pulm Circ. 2024 Nov 13;14(4):e70009. doi: 10.1002/pul2.70009. PMID: 39544193; PMCID: PMC11560803. https://pmc.ncbi.nlm.nih.gov/articles/PMC11560803/ (Full text)