Myeloid inflammation and complement activation are linked to long COVID symptoms; distinct profiles observed in cognitive impairment and GI symptoms.
A study has found that myeloid inflammation and complement activation were linked to all symptoms of long COVID. Signs of neurodegeneration and dysregulation were observed in cognitive impairment (CI) and GI symptoms.
“In this study we aimed to understand inflammatory profiles underlying long COVID symptoms, and determine, if these inflammatory profiles could be correlated with certain symptoms, to reveal mechanisms of disease,” said Felicity Liew, MRCP, MBBS, at the 2023 ERS International Congress. Posthospitalization data from 719 adults was obtained from the PHOSP-COVID study and besides clinical information, 368 immune mediators were determined. Due to the expectation that these immune mediators may be connected by networks and thus in possible correlation, a penalized logistic regression was performed to determine the most accurate effect size.
Of all included patients, 250 were identified as recovered and used as controls. All had been hospitalized a median of 6 months ago. The patients with long COVID were grouped by present symptoms, among them cardio-respiratory impairment, fatigue, CI, GI symptoms, and anxiety/depression. Comparing the primary characteristics of patients with long COVID with those who had recovered, no intergroup differences were found. The sputum in both groups was tested negative for SARS-CoV2.
“Across all symptom groups, we saw elevated markers of myeloid inflammation and complement activation; however, there were subtle differences in the inflammatory profiles of those with GI symptoms and cognitive impairment,” Dr. Liew said. CSF3, known for the promotion of neutrophilic inflammation was increased in GI symptoms, fatigue, and anxiety/depression, while C1QA, a sign of activation of the complement pathway was heightened in GI symptoms and CI. Of note, elevated SCG3, linked to an impairment of the brain-gut-axis in patients with irritable bowel syndrome, was present in the group with GI symptoms. Furthermore, DPP10, a modulator of tissue inflammation in ulcerative colitis, was augmented, which points to enteric inflammation underlying the GI symptoms in long COVID. In CI, markers of neural growth and neuroinflammation were elevated.
“Importantly, we found that sCD58 is positively associated with recovery and this mediator is known to suppress interaction between monocytes and lymphocytes downstream of IL-1 and IL-6 signaling,” Dr. Liew said, pointing out that this supports their hypothesis that myeloid inflammation and complement activation could be driving long COVID symptoms.
Dr. Liew concluded that the study was not designed to be a mechanistic study or a study for the identification of diagnostic and prognostic markers. Although the investigation found common pathways, the possibility of distinct inflammatory profiles that could represent alternative underlying mechanisms, may need to be included in future clinical treatment trials.
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