Elevated myeloid inflammation and complement activation present in various phenotypes of long COVID

An association between increased markers of myeloid inflammation and complement activation was identified in patients with long COVID symptoms. Patients exhibiting cognitive impairment or gastrointestinal (GI) symptoms had distinct inflammatory profiles.

“Long COVID is a common and debilitating condition that affects 65 million people globally. However, despite the scale of this clinical issue, there is still very little known about the disease, including phenotypes and possible mechanisms,” Dr Felicity Liew (Imperial College London, UK) informed [1]. The present study strove to understand inflammatory profiles underlying long COVID symptoms and determined if these inflammatory profiles could be correlated with certain symptoms.

Post-hospitalisation data from 719 adults was obtained from the PHOSP-COVID study (ISRCTN10980107) 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 penalised logistic regression was performed to determine the most accurate effect size. Of all included individuals, 250 were identified as ‘recovered’ and participated as controls. All participants had been hospitalised a median of 6 months prior. The long COVID patients were grouped by present symptoms, among them cardio-respiratory impairment, fatigue, cognitive impairment, GI symptoms, and anxiety/depression.

No differences were found in the primary characteristics between individuals with long COVID and those who had recovered. The sputum in both groups was tested negative for SARS-CoV-2. “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 disclosed. CSF3, known for the promotion of neutrophilic inflammation, was increased in participants with GI symptoms, fatigue, and anxiety/depression, while C1QA, a sign of activation of the complement pathway, was heightened in participants with GI symptoms and cognitive impairment. 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 cognitive impairment, markers of neural growth and neuroinflammation were elevated. “Importantly, we found that sCD58 positively associated with recovery, and this mediator is known to suppress interaction between monocytes and lymphocytes downstream of IL-1 and IL-6 signalling,” Dr Liew stated, pointing out that this supports their hypothesis that myeloid inflammation and complement activation could be driving long COVID symptoms.

In conclusion, Dr Liew underlined 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.

1. Liew F, et al. Large-scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease. Abstract 4070, ERS 2023 International Congress, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023