Researchers used non-invasive skin biopsy to identify clots in small venous and arterial blood vessels in the skin of patients with severe COVID-19 that appeared normal.

The clots were, however, not seen in the skin of patients with other types of severe infectious lung disease, or in individuals with only mild or moderate COVID, as revealed in the findings published in The American Journal of Pathology. Prior to this study, researchers were using invasive procedures such as nerve, kidney, or lung biopsy.

"We were the first group to recognise that the lung disease of acute COVID-19 was different from other severe critical respiratory infections and that the unusual pathology was systemic," explained lead investigator Jeffrey Laurence, Department of Medicine, at Weill Cornell Medicine, US.

For the study, the team collected simple 4 mm punch biopsy samples of normal-appearing deltoid skin from 15 patients who were in intensive care with COVID and six patients with mild to moderate COVIDsymptoms, such as fever, chills, cough, or shortness of breath. Biopsy samples from nine hospitalised patients with severe or critical respiratory or kidney disease who died before the COVID era were also included in the study.

Microthrombi were detected in 13 of the 15 patients with severe or critical COVID-19. No microthrombi were detected in the biopsies of patients who had mild to moderate COVID or the pre-COVID era patients with severe respiratory illness or kidney diseases. It is likely that these microvascular changes may be a unique characteristic of COVID respiratory disorder compared to other acute respiratory diseases.

An antiviral protein capable of blocking COVID growth, MxA, was found in all six mild to moderate COVID patients, indicating that their immune systems were actively fighting the virus, versus only two patients with severe to critical disease. An interferon-induced inflammatory protein, SIN3A, was prominent in the microvascular of normal-appearing skin from patients with severe or critical COVID, but not in similar samples from normal control subjects.

Increased SN3A levels in plasma and expression in skin microvasculature were associated with the severity of the patient's disease and could contribute to the cytokine storm characteristic in such patients.

"If validated in a longitudinal cohort, earlier identification of factors linked to severe COVID -19 using a simple skin biopsy in patients at early stages of SARS-CoV-2 infection may help identify individuals at risk of acute disease progression and long COVID and enable early targeted interventions," Laurence said.