Using skin biopsy samples, the researchers found that patients with severe COVID-19 had clots in small venous and arterial blood vessels in the skin that looked normal. This was not seen on patent skin with other types of severe infectious lung disease, or in individuals with only mild or moderate COVID-19. His findings appear in The American Journal of Pathology, published by Elsevier.
Researchers document, for the first time in premortal testing, that a minimally invasive skin biopsy may help assess COVID-19-related tissue damage, as well as help distinguish this pathology from blood vessels from other forms of severe respiratory disease. Prior to this study, invasive procedures such as nerve, kidney, or lung biopsy would have been necessary.
We were the first group to recognize that acute COVID-19 lung disease was different from other severe critical respiratory infections and that the unusual pathology was systemic. “
Jeffrey Laurence, MD, Principal Investigator, Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA
The researchers collected simple samples of a 4-mm puncture biopsy of normal-looking deltoid skin from 15 patients who were in intensive care with COVID-19 and six patients with mild to moderate symptoms of COVID-19, such as fever, chills , cough or difficulty breathing. . Biopsy samples from nine hospitalized patients with severe or critical respiratory or renal disease who died before the COVID-19 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 biopsies of patients who had mild to moderate COVID-19 or patients from the pre-COVID-19 era with severe respiratory disease or kidney disease. These microvascular changes are likely to be a unique feature of COVID-19 respiratory disorder compared to other acute respiratory diseases.
An antiviral protein capable of blocking the growth of SARS-CoV-2, MxA, was found in all six patients with mild to moderate COVID-19, indicating that their immune systems were actively fighting the virus, compared with only two patients with severe or critical illness.
An interferon-induced inflammatory protein, SIN3A, was prominent in the normal-looking skin microvascular of patients with severe or critical COVID-19, but not in similar samples from normal control subjects. Increased plasma SN3A levels and expression in the skin microvasculature were associated with the severity of the patient’s disease and could contribute to the storm cytokine characteristic in these patients.
Dr. Laurence notes that these results have clinical implications. “Although anticoagulants were used in the pre-COVID-19 era in sepsis-associated pneumonia to reduce macrovessal thromboembolism, most randomized trials to date have not found that this treatment benefits hospitalized patients who are seriously ill with COVID-19 acute respiratory distress syndrome. Drugs may not be able to reduce microvessel thrombosis that is associated with SARS-CoV-2 infection. “
Researchers recognize that their work is limited by their non-random referral process, and before the clinical significance of these findings can be established as actionable correlations of disease progression, a prospective study using biopsy samples is needed. in series of normal-looking skin. However, they emphasize that single-stitch skin biopsy allows a tissue-based assessment of microvascular thrombosis, complement disposition, and MxA and SN3A levels at different times.
“If validated in a longitudinal cohort, prior identification of severe COVID-19-related factors by a simple skin biopsy in patients in early stages of SARS-CoV-2 infection may help identify people at risk for progression acute disease and COVID-19 long and allow targeted early interventions, “said Dr. Laurence.
Source:
Magazine reference:
Laurence, J., et al. (2022) Premortal skin biopsy evaluating microthrombi, type I antiviral and regulatory interferon proteins, and complement deposition correlates with the clinical stage of coronavirus disease 2019. American Journal of Pathology. doi.org/10.1016/j.ajpath.2022.05.006.