IMPACT of COVID-19 TREATMENTS on PERIPHERAL CAPILLARY DENSITY EVALUATED by NAILFOLD VIDEOCAPILLAROSCOPY

ABSTRACT

Background: Human SARS-CoV-2 infection can induce a wide spectrum of organ dysfunctions, including microvascular impairment [1]. S1 subunit of viral receptor-binding domain binds to the angiotensin-converting enzyme 2 receptor on endothelium and S2 subunit allows the virus to enter endothelial cells. The resulting breakdown of barrier integrity drives a cascade of infammatory and thrombotic events, that aggravate the course of COVID-19 together with other risk factors [2-4]. Up to date, a lower capillary density has been reported in several distinct body districts, using sublingual video microscopy, ocular optical coherence tomography angiography, skin functional laser Doppler perfusion imaging and nailfold videocapillaroscopy (NVC) [5-8]. NVC examination has been performed in adult COVID-19 patients, however, without a control group [8]. Objectives: To confrm the statistical signifcance of the reduction in capillary density per linear millimeter evaluated by NVC in comparison with primary Ray-naud's phenomenon (PRP) patients and control subjects (CNT) and to evaluate the impact of an aggressive therapy against COVID-19 on the sparing in the number of capillaries. Methods: Sixty-one COVID-19 survivors, thirty-one PRP patients and thirty CNT age and sex-matched underwent NVC analysis. Demographic and clinical data of COVID-19 survivors were collected with special regard to concomitant therapies, that included antivirals, antibiotics, anticoagulants and anti-infamma-tory/immunomodulant drugs (glucocorticoids, hydroxychloroquine, IL-6 receptor antagonist). COVID-19 survivors were divided in two subgroups according to the severity of the active infection thirty-four survivors with past mild-moderate disease (either unneedy for oxygen supplementation or need for Venturi mask) and twenty-seven survivors with past severe disease (need for Continuous Positive Airways Pressure and/or mechanical ventilation). The same Rheumatologist performed NVC evaluations in all patients and controls, using an optical probe, equipped with a 200x magnifcation lens and connected to a picture analysis software (Videocap, DS Medica, Milan, Italy). Absolute capillary number per linear millimeter was counted. Results: COVID-19 survivors underwent NVC examination after a mean period of 126±53 days from the disease onset. Multivariate analysis showed differences in absolute capillary number per linear millimeter (p<0.001) after adjusting for age, sex, body mass index, comorbidities and concomitant drugs. The mean (± standard deviation) absolute nailfold capillary number per linear millimeter was signifcantly lower in severe (8.2±1.15) and mild-moderate (8.4±0.75) COVID-19 survivors than in both PRP (8.7±0.68) and CNT subjects (9.3±0.53) (p<0.001). The analysis of the impact of treatments on capillary density in the severe COVID-19 patients showed a positive trend (preservation of the capillary number) with antivirals (no 7.8±1.53;yes 8.5±0.64;p=0.35) and anti-IL-6 receptor antagonist administration (no 7.8±1.36;yes 8.6±0.74;p=0.16), while none of the other drugs was shown to be effective (glucocorticoids p = 0.46;antibiotics = 0.52;anticoagulants not evaluable as they were used in all COVID-19 patients). Conclusion: SARS-CoV-2 infection seems associated to a signifcant capillary loss as distinctive NVC feature and data concerning the comparison of capillary density pre COVID-19 and post COVID-19 are desirable to reinforce this observation. The positive trend in saving the number of capillaries induced by aggressive anti-infammatory therapies in COVID-19 survivors needs larger cohorts of patients.