Abstract: Background. Vasoactive peptides play an important role in a wide range of physiological and pathological conditions. Due to its known functions, the calcitonin gene-related peptide (CGRP) has been suggested as a possible modulator of the hyperimmune response in COVID-19 and thus, blocking its action may lessen the pulmonary effects of COVID-19. Aim of the Study. To compare the circulating levels of CGRP ?and CGRP ?in healthy controls compared to hospitalized COVID-19 patients. The study also analyzed how dif- ferent comorbidities and treatments may affect these concentrations in cases of COVID- 19 infection with pulmonary involvement Methods. Serum samples were collected from the antecubital vein of 51 control subjects (mean age = 55 ±14 years; range = 26?77; 56.9% female) and 52 patients hospitalized with COVID-19 infection (mean age = 55 ±13; range = 23?77; 55.8% female) from December 2020 to May 2021. Enzyme-linked immunosorbent assays (ELISAs) were used for CGRP ?(Abbexa, UK) and CGRP ?(CUSABIO, China) measurements. Comorbidities, symptoms, and treatments of infection were listed. Results. The results showed that the serum levels of both isoforms of CGRP were significantly higher in patients with COVID-19 ( ?: 57.9 ±35.8 pg/mL; ?: 6.1 ±2.6 pg/mL) compared to controls ( ?: 41.8 ±25.4 pg/mL; ?: 4.5 ±2.4 pg/mL) ( p < 0.01). Also, the presence of arterial hypertension (HT), obesity, or corticosteroid treatment significantly alter the serum concentration of CGRP ?in the subgroups compared to controls. Conclusion. The elevated serum CGRP levels found in our COVID-19 group compared to controls may suggest that CGRP plays a role in the pathophysiology of the disease, more specifically, in the cytokine storm and in the pulmonary involvement. Future studies should focus on the source of this CGRP elevation.

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