tetano
Editor, Senior Moderator
J Endocr Soc
. 2021 Jan 4;5(3):bvaa199.
doi: 10.1210/jendso/bvaa199. eCollection 2021 Mar 1.
Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients
Laura Ochoa-Callejero[SUP] 1 [/SUP], Josune Garc?a-Sanmart?n[SUP] 1 [/SUP], Pablo Villoslada-Blanco[SUP] 2 [/SUP], Mar?a ??iguez[SUP] 2 [/SUP], Patricia P?rez-Matute[SUP] 2 [/SUP], Elisabet Pujadas[SUP] 3 [/SUP], Mary E Fowkes[SUP] 3 [/SUP], Rachel Brody[SUP] 3 [/SUP], Jos? A Oteo[SUP] 2 4 [/SUP], Alfredo Mart?nez[SUP] 1 [/SUP]
Affiliations
Abstract
Background: To better understand the biology of COVID-19, we have explored the behavior of calcitonin gene-related peptide (CGRP), an angiogenic, vasodilating, and immune modulating peptide, in severe acute respiratory syndrome coronavirus 2 positive patients.
Methods: Levels of CGRP in the serum of 57 COVID-19 patients (24 asymptomatic, 23 hospitalized in the general ward, and 10 admitted to the intensive care unit) and healthy donors (n = 24) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, to better understand the physiological consequences of the observed variations, we investigated by immunofluorescence the distribution of receptor activity modifying protein 1 (RAMP1), one of the components of the CGRP receptor, in autopsy lung specimens.
Results: CGRP levels were greatly decreased in COVID-19 patients (P < 0.001) when compared to controls, and there were no significant differences due to disease severity, sex, age, or comorbidities. We found that COVID-19 patients treated with proton pump inhibitors had lower levels of CGRP than other patients not taking this treatment (P = 0.001). RAMP1 immunoreactivity was found in smooth muscle cells of large blood vessels and the bronchial tree and in the airways? epithelium. In COVID-19 samples, RAMP1 was also found in proliferating type II pneumocytes, a common finding in these patients.
Conclusions: The lower levels of CGRP should negatively impact the respiratory physiology of COVID-19 patients due to vasoconstriction, improper angiogenesis, less epithelial repair, and faulty immune response. Therefore, restoring CGRP levels in these patients may represent a novel therapeutic approach for COVID-19.
Keywords: CGRP; COVID-19; ILC2; RAMP1; airway hyperresponsiveness; proton pump inhibitors; type II pneumocyte hyperplasia.
. 2021 Jan 4;5(3):bvaa199.
doi: 10.1210/jendso/bvaa199. eCollection 2021 Mar 1.
Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients
Laura Ochoa-Callejero[SUP] 1 [/SUP], Josune Garc?a-Sanmart?n[SUP] 1 [/SUP], Pablo Villoslada-Blanco[SUP] 2 [/SUP], Mar?a ??iguez[SUP] 2 [/SUP], Patricia P?rez-Matute[SUP] 2 [/SUP], Elisabet Pujadas[SUP] 3 [/SUP], Mary E Fowkes[SUP] 3 [/SUP], Rachel Brody[SUP] 3 [/SUP], Jos? A Oteo[SUP] 2 4 [/SUP], Alfredo Mart?nez[SUP] 1 [/SUP]
Affiliations
- PMID: 33506161
- PMCID: PMC7798995
- DOI: 10.1210/jendso/bvaa199
Abstract
Background: To better understand the biology of COVID-19, we have explored the behavior of calcitonin gene-related peptide (CGRP), an angiogenic, vasodilating, and immune modulating peptide, in severe acute respiratory syndrome coronavirus 2 positive patients.
Methods: Levels of CGRP in the serum of 57 COVID-19 patients (24 asymptomatic, 23 hospitalized in the general ward, and 10 admitted to the intensive care unit) and healthy donors (n = 24) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, to better understand the physiological consequences of the observed variations, we investigated by immunofluorescence the distribution of receptor activity modifying protein 1 (RAMP1), one of the components of the CGRP receptor, in autopsy lung specimens.
Results: CGRP levels were greatly decreased in COVID-19 patients (P < 0.001) when compared to controls, and there were no significant differences due to disease severity, sex, age, or comorbidities. We found that COVID-19 patients treated with proton pump inhibitors had lower levels of CGRP than other patients not taking this treatment (P = 0.001). RAMP1 immunoreactivity was found in smooth muscle cells of large blood vessels and the bronchial tree and in the airways? epithelium. In COVID-19 samples, RAMP1 was also found in proliferating type II pneumocytes, a common finding in these patients.
Conclusions: The lower levels of CGRP should negatively impact the respiratory physiology of COVID-19 patients due to vasoconstriction, improper angiogenesis, less epithelial repair, and faulty immune response. Therefore, restoring CGRP levels in these patients may represent a novel therapeutic approach for COVID-19.
Keywords: CGRP; COVID-19; ILC2; RAMP1; airway hyperresponsiveness; proton pump inhibitors; type II pneumocyte hyperplasia.