Thiago S Moreira1, José A Barreto-Filho2,3, Juliane D Seabra-Garcez2,3, Flavia Barreto Garcez4, Luciano F Drager5,6. 1. Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil. 2. Division of Cardiology, Federal University of Sergipe, Sergipe, Brazil. 3. Division of Cardiology, Hospital São Lucas Rede São Luiz D'Or, Sergipe, Brazil. 4. Division of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil. 5. Hypertension Unit, Renal Division, University of Sao Paulo Medical School, Sao Paulo, Brazil. 6. Hypertension Unit, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
to the editor: We thank the authors of the Commentaries (1) in response to our recent Viewpoint (2) in the Journal of Applied Physiology. The primary objective of the respiratory system is to have precise mechanisms to exchange gases in harmony with the organism’s metabolic needs to set the level of pulmonary ventilation (VE). Ventilation is a product of breathing frequency (fR) and the quantity of air inspired with each breath (tidal volume, VT). Any given VE theoretically can originate from a variety of combinations between VT and fR, that is, from a pattern of breathing extremely shallow and fast to one very deep and slow, with all the combinations in between (3). Chemosensors located in the carotid artery and within the central nervous system are the main receptors for detecting changes in arterial blood oxygen levels, and the resulting chemoreflex is a potent regulator of breathing and blood pressure (4). Therefore, the chemoreflex together with brainstem areas involved in respiratory control should be in consonance to maintain physiological homeostasis.The novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the epidemic disease called coronavirus disease-19 (COVID-19) is a multifaceted disease and respiratory failure is a common manifestation. From a recent Viewpoint (2), we explored potential pathways associated with the so-called nondyspnogenic acute hypoxia. Despite this mechanism, it is important to point out that SARS-CoV-2 may affect the respiratory frequency and tidal volume differently. Increases in VT are presumably due to higher recruitment of respiratory premotor neurons, whereas increases in fR are due to an increase in the network activity of the core of neurons located in the pre-Botzinger complex (5). We still do not know, but the invasion of the virus through the olfactory system can spread to the entire central nervous system, including the brainstem respiratory column. A possible mechanism in which the SARS-CoV-2 transfects the respiratory neurons is the presence of angiotensin receptors in the premotor neurons as well as in the pre-Botzinger complex (6). Therefore, the transfection of both neurons involved in VT and fR start a degeneration process, leading to respiratory impairment. We believe that it is highly necessary to perform neuroanatomical and electrophysiological experiments to better understand the effects of SARS-CoV-2 on neurons involved in breathing pattern.
GRANTS
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Grant 2015/23376-1 (to T.S.M).
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the authors.
AUTHOR CONTRIBUTIONS
T.S.M., J.A.B-F., J.D.S-G., F.B.G., and L.F.D. drafted, edited and revised, and approved final version of manuscript.