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Silent hypoxia: higher NO in red blood cells of COVID-19 patients.
BMC Pulm Med. 2020 Oct 16; 20(1):269.BP

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects.

METHODS

We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA).

RESULTS

The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group.

CONCLUSIONS

This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.

Authors+Show Affiliations

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Tracheal Disease Research Center, National Research Institute of Tuberculosisand Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran. mmalekmohammad@yahoo.com.Chronic Respiratory Diseases Research Center, National Research Institute ofTuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Chronic Respiratory Diseases Research Center, National Research Institute ofTuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Chronic Respiratory Diseases Research Center, National Research Institute ofTuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Chronic Respiratory Diseases Research Center, National Research Institute ofTuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery, Education and research Hospital, Department of pulmonology, Istanbul, Turkey.Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK. Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33066765

Citation

Mortaz, Esmaeil, et al. "Silent Hypoxia: Higher NO in Red Blood Cells of COVID-19 Patients." BMC Pulmonary Medicine, vol. 20, no. 1, 2020, p. 269.
Mortaz E, Malkmohammad M, Jamaati H, et al. Silent hypoxia: higher NO in red blood cells of COVID-19 patients. BMC Pulm Med. 2020;20(1):269.
Mortaz, E., Malkmohammad, M., Jamaati, H., Naghan, P. A., Hashemian, S. M., Tabarsi, P., Varahram, M., Zaheri, H., Chousein, E. G. U., Folkerts, G., & Adcock, I. M. (2020). Silent hypoxia: higher NO in red blood cells of COVID-19 patients. BMC Pulmonary Medicine, 20(1), 269. https://doi.org/10.1186/s12890-020-01310-8
Mortaz E, et al. Silent Hypoxia: Higher NO in Red Blood Cells of COVID-19 Patients. BMC Pulm Med. 2020 Oct 16;20(1):269. PubMed PMID: 33066765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silent hypoxia: higher NO in red blood cells of COVID-19 patients. AU - Mortaz,Esmaeil, AU - Malkmohammad,Majid, AU - Jamaati,Hamidreza, AU - Naghan,Parisa Adimi, AU - Hashemian,Seyed MohamadReza, AU - Tabarsi,Payam, AU - Varahram,Maohammad, AU - Zaheri,Hamidreza, AU - Chousein,Efsun Gonca Uğur, AU - Folkerts,Gert, AU - Adcock,Ian M, Y1 - 2020/10/16/ PY - 2020/07/03/received PY - 2020/10/09/accepted PY - 2020/10/17/entrez PY - 2020/10/18/pubmed PY - 2020/10/24/medline KW - COVID-19 KW - Hypoxia KW - NO SP - 269 EP - 269 JF - BMC pulmonary medicine JO - BMC Pulm Med VL - 20 IS - 1 N2 - BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients. SN - 1471-2466 UR - https://www.unboundmedicine.com/medline/citation/33066765/Silent_hypoxia:_higher_NO_in_red_blood_cells_of_COVID_19_patients_ L2 - https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-020-01310-8 DB - PRIME DP - Unbound Medicine ER -