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1.
Viruses ; 14(4)2022 04 10.
Article in English | MEDLINE | ID: covidwho-1786081

ABSTRACT

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease, n = 65; severe, n = 132, intubated and/or died, n = 42). All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death (hazard ratio 1.749, 95%CI 1.041-2.939, p = 0.035) after adjustment for other known risk factors. Youden's index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predictive value: 57% and 91%, respectively). Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.


Subject(s)
COVID-19 , Receptors, Interleukin-2 , Respiratory Insufficiency , Biomarkers , COVID-19/metabolism , COVID-19/pathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Receptors, Interleukin-2/blood , Receptors, Interleukin-2/metabolism , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/metabolism
2.
Int J Mol Sci ; 22(23)2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1542585

ABSTRACT

Pulmonary fibrosis is a chronic, fibrotic lung disease affecting 3 million people worldwide. The ACE2/Ang-(1-7)/MasR axis is of interest in pulmonary fibrosis due to evidence of its anti-fibrotic action. Current scientific evidence supports that inhibition of ACE2 causes enhanced fibrosis. ACE2 is also the primary receptor that facilitates the entry of SARS-CoV-2, the virus responsible for the current COVID-19 pandemic. COVID-19 is associated with a myriad of symptoms ranging from asymptomatic to severe pneumonia and acute respiratory distress syndrome (ARDS) leading to respiratory failure, mechanical ventilation, and often death. One of the potential complications in people who recover from COVID-19 is pulmonary fibrosis. Cigarette smoking is a risk factor for fibrotic lung diseases, including the idiopathic form of this disease (idiopathic pulmonary fibrosis), which has a prevalence of 41% to 83%. Cigarette smoke increases the expression of pulmonary ACE2 and is thought to alter susceptibility to COVID-19. Cannabis is another popular combustible product that shares some similarities with cigarette smoke, however, cannabis contains cannabinoids that may reduce inflammation and/or ACE2 levels. The role of cannabis smoke in the pathogenesis of pulmonary fibrosis remains unknown. This review aimed to characterize the ACE2-Ang-(1-7)-MasR Axis in the context of pulmonary fibrosis with an emphasis on risk factors, including the SARS-CoV-2 virus and exposure to environmental toxicants. In the context of the pandemic, there is a dire need for an understanding of pulmonary fibrotic events. More research is needed to understand the interplay between ACE2, pulmonary fibrosis, and susceptibility to coronavirus infection.


Subject(s)
Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Fibrosis/metabolism , Peptide Fragments/metabolism , /metabolism , Cannabis , Cigarette Smoking , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Inflammation , Lung/pathology , Pandemics , Respiration, Artificial , Respiratory Distress Syndrome , Respiratory Insufficiency/metabolism , Risk Factors , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Am J Physiol Lung Cell Mol Physiol ; 321(2): L485-L489, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1299247

ABSTRACT

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.


Subject(s)
COVID-19/complications , Complement Activation/immunology , Complement C3b/immunology , Complement C4b/immunology , Erythrocytes/immunology , Peptide Fragments/immunology , Respiratory Insufficiency/diagnosis , Sepsis/diagnosis , COVID-19/immunology , COVID-19/virology , Complement C3b/metabolism , Complement C4b/metabolism , Erythrocytes/metabolism , Erythrocytes/virology , Female , Humans , Male , Middle Aged , Peptide Fragments/metabolism , Respiratory Insufficiency/immunology , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/virology , SARS-CoV-2/isolation & purification , Sepsis/immunology , Sepsis/metabolism , Sepsis/virology
4.
J Pediatr ; 237: 143-147, 2021 10.
Article in English | MEDLINE | ID: covidwho-1242546

ABSTRACT

OBJECTIVE: To assess whether use of an N95 mask by children is associated with episodes of desaturation or respiratory distress. STUDY DESIGN: Twenty-two healthy children were assigned at random to 1 of 2 groups: one group wearing N95 masks without an exhalation valve and the other group wearing N95 masks with an exhalation valve. We tracked changes in partial pressure of end-tidal carbon dioxide (PETCO2), oxygen saturation, pulse rate, and respiratory rate over 72 minutes of mask use. All subjects were monitored every 15 minutes, the first 30 minutes while not wearing a mask and the next 30 minutes while wearing a mask. They then performed a 12-minute walking test. RESULTS: The children did not experience a statistically significant change in oxygen saturation or pulse rate during the study. There were significant increases in respiratory rate and PETCO2 in the children wearing an N95 mask without an exhalation valve, whereas these increases were seen in the children wearing a mask with an exhalation valve only after the walking test. CONCLUSIONS: The use of an N95 mask could potentially cause breathing difficulties in children if the mask does not have an exhalation valve, particularly during a physical activity. We believe that wearing a surgical mask may be more appropriate for children.


Subject(s)
N95 Respirators/adverse effects , Respiratory Insufficiency/etiology , Biomarkers/metabolism , Carbon Dioxide/metabolism , Child , Child, Preschool , Exercise/physiology , Female , Heart Rate , Humans , Male , Oxygen/metabolism , Respiratory Function Tests , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/metabolism , Respiratory Rate , Risk Factors , Walk Test
6.
Trials ; 21(1): 1014, 2020 Dec 10.
Article in English | MEDLINE | ID: covidwho-966433

ABSTRACT

OBJECTIVES: SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. TRIAL DESIGN: This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. PARTICIPANTS: This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. INTERVENTION AND COMPARATOR: Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plans for the surfactant are as follows. Cohort 1: Three patients will receive 10 vials (1080 mg) each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 2: Three patients will receive 10 vials (1080 mg) of surfactant at dosing times of 0 hours and 8 hours, and 30 vials (3240 mg) at a dosing time of 24 hours. 2 controls with no placebo intervention. Cohort 3: Three patients will receive 10 vials (1080 mg) of surfactant at a dosing time of 0 hours, and 30 vials (3240 mg) at dosing times of 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 4: Three patients will receive 30 (3240 mg) vials each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls. 2 controls with no placebo intervention. The trial steering committee, advised by the data monitoring committee, will review trial progression and dose escalation/maintenance/reduction after each cohort is completed (48-hour primary outcome timepoint reached) based on available feasibility, adverse event, safety and efficacy data. The trial will not be discontinued on the basis of lack of efficacy. The trial may be stopped early on the basis of safety or feasibility concerns. Comparator: No placebo intervention. All participants will receive usual standard of care in accordance with the local policies for mechanically ventilated patients and all other treatments will be left to the discretion of the attending physician. MAIN OUTCOMES: The co-primary outcome is the improvement in oxygenation (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP - PEEP) × PaCO2]/1000) at 48 hours after study initiation. The secondary outcomes include frequency and severity of adverse events (AEs), Adverse Device Effects (ADEs), Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs), change in pulmonary compliance, change in positive end-expiratory pressure (PEEP) requirement of ventilatory support at 24 and 48 hours after study initiation, clinical improvement defined by time to one improvement point on the ordinal scale described in the WHO master protocol (2020) recorded while hospitalised, days of mechanical ventilation, mechanical ventilator free days (VFD) at day 21, length of intensive care unit stay, number of days hospitalised and mortality at day 28. Exploratory end points will include quantification of SARS-CoV-2 viral load from tracheal aspirates using PCR, surfactant dynamics (synthesis and turnover) and function (surface tension reduction) from deep tracheal aspirate samples (DTAS), surfactant phospholipid concentrations in plasma and DTAS, inflammatory markers (cellular and cytokine) in plasma and DTAS, and blood oxidative stress markers. RANDOMISATION: After informed assent, patients fulfilling inclusion criteria will be randomised to 3:2 for the treatment and control arms using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV) in combination with electronic data collection. Randomisation will be done by the recruiting centre with a unique subject identifier specific to that centre. BLINDING (MASKING): This is an open-labelled unblinded study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total sample size is 20 COVID-19 mechanically ventilated patients (12 intervention; 8 control). TRIAL STATUS: Current protocol version is V2 dated 5th of June 2020. The recruitment is currently ongoing and started on the 14th of October 2020. The anticipated study completion date is November 2021. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04362059 (Registered 24 April 2020), EUDAMED number: CIV-GB-20-06-033328, EudraCT number: 2020-001886-35 (Registered 11 May 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
COVID-19/drug therapy , Nebulizers and Vaporizers/standards , SARS-CoV-2/genetics , Surface-Active Agents/therapeutic use , Adult , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Feasibility Studies , Humans , Intensive Care Units/statistics & numerical data , London/epidemiology , Mortality/trends , Nebulizers and Vaporizers/statistics & numerical data , Respiration, Artificial/methods , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Safety , Surface-Active Agents/administration & dosage , Surface-Active Agents/chemistry , Treatment Outcome , Ventilation/statistics & numerical data
7.
FEBS J ; 287(17): 3681-3688, 2020 09.
Article in English | MEDLINE | ID: covidwho-960853

ABSTRACT

In coronavirus disease 2019 (COVID-19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID-19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin-converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID-19. In our opinion, sympathetic overactivation could represent a so-far undervalued mechanism for a vicious circle between COVID-19 and comorbidities.


Subject(s)
COVID-19/metabolism , Coronary Disease/metabolism , Diabetes Mellitus/metabolism , Hypertension/metabolism , Kidney Failure, Chronic/metabolism , Obesity/metabolism , Respiratory Insufficiency/metabolism , Sympathetic Nervous System/metabolism , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Comorbidity , Coronary Disease/mortality , Coronary Disease/pathology , Coronary Disease/virology , Diabetes Mellitus/mortality , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Female , Humans , Hypertension/mortality , Hypertension/pathology , Hypertension/virology , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/virology , Male , Obesity/mortality , Obesity/pathology , Obesity/virology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Severity of Illness Index , Sex Factors , Survival Analysis , Sympathetic Nervous System/physiopathology , Sympathetic Nervous System/virology
8.
J Med Virol ; 92(10): 1902-1914, 2020 10.
Article in English | MEDLINE | ID: covidwho-763159

ABSTRACT

We aimed to systematically review the clinical characteristics of coronavirus disease 2019 (COVID-19). Seven databases were searched to collect studies about the clinical characteristics of COVID-19 from January 1, 2020 to February 28, 2020. Then, meta-analysis was performed by using Stata12.0 software. A total of 38 studies involving 3062 COVID-19 patients were included. Meta-analysis showed that a higher proportion of infected patients was male (56.9%). The incidence rate of respiratory failure or acute respiratory distress syndrome was 19.5% and the fatality rate was 5.5%. Fever (80.4%), fatigue (46%), cough (63.1%), and expectoration (41.8%) were the most common clinical manifestations. Other common symptoms included muscle soreness (33%), anorexia (38.8%), chest tightness (35.7%), shortness of breath (35%), dyspnea (33.9%). Minor symptoms included nausea and vomiting (10.2%), diarrhea (12.9%), headache (15.4%), pharyngalgia (13.1%), shivering (10.9%), and abdominal pain (4.4%). The proportion of patients that was asymptomatic was 11.9%. Normal leukocyte counts (69.7%), lymphopenia (56.5%), elevated C-reactive protein levels (73.6%), elevated ESR (65.6%), and oxygenation index decreased (63.6%) were observed in most patients. About 37.2% of patients were found with elevated D-dimer, 25.9% of patients with leukopenia, along with abnormal levels of liver function (29%), and renal function (25.5%). Other findings included leukocytosis (12.6%) and elevated procalcitonin (17.5%). Only 25.8% of patients had lesions involving a single lung and 75.7% of patients had lesions involving bilateral lungs. The most commonly experienced symptoms of COVID-19 patients were fever, fatigue, cough, and expectoration. A relatively small percentage of patients were asymptomatic. Most patients showed normal leucocytes counts, lymphopenia, elevated levels of C-reactive protein and ESR. Bilateral lung involvement was common.


Subject(s)
COVID-19/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/virology , Child , Cough/diagnosis , Cough/metabolism , Cough/virology , Diarrhea/diagnosis , Diarrhea/metabolism , Diarrhea/virology , Fatigue/diagnosis , Fatigue/metabolism , Fatigue/virology , Female , Fever/diagnosis , Fever/metabolism , Fever/virology , Humans , Lung/metabolism , Lung/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/virology , SARS-CoV-2/pathogenicity , Young Adult
9.
Respir Res ; 21(1): 198, 2020 Jul 28.
Article in English | MEDLINE | ID: covidwho-680693

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient's clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Hypoxia/etiology , Lung/physiopathology , Oxygen Consumption/physiology , Pandemics , Pneumonia, Viral/complications , Respiratory Insufficiency/complications , COVID-19 , Coronavirus Infections/epidemiology , Critical Illness , Humans , Hypoxia/metabolism , Hypoxia/physiopathology , Pneumonia, Viral/epidemiology , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/physiopathology , SARS-CoV-2
10.
Int J Mol Sci ; 21(13)2020 Jun 30.
Article in English | MEDLINE | ID: covidwho-635461

ABSTRACT

By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures.


Subject(s)
Betacoronavirus/physiology , HMGB1 Protein/metabolism , Respiratory Insufficiency/pathology , Sepsis/pathology , Angiotensin-Converting Enzyme 2 , HMGB1 Protein/antagonists & inhibitors , Humans , Macrophages/cytology , Macrophages/metabolism , Macrophages/virology , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Plant Exudates/chemistry , Plant Exudates/pharmacology , Plants, Medicinal/chemistry , Plants, Medicinal/metabolism , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/prevention & control , SARS-CoV-2 , Sepsis/metabolism , Sepsis/prevention & control , Virus Internalization/drug effects
11.
Neurology ; 95(10): 454-457, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-616669
12.
ACS Chem Neurosci ; 11(16): 2416-2421, 2020 08 19.
Article in English | MEDLINE | ID: covidwho-618646

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been established as a cause of severe alveolar damage and pneumonia in patients with advanced Coronavirus disease (COVID-19). The consolidation of lung parenchyma precipitates the alterations in blood gases in COVID-19 patients that are known to complicate and cause hypoxemic respiratory failure. With SARS-CoV-2 damaging multiple organs in COVID-19, including the central nervous system that regulates the breathing process, it is a daunting task to compute the extent to which the failure of the central regulation of the breathing process contributes to the mortality of COVID-19 affected patients. Emerging data on COVID-19 cases from hospitals and autopsies in the last few months have helped in the understanding of the pathogenesis of respiratory failures in COVID-19. Recent reports have provided overwhelming evidence of the occurrence of acute respiratory failures in COVID-19 due to neurotropism of the brainstem by SARS-CoV-2. In this review, a cascade of events that may follow the alterations in blood gases and possible neurological damage to the respiratory regulation centers in the central nervous system (CNS) in COVID-19 are related to the basic mechanism of respiratory regulation in order to understand the acute respiratory failure reported in this disease. Though a complex metabolic and respiratory dysregulation also occurs with infections caused by SARS-CoV-1 and MERS that are known to contribute toward deaths of the patients in the past, we highlight here the role of systemic dysregulation and the CNS respiratory regulation mechanisms in the causation of mortalities seen in COVID-19. The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with COVID-19, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19. This debate is important for many reasons, one of which is the fact that permanent damage to the medullary respiratory centers by SARS-CoV-2 would not benefit from mechanical ventilators, as is possibly occurring during the management of COVID-19 patients.


Subject(s)
Coronavirus Infections/physiopathology , Hypoxia/physiopathology , Pneumonia, Viral/physiopathology , Respiratory Center/physiopathology , Respiratory Insufficiency/physiopathology , Betacoronavirus , Blood Gas Analysis , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Humans , Hypoxia/metabolism , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/mortality , Respiratory Center/metabolism , Respiratory Center/virology , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/mortality , SARS-CoV-2 , Viral Tropism
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