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1.
Drug Discov Ther ; 15(5): 273-277, 2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1542926

ABSTRACT

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Hypoxia/prevention & control , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Adult , COVID-19/complications , Disease Progression , Female , Humans , Hypoxia/drug therapy , Hypoxia/etiology , Kaplan-Meier Estimate , Male , Middle Aged , Treatment Outcome
2.
J Med Virol ; 93(3): 1320-1342, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196505

ABSTRACT

The 2019 novel coronavirus disease (COVID-19) now is considered a global public health emergency. One of the unprecedented challenges is defining the optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID-19. The optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of COVID-19, there have been many prepublications and publications reviewing the therapy of COVID-19 as well as many prepublications and publications reviewing the pathogenesis of SARS-CoV-2. However, there have been no comprehensive reviews that link COVID-19 therapies to the pathogenic mechanisms of SARS-CoV-2. To link COVID-19 therapies to pathogenic mechanisms of SARS-CoV-2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID-19, SARS-CoV-2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune-based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID-19 therapies with pathogenic mechanisms of SARS-CoV-2 has resulted in six major therapeutic goals for COVID-19 therapy based on the pathogenic mechanisms of SARS-CoV-2. These goals are listed below: 1. The first goal is identifying COVID-19 patients that require both testing and therapy. This is best accomplished with a COVID-19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. Whether a symptomatic respiratory illness is COVID-19, influenza, or another respiratory pathogen, an oxygen saturation less than 90% means that the patient requires medical assistance. 2. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory-directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID-19. 3. The third goal is to reduce the viral load of SARS-CoV-2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS-CoV-2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS-CoV-2. These are post-Covid-19 plasma with a high neutralizing antibody titer against SARS-CoV-2 or intravenous remdesivir; both options require hospitalization. 4. The fourth goal is to identify and address the hyperinflammation phase often seen in hospitalized COVID-19 patients. Currently, fever with an elevated C-reactive protein is useful for diagnosing this hyperinflammation syndrome. Low-dose dexamethasone therapy currently is the best therapeutic approach. 5. The fifth goal is to identify and address the hypercoagulability phase seen in many hospitalized COVID-19 patients. Patients who would benefit from anticoagulation therapy can be identified by a marked increase in d-dimer and prothrombin time with a decrease in fibrinogen. To correct this disseminated intravascular coagulation-like phase, anticoagulation therapy with low molecular weight heparin is preferred. Anticoagulation therapy with unfractionated heparin is preferred in COVID-19 patients with acute kidney injuries. 6. The last goal is prophylaxis for persons who are not yet infected. Potential supplements include vitamin D and zinc. Although the data for such supplements is not extremely strong, it can be argued that almost 50% of the population worldwide has a vitamin D deficiency. Correcting this deficiency would be beneficial regardless of any impact of COVID-19. Similarly, zinc is an important supplement that is important in one's diet regardless of any effect on SARS-CoV-2. As emerging therapies are found to be more effective against the SARS-CoV-2 pathogenic mechanisms identified, they can be substituted for those therapies presented in this review.


Subject(s)
COVID-19/physiopathology , COVID-19/therapy , Lung/pathology , SARS-CoV-2/pathogenicity , Antiviral Agents/therapeutic use , COVID-19/complications , Humans , Hypoxia/prevention & control , Inflammation/drug therapy , Viral Load/drug effects
6.
A A Pract ; 14(14): e01360, 2020 Dec 17.
Article in English | MEDLINE | ID: covidwho-1067373

ABSTRACT

This single-center retrospective study evaluated a protocol for the intubation of patients with confirmed or suspected coronavirus disease 2019 (COVID-19). Twenty-one patients were intubated, 9 of whom were found to have COVID-19. Adherence to the airway management protocol was high. COVID-19 patients had lower peripheral capillary oxygen saturation by pulse oximetry (Spo2) nadirs during intubation (Spo2, 73% [72%-77%] vs 89% [86%-94%], P = .024), and a greater percentage experienced severe hypoxemia defined as Spo2 ≤80% (89% vs 25%, P = .008). The incidence of severe hypoxemia in COVID-19 patients should be considered in the development of guidelines that incorporate high-flow nasal cannula and noninvasive positive pressure ventilation.


Subject(s)
COVID-19/therapy , Hypoxia/therapy , Intubation, Intratracheal/methods , Rapid Sequence Induction and Intubation/methods , Respiratory Insufficiency/therapy , Adult , Aged , Airway Management , Cannula , Female , Humans , Hypoxia/prevention & control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Laryngoscopy , Male , Middle Aged , N95 Respirators , Noninvasive Ventilation , Oximetry , Oxygen Inhalation Therapy , Patient Isolators , Personal Protective Equipment , Positive-Pressure Respiration , Practice Guidelines as Topic , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
8.
BMJ Open ; 10(12): e040580, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-955465

ABSTRACT

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused an international pandemic of respiratory illness, resulting in significant healthcare and economic turmoil. To date, no robust vaccine or treatment has been identified. Elemental zinc has previously been demonstrated to have beneficial effects on coronaviruses and other viral respiratory infections due to its effect on RNA polymerase. Additionally, zinc has well-demonstrated protective effects against hypoxic injury-a clear mechanism of end-organ injury in respiratory distress syndrome. We aimed to assess the effect of high-dose intravenous zinc (HDIVZn) on SARS-CoV-2 infection. The end of study analyses will evaluate the reduction of impact of oxygen saturations or requirement of oxygen supplementation. METHODS AND ANALYSIS: We designed a double-blind randomised controlled trial of daily HDIVZn (0.5 mg/kg) versus placebo. Primary outcome measures are lowest oxygen saturation (or greatest level of supplemental oxygenation) for non-ventilated patients and worst PaO2/FiO2 for ventilated patients. Following power calculations, 60 hospitalised patients and 100 ventilated patients will be recruited to demonstrate a 20% difference. The duration of follow-up is up to the point of discharge. ETHICS AND DISSEMINATION: Ethical approval was obtained through the independent Human Research Ethics Committee. Participant recruitment will commence in May 2020. Results will be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: ACTRN126200000454976.


Subject(s)
COVID-19/drug therapy , Zinc/administration & dosage , Administration, Intravenous , Adult , Clinical Trials, Phase II as Topic , Double-Blind Method , Female , Humans , Hypoxia/prevention & control , Male , Oxygen/blood , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2 , Zinc/adverse effects
9.
Int J Environ Res Public Health ; 17(22)2020 11 20.
Article in English | MEDLINE | ID: covidwho-945803

ABSTRACT

Respiratory diseases are currently considered to be amongst the most frequent causes of death and disability worldwide, and even more so during the year 2020 because of the COVID-19 global pandemic. Aiming to reduce the impact of these diseases, in this work a methodology is developed that allows the early detection and prevention of potential hypoxemic clinical cases in patients vulnerable to respiratory diseases. Starting from the methodology proposed by the authors in a previous work and grounded in the definition of a set of expert systems, the methodology can generate alerts about the patient's hypoxemic status by means of the interpretation and combination of data coming both from physical measurements and from the considerations of health professionals. A concurrent set of Mamdani-type fuzzy-logic inference systems allows the collecting and processing of information, thus determining a final alert associated with the measurement of the global hypoxemic risk. This new methodology has been tested experimentally, producing positive results so far from the viewpoint of time reduction in the detection of a blood oxygen saturation deficit condition, thus implicitly improving the consequent treatment options and reducing the potential adverse effects on the patient's health.


Subject(s)
COVID-19/diagnosis , Expert Systems , Hypoxia/diagnosis , Hypoxia/prevention & control , Fuzzy Logic , Humans
10.
Tuberk Toraks ; 68(3): 331-336, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-934593

ABSTRACT

Prone positioning is a well-known supportive maneuver to improve oxygenation for patients with moderate to severe acute respiratory distress syndrome (ARDS). Although this technique is usually performed to sedated patients on invasive mechanical ventilation, it has been used in non-intubated patients frequently during the coronavirus diseases-2019 (COVID-19) pandemic. Favorable outcomes have been reported mainly in combining the prone positioning with high flow nasal cannula (HFNC) or non-invasive ventilation (NIV). Due to limited data, a standard approach for the awake prone positioning has not yet been defined. In this manuscript, we reviewed the literature data about prone positioning in non-intubated patients with COVID-19. According to available literature data, we concluded that prone positioning in non-intubated COVID-19 patients may improve oxygenation and prevent the need for invasive mechanical ventilation. But the efficacy is still controversial in the early stage of the disease due to pulmonary mechanics. Further studies are needed to the defined optimal approach of awake prone positioning in COVID-19 patients with hypoxemic respiratory failure.


Subject(s)
COVID-19/therapy , Hypoxia/prevention & control , Patient Positioning/methods , Prone Position/physiology , COVID-19/prevention & control , Female , Humans , Male , Noninvasive Ventilation , Respiration, Artificial/methods , Respiratory Insufficiency/prevention & control , SARS-CoV-2
12.
BMC Med ; 18(1): 260, 2020 08 19.
Article in English | MEDLINE | ID: covidwho-721302

ABSTRACT

BACKGROUND: The current target oxygen saturation range for patients with COVID-19 recommended by the National Institutes of Health is 92-96%. MAIN BODY: This article critically examines the evidence guiding current target oxygen saturation recommendation for COVID-19 patients, and raises important concerns in the extrapolation of data from the two studies stated to be guiding the recommendation. Next, it examines the influence of hypoxia on upregulation of ACE2 (target receptor for SARS-CoV-2 entry) expression, with supporting transcriptomic analysis of a publicly available gene expression profile dataset of human renal proximal tubular epithelial cells cultured in normoxic or hypoxic conditions. Finally, it discusses potential implications of specific clinical observations and considerations in COVID-19 patients on target oxygen saturation, such as diffuse systemic endothelitis and microthrombi playing an important pathogenic role in the wide range of systemic manifestations, exacerbation of hypoxic pulmonary vasoconstriction in the setting of pulmonary vascular endothelitis/microthrombi, the phenomenon of "silent hypoxemia" with some patients presenting to the hospital with severe hypoxemia disproportional to symptoms, and overburdened health systems and public health resources in many parts of the world with adverse implications on outpatient monitoring and early institution of oxygen supplementation. CONCLUSIONS: The above factors and analyses, put together, call for an urgent exploration and re-evaluation of target oxygen saturation in COVID-19 patients, both in the inpatient and outpatient settings. Until data from such trials become available, where possible, it may be prudent to target an oxygen saturation at least at the upper end of the recommended 92-96% range in COVID-19 patients both in the inpatient and outpatient settings (in patients that are normoxemic at pre-COVID baseline). Home pulse oximetry, tele-monitoring, and earlier institution of oxygen supplementation for hypoxemic COVID-19 outpatients could be beneficial, where public health resources allow for their implementation.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Hypoxia/prevention & control , Oxygen/blood , Pneumonia, Viral/blood , Biomarkers/blood , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Humans , Hypoxia/blood , Hypoxia/diagnosis , Hypoxia/etiology , Oximetry , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Practice Guidelines as Topic , SARS-CoV-2 , Telemedicine
13.
Acta Paediatr ; 109(8): 1539-1544, 2020 08.
Article in English | MEDLINE | ID: covidwho-458994

ABSTRACT

The world is facing an explosive COVID-19 pandemic. Some cases rapidly develop deteriorating lung function, which causes deep hypoxaemia and requires urgent treatment. Many centres have started treating patients in the prone position, and oxygenation has improved considerably in some cases. Questions have been raised regarding the mechanisms behind this. The mini review provides some insights into the role of supine and prone body positions and summarises the latest understanding of the responsible mechanisms. The scope for discussion is outside the neonatal period and entirely based on experimental and clinical experiences related to adults. The human respiratory system is a complex interplay of many different variables. Therefore, this mini review has prioritised previous and ongoing research to find explanations based on three scientific areas: gravity, lung structure and fractal geometry and vascular regulation. It concludes that gravity is one of the variables responsible for ventilation/perfusion matching but in concert with lung structure and fractal geometry, ventilation and regulation of lung vascular tone. Since ventilation distribution does not change between supine and prone positions, the higher expression of nitric oxide in dorsal lung vessels than in ventral vessels is likely to be the most important mechanism behind enhanced oxygenation in the prone position.


Subject(s)
Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Hypoxia/prevention & control , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , COVID-19 , Humans , Pandemics , Prone Position/physiology
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