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1.
Clin Infect Dis ; 2020 Jul 01.
Article in English | MEDLINE | ID: covidwho-1621566

ABSTRACT

We are learning that the host response to SARS-CoV-2 infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a "one size fits all" approach to immunomodulation in patients with COVID-19.  We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anti-cytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.

2.
Can J Anaesth ; 67(9): 1217-1248, 2020 09.
Article in English | MEDLINE | ID: covidwho-1536371

ABSTRACT

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.


Subject(s)
Coronavirus Infections/therapy , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Aerosols , COVID-19 , Cannula , Coronavirus Infections/complications , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Randomized Controlled Trials as Topic , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/virology
4.
Am J Chin Med ; 48(6): 1315-1330, 2020.
Article in English | MEDLINE | ID: covidwho-1243726

ABSTRACT

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Immunologic Factors/therapeutic use , Medicine, Chinese Traditional , Pneumonia, Viral/drug therapy , Sepsis/drug therapy , Artemisinins/therapeutic use , Astragalus propinquus , Berberine/therapeutic use , Betacoronavirus , COVID-19 , Critical Illness , Emodin/therapeutic use , Humans , Intensive Care Units , Intestinal Mucosa , Microcirculation , Pandemics , Permeability , Rheum , SARS-CoV-2 , Salvia miltiorrhiza
5.
Ann Pharmacother ; 56(1): 5-15, 2022 01.
Article in English | MEDLINE | ID: covidwho-1228971

ABSTRACT

BACKGROUND: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. OBJECTIVE: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. METHODS: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. RESULTS: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. CONCLUSION AND RELEVANCE: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.


Subject(s)
COVID-19 , Pancreatitis , Propofol , Acute Disease , Adult , Humans , Intensive Care Units , Propofol/adverse effects , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
6.
J Trauma Acute Care Surg ; 89(6): 1092-1098, 2020 12.
Article in English | MEDLINE | ID: covidwho-1214720

ABSTRACT

BACKGROUND: Invasive mechanical ventilation (IMV) is a lifesaving strategy for critically ill patients with coronavirus disease 2019 (COVID-19). We aim to report the case series of critical patients receiving IMV in Wuhan and to discuss the timing of IMV in these patients. METHODS: Data of 657 patients admitted to emergency intensive care unit of Zhongnan Hospital and isolated isolation wards of Wuhan Union Hospital from January 1 to March 10, 2020, were retrospectively reviewed. All medical records of 40 COVID-19 patients who required IMV were collected at different time points, including baseline (at admission), before receiving IMV, and before death or hospital discharge. RESULTS: Among 40 COVID-19 patients with IMV, 31 died, and 9 survived and was discharged. The median age was 70 years (interquartile range [IQR], 62-76 years), and nonsurvivors were older than survivors. The median period from the noninvasive mechanic ventilation (NIV) or high-flow nasal cannula oxygen therapy (HFNC) to intubation was 7 hours (IQR, 2-42 hours) in IMV survivors and 54 hours (IQR, 28-143 hours) in IMV nonsurvivors. We observed that, when the time interval from NIV/HFNC to intubation was less than 50 hours (about 2 calendar days), together with Acute Physiology and Chronic Health Evaluation II (APACHE II) score of less than 10 or pneumonia severity index (PSI) score of less than 100, mortality can be reduced to 60% or less. Prolonged interval from NIV/HFNC to intubation and high levels of APACHE II and PSI before intubation were associated with higher mortality in critically ill patients. Multiple organ damage was common among these nonsurvivors in the course of treatment. CONCLUSION: Early initial intubation after NIV/HFNC might have a beneficial effect in reducing mortality for critically ill patients meeting IMV indication. Considering APACHE II and PSI scores might help physicians in decision making about timing of intubation for curbing subsequent mortality. LEVEL OF EVIDENCE: Therapeutic, level V.


Subject(s)
Coronavirus Infections/therapy , Critical Illness/therapy , Hospital Mortality , Noninvasive Ventilation/methods , Oxygen/administration & dosage , Pneumonia, Viral/therapy , APACHE , Aged , Betacoronavirus , COVID-19 , China , Coronavirus Infections/mortality , Critical Illness/mortality , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Oxygen Inhalation Therapy/methods , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , SARS-CoV-2 , Time Factors
8.
Pan Afr Med J ; 35(Suppl 2): 141, 2020.
Article in English | MEDLINE | ID: covidwho-1106487

ABSTRACT

Novel coronavirus 2019 (COVID-19) is a severe respiratory infection leading to acute respiratory distress syndrome [ARDS] accounting for thousands of cases and deaths across the world. Several alternatives in treatment options have been assessed and used in this patient population. However, when mechanical ventilation and prone positioning are unsuccessful, venovenous extracorporeal membrane oxygenation [VV-ECMO] may be used. We present a case of a 62-year-old female, diabetic, admitted to the intensive care unit with fever, flu-like symptoms and a positive COVID-19 test. Ultimately, she worsened on mechanical ventilation and prone positioning and required VV-ECMO. The use of VV-ECMO in COVID-19 infected patients is still controversial. While some studies have shown a high mortality rate despite aggressive treatment, such as in our case, the lack of large sample size studies and treatment alternatives places healthcare providers against a wall without options in patients with severe refractory ARDS due to COVID-19.


Subject(s)
Betacoronavirus , Continuous Renal Replacement Therapy/methods , Coronavirus Infections/complications , Critical Illness , Extracorporeal Membrane Oxygenation/instrumentation , Pneumonia, Viral/complications , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Bacteremia/complications , COVID-19 , Combined Modality Therapy , Continuous Renal Replacement Therapy/instrumentation , Coronavirus Infections/drug therapy , Critical Illness/therapy , Cytokine Release Syndrome/etiology , Diabetes Mellitus, Type 2/complications , Fatal Outcome , Female , Gram-Positive Bacterial Infections/complications , Humans , Middle Aged , Morocco , Pandemics , Respiration, Artificial , Respiratory Distress Syndrome/etiology , SARS-CoV-2
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(10): 1174-1177, 2020 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1067794

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics and prognosis of coronavirus disease 2019 (COVID-19) patients complicated with pneumothorax. METHODS: The clinical data of 7 COVID-19 patients complicated with pneumothorax admitted to Huanggang Central Hospital from January 3 to March 10, 2020 were retrospectively analyzed. The clinical features, diagnosis and treatment were summarized, and experience in the treatment of COVID-19 was shared. RESULTS: (1) General information: among the 7 patients, 5 were males and 2 were females. Four of them had no underlying disease, and 1 had a history of diabetes and hypertension. One patient had only a history of hypertension. There were 6 cases of right pneumothorax and 1 case of bilateral pneumothorax. The 7 patients had a long hospital stay, all over 4 weeks, mostly complicated with multiple organ dysfunction. (2) Imaging examination: 1 case evolved from the early stage to the advanced stage within 1 week and to the severe stage within 2 weeks. Pneumothorax occurred 4 weeks later, and was absorbed within 2 weeks. The remaining 6 patients presented progressive stage on admission, all of them advanced to severe stage within 1 to 2 weeks, and most of them presented diffused consolidation shadows, striation shadows and fibrosis of both lungs, obvious pleural adhesion, and extremely slow lesion absorption. (3) Treatment: 1 severe patient with pneumothorax 4 weeks after onset was given non-invasive mechanical ventilation. The remaining 6 critically ill patients were treated with endotracheal intubation and mechanical ventilation. Five patients were treated with mechanical ventilation within 3 days after the occurrence of pneumothorax, and 1 patient was treated with mechanical ventilation after 11 days. (4) Outcome: 1 patient without endotracheal intubation was continuously given nasal high-flow oxygen therapy, and the condition was stable. Four of the 6 patients complicated with pneumothorax after endotracheal intubation died, and the other 2 patients successfully removed the drainage tube within 2 weeks of closed thoracic drainage, and their condition gradually stabilized. CONCLUSIONS: COVID-19 complicated with pneumothorax is a dangerous disease with poor prognosis, and should be paid adequate attention.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Pneumothorax , COVID-19 , Coronavirus Infections/complications , Female , Humans , Male , Pneumonia, Viral/complications , Pneumothorax/etiology , Retrospective Studies , SARS-CoV-2
10.
Ann Surg ; 272(3): e181-e186, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-1066507

ABSTRACT

OBJECTIVE: To determine the outcomes of patients undergoing tracheostomy for COVID-19 and of healthcare workers performing these procedures. BACKGROUND: Tracheostomy is often performed for prolonged endotracheal intubation in critically ill patients. However, in the context of COVID-19, tracheostomy placement pathways have been altered due to the poor prognosis of intubated patients and the risk of transmission to providers through this highly aerosolizing procedure. METHODS: A prospective single-system multi-center observational cohort study was performed on patients who underwent tracheostomy after acute respiratory failure secondary to COVID-19. RESULTS: Of the 53 patients who underwent tracheostomy, the average time from endotracheal intubation to tracheostomy was 19.7 days ±â€Š6.9 days. The most common indication for tracheostomy was acute respiratory distress syndrome, followed by failure to wean ventilation and post-extracorporeal membrane oxygenation decannulation. Thirty patients (56.6%) were liberated from the ventilator, 16 (30.2%) have been discharged alive, 7 (13.2%) have been decannulated, and 6 (11.3%) died. The average time from tracheostomy to ventilator liberation was 11.8 days ±â€Š6.9 days (range 2-32 days). Both open surgical and percutaneous dilational tracheostomy techniques were performed utilizing methods to mitigate aerosols. No healthcare worker transmissions resulted from performing the procedure. CONCLUSIONS: Alterations to tracheostomy practices and processes were successfully instituted. Following these steps, tracheostomy in COVID-19 intubated patients seems safe for both patients and healthcare workers performing the procedure.


Subject(s)
COVID-19/therapy , Critical Care , Intubation, Intratracheal , Respiration, Artificial , Tracheostomy , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/mortality , Extracorporeal Membrane Oxygenation , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Young Adult
11.
Diabetes Metab Syndr ; 14(6): 1641-1644, 2020.
Article in English | MEDLINE | ID: covidwho-1059501

ABSTRACT

BACKGROUND & AIMS: At-admission hyperglycemia have been associated with poorer outcome during critical illnesses. At-admission hyperglycemia in previously unknown diabetes is not uncommonly encountered entity in patients with COVID-19. We sought to find out the outcomes of at-admission hyperglycemia and effect of early intervention to achieve optimal glycemic control in relation to COVID-19 patients. METHODS: We searched the PubMed and Google Scholar database up till August 20, 2020 using specific keywords related to our aims and objectives. RESULTS: All currently available evidences clearly hint that at-admission hyperglycemia in patients with COVID-19 is associated with a poorer outcome, compared with normoglycemic individuals. Fortunately, early intervention by achieving an optimal glycemic control has also been associated with a significant improvement in the outcomes in patients with COVID-19. CONCLUSION: At-admission hyperglycemia should be taken seriously by all clinicians treating patients with COVID-19. All efforts should be made towards an optimal glycemic control in patients with COVID-19, even in absence of pre-existing diabetes.


Subject(s)
Blood Glucose/metabolism , COVID-19/diagnosis , Early Medical Intervention/trends , Hyperglycemia/diagnosis , Patient Admission/trends , COVID-19/blood , COVID-19/epidemiology , Early Medical Intervention/methods , Humans , Hyperglycemia/blood , Hyperglycemia/epidemiology , Prognosis , Risk Factors , Treatment Outcome
13.
Front Endocrinol (Lausanne) ; 11: 593179, 2020.
Article in English | MEDLINE | ID: covidwho-1045524

ABSTRACT

Background: The majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency. Methods: We summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19. Results: High percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI. Conclusion: We demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.


Subject(s)
Adrenal Cortex Diseases/drug therapy , Adrenal Cortex Diseases/virology , Adrenal Cortex/virology , COVID-19/virology , Adrenal Cortex/enzymology , Adrenal Insufficiency/etiology , Adrenal Insufficiency/therapy , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , Critical Illness , Dexamethasone/therapeutic use , Female , Humans , Hydrocortisone/blood , Male , Middle Aged , Serine Endopeptidases/metabolism , Vasoconstrictor Agents/therapeutic use , Zona Fasciculata/metabolism , Zona Reticularis/metabolism
14.
J Cardiovasc Echogr ; 30(Suppl 2): S6-S10, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1045341

ABSTRACT

Lung ultrasound (LUS) is one of the most important and innovative applications in emergency and critical care medicine for the management of critically ill patients. Ultrasound has been widely used in the COVID-19 pandemic as an extremely reliable technique and has proved to have a key role in the diagnosis and monitoring of patients with acute respiratory failure. The diagnostic accuracy of LUS is higher than chest X-ray and similar to computed tomography, which is considered the gold standard. COVID-19 pneumonia has some distinctive ultrasonographic signs but not pathognomonic, and LUS significantly improves the management of COVID-19 patients speeding up the diagnostic path. The examination is bedside; reduces the risk of contamination, avoiding mobilization of the patients; cuts down the amount of radioactive exposure; and gives real-time answers to many diagnostic and therapeutic doubts. Finally, the instruments are small and the scanner and the probes can be protected from contamination easily.

15.
J Transl Int Med ; 8(4): 255-260, 2020 12.
Article in English | MEDLINE | ID: covidwho-1043815

ABSTRACT

Background and Objectives: SARS-CoV-2-induced ARDS is a new entity that should be characterized as it appears to be different from standard ARDS. Hypernatremia is a biological alteration that seems to occur very often in this population without any clear cause. The present study aims to clarify the possible causes of hypernatremia and evaluate its impact on patient outcome. Patients and Methods: We conducted a retrospective one-day prevalence study in 2 intensive care units, which only treated COVID-19 patients with moderate to severe ARDS. We measured blood and urine electrolytes in all the patients. Patients with chronic renal failure or renal replacement therapy were excluded from the study. Hypernatremia was defined as plasma sodium levels above 145 mmol/L. Results: Inclusion criteria were met in 17 out of 24 patients. Hypernatremia was present in 52% patients. All had a natriuresis higher than 20 mmol/L and a urine osmolality above 600 mOsm/L. Hypernatremia was acquired in ICU as all the patients had a normal serum sodium level at admission. Conclusion: The incidence of hypernatremia was elevated and appears to be linked to significant insensible water losses. This should trigger us to optimize the maintenance fluid therapy in critically ill patients with SARS-CoV-2-induced ARDS.

16.
17.
Front Med (Lausanne) ; 7: 614569, 2020.
Article in English | MEDLINE | ID: covidwho-1000108

ABSTRACT

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3-11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3-5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0-6.3] to 3.4 [2.5-3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO2/FiO2 ratio significantly increased from 68 [58-89] to 168 [137-218] and the oxygenation index significantly decreased from 28 [26-35] to 13 [10-15]. The duration of ECMO was 12 [8-25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.

18.
Front Med (Lausanne) ; 7: 589060, 2020.
Article in English | MEDLINE | ID: covidwho-1000101

ABSTRACT

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill.

19.
World J Clin Cases ; 8(23): 5952-5961, 2020 Dec 06.
Article in English | MEDLINE | ID: covidwho-994302

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has brought great challenges to public health. Aggravation of COVID-19 is closely related to the secondary systemic inflammatory response. Glucocorticoids are used to control severe diseases caused by the cytokine storm, owing to their anti-inflammatory effects. However, glucocorticoids are a double-edged sword, as the use of large doses has the potential risk of secondary infection and long-term serious complications, and may prolong virus clearance time. Nonetheless, the risks and benefits of glucocorticoid adjuvant therapy for COVID-19 are inconclusive. AIM: To determine the effect of methylprednisolone in severe and critically ill patients with COVID-19. METHODS: This single-center retrospective study included 102 adult COVID-19 patients admitted to a ward of a designated hospital in Wuhan, Hubei Province from January to March 2020. All patients received general symptomatic treatment and organ function support, and were given different respiratory support measures according to their conditions. In case of deterioration, considering the hyperinflammatory state of the patients, methylprednisolone was intravenously administered at 0.75-1.5 mg/kg/d, usually for less than 14 d. Patient vital signs and oxygenation were closely monitored, in combination with imaging and routine blood tests such as C-reactive protein, biochemical indicators (liver and kidney function, myocardial enzymes, electrolytes, etc.), and coagulation function. Patient clinical outcomes were discharge or death. RESULTS: A total of 102 severe and critically ill COVID-19 patients were included in this study. They were divided into treatment (69, 67.6%) and control groups (33, 32.4%) according to methylprednisolone use. Comparison of baseline data between the two groups showed that the treatment group patients had higher aspartic acid aminotransferase, globulin, hydroxybutyrate dehydrogenase, and lactate dehydrogenase. There was no significant difference in other baseline data between the two groups. With regard to prognosis, 29 (78.4%) patients in the treatment group died as opposed to 40 (61.5%) in the control group. The mortality was higher in the treatment group than in the control group; however, according to the log-rank test and the Kaplan-Meier survival curve, the difference in mortality between both groups was insignificant (P = 0.655). The COX regression equation was used to correct the variables with differences, and the results showed that methylprednisolone treatment did not improve prognosis. CONCLUSION: Methylprednisolone treatment does not improve prognosis in severe and critical COVID-19 patients.

20.
Infect Drug Resist ; 13: 4427-4438, 2020.
Article in English | MEDLINE | ID: covidwho-992957

ABSTRACT

Background: COVID-19 caused by SARS-CoV-2 virus emerged as an unprecedented challenge to discover effective drugs for its prevention and cure. Hyperinflammation-induced lung damage is one of the poor prognostic indicators causing a higher rate of morbidity and mortality of COVID-19 patients. Favipiravir, an antiviral drug, is being used for COVID-19 treatment, and we currently have limited information regarding its efficacy and safety. Thus, the present study was undertaken to evaluate the adverse drug events (ADEs) reported in the WHO pharmacovigilance database. Methods: This study analyzed all suspected ADEs related to favipiravir reported from 2015. The reports were analyzed based on age, gender, and seriousness of ADEs at the System Organ Classification (SOC) level and the individual Preferred Term (PT) level. Results: This study is based on 194 ADEs reported from 93 patients. Most frequent ADEs suspected to be caused by the favipiravir included increased hepatic enzymes, nausea and vomiting, tachycardia, and diarrhea. Severe and fatal ADEs occurred more frequently in men and those over the age of 64 years. Blood and lymphatic disorders, cardiac disorders, hepatobiliary disorders, injury poisoning, and procedural complications were more common manifestations of severe ADEs. Conclusion: This study revealed that favipiravir appears to be a relatively safe drug. An undiscovered anti-inflammatory activity of favipiravir may explain the improvement in critically ill patients and reduce inflammatory markers. Currently, the data is based on very few patients. A more detailed assessment of the uncommon ADEs needs to be analyzed when more information will be available.

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