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1.
Open Heart ; 7(2)2020 12.
Article in English | MEDLINE | ID: covidwho-1066930

ABSTRACT

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.


Subject(s)
/metabolism , /metabolism , Renin-Angiotensin System/drug effects , /genetics , Adult , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , /virology , Down-Regulation , Female , Humans , Immunity/immunology , Lung Injury/drug therapy , Lung Injury/physiopathology , Male , Mice , Middle Aged , Models, Animal , Pneumonia, Viral/drug therapy , Risk Factors , Virus Internalization/drug effects
2.
BMJ Case Rep ; 14(2)2021 Feb 04.
Article in English | MEDLINE | ID: covidwho-1066845

ABSTRACT

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Dexamethasone/adverse effects , Viremia/drug therapy , Aged , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Dexamethasone/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Male , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Self Medication/methods , Steroids/adverse effects , Steroids/therapeutic use , Treatment Outcome , Viremia/complications
3.
Medicine (Baltimore) ; 100(4): e24475, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1061053

ABSTRACT

ABSTRACT: To evaluate the antiviral effect and safety of arbidol and Lianhuaqingwen Capsule (LH) in treating patients with Coronavirus disease 2019 (COVID-19).108 patients with COVID-19 were divided into 2 groups, including 40 patients in the arbidol group and 68 patients in the arbidol + LH group. Patients in the arbidol + LH group received 200 mg of arbidol and 1400 mg of LH per 8 hour, and the arbidol group was given 200 mg arbidol per 8 hour. Blood routine examination, blood biochemistry detection, SARS-CoV-2 nucleic acid detection, and chest CT scans were performed to evaluate the clinical effects between the 2 groups.No statistically significant differences were observed between the 2 groups in terms of preoperative characteristics including the baseline characteristics, laboratory indicators, and chest CT. On day 7 after admission, patients in the arbidol + LH group showed a higher level of Lymphocytes count, and a lower level of serum amyloid A and C-reactive protein levels (P < .05). Moreover, the median time from admission to the first negative result of the SARS-CoV-2 nucleic acid detection was shorter in the arbidol + LH group (P < .05). Analysis based on CT scan results showed a better extinction of lung inflammation in the arbidol + LH group. No apparent side effects were found in both groups. No patients were transferred to the intensive care unit (ICU) treatment.Arbidol combined with LH treatment may be more effective in improving the prognosis and accelerating the SARS-CoV-2 clearance in patients with COVID-19.


Subject(s)
/drug therapy , Drugs, Chinese Herbal/therapeutic use , Indoles/therapeutic use , Pneumonia, Viral/drug therapy , Capsules , Drug Therapy, Combination , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Pneumonia, Viral/virology , Retrospective Studies
4.
Int J Risk Saf Med ; 32(1): 3-17, 2021.
Article in English | MEDLINE | ID: covidwho-1058394

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.


Subject(s)
Antiviral Agents/therapeutic use , Fetus/drug effects , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Antiviral Agents/adverse effects , Drugs, Investigational , Female , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , India/epidemiology , Off-Label Use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnant Women , Steroids/adverse effects , Steroids/therapeutic use
6.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 23.
Article in English | MEDLINE | ID: covidwho-1042105

ABSTRACT

We report the case of a man affected by cystic fibrosis who developed a severe SARS-CoV-2 related pneumonia in March 2020. In addition to lopinavir/ritonavir and hydroxychloroquine, he was treated with two doses of tocilizumab, displaying a significant clinical improvement. This is the first case described in the literature of an adult patient affected by cystic fibrosis who received tocilizumab for COVID-19, with documented total recovery, also assessed by a spirometry.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Cystic Fibrosis , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral , Respiratory Tract Infections/microbiology , Ritonavir/administration & dosage , /isolation & purification , Adult , Antiviral Agents/administration & dosage , /diagnosis , /physiopathology , Cystic Fibrosis/complications , Cystic Fibrosis/immunology , Cystic Fibrosis/physiopathology , Drug Combinations , Humans , Lung/diagnostic imaging , Lung/physiopathology , Male , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Receptors, Interleukin-6/antagonists & inhibitors , Respiratory Function Tests/methods , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/etiology , Tomography, X-Ray Computed/methods , Treatment Outcome
7.
Ann Intern Med ; 174(1): JC2, 2021 01.
Article in English | MEDLINE | ID: covidwho-1034497

ABSTRACT

SOURCE CITATION: Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. 32887691.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Practice Guidelines as Topic , Betacoronavirus , Critical Illness , Humans , Pandemics , World Health Organization
9.
Int J Obes (Lond) ; 44(8): 1793-1799, 2020 08.
Article in English | MEDLINE | ID: covidwho-1023842

ABSTRACT

OBJECTIVE: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). METHODS: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. RESULTS: At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. CONCLUSIONS: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colchicine/therapeutic use , Coronavirus Infections/immunology , Metabolic Syndrome/complications , Metabolic Syndrome/immunology , Obesity/immunology , Pneumonia, Viral/immunology , Adult , Anti-Inflammatory Agents/pharmacology , Betacoronavirus/drug effects , C-Reactive Protein , Colchicine/pharmacology , Coronavirus Infections/drug therapy , Double-Blind Method , Female , Humans , Interleukin-6 , Male , Metabolic Syndrome/drug therapy , Middle Aged , Obesity/complications , Obesity/drug therapy , Pandemics , Pilot Projects , Pneumonia, Viral/drug therapy , Treatment Outcome , Young Adult
12.
Molecules ; 25(19)2020 Sep 23.
Article in English | MEDLINE | ID: covidwho-803884

ABSTRACT

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10-15 years in order to identify the most promising areas.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Photochemotherapy/methods , Pneumonia, Viral/drug therapy , Porphyrins/pharmacology , Antiviral Agents/chemistry , Humans , Indoles/chemistry , Indoles/pharmacology , Pandemics , Photochemical Processes , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/chemistry , Virus Attachment/drug effects
13.
J Intensive Care Med ; 36(2): 135-156, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1024315

ABSTRACT

In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.


Subject(s)
/drug therapy , Clinical Protocols , Intensive Care Units/organization & administration , Pneumonia, Viral/drug therapy , Ascorbic Acid/therapeutic use , Drug Therapy, Combination , Heparin/therapeutic use , Hospitalization , Humans , Methylprednisolone/therapeutic use , Pneumonia, Viral/epidemiology , Respiration, Artificial , Thiamine/therapeutic use
14.
Medicine (Baltimore) ; 100(1): e23582, 2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1024157

ABSTRACT

ABSTRACT: COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Pneumonia, Viral/drug therapy , Aged , Female , Humans , Male , Middle Aged , Pneumonia, Viral/virology , Prognosis , Retrospective Studies
15.
Environ Res ; 192: 110294, 2021 01.
Article in English | MEDLINE | ID: covidwho-1023560

ABSTRACT

The rapid spread of COVID-19 has led to nationwide lockdowns in many countries. The COVID-19 pandemic has played serious havoc on economic activities throughout the world. Researchers are immensely curious about how to give the best protection to people before a vaccine becomes available. The coronavirus spreads principally through saliva droplets. Thus, it would be a great opportunity if the virus spread could be controlled at an early stage. The face mask can limit virus spread from both inside and outside the mask. This is the first study that has endeavoured to explore the design and fabrication of an antiviral face mask using licorice root extract, which has antimicrobial properties due to glycyrrhetinic acid (GA) and glycyrrhizin (GL). An electrospinning process was utilized to fabricate nanofibrous membrane and virus deactivation mechanisms discussed. The nanofiber mask material was characterized by SEM and airflow rate testing. SEM results indicated that the nanofibers from electrospinning are about 15-30 µm in diameter with random porosity and orientation which have the potential to capture and kill the virus. Theoretical estimation signifies that an 85 L/min rate of airflow through the face mask is possible which ensures good breathability over an extensive range of pressure drops and pore sizes. Finally, it can be concluded that licorice root membrane may be used to produce a biobased face mask to control COVID-19 spread.


Subject(s)
Antiviral Agents , Betacoronavirus , Coronavirus , Pneumonia, Viral , Antiviral Agents/therapeutic use , Glycyrrhiza , Humans , Masks , Nanofibers , Pandemics , Pneumonia, Viral/drug therapy
18.
Washington; Pan American Health Organization; Jan. 13, 2020. 171 p.
Non-conventional in English | LILACS (Americas) | ID: covidwho-1022980

ABSTRACT

This is the fourteenth edition of this database of evidence on potential therapeutic options for COVID-19, in which 68 therapeutic options are examined. This information will help investigators, policy makers, and prescribers navigate the flood of relevant data to ensure that management of COVID-19, at both individual and population levels, is based on the best available knowledge. This resource will be continually updated as more research is released into the public space.


Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Immunologic Factors/immunology
19.
Sheng Wu Gong Cheng Xue Bao ; 36(4): 605-611, 2020 Apr 25.
Article in Chinese | MEDLINE | ID: covidwho-1024807

ABSTRACT

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections , Coronavirus/drug effects , Coronavirus/growth & development , Cyclophilin A/antagonists & inhibitors , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cyclosporine/chemistry , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , Virus Replication/drug effects
20.
Int J Mol Sci ; 21(16)2020 Aug 07.
Article in English | MEDLINE | ID: covidwho-1024585

ABSTRACT

Gitelman's syndrome (GS) and Bartter's syndrome (BS) are rare inherited salt-losing tubulopathies whose variations in genotype do not correlate well with either clinical course or electrolyte requirements. Using GS/BS patients as nature's experiments, we found them to be a human model of endogenous Ang II antagonism with activated Renin-Angiotensin System (RAS), resulting in high Ang II levels with blunted cardiovascular effects. These patients are also characterized by increased and directly correlated levels of both Angiotensin Converting Enzyme 2 (ACE2) and Ang 1-7. Understanding the myriad of distinctive and frequently overlapping clinical presentations of GS/BS arises remains challenging. Efforts to find a treatment for COVID-19 has fueled a recent surge in interest in chloroquine/hydroxychloroquine and its effects. Of specific interest are chloroquine/hydroxychloroquine's ability to inhibit SARS-CoV infection by impairing ACE2, the SARS-CoV2 entry point, through terminal glycosylation via effects on TGN/post-Golgi pH homeostasis. Several different studies with a GS or a BS phenotype, along with a nonsyndromic form of X-linked intellectual disability linked to a mutated SLC9A7, provide additional evidence that specific gene defects can act via misregulation of TGN/post-Golgi pH homeostasis, which leads to a common mechanistic basis resulting in overlapping phenotypes. We suggest that linkage between the specific gene defects identified in GS and BS and the myriad of distinctive and frequently overlapping clinical findings may be the result of aberrant glycosylation of ACE2 driven by altered TGN/endosome system acidification caused by the metabolic alkalosis brought about by these salt-losing tubulopathies in addition to their altered intracellular calcium signaling due to a blunted second messenger induced intracellular calcium release that is, in turn, amplified by the RAS system.


Subject(s)
Bartter Syndrome/genetics , Coronavirus Infections/drug therapy , Gitelman Syndrome/genetics , Peptidyl-Dipeptidase A/metabolism , Phenotype , Pneumonia, Viral/drug therapy , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Bartter Syndrome/metabolism , Bartter Syndrome/pathology , Endosomes/drug effects , Endosomes/metabolism , Gitelman Syndrome/metabolism , Gitelman Syndrome/pathology , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Pandemics
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