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1.
J Infect Dis ; 224(3): 415-419, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1526165

ABSTRACT

Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. ß-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.


Subject(s)
Antiviral Agents/pharmacology , Cytidine/analogs & derivatives , Mutagens/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/adverse effects , CHO Cells/drug effects , Cells, Cultured , Cricetulus , Cytidine/adverse effects , Cytidine/pharmacology , Dose-Response Relationship, Drug , Mutagenesis/drug effects , Mutagens/adverse effects , SARS-CoV-2/genetics , Virus Replication/drug effects
3.
Br J Clin Pharmacol ; 87(9): 3462-3480, 2021 09.
Article in English | MEDLINE | ID: covidwho-1494604

ABSTRACT

AIM: Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and paediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provide a baseline risk assessment and identify gaps for targeted investigation. METHODS: Clinical trials have been searched and reviewed; 23 repurposed drugs and drug combinations and nine candidate vaccines have been assessed regarding the availability of relevant data in paediatrics and pregnant women and to evaluate expected or unanticipated risk. RESULTS: Thirteen of the repurposed drugs or drug combinations are indicated for use in paediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have paediatric subgroups been planned for enrolment. Data from individual case studies and RWD may suggest that subpopulations of both paediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. CONCLUSION: In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Child , Clinical Trials as Topic , Drug Combinations , Female , Humans , Pandemics , Pregnancy , Pregnant Women , Prospective Studies , Risk Assessment
4.
Medicine (Baltimore) ; 100(28): e26538, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1494086

ABSTRACT

ABSTRACT: Corrected QT (QTc) interval prolongation has been associated with poor patient prognosis. In this study, we assessed the effects of different drugs and cardiac injury on QTc interval prolongation in patients with coronavirus disease 2019 (COVID-19).The study cohort consisted of 395 confirmed COVID-19 cases from the Wuhan Union Hospital West Campus. All hospitalized patients were treated with chloroquine/hydroxychloroquine (CQ/HCQ), lopinavir/ritonavir (LPV/r), quinolones, interferon, Arbidol, or Qingfei Paidu decoction (QPD) and received at least 1 electrocardiogram after drug administration.Fifty one (12.9%) patients exhibited QTc prolongation (QTc ≥ 470 ms). QTc interval prolongation was associated with COVID-19 severity and mortality (both P < .001). Administration of CQ/HCQ (odds ratio [OR], 2.759; 95% confidence interval [CI], 1.318-5.775; P = .007), LPV/r (OR, 2.342; 95% CI, 1.152-4.760; P = .019), and quinolones (OR, 2.268; 95% CI, 1.171-4.392; P = .015) increased the risk of QTc prolongation. In contrast, the administration of Arbidol, interferon, or QPD did not increase the risk of QTc prolongation. Notably, patients treated with QPD had a shorter QTc duration than those without QPD treatment (412.10 [384.39-433.77] vs 420.86 [388.19-459.58]; P = .042). The QTc interval was positively correlated with the levels of cardiac biomarkers (creatine kinase-MB fraction [rho = 0.14, P = .016], high-sensitivity troponin I [rho = .22, P < .001], and B-type natriuretic peptide [rho = 0.27, P < .001]).In conclusion, QTc prolongation was associated with COVID-19 severity and mortality. The risk of QTc prolongation was higher in patients receiving CQ/HCQ, LPV/r, and quinolones. QPD had less significant effects on QTc prolongation than other antiviral agents.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Long QT Syndrome/mortality , SARS-CoV-2 , Aged , COVID-19/virology , Chloroquine/adverse effects , Drug Therapy, Combination , Drugs, Chinese Herbal/adverse effects , Electrocardiography , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/adverse effects , Indoles/adverse effects , Interferons/adverse effects , Long QT Syndrome/chemically induced , Lopinavir/adverse effects , Male , Middle Aged , Odds Ratio , Quinolones/adverse effects , Retrospective Studies , Ritonavir/adverse effects , Severity of Illness Index
5.
Am J Epidemiol ; 190(11): 2339-2349, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1493666

ABSTRACT

We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir that is currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic eXtract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled at least 1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by International Classification of Diseases, Ninth Revision, codes using validated algorithms. Relative risks and 95% confidence intervals were estimated using propensity score stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted relative risk was 1.21 (95% confidence interval: 0.77, 1.90). Estimates for specific malformations were imprecise. The pooled relative risk from the meta-analysis with 6 prior studies was 0.88 (95% confidence interval: 0.75, 1.03). Based on evidence accumulated in patients with HIV, first-trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared with other ART.


Subject(s)
Antiviral Agents/adverse effects , Pregnancy Complications, Infectious/drug therapy , Tenofovir/adverse effects , Adult , Anti-HIV Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Cohort Studies , Female , HIV Infections/drug therapy , Humans , Pandemics , Pregnancy , Pregnancy Outcome , Pregnant Women , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/therapeutic use , SARS-CoV-2 , Tenofovir/therapeutic use
6.
Immunopharmacol Immunotoxicol ; 43(6): 644-650, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1483237

ABSTRACT

BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism. MATERIAL AND METHODS: A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12th to 24th, 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21. RESULTS: A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission (p < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped (p = .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group (p = .3152). CONCLUSIONS: IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.


Subject(s)
Anemia/chemically induced , Antiviral Agents/adverse effects , COVID-19/drug therapy , Interferon alpha-2/adverse effects , SARS-CoV-2/drug effects , Administration, Inhalation , Adult , Aged , Aged, 80 and over , Anemia/blood , Anemia/diagnosis , Antiviral Agents/administration & dosage , Biomarkers/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , China , Female , Hemoglobins/metabolism , Host-Pathogen Interactions , Humans , Interferon alpha-2/administration & dosage , Male , Middle Aged , Nebulizers and Vaporizers , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
7.
BMC Pharmacol Toxicol ; 22(1): 61, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1477468

ABSTRACT

BACKGROUND: The emergence and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in thelate 2019 has caused a devastating global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19). Although vaccines have been and are being developed, they are not accessible to everyone and not everyone can receive these vaccines. Also, it typically takes more than 10 years until a new therapeutic agent is approved for usage. Therefore, repurposing of known drugs can lend itself well as a key approach for significantly expediting the development of new therapies for COVID-19. METHODS: We have incorporated machine learning-based computational tools and in silico models into the drug discovery process to predict Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of 90 potential drugs for COVID-19 treatment identified from two independent studies mainly with the purpose of mitigating late-phase failures because of inferior pharmacokinetics and toxicity. RESULTS: Here, we summarize the cardiotoxicity and general toxicity profiles of 90 potential drugs for COVID-19 treatment and outline the risks of repurposing and propose a stratification of patients accordingly. We shortlist a total of five compounds based on their non-toxic properties. CONCLUSION: In summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for healthcare practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for treating COVID-19.


Subject(s)
Antiviral Agents/toxicity , COVID-19/drug therapy , Drug Discovery , Drug Repositioning , Animals , Antiviral Agents/adverse effects , Captopril/therapeutic use , Cardiotoxins/toxicity , Catechols/therapeutic use , Computational Biology , Cytochrome P-450 Enzyme System/metabolism , Drug Discovery/methods , Humans , Indomethacin/therapeutic use , Linezolid/therapeutic use , Liver/drug effects , Mice , Models, Biological , Nitriles/therapeutic use , Rats , Reproduction/drug effects , Software , Valproic Acid/therapeutic use
8.
Front Immunol ; 12: 730022, 2021.
Article in English | MEDLINE | ID: covidwho-1468343

ABSTRACT

Pulmonary surfactant is a complex and highly surface-active material. It covers the alveolar epithelium and consists of 90% lipids and 10% proteins. Pulmonary surfactant lipids together with pulmonary surfactant proteins facilitate breathing by reducing surface tension of the air-water interface within the lungs, thereby preventing alveolar collapse and the mechanical work required to breathe. Moreover, pulmonary surfactant lipids, such as phosphatidylglycerol and phosphatidylinositol, and pulmonary surfactant proteins, such as surfactant protein A and D, participate in the pulmonary host defense and modify immune responses. Emerging data have shown that pulmonary surfactant lipids modulate the inflammatory response and antiviral effects in some respiratory viral infections, and pulmonary surfactant lipids have shown promise for therapeutic applications in some respiratory viral infections. Here, we briefly review the composition, antiviral properties, and potential therapeutic applications of pulmonary surfactant lipids in respiratory viral infections.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Lipids/therapeutic use , Lung/drug effects , Pulmonary Surfactants/therapeutic use , SARS-CoV-2/pathogenicity , Animals , Antiviral Agents/adverse effects , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions , Humans , Lipids/adverse effects , Lung/immunology , Lung/virology , Pulmonary Surfactants/adverse effects , SARS-CoV-2/immunology
9.
BMJ Case Rep ; 14(9)2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1467682

ABSTRACT

An 82-year-old man with a history of herpes simplex keratitis 40 years previously presented with recurrence, 1 day following vaccination for novel COVID-19. His condition worsened despite topical treatment with ganciclovir gel. A diagnosis of herpetic stromal keratitis was made, requiring systemic aciclovir, topical prednisolone, moxifloxacin and atropine, and oral doxycycline. He improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from 6/36 corrected at presentation, to 6/24 following treatment. Clearly, public and personal health benefits from vaccination are hugely important and we would not suggest avoiding vaccination in such patients. It is, however, important for ophthalmic providers to be aware of the rare potential for reactivation of herpetic eye disease following vaccination to enable prompt diagnosis and treatment.


Subject(s)
COVID-19 , Keratitis, Herpetic , Acyclovir/therapeutic use , Aged, 80 and over , Antiviral Agents/adverse effects , Humans , Keratitis, Herpetic/chemically induced , Keratitis, Herpetic/diagnosis , Keratitis, Herpetic/drug therapy , Male , Prednisolone/therapeutic use , SARS-CoV-2 , Vaccination/adverse effects
10.
Sci Rep ; 11(1): 19998, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462031

ABSTRACT

Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.


Subject(s)
Antiviral Agents/metabolism , COVID-19/drug therapy , Drug Discovery , SARS-CoV-2/drug effects , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/metabolism , Adenine/pharmacology , Adenosine/adverse effects , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/pharmacology , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/pharmacology , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/metabolism , Alanine/pharmacology , Amides/adverse effects , Amides/metabolism , Amides/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , COVID-19/metabolism , Chloroquine/adverse effects , Chloroquine/analogs & derivatives , Chloroquine/metabolism , Chloroquine/pharmacology , Drug Design , Humans , Metabolic Networks and Pathways , Molecular Docking Simulation , Nitro Compounds/adverse effects , Nitro Compounds/metabolism , Nitro Compounds/pharmacology , Pyrazines/adverse effects , Pyrazines/metabolism , Pyrazines/pharmacology , Pyrrolidines/adverse effects , Pyrrolidines/metabolism , Pyrrolidines/pharmacology , Ribavirin/adverse effects , Ribavirin/metabolism , Ribavirin/pharmacology , SARS-CoV-2/metabolism , Thiazoles/adverse effects , Thiazoles/metabolism , Thiazoles/pharmacology
11.
Curr Res Transl Med ; 69(4): 103309, 2021 10.
Article in English | MEDLINE | ID: covidwho-1459004

ABSTRACT

PURPOSE OF THE STUDY: Currently no treatment has been proven to be efficacious for patients with early symptoms of COVID-19. Although most patients present mild or moderate symptoms, up to 5-10% may have a poor disease progression, so there is an urgent need for effective drugs, which can be administered even before the onset of severe symptoms, i.e. when the course of the disease is modifiable. Recently, promising results of several studies on oral ivermectin have been published, which has prompted us to conduct the present review of the scientific literature. METHODS: A narrative review has been carried out, focusing on the following four main topics: a) short-term efficacy in the treatment of the disease, b) long-term efficacy in the treatment of patients with post-acute symptoms of COVID-19, c) efficacy in the prophylaxis of the disease, and c) safety of ivermectin. RESULTS: The reviewed literature suggests that there seems to be sufficient evidence about the safety of oral ivermectin, as well as the efficacy of the drug in the early-treatment and the prophylaxis of COVID-19. CONCLUSIONS: In the view of the available evidence, the Frontline COVID-19 Critical Care Alliance (FLCCC) recommends the use of oral ivermectin for both prophylaxis and early-treatment of COVID-19. Further well-designed studies should be conducted in order to explore the efficacy and safety of invermectin at low and high doses, following different dosing schedules, in both, the short and long-term treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Ivermectin/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/adverse effects , COVID-19/prevention & control , Case-Control Studies , Dose-Response Relationship, Drug , Humans , Ivermectin/administration & dosage , Ivermectin/adverse effects , Ivermectin/pharmacology , Meta-Analysis as Topic , Multicenter Studies as Topic , Practice Guidelines as Topic , Protein Transport/drug effects , RNA Viruses/drug effects , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome
12.
Anaesthesist ; 70(2): 121-126, 2021 Feb.
Article in German | MEDLINE | ID: covidwho-1453674

ABSTRACT

A 59-year-old male patient was admitted to hospital diagnosed with moderate pneumonia associated with COVID-19. Upfront treatment with hydroxychloroquine and azithromycin was started. Due to a clinical deterioration (ARDS, circulatory shock) and greatly increased inflammation markers 6 days after admission, a cytokine storm was suspected and off-label treatment with the IL­6 receptor antagonist tocilizumab was initiated. Subsequently there was a dramatic rise of D­dimers indicating pulmonary intravascular coagulopathy and respiratory insufficiency worsened. After a second dose of tocilizumab was administered severe perimyocarditis with cardiac arrhythmia, hemodynamic instability and ST elevation occurred. Shortly afterwards the patient died due to multiorgan failure. From our experience, exacerbation of COVID-19 following treatment with tocilizumab cannot be ruled out. Randomized controlled studies are necessary to further investigate the efficacy, safety and patient selection criteria for tocilizumab treatment in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Blood Coagulation Disorders/etiology , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Myocarditis/etiology , Receptors, Interleukin-6/antagonists & inhibitors , Fatal Outcome , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Off-Label Use , Respiratory Distress Syndrome/etiology , Respiratory Insufficiency , Treatment Outcome
14.
Pharmacotherapy ; 40(5): 416-437, 2020 05.
Article in English | MEDLINE | ID: covidwho-1449937

ABSTRACT

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Immunomodulation , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Azetidines/administration & dosage , Azetidines/adverse effects , Betacoronavirus , COVID-19 , Chloroquine/administration & dosage , Chloroquine/adverse effects , Coronavirus Infections/therapy , Drug Combinations , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Immunization, Passive , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Lopinavir/administration & dosage , Lopinavir/adverse effects , Nelfinavir/administration & dosage , Nelfinavir/adverse effects , Pandemics , Ribavirin/administration & dosage , Ribavirin/adverse effects , Ritonavir/administration & dosage , Ritonavir/adverse effects , SARS-CoV-2 , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Thiazoles/administration & dosage , Thiazoles/adverse effects
15.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1439023

ABSTRACT

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.


Subject(s)
Ambulatory Care , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Early Medical Intervention , Hydroxychloroquine/therapeutic use , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Drug Therapy, Combination , Female , France , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Outpatients , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Young Adult
16.
Biosci Trends ; 15(4): 201-204, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1436244

ABSTRACT

Traditional Chinese medicine (TCM) is a valuable form of medicine with a long history in China. It has played a significant role in the control and prevention of infectious diseases including SARS and H7N9 flu. After the outbreak of COVID-19, China's National Health Commission included TCM in the Diagnosis and Treatment Protocol for COVID-19. During the COVID-19 pandemic, three traditional Chinese medicines (Jinhua Qinggan granules, Lianhua Qingwen medicine, and a Xuebijing Injection) and three TCM preparations (a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction) have been screened for their efficacy against COVID-19. More than 150 trials involving TCMs are registered in the Chinese Clinical Trial Registry (ChiCTR), and those trials cover prevention, treatment, recovery, and illnesses diagnosed in accordance with TCM principles. TCM can effectively alleviate the symptoms of patients with COVID-19, delay the disease's progression from mild to severe or critical, and reduce severe and critical all-cause mortality. The underlying mechanisms of TCM mainly involve action against SARS-CoV-2, anti-inflammatory and immunomodulatory action, and organ protection. The current work provides a brief description of the current status of and issues with TCM to treat this novel infectious disease. The hope is that TCM can help considerably to control this global epidemic.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , China , Clinical Trials as Topic , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional
17.
Adv Respir Med ; 89(4): 413-418, 2021.
Article in English | MEDLINE | ID: covidwho-1399544

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected almost every country in the world since De-cember 2019. Despite the efforts of the human race to combat the virus, we are still looking for an evidence-based permanent cure for the disease. Ivermectin has recently emerged as one of the therapies having a beneficial effect on COVID-19. Ivermectin, owing to its properties, continues to be a possible treatment against the COVID-19 disease. Already being a mainstream drug with minimal adverse effects, it garners valid consideration. It's use in hospitalized patients, randomized controlled trials, and observational studies has also supported its implementation. In this article, we have reviewed recent studies and explored the effectiveness of ivermectin in hospitalized COVID-19 patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ivermectin/therapeutic use , Antiviral Agents/adverse effects , COVID-19/therapy , Humans , Ivermectin/adverse effects , Length of Stay/statistics & numerical data
18.
Int Immunopharmacol ; 95: 107522, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1385749

ABSTRACT

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.


Subject(s)
Amides/administration & dosage , Amides/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/drug therapy , Pyrazines/administration & dosage , Pyrazines/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Intubation , Kaplan-Meier Estimate , Length of Stay , Lopinavir/administration & dosage , Lopinavir/adverse effects , Male , Middle Aged , Oxygen/blood , Ritonavir/administration & dosage , Ritonavir/adverse effects , Severity of Illness Index , Treatment Outcome , Young Adult
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