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2.
Molecules ; 26(20)2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1526851

ABSTRACT

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = -7.78, -7.65, -6.39, -6.28, -8.84 Kcal/mol) for the main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.


Subject(s)
Alkaloids/chemistry , SARS-CoV-2/metabolism , Alkaloids/isolation & purification , Alkaloids/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Halogenation , Humans , Isoxazoles/chemistry , Isoxazoles/metabolism , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Tyrosine/analogs & derivatives , Tyrosine/chemistry , Tyrosine/metabolism
3.
J Korean Med Sci ; 36(44): e309, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526761

ABSTRACT

BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19). METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU. RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred. CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.


Subject(s)
COVID-19/mortality , Pregnancy Complications, Infectious/mortality , Puerperal Disorders/mortality , SARS-CoV-2 , Adult , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/therapy , Cesarean Section , Combined Modality Therapy , Critical Illness/mortality , Delivery, Obstetric/statistics & numerical data , Female , Hospital Mortality , Humans , Infant, Newborn , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Oxygen Inhalation Therapy , Pregnancy , Pregnancy Outcome , Respiration, Artificial , Retrospective Studies , Treatment Outcome , Young Adult
4.
Ann Intern Med ; 174(1): JC3, 2021 01.
Article in English | MEDLINE | ID: covidwho-1518748

ABSTRACT

SOURCE CITATION: RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396:1345-52. 33031764.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Hospitalization , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Administration, Oral , Aged , Antiviral Agents/administration & dosage , COVID-19/mortality , Drug Combinations , Female , Humans , Lopinavir/administration & dosage , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Ritonavir/administration & dosage , SARS-CoV-2 , United Kingdom
5.
Molecules ; 26(20)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1518621

ABSTRACT

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The applied selection methods aimed to pick the most relevant inhibitor of SARS-CoV-2 nsp10. At first, a structural similarity study against the co-crystallized ligand, S-Adenosyl Methionine (SAM), of SARS-CoV-2 nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. The similarity analysis culled 30 candidates. Secondly, a fingerprint study against SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. The docking studies picked 48, 182, 220, 221, and 284. While the ADMET analysis expected the likeness of the five candidates to be drugs, the toxicity study preferred compounds 48 and 182. Finally, a density-functional theory (DFT) study suggested vidarabine (182) to be the most relevant SARS-Cov-2 nsp10 inhibitor.


Subject(s)
Antiviral Agents/chemistry , Biological Products/chemistry , SARS-CoV-2/metabolism , Viral Regulatory and Accessory Proteins/antagonists & inhibitors , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Binding Sites , Biological Products/metabolism , Biological Products/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , Density Functional Theory , Humans , Ligands , Molecular Docking Simulation , S-Adenosylmethionine/chemistry , S-Adenosylmethionine/metabolism , SARS-CoV-2/isolation & purification , Small Molecule Libraries/chemistry , Small Molecule Libraries/metabolism , Small Molecule Libraries/therapeutic use , Vidarabine/chemistry , Vidarabine/metabolism , Vidarabine/therapeutic use , Viral Regulatory and Accessory Proteins/metabolism
6.
Ann Intern Med ; 174(10): 1409-1419, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1515633

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Subject(s)
COVID-19/therapy , Hospitalization/trends , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Age Distribution , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/ethnology , COVID-19/mortality , Critical Care/trends , Cross-Sectional Studies , Female , Humans , Intensive Care Units/trends , Length of Stay/trends , Male , Middle Aged , Pandemics , Respiration, Artificial/trends , SARS-CoV-2 , United States/epidemiology , Vasoconstrictor Agents/therapeutic use , Young Adult
7.
Saudi Med J ; 42(4): 355-362, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1513256

ABSTRACT

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and viral pneumonia in pediatrics worldwide. In the Kingdom of Saudi Arabia (KSA), the prevalence of RSV is 23.5% in pediatric patients with acute lower respiratory tract illness. Coronavirus disease (COVID-19) poses critical public health and socioeconomic challenges in KSA. The Saudi Pediatric Pulmonology Association (SPPA), a subsidiary of the Saudi Thoracic Society (STS), developed a task force to determine the potential challenges and barriers to the RSV immunoprophylaxis program during the era of COVID-19 and to compose a practical, nationwide, and multidisciplinary approach to address these challenges. Some of the recommendations to manage these challenges include increasing the number of RSV immunoprophylaxis clinics, drive-thru visits, home-care services, and swift referrals to the RSV immunoprophylaxis program specialists. Additional training is required for healthcare personnel to add RSV immunoprophylaxis to the regular immunization schedule.


Subject(s)
Antiviral Agents/therapeutic use , Bronchiolitis, Viral/prevention & control , Delivery of Health Care/methods , Immunization Programs/methods , Palivizumab/therapeutic use , Respiratory Syncytial Virus Infections/prevention & control , Advisory Committees , COVID-19/epidemiology , COVID-19/prevention & control , Home Care Services , Humans , Infant , Infant, Newborn , Injections , Pulmonary Medicine , SARS-CoV-2 , Saudi Arabia , Societies, Medical
8.
Int J Mol Sci ; 22(21)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1512382

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with a great impact on social and economic activities, as well as public health. In most patients, the symptoms of COVID-19 are a high-grade fever and a dry cough, and spontaneously resolve within ten days. However, in severe cases, COVID-19 leads to atypical bilateral interstitial pneumonia, acute respiratory distress syndrome, and systemic thromboembolism, resulting in multiple organ failure with high mortality and morbidity. SARS-CoV-2 has immune evasion mechanisms, including inhibition of interferon signaling and suppression of T cell and B cell responses. SARS-CoV-2 infection directly and indirectly causes dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction, which interact with each other and are exacerbated by cardiovascular risk factors. In this review, we summarize current knowledge on the pathogenic basis of thromboinflammation and endothelial injury in COVID-19. We highlight the distinct contributions of dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction to the pathogenesis of COVID-19. In addition, we discuss potential therapeutic strategies targeting these mechanisms.


Subject(s)
COVID-19/pathology , Endothelium, Vascular/physiopathology , Thrombosis/etiology , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Blood Coagulation , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Endothelium, Vascular/metabolism , Humans , Immunity, Innate , Platelet Activation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
9.
Mol Med Rep ; 24(6)2021 12.
Article in English | MEDLINE | ID: covidwho-1504040

ABSTRACT

The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID­19). To date, there is no specific therapy established to treat COVID­19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS­CoV­2 in humans. For the present review, >100 publications on therapeutic agents for COVID­19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta­analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS­CoV­2 infection were highlighted. Since the outbreak of COVID­19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID­19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID­19. The molecular mechanisms of these therapeutic agents against SARS­CoV2 have been investigated, including inhibition of viral interactions with angiotensin­converting enzyme 2 receptors in human cells, viral RNA­dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID­19 were acknowledged.


Subject(s)
COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Animals , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , Chloroquine/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , SARS-CoV-2/isolation & purification
10.
Medicine (Baltimore) ; 100(37): e27228, 2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1501195

ABSTRACT

ABSTRACT: Remdesivir is the only antiviral approved for lower respiratory tract infection produced by SARS-CoV-2. The main objective of this study was to determine the mortality rate, readmissions, mean hospital stay, need for higher levels of oxygen support, and adverse effect-induced abandonment rate in hospitalized patients diagnosed with COVID-19 and treated with remdesivir (RDSV). The secondary objective was to determine mortality-related risk factors in these patients.The study included a prospective cohort of patients admitted to a third level Spanish hospital between July 5, 2020 and February 3, 2021 for COVID-19 diagnosed by SARS-CoV-2 polymerase chain reaction and/or antigen test and treated with RDSV.Remdesivir was received by 185 patients (69.7% males) with a mean age of 62.5 years, median Charlson index of 3 (interquartile range [IQR]: 1-4), and median ambient air oxygen saturation of 91% (IQR: 90-93); 61.6% of patients had hyper-inflammatory syndrome at admission. Median time with symptoms before RDSV treatment was 5 days (IQR: 3-6) and the median hospital stay was 10 days (IQR: 7-15); 19 patients (10.3%) died after a median stay of 13.5 days (IQR: 9.7-24 days), 58 patients (12.9%) were admitted to ICU, 58 (31.4%) needed higher levels of oxygen support, 0.5% abandoned the treatment due to adverse effects, and there were no readmissions. The only mortality-related factor was the need for higher levels of oxygen support (odds ratio 12.02; 95% confidence interval 2.25-64.2).All studied patients were admitted to hospital with a diagnosis of COVID-19 and in respiratory failure, needing initial low-flow oxygen support, and all received RDSV within 1 week of symptom onset. The percent mortality was lower in these patients than was observed in all patients with severe COVID-19 admitted to our center (10.3% vs 20.3%, respectively). Despite receiving RDSV, 1 in 3 patients needed higher levels of oxygen support, the sole mortality-related factor.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Aged , Alanine/pharmacology , Alanine/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Retrospective Studies , Spain , Statistics, Nonparametric
12.
Sci Rep ; 11(1): 21462, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500517

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Heme Oxygenase-1/metabolism , Hemin/therapeutic use , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/genetics , Hemin/chemistry , Hemin/pharmacology , Humans , RNA Interference , RNA, Small Interfering/metabolism , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Up-Regulation/drug effects , Vero Cells , Virus Replication/drug effects
13.
Tohoku J Exp Med ; 255(1): 61-69, 2021 09.
Article in English | MEDLINE | ID: covidwho-1496649

ABSTRACT

North Italy emerged as an epicenter of COVID-19 in the Western world. The majority of studies of patients with COVID-19 have focused on hospitalized patients, and data on early outpatient treatment are limited. This research retrospectively examines consecutive symptomatic adults who did not present to a hospital but who experience laboratory confirmed (nasopharyngeal swabs) or probable COVID-19 infection. From March 12 to April 12, 2020, 124 consecutive patients with laboratory-confirmed COVID-19 infection (84%) or with epidemiologically linked exposure to a person with confirmed infection (16%) were managed at home. The diagnosis of pneumonia was made with a portable ultrasound. COVID-19 treatment was based on low-dose hydroxychloroquine with or without darunavir/cobicistat or azithromycin and enoxaparine for bedridden patients. The patients were monitored by telemedicine. The primary endpoints were clinical improvement or hospitalization, and the secondary endpoints were mortality at day 30 and at day 60. Forty-seven (37.9%) patients had mild COVID-19 infection, 44 (35.5%) had moderate COVID-19 infection, and 33 (26.6%) had severe COVID-19 infection. Four patients (3.2%) were hospitalized and there were no deaths at day 30 and at day 60. Only mild side effects were reported. Early home treatment of COVID-19 patients resulted in a low hospitalization rate with no deaths, with the limitations of the small sample size and that it was conducted within a single geographic area. We believe that this model may be easily reproduced in both cities and rural areas around the world to treat COVID-19 infection.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Testing , Cobicistat/therapeutic use , Darunavir/therapeutic use , Drug Combinations , Female , Home Care Services , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Telemedicine , Young Adult
14.
PLoS One ; 16(11): e0259317, 2021.
Article in English | MEDLINE | ID: covidwho-1496536

ABSTRACT

BACKGROUND: Previous studies have assessed the prevalence and characteristics of self-medication in COVID-19. However, no systematic review has summarized their findings. OBJECTIVE: We conducted a systematic review to assess the prevalence of self-medication to prevent or manage COVID-19. METHODS: We used different keywords and searched studies published in PubMed, Scopus, Web of Science, Embase, two preprint repositories, Google, and Google Scholar. We included studies that reported original data and assessed self-medication to prevent or manage COVID-19. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) modified for cross-sectional studies. RESULTS: We identified eight studies, all studies were cross-sectional, and only one detailed the question used to assess self-medication. The recall period was heterogeneous across studies. Of the eight studies, seven assessed self-medication without focusing on a specific symptom: four performed in the general population (self-medication prevalence ranged between <4% to 88.3%) and three in specific populations (range: 33.9% to 51.3%). In these seven studies, the most used medications varied widely, including antibiotics, chloroquine or hydroxychloroquine, acetaminophen, vitamins or supplements, ivermectin, and ibuprofen. The last study only assessed self-medication for fever due to COVID-19. Most studies had a risk of bias in the "representativeness of the sample" and "assessment of outcome" items of the NOS. CONCLUSIONS: Studies that assessed self-medication for COVID-19 found heterogeneous results regarding self-medication prevalence and medications used. More well-designed and adequately reported studies are warranted to assess this topic.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Self Medication/statistics & numerical data , Cross-Sectional Studies , Fever/drug therapy , Humans , Prevalence
15.
17.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
18.
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
19.
Curr Med Chem ; 28(6): 1068-1090, 2021.
Article in English | MEDLINE | ID: covidwho-1445716

ABSTRACT

BACKGROUND: Influenza is a seasonal disease that affects millions of people every year and has a significant economic impact. Vaccines are the best strategy to fight this viral pathology, but they are not always available or administrable, prompting the search for antiviral drugs. RNA-dependent RNA polymerase (RdRp) recently emerged as a promising target because of its key role in viral replication and its high conservation among viral strains. DISCUSSION: This review presents an overview of the most interesting RdRp inhibitors that have been discussed in the literature since 2000. Compounds already approved or in clinical trials and a selection of inhibitors endowed with different scaffolds are described, along with the main features responsible for their activity. RESULTS: RdRp inhibitors are emerging as a new strategy to fight viral infections and the importance of this class of drugs has been confirmed by the FDA approval of baloxavir marboxil in 2018. Despite the complexity of the RdRp machine makes the identification of new compounds a challenging research topic, it is likely that in the coming years, this field will attract the interest of a number of academic and industrial scientists because of the potential strength of this therapeutic approach.


Subject(s)
Influenza, Human , Viral Proteins , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Influenza, Human/drug therapy , RNA-Dependent RNA Polymerase , Virus Replication
20.
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
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