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1.
Medicine (Baltimore) ; 100(19): e25917, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-2191007

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) has become a global pandemic. Invasive mechanical ventilation is recommended for the management of patients with COVID-19 who have severe respiratory symptoms. However, various complications can develop after its use. The efficient and appropriate management of patients requires the identification of factors associated with an aggravation of COVID-19 respiratory symptoms to a degree where invasive mechanical ventilation becomes necessary, thereby enabling clinicians to prevent such ventilation. This retrospective study included 138 inpatients with COVID-19 at a tertiary hospital. We evaluated the differences in the demographic and clinical data between 27 patients who required invasive mechanical ventilation and 111 patients who did not. Multivariate logistic regression analysis indicated that the duration of fever, national early warning score (NEWS), and lactate dehydrogenase (LDH) levels on admission were significantly associated with invasive mechanical ventilation in this cohort. The optimal cut-off values were: fever duration ≥1 day (sensitivity 100.0%, specificity 54.95%), NEWS ≥7 (sensitivity 72.73%, specificity 92.52%), and LDH >810 mg/dL (sensitivity 56.0%, specificity 90.29%). These findings can assist in the early identification of patients who will require invasive mechanical ventilation. Further studies in larger patient populations are recommended to validate our findings.


Subject(s)
COVID-19/physiopathology , Early Warning Score , Respiration, Artificial/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Female , Fever/physiopathology , Humans , Hydroxychloroquine/therapeutic use , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Republic of Korea , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Sex Factors , Socioeconomic Factors , Tertiary Care Centers , Young Adult
3.
Lancet ; 399(10339): 1941-1953, 2022 05 21.
Article in English | MEDLINE | ID: covidwho-2159958

ABSTRACT

BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-ß1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-ß1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both). FUNDING: WHO.


Subject(s)
Antiviral Agents , COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Hydroxychloroquine/therapeutic use , Interferon beta-1a/therapeutic use , Lopinavir/therapeutic use , Oxygen/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome , World Health Organization
5.
Environ Sci Pollut Res Int ; 28(30): 40431-40444, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-2113716

ABSTRACT

The outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the entire world with its infectious spread and mortality rate. The severe cases of coronavirus disease 2019 (COVID-19) are characterized by hypoxia and acute respiratory distress syndrome. In the absence of any specific treatment, just the preventive and supportive care options are available. Therefore, much focus is given to assess the available therapeutic options not only to avoid acute respiratory failure and hypoxia but also to reduce the viral load to control the severity of the disease. The antimalarial drug hydroxychloroquine (HCQ) is among the much-discussed drugs for the treatment and management of COVID-19 patients. This article reviews the therapeutic potential of HCQ in the treatment of COVID-19 based on the available in vitro and clinical evidence, current status of registered HCQ-based clinical trials investigating therapeutic options for COVID-19, and environmental implications of HCQ.


Subject(s)
COVID-19 , Coronavirus Infections , Antiviral Agents , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2
7.
Turk J Ophthalmol ; 52(5): 324-330, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2100078

ABSTRACT

Objectives: Retinal vascular complications have been described in patients with coronavirus disease 2019 (COVID-19). This study aimed to analyze retinal microvascular changes and their correlations with clinical findings. Materials and Methods: This case-controlled study was conducted in a university hospital. The right eyes of 52 otherwise healthy patients recovered from COVID-19 and 42 healthy controls were examined with optical coherence tomography angiography. Mann-Whitney U test was used to compare vessel density (VD) and foveal avascular zone (FAZ) parameters. Associations with treatment choices, pneumonia, and laboratory findings were analyzed. Results: Twenty-nine patients (56%) and 18 healthy controls (43%) were men. Mean age of the COVID-19 group was 39.00±13.04 years. Twenty-two patients had pneumonia, 18 (35%) received hydroxychloroquine (HCQ), 17 (33%) received HCQ plus low-molecular-weight heparin (LMWH), and 10 (19%) received favipiravir. The patient group had lower parafoveal VD in the superficial capillary plexus (SCP) and lower parafoveal VD and perifoveal VD in the deep capillary plexus (DCP) than controls (p=0.003, p=0.004, p=0.001). FAZ area did not differ significantly (p=0.953). Perifoveal VD in the DCP was also significantly lower in the HCQ+LMWH group than the HCQ group (p=0.020) and in the presence of pneumonia (p=0.040). C-reactive protein (CRP) and ferritin levels were negatively correlated with perifoveal VD in the DCP (r=-0.445, p=0.023; r=-0.451, p=0.040). Ferritin was also negatively correlated with parafoveal VD in the SCP (r=-0.532, p=0.013). Conclusion: Parafoveal and perifoveal VD was found to be lower in the COVID-19 group. Presence of pneumonia, need for LMWH prophylaxis, and levels of CRP and ferritin were found to be negatively associated with retinal VD. Large-scale studies are needed to evaluate the clinical importance.


Subject(s)
COVID-19 , Tomography, Optical Coherence , Male , Humans , Adult , Middle Aged , Female , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Fovea Centralis , COVID-19/complications , Heparin, Low-Molecular-Weight , Hydroxychloroquine/therapeutic use , Ferritins
9.
Med Trop Sante Int ; 2(3)2022 09 30.
Article in French | MEDLINE | ID: covidwho-2091754

ABSTRACT

The authors report on their experience of managing COVID-19 at the Regional hospital of Lambaréné, capital of the Moyen-Ogooué province in central Gabon.The infectious diseases department was the referral and follow-up site for COVID-19, with an intervention team to follow up outpatients. The department followed national recommendations for overall management with mild cases receiving vitamin therapy, moderate cases hydroxychloroquine and azithromycin, severe cases azithromycin, another antibiotic and oxygen.Over 1 year in 2020, 495 cases (RT-PCR +) were recruited; 92 were hospitalized (comorbidities or severe signs). The average duration of hospitalization was 21 +/- 3 days.These 92 cases are composed of 38 mild cases all cured by symptomatic treatments; 32 moderate cases treated and cured; and 26 severe cases treated with azithromycin plus a second antibiotic with 24 cured without sequelae, 1 with sequelae and 1 death (co-infected with HIV).The 399 cases followed up in the outpatient department all recovered and are distributed as follows: 199 asymptomatic and without co-morbidity, untreated; 102 with mild signs under vitamins; 98 with moderate signs treated with azithromycin + HCHQ + vitamins.In total, all 495 cases recovered without sequelae except for 1 patient with sequelae and 1 death; 199 received no treatment. However, 6 deaths occurred before the diagnosis was made. This strategy encountered difficulties in terms of overloading the carers and feeding the patients.


Subject(s)
COVID-19 , Hydroxychloroquine , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Azithromycin/therapeutic use , Gabon , Treatment Outcome , Hospitals , Anti-Bacterial Agents/therapeutic use , Vitamins , Oxygen
10.
Med J Aust ; 217 Suppl 9: S7-S13, 2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2090766

ABSTRACT

Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication, anti-SARS-CoV-2 monoclonal antibody formulations that provide passive immunisation, and immunomodulatory drugs that suppress the body's inflammatory response. Several drugs with different modes of action are approved in Australia for early treatment of COVID-19, including nirmatrelvir plus ritonavir, molnupiravir, and monoclonal antibody formulations. Although these drugs are recommended, clinicians are encouraged to remain up to date on current indications, contraindications and the clinical efficacy of these drugs against SARS-CoV-2 variants currently circulating in communities. Other treatments, including hydroxychloroquine, ivermectin and dietary supplements, have been popularised but are not recommended for early treatment of COVID-19. As new drugs and new data on use of existing approved drugs become available, clinicians face a growing challenge in determining the optimal treatments from the array of options. As it stands, early treatment of COVID-19 needs to be individualised depending on age, pregnancy status, existing medications, and renal and liver disease status. Future treatments in development might have roles in patients with lower risk profiles and in reducing transmission as we learn to live with SARS-CoV-2.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Humans , Pregnancy , Female , SARS-CoV-2 , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Antibodies, Viral , Antibodies, Monoclonal , Antiviral Agents/therapeutic use
11.
Science ; 378(6617): 231, 2022 10 21.
Article in English | MEDLINE | ID: covidwho-2088386

ABSTRACT

When the advocacy group America's Frontline Doctors appeared on the steps of the United States Supreme Court in 2020, falsely stating that hydroxychloroquine was a cure for COVID-19, their pronouncement was virally shared by right-wing media and soundly debunked by medical academicians. A year later, one of these frontliners, Joseph Ladapo, became the surgeon general of Florida and a faculty member at the University of Florida College of Medicine. He has continued to spread dangerous misinformation about COVID-19 while his academic colleagues are shamefully silent.


Subject(s)
COVID-19 , Consumer Advocacy , Faculty, Medical , Hydroxychloroquine , Physicians , Humans , Male , COVID-19/drug therapy , Florida , Hydroxychloroquine/therapeutic use , Physicians/ethics , Universities , Consumer Advocacy/ethics , Communication , Faculty, Medical/ethics
12.
Sci Rep ; 12(1): 17955, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2087312

ABSTRACT

Progress has been made in COVID-19 vaccine development, with encouraging safety and efficacy data. The purpose of this study was to investigate the immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Patients with AIIRD (n = 101) were included in this study. All patients received 2 doses of inactivated COVID-19 vaccine. Serum anti-S1/RBD protein IgG was detected 2-16 weeks after the second vaccination. Seropositivity was defined as IgG ≥ 1.00 bound antibody unit S/CO. Immunogenicity of inactivated COVID-19 vaccine was assessed by seropositivity rate and the levels of serum IgG antibody against anti-S1/RBD protein, compared with the general population (n = 46). There was no difference by statistical significance in the seropositivity rate between patients with AIIRD (82.2%) and SLE (86.1%) and the control group (93.5%), p > 0.05. The level of anti-S1/RBD protein IgG antibodies in patients with AIIRD (median [IQR], 8.8 [2.2-17.3]) and SLE (median [IQR], 9.6 [2.4-20.4]) was comparable to that in the control group (median [IQR], 7.2 [3.1-14.2]), p > 0.05. Patients treated with glucocorticoids(GCs) (median dose, [IQR]: 2.5 mg/day [IQR 2.5-5.0]) or hydroxychloroquine(HCQ) or GCs + HCQ without other immunomodulatory medications, had an appropriate immunogenic response(88.1%) with high levels of anti-S1/RBD protein IgG(median [IQR], 12.1 [6.5-20.4]). Neither of patients treated with rituximab had positive serum antibodies, which was statistically significant, compared with the control group (p < 0.01). Compared with the control group, methotrexate(MTX) and iguratimod(IGU) was significantly reduced the level of anti-S1/RBD protein IgG antibodies. Inactivated COVID-19 vaccine had appropriate immunogenicity in patients with AIIRD. Immunogenicity of inactivated COVID-19 vaccine was severely impaired by rituximab, and also suppressed by MTX and IGU, while low doses of GC and HCQ had negligible effect.


Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Rheumatic Diseases , Rheumatic Fever , Humans , COVID-19 Vaccines , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , Hydroxychloroquine/therapeutic use , Methotrexate/therapeutic use , Rituximab/therapeutic use , Autoimmune Diseases/epidemiology , COVID-19/prevention & control , Immunoglobulin G/therapeutic use , Antibodies, Viral/therapeutic use , Immunogenicity, Vaccine
13.
Hist Philos Life Sci ; 44(4): 47, 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2075759

ABSTRACT

The current strategy of searching for an effective treatment for COVID-19 relies mainly on repurposing existing therapies developed to target other diseases. Conflicting results have emerged in regard to the efficacy of several tested compounds but later results were negative. The number of conducted and ongoing trials and the urgent need for a treatment pose the risk that false-positive results will be incorrectly interpreted as evidence for treatments' efficacy and a ground for drug approval. Our purpose is twofold. First, we show that the number of drug-repurposing trials can explain the false-positive results. Second, we assess the evidence for treatments' efficacy from the perspective of evidential pluralism and argue that considering mechanistic evidence is particularly needed in cases when the evidence from clinical trials is conflicting or of low quality. Our analysis is an application of the program of Evidence Based Medicine Plus (EBM+) to the drug repurposing trials for COVID. Our study shows that if decision-makers applied EBM+, authorizing the use of ineffective treatments would be less likely. We analyze the example of trials assessing the efficacy of hydroxychloroquine as a treatment for COVID-19 and mechanistic evidence in favor of and against its therapeutic power to draw a lesson for decision-makers and drug agencies on how excessive hypothesis testing can lead to spurious findings and how studying negative mechanistic evidence can be helpful in discriminating genuine from spurious results.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , Drug Repositioning , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Research Design
14.
East Mediterr Health J ; 28(9): 673-681, 2022 Sep 29.
Article in English | MEDLINE | ID: covidwho-2067577

ABSTRACT

Background: Incomplete data are often presented for determining the role of vitamin A supplement therapy for improving treatment outcomes in patients with COVID-19. Aims: We compared treatment effects between a group that received vitamin A added to the standard COVID-19 treatment and another group that received the standard drug treatment alone. Methods: Participants in this triple-blind controlled trial comprised 182 COVID-19 outpatients in Saveh City, Markazi Province, Islamic Republic of Iran, in 2020. Patients were randomly divided into experimental (n = 91) and control (n = 91) groups. Patients in the control group received the national standard treatment for COVID-19 (hydroxychloroquine), and those in the intervention group received 25 000 IU/d oral vitamin A for 10 days in addition to the standard treatment recommended by the national protocol. We evaluated the clinical symptoms, paraclinical criteria, and hospitalization status before and after 10 days of interventions. Results: The treatment groups did not differ significantly in clinical and paraclinical symptoms before the intervention. However, clinical symptoms such as fever, body ache, weakness and fatigue, paraclinical symptoms, white blood cell count, and C-reactive protein showed significantly greater decreases in the experimental group 10 days post-intervention compared with the standard treatment alone (P < 0.05). Conclusion: Vitamin A supplementation demonstrated efficacy in improving some clinical and paraclinical symptoms in patients with COVID-19. Future studies should evaluate vitamin A supplementation with a larger sample size and compare different dosages, especially in hospitalized patients.


Subject(s)
COVID-19 , C-Reactive Protein , COVID-19/drug therapy , Dietary Supplements , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Treatment Outcome , Vitamin A/therapeutic use
15.
J Med Virol ; 94(12): 6091-6096, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2059508

ABSTRACT

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Viral Load
16.
PLoS One ; 17(9): e0267815, 2022.
Article in English | MEDLINE | ID: covidwho-2043198

ABSTRACT

OBJECTIVE: To describe differences by race and ethnicity in treatment patterns among hospitalized COVID-19 patients in the US from March-August 2020. METHODS: Among patients in de-identified Optum electronic health record data hospitalized with COVID-19 (March-August 2020), we estimated odds ratios of receiving COVID-19 treatments of interest (azithromycin, dexamethasone, hydroxychloroquine, remdesivir, and other steroids) at hospital admission, by race and ethnicity, after adjusting for key covariates of interest. RESULTS: After adjusting for key covariates, Black/African American patients were less likely to receive dexamethasone (adj. OR [95% CI]: 0.83 [0.71, 0.96]) and more likely to receive other steroids corticosteroids (adj. OR [95% CI]: 2.13 [1.90, 2.39]), relative to White patients. Hispanic/Latino patients were less likely to receive dexamethasone than Not Hispanic/Latino patients (adj. OR [95% CI]: 0.69 [0.58, 0.82]). CONCLUSIONS: Our findings suggest that COVID-19 treatments patients received in Optum varied by race and ethnicity after adjustment for other possible explanatory factors. In the face of rapidly evolving treatment landscapes, policies are needed to ensure equitable access to novel and repurposed therapeutics to avoid disparities in care by race and ethnicity.


Subject(s)
COVID-19 , Pandemics , Azithromycin/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Dexamethasone/therapeutic use , Ethnicity , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , United States , Whites
18.
Int J Med Inform ; 166: 104842, 2022 10.
Article in English | MEDLINE | ID: covidwho-2036077

ABSTRACT

PURPOSE: To evaluate the number, characteristics, and outcomes of patients identified hospitalized with coronavirus disease 2019 (COVID-19) using two different case definitions. PROCEDURES: Electronic Health Record data were evaluated from patients hospitalized with COVID-19 through May 2020 at 52 health systems across the United States. Characteristics of inpatients with positive laboratory tests for SARS-CoV-2 were compared with those with clinical diagnosis of COVID-19 but without a confirmatory lab result. FINDINGS: Of 14,371 inpatients with COVID-19, 6623 (46.1 %) had a positive laboratory result, and n = 7748 (52.9 %) had only a clinical diagnosis of COVID-19. Compared with clinically diagnosed cases, those with laboratory-confirmed COVID were similar in age and sex, but differed by race, ethnicity, and insurance status. Laboratory-confirmed cases were more likely to receive certain COVID-19 therapies including hydroxychloroquine, anti-IL6 agents and antivirals (p < 0.001). Those with laboratory-confirmed COVID-19 had lower rates of most complications such as myocardial infarction, but higher overall mortality (p < 0.001). CONCLUSION: We observed a two-fold difference in the number of patients hospitalized with COVID-19 depending on whether the case definition required laboratory confirmation. Variations in case definitions also led to differences in cohort characteristics, treatments, and outcomes.


Subject(s)
COVID-19 , Antiviral Agents , COVID-19/diagnosis , COVID-19/epidemiology , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , United States/epidemiology
19.
Eur J Epidemiol ; 37(8): 789-796, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2035117

ABSTRACT

BACKGROUND: Recruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19. METHODS: A search of PubMed, medRxiv, and clinicaltrials.gov combined with expert consultation found 11 completed randomized trials: 7 pre-exposure prophylaxis trials and 4 post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates. RESULTS: The pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58-0.90) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.55-0.95) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.72-1.16) and 0.91 (95% CI: 0.62-1.35). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups. DISCUSSION: A benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the "not statistically significant" findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.


Subject(s)
COVID-19 , Hydroxychloroquine , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Testing , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Randomized Controlled Trials as Topic , SARS-CoV-2
20.
Rapid Commun Mass Spectrom ; 36(20): e9358, 2022 Oct 30.
Article in English | MEDLINE | ID: covidwho-2003636

ABSTRACT

RATIONALE: Hydroxychloroquine sulfate is effective in the treatment of malaria and autoimmune diseases and as an antiviral drug. However, unreported impurities are often detected in this drug, which pose a health risk. In this study, the structures of hydroxychloroquine and six unknown impurities were analyzed using ultra-high-performance liquid chromatography-quadrupole/time-of-flight-tandem mass spectrometry (UHPLC-Q/TOF/MS/MS), and the structures were characterized using liquid chromatography-solid-phase extraction-nuclear magnetic resonance (LC-SPE-NMR) spectroscopy. METHODS: An Agilent InfinityLad Poroshell HPH-C18 column (100 × 4.6 mm, 2.7 µm) was used. For the analysis of hydroxychloroquine and six unknown impurities, the mobile phase was 20 mM ammonium formate aqueous solution and methanol/acetonitrile (80:20, v/v) using gradient elution. Full-scan MS and MS2 were performed to obtain as much structural information as possible. In addition, six unknown impurities were separated by semi-preparative liquid chromatography and characterized using LC-SPE-NMR. RESULTS: The MS2 fragmentation patterns of the impurities were investigated, leading to more structural information and an understanding of the fragmentation pathways of the impurities. The structures of the unknown impurities were confirmed using NMR. In addition, some possible pathways of the formation of the impurities in the drugs were outlined, and these impurities were found to be process impurities. CONCLUSIONS: Based on the identification and characterization of these impurities, this study also describes the cause of the production of the impurities and provides insights for companies to improve their production processes and a scientific basis for the improvement of the related pharmacopoeias.


Subject(s)
COVID-19 , Hydroxychloroquine , COVID-19/drug therapy , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Drug Contamination , Humans , Hydroxychloroquine/therapeutic use , Magnetic Resonance Spectroscopy , Solid Phase Extraction , Tandem Mass Spectrometry
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