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1.
J Pak Med Assoc ; 72(7): 1384-1390, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2057184

ABSTRACT

OBJECTIVE: To identify various emerging diagnostics parameters of coronavirus disease 2019 related to disease progression and fatality. METHODS: The cross-sectional study was conducted at Mardan Medical Complex, Khyber Pakhtunkhwah, Pakistan, from February 9, 2021, to April 21, 2021, and comprised patients of either gender aged >18 years diagnosed with coronavirus disease 2019 on the basis of polymerase chain reaction testing and who were admitted to the hospital using the World Health Organisation interim guidelines. Disease progression was categorised as mild, moderate, severe and critical, and they were monitored closely till the final outcome. Data was analysed using SPSS 26. RESULTS: Of the 408 patients, 215(52.69%) were male and 193(47.30%) were female. The overall median age of the sample was 55 years (interquartile range: 18-84 years). Symptoms included cough 92(22.54%), fever 80(19.60%), shortness of breath 78(19.60%), fatigue 60(14.70%) and loss of smell and test 52(12.74%), while 46(11.27%) were asymptomatic. Azithromycin was the most used drug 304(74.50%), while antiviral Remdesivir was given to 279(68.38%) patients and hydrocortisone to 143(35.04%). Plasma treatment was given to 55(13.48%) patients and mechanical ventilation to 87(21.32%). Compared to baseline, disease progression was mild in 72(17.64%) patients, moderate 96(23.52%), severe 98(24.01%) and critical in 89(21.81%), while no change was seen 53(12.99%) cases. Severity level was significantly associated with liver and renal function parameters (p<0.05). Overall, 47(11.51%) patients died. CONCLUSIONS: Different severity levels during hospitalisation among patients of coronavirus disease 2019 were noted, and severity level was significantly associated with liver and renal function parameters.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/diagnosis , COVID-19 Testing , Cross-Sectional Studies , Disease Progression , Female , Humans , Hydrocortisone , Male , Middle Aged , SARS-CoV-2 , Young Adult
2.
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
3.
PLoS One ; 17(5): e0267645, 2022.
Article in English | MEDLINE | ID: covidwho-1910614

ABSTRACT

OBJECTIVES: To assess efficacy and safety of the combined treatment of antibiotics (3rd-generation cephalosporin and azithromycin) and antiviral agents (lopinavir/ritonavir or hydroxychloroquine) on moderate COVID-19 patients in South Korea. METHODS: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 299 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were used to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with either CA/LoP (cephalosporin, azithromycin, and lopinavir/ritonavir) (n = 57), CA/HQ (cephalosporin, azithromycin, and hydroxychloroquine) (n = 25) or standard supportive care (n = 217). We analyzed the association between treatment group and standard supportive group in terms of three endpoints: time to symptom resolution, time to viral clearance, and hospital stay duration. Using propensity-score matching analysis, three rounds of propensity-matching analysis were performed to balance baseline characteristics among three cohorts. RESULTS: Kaplan-Meier curves fitted using propensity score-matched data revealed no significant differences on time to symptom resolution, time to viral clearance, hospital stay duration among the three treatment arms (CA/LoP vs Standard, log-rank p-value = 0.2, 0.58, and 0.74 respectively for the three endpoints) (CA/HQ vs Standard, log-rank p-value = 0.46, 0.99, and 0.75 respectively). Similarly, Cox regression analysis on matched cohorts of CA/LoP and standard supportive group showed that hazard ratios of time to symptom resolution (HR: 1.447 [95%-CI: 0.813-2.577]), time to viral clearance(HR: 0.861, [95%-CI: 0.485-1.527]), and hospital stay duration (HR: 0.902, [95%-CI: 0.510-1.595]) were not significant. For CA/HQ and standard supportive group, hazard ratios of the three endpoints all showed no statistical significance (HR: 1.331 [95%-CI:0.631-2.809], 1.005 [95%-CI:0.480-2.105], and 0.887, [95%-CI:0.422-1.862] respectively). No severe adverse event or death was observed in all groups. CONCLUSIONS: Combined treatment of 3rd cephalosporin, azithromycin and either low-dose lopinavir/ritonavir or hydroxychloroquine was not associated with better clinical outcomes in terms of time to symptom resolution, time to viral clearance, and hospital stay duration compared to standard supportive treatment alone. Microbiological evidence should be closely monitored when treating SARS-CoV-2 patients with antibiotics to prevent indiscreet administration of empirical antimicrobial treatments.


Subject(s)
COVID-19 , SARS-CoV-2 , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Cephalosporins/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , Treatment Outcome
4.
J Clin Lab Anal ; 36(6): e24427, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1877605

ABSTRACT

BACKGROUND: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide. METHODS: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies. RESULTS: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections. CONCLUSIONS: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.


Subject(s)
Azithromycin , Cystic Fibrosis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Bacterial Proteins , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Humans
5.
Acta Obstet Gynecol Scand ; 101(8): 889-900, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1874382

ABSTRACT

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibiotic Prophylaxis/adverse effects , Azithromycin/therapeutic use , COVID-19/drug therapy , Cefuroxime/therapeutic use , Cesarean Section/adverse effects , Cesarean Section/methods , China , Cicatrix/epidemiology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Sodium
6.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 371-386, 2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1870146

ABSTRACT

Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit significantly in the Furin catalytic pocket having the lowest binding score (-9.9 Kcal/mol) with respect to azithromycin (-9.4 Kcal/mol) and can interact and block both Asp154 and Ser368 residues by Van der Walls interaction as well as bound to His194 and Ser368 residues via hydrogen bonds. Good results were also obtained with the Tmprss-2 receptor. A Molecular Dynamic simulation was assessed to confirm this interaction. Additionally, detailed receptor-ligand interactions with SARS-CoV-2 and pro-inflammatory mediators were investigated suggesting more target information with interesting results. The findings of this study are very efficient and provide a basis for the development of dirithromycin for clinical trial applications to be efficient in treating SARS-CoV-2 infections.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Azithromycin/chemistry , Azithromycin/pharmacology , Azithromycin/therapeutic use , COVID-19/drug therapy , Erythromycin/analogs & derivatives , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism
7.
J Infect Chemother ; 28(7): 948-954, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1851524

ABSTRACT

INTRODUCTION: Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. METHODS: We investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein. A retrospective cohort study was performed on intensive care COVID-19 patients. RESULTS: Co-incubation of clarithromycin with spike protein-stimulated healthy volunteer PBMCs ex vivo resulted in an increase in CD8+ (p = 0.004) and CD4+ (p = 0.007) IL-2, with a decrease in CD8+ (p = 0.032) and CD4+ (p = 0.007) IL-10. The addition of amoxicillin to clarithromycin resulted in an increase in CD8+ IL-6 (p = 0.010), decrease in CD8+ (p = 0.014) and CD4+ (p = 0.022) TNF-alpha, and decrease in CD8+ IFN-alpha (p = 0.038). Amoxicillin alone had no effect on CD4+ or CD8+ cytokines. Co-incubation of azithromycin resulted in increased CD8+ (p = 0.007) and CD4+ (p = 0.011) IL-2. There were no effects on monocyte phagocytosis. 102 COVID-19 ICU patients received antibiotics on hospital admission; 62 (61%) received clarithromycin. Clarithromycin use was associated with reduction in mortality on univariate analysis (p = 0.023), but not following adjustment for confounders (HR = 0.540; p = 0.076). CONCLUSIONS: Clarithromycin has immunomodulatory properties over and above azithromycin. Amoxicillin in addition to clarithromycin is associated with synergistic ex vivo immunomodulatory properties. The potential benefit of clarithromycin in critically ill patients with COVID-19 and other viral pneumonitis merits further exploration.


Subject(s)
COVID-19 , Clarithromycin , Amoxicillin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , COVID-19/drug therapy , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Cytokines , Humans , Interleukin-2 , Macrolides/pharmacology , Retrospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
PLoS One ; 17(2): e0263437, 2022.
Article in English | MEDLINE | ID: covidwho-1793528

ABSTRACT

BACKGROUND: During the initial phase of the COVID-19 pandemic, there was great enthusiasm for the use of azithromycin with or without hydroxychloroquine. OBJECTIVES: We analyzed azithromycin consumption in Croatia in 2020 and compared this to the period 2017-2019. METHODS: Azithromycin consumption was evaluated using the IQVIA Adriatic d.o.o. database which collects data on azithromycin distribution from wholesale pharmacies to hospital and non-hospital pharmacies in Croatia. We analyzed data for the period from January 2017 to December 2020. Azithromycin distribution was measured as days of therapy (DOT) and reported as per 1000 inhabitants or per 1000 inhabitant-days. RESULTS: In the period 2017-2020, total azithromycin DOT in Croatia increased in 2017, 2018, 2019, and 2020 (1.76, 1.91, 1.91 and 2.01/1000 inhabitant-days, respectively). Non-hospital pharmacies received 2.18 times and hospital pharmacies 4.39 times more DOT units/1000 inhabitants of azithromycin in March 2020 compared to the average distribution rate in March 2017-2019. During the peak of the COVID-19 epidemic (November and December 2020) azithromycin distribution increased considerably in hospital (3.62 and 3.19 times, respectively) and non-hospital pharmacies (1.93 and 1.84 times, respectively) compared to the average consumption in the same months in 2017-2019. CONCLUSIONS: Our data showed increased azithromycin distribution in the period 2017-2020 which indicates azithromycin overuse. Preliminary information on COVID-19 treatments with a desire to offer and try what is available even in the absence of strong scientific evidence may have influenced practices of antimicrobial prescriptions.


Subject(s)
Azithromycin/therapeutic use , Drug Utilization/trends , Practice Patterns, Physicians'/trends , Anti-Bacterial Agents , Anti-Infective Agents , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Croatia/epidemiology , Databases, Factual , Drug Therapy, Combination , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Pandemics , Practice Patterns, Physicians'/statistics & numerical data , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
9.
Monaldi Arch Chest Dis ; 92(4)2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1715883

ABSTRACT

To The Editor, The Global Initiative for Asthma (GINA) 2021 update was published on the 28th of April, 2021. There are significant changes, including treatment of mild asthma, the role of azithromycin, treatment of asthma in COVID-19 times, and role of biologics...


Subject(s)
Asthma , Biological Products , COVID-19 , Asthma/drug therapy , Azithromycin/therapeutic use , Humans
10.
Medicina (Kaunas) ; 58(3)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1715544

ABSTRACT

The warning by the Italian Medicines Agency on the high shortage of azithromycin in the country in January 2022 represents a paradigmatic lesson learnt from improper use of antibiotics during COVID-19 pandemic.


Subject(s)
Azithromycin , COVID-19 , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Humans , Italy/epidemiology , Pandemics
11.
Biomed Pharmacother ; 147: 112682, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664682

ABSTRACT

Viral infections have a great impact on human health. The urgent need to find a cure against different viruses led us to investigations in a vast range of drugs. Azithromycin (AZT), classified as a macrolide, showed various effects on different known viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Zika, Ebola, Enterovirus (EVs) and Rhinoviruses (RVs), and Influenza A previously; namely, these viruses, which caused global concerns, are considered as targets for AZT different actions. Due to AZT background in the treatment of known viral infections mentioned above (which is described in this study), in the early stages of COVID-19 (a new zoonotic disease caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) development, AZT drew attention to itself due to its antiviral and immunomodulatory effects as a valuable candidate for COVID-19 treatment. AZT usage instructions for treating different viral infections have always been under observation, and COVID-19 is no exception. There are still debates about the use of AZT in COVID-19 treatment. However, eventually, novel researches convinced WHO to announce the discontinuation of AZT use (alone or in combination with hydroxychloroquine) in treating SARS-CoV-2 infection. This research aims to study the structure of all of the viruses mentioned above and the molecular and clinical effects of AZT against the virus.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Anti-Bacterial Agents , Antiviral Agents/pharmacology , Azithromycin/pharmacology , Ebolavirus/drug effects , Humans , Influenza A virus/drug effects , SARS Virus/drug effects , SARS-CoV-2/drug effects , Zika Virus/drug effects
12.
J Pediatr Hematol Oncol ; 44(1): e134-e137, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1632085

ABSTRACT

To this day, there are limited data about the effects and management of coronavirus disease infection in pediatric patients with sickle cell disease. We present the management and successful clinical course of an 8-year-old female with homozygous sickle cell disease (SS) and severe acute chest syndrome secondary to coronavirus disease 2019 infection, complicated by cortical vein thrombosis.


Subject(s)
Anemia, Sickle Cell/complications , COVID-19/complications , Systemic Inflammatory Response Syndrome/complications , Anemia, Sickle Cell/pathology , Anemia, Sickle Cell/therapy , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/pathology , COVID-19/therapy , Ceftriaxone/therapeutic use , Child , Erythrocyte Transfusion , Female , Humans , Intensive Care Units , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy
13.
PLoS One ; 16(3): e0248128, 2021.
Article in English | MEDLINE | ID: covidwho-1575679

ABSTRACT

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Data Management/methods , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Male , SARS-CoV-2/drug effects
14.
J Med Virol ; 93(12): 6737-6749, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544327

ABSTRACT

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID-19) infection. The network meta-analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID-19 infection. The outcomes of interest were all-cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random-effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168-1.887]), AZ alone (OR = 0.965 [95% CI: 0.865-1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995-1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ2 = 0; I2 = 0% [95% CI: 0%-0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID-19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Adult , Aged , Chloroquine/therapeutic use , Female , Humans , Male , Middle Aged , Network Meta-Analysis , Randomized Controlled Trials as Topic , Respiration, Artificial/methods
15.
J Med Virol ; 94(1): 291-297, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544344

ABSTRACT

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Care/statistics & numerical data , Severity of Illness Index , Aged , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/pathology , Comorbidity , Drug Combinations , Enoxaparin/therapeutic use , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Pyrazines/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Turkey/epidemiology
16.
Antiviral Res ; 197: 105212, 2022 01.
Article in English | MEDLINE | ID: covidwho-1530602

ABSTRACT

Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of preclinical assessment, many clinical trials were set up using these molecules. In the present study, we show that hydroxychloroquine and azithromycin alone or combined does not block SARS-CoV-2 replication in human bronchial airway epithelia. When tested in a Syrian hamster model, hydroxychloroquine and azithromycin administrated alone or combined displayed no significant effect on viral replication, clinical course of the disease and lung impairments, even at high doses. Hydroxychloroquine quantification in lung tissues confirmed strong exposure to the drug, above in vitro inhibitory concentrations. Overall, this study does not support the use of hydroxychloroquine and azithromycin as antiviral drugs for the treatment of SARS-CoV-2 infections.


Subject(s)
Anti-Infective Agents/pharmacology , Azithromycin/pharmacology , COVID-19/drug therapy , Hydroxychloroquine/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/therapeutic use , Azithromycin/administration & dosage , Azithromycin/pharmacokinetics , Azithromycin/therapeutic use , Bronchi/cytology , Bronchi/virology , Chlorocebus aethiops , Cricetinae , Disease Models, Animal , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/therapeutic use , Lung/pathology , Mesocricetus , Middle Aged , Plasma/virology , Real-Time Polymerase Chain Reaction , Vero Cells
17.
Immunol Res ; 70(1): 129-133, 2022 02.
Article in English | MEDLINE | ID: covidwho-1504961

ABSTRACT

Azithromycin is a macrolide antibiotic. Recent evidence has demonstrated in vitro activity against a wide variety of respiratory tract viruses, including SARS-CoV-2 responsible for the current global pandemic COVID-19. A mechanism of action acting on different phases of the viral cycle is assumed. In addition to its in vitro antiviral properties, some evidence also suggests immunomodulatory and antifibrotic activity. These properties of azithromycin could be useful in the treatment of viral respiratory tract infections such as COVID-19. However, clinical data on the antiviral efficacy of azithromycin in the treatment of respiratory tract infections are inconsistent, both when used as monotherapy and in polypharmacological combination. In addition, cases of azithromycin-induced QT long and malignant arrhythmias are reported. In this short review, we attempt to determine the role of azithromycin in the treatment of viral respiratory tract infections such as COVID-19, therapeutic efficacy, or inefficacy?


Subject(s)
Antiviral Agents/administration & dosage , Azithromycin/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/metabolism , Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19/metabolism , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/metabolism
18.
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
19.
Am J Epidemiol ; 190(11): 2405-2419, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1493668

ABSTRACT

Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ among patients hospitalized with COVID-19. We examined the effects of HCQ alone and in combination with azithromycin in a hospitalized population of US veterans with COVID-19, using a propensity score-adjusted survival analysis with imputation of missing data. According to electronic health record data from the US Department of Veterans Affairs health care system, 64,055 US Veterans were tested for the virus that causes COVID-19 between March 1, 2020 and April 30, 2020. Of the 7,193 veterans who tested positive, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and there was an increased risk of intubation when HCQ was used in combination with azithromycin (hazard ratio = 1.55; 95% confidence interval: 1.07, 2.24). In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treatment of patients hospitalized with COVID-19, using a national sample of the US veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hospitalization/statistics & numerical data , Hydroxychloroquine/therapeutic use , Veterans/statistics & numerical data , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , COVID-19/mortality , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/adverse effects , Intention to Treat Analysis , Machine Learning , Male , Middle Aged , Pharmacoepidemiology , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , United States/epidemiology
20.
Card Electrophysiol Clin ; 14(1): 95-104, 2022 03.
Article in English | MEDLINE | ID: covidwho-1487631

ABSTRACT

While looking for a solution to treat COVID-19, the massive off-label use of several drugs in COVID-19 has generated concerns in the early phase of the pandemic because of possible arrhythmogenic effects in relation to QTc interval prolongation. Indeed, some of these drugs have been historically associated with QT prolongation and Torsade de Point, a potentially lethal ventricular arrhythmia, and their first-time use on a very large scale has raised several concerns in the scientific community. This work aims to summarize the underlying arrhythmogenic mechanisms related to the use of potentially QT-prolonging drugs used during the pandemic to treat COVID-19.


Subject(s)
Arrhythmias, Cardiac , COVID-19 , Long QT Syndrome , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/virology , Azithromycin/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Electrocardiography , Humans , Hydroxychloroquine/therapeutic use , Long QT Syndrome/chemically induced , Risk Factors , SARS-CoV-2
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