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1.
Cornea ; 40(11): 1502-1504, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-2063050

ABSTRACT

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.


Subject(s)
COVID-19/diagnosis , Conjunctivitis, Viral/diagnosis , Eye Infections, Viral/diagnosis , Keratoconjunctivitis/diagnosis , SARS-CoV-2/pathogenicity , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Ascorbic Acid/administration & dosage , Azithromycin/administration & dosage , COVID-19/drug therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Child, Preschool , Conjunctivitis, Viral/drug therapy , Conjunctivitis, Viral/virology , Drug Therapy, Combination , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Fluorometholone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Keratoconjunctivitis/drug therapy , Keratoconjunctivitis/virology , Male , Ophthalmic Solutions , Slit Lamp Microscopy , Tomography, Optical Coherence , Visual Acuity/physiology
2.
Eur J Clin Pharmacol ; 77(10): 1513-1521, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1813653

ABSTRACT

PURPOSE: To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches. METHODS: The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated. RESULTS: One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34). CONCLUSIONS: The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.


Subject(s)
Azithromycin/adverse effects , Chloroquine/adverse effects , Hydroxychloroquine/adverse effects , Torsades de Pointes/chemically induced , Adult , Aged , Azithromycin/administration & dosage , Chloroquine/administration & dosage , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Male , Middle Aged , Pharmacovigilance , Retrospective Studies
3.
Turk J Haematol ; 39(1): 43-54, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1707760

ABSTRACT

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.


Subject(s)
COVID-19 , Hematologic Neoplasms , Adult , Amides/administration & dosage , Azithromycin/administration & dosage , COVID-19/complications , COVID-19/mortality , Child , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Pyrazines/administration & dosage , SARS-CoV-2 , Turkey/epidemiology
4.
Pan Afr Med J ; 38: 382, 2021.
Article in French | MEDLINE | ID: covidwho-1547778

ABSTRACT

SARS-CoV-2 infection is a major concern and a new threat to immunocompromised patients. Patients with chronic inflammatory bowel diseases (IBDs) are at increased risk of infections, in particular when they have active disease and are on immunosuppressive treatment. The purpose of this study was to assess the clinical, biological and radiological features of three patients with COVID-19 associated with chronic IBD as well as their management and outcomes. The study was conducted at the Hassan II University Teaching Hospital in Fes, Morocco over a 3-month period. We assessed all patients with disease onset. All patients had mild symptoms or were asymptomatic. No changes or delays in treatment regimens occurred and none of patients developed severe COVID-19. Reverse transcription polymerase chain reaction (RT-PCR) test results were positive in all patients. Radiological examinations were conducted. Chest scanner showed ground-glass opacities in one case. Treatment was based on hydroxychloroquine with azithromycin. Outcome was good in all cases. This preliminary report suggests that patients with chronic IBD aren't at higher risk of developing COVID-19 compared to the general population.


Subject(s)
COVID-19/physiopathology , Immunosuppressive Agents/administration & dosage , Inflammatory Bowel Diseases/physiopathology , Adult , Azithromycin/administration & dosage , COVID-19/diagnosis , COVID-19/drug therapy , Female , Hospitals, University , Humans , Hydroxychloroquine/administration & dosage , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged , Morocco
6.
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
7.
Clin Transl Sci ; 14(6): 2431-2439, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526358

ABSTRACT

To utilize noninvasive collection of amniotic fluid in the setting of preterm premature rupture of membranes (PPROMs) to report the time concentration profile of azithromycin in amniotic fluid over 7 days from a single dose, and evaluate the correlation between azithromycin concentration and inflammatory markers in amniotic fluid. Prospective cohort study of five pregnant patients admitted with PPROMs and treated with a single 1 g oral azithromycin dose. Amniotic fluid was collected from pads and used to quantify azithromycin concentration as well as TNFa, IL-1a, IL-1b, IL-6, IL-8, and IL-10 concentrations. Primary outcome was time/concentration profile of azithromycin in amniotic fluid. Secondary outcome included correlation between azithromycin concentration and cytokine concentrations. Five patients were enrolled. Mean gestational age on admission with PPROM was 27.5 ± 2.3 weeks with a median latency of 7 days (interquartile range [IQR] = 4-13). A median of two samples/day (IQR = 1-3) were collected per participant. Azithromycin was quantified in duplicate; intra-assay coefficient of variation was 17%. Azithromycin concentration was less than 60 ng/ml after day 3. Azithromycin concentration was positively correlated with IL-8 (r = 0.38, p = 0.03), IL1a (r = 0.39, p = 0.03), and IL-1b (r = 0.36, p = 0.04) in amniotic fluid. Azithromycin is detectable in amniotic fluid over 7 days from a single 1 g maternal dose, however, it is not sustained over the range of minimum inhibitory concentration for common genitourinary flora. Based on correlation with specific cytokines, azithromycin penetration in amniotic fluid may relate to maternal monocyte concentration in amniotic fluid in the setting of PPROM.


Subject(s)
Amniotic Fluid/chemistry , Azithromycin/administration & dosage , Azithromycin/analysis , Cytokines/administration & dosage , Cytokines/analysis , Adult , Female , Humans , Longitudinal Studies , Pregnancy , Prospective Studies
8.
Sci Rep ; 11(1): 20964, 2021 10 25.
Article in English | MEDLINE | ID: covidwho-1483147

ABSTRACT

Multicentre, retrospective cohort study with multivariable Cox proportional-hazards modelling and survival-time inverse-probability-weighting, evaluating the impact of different treatments on survival of proven COVID-19 patients admitted to two Hospitals in the province of Piacenza, Italy. Use of tocilizumab and of high doses of low molecular weight heparin, but not of antivirals (either alone or in combination), azithromycin, and any corticosteroid, was independently associated with lower mortality. Our results support further clinical evaluation of high doses of low molecular weight heparin and tocilizumab as COVID-19 therapeutics.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/drug therapy , COVID-19/epidemiology , Heparin/administration & dosage , Adrenal Cortex Hormones/administration & dosage , Aged , Azithromycin/administration & dosage , Female , Hospital Mortality , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Patient Admission , Probability , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
11.
JAMA ; 326(6): 490-498, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1363618

ABSTRACT

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results: Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial Registration: ClinicalTrials.gov Identifier: NCT04332107.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/complications , Female , Humans , Male , Middle Aged , Outpatients , Symptom Assessment , Treatment Failure
12.
JAMA Netw Open ; 4(4): e216842, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1198342

ABSTRACT

Importance: Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). Objective: To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. Design, Setting, and Participants: This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline. Exposures: COVID-19, hydroxychloroquine, azithromycin. Main Outcomes and Measures: Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater. Results: A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models (5-day, patients with COVID-19: 20.81 [95% CI, 15.29 to 26.33] milliseconds; P < .001; patients without COVID-19: -2.01 [95% CI, -17.31 to 21.32] milliseconds; P = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds; P < .001; patients without COVID-19: 0.11 [95% CI, -12.60 to 12.81] milliseconds; P = .99). COVID-19 infection was independently associated with a modeled mean 27.32 (95% CI, 4.63-43.21) millisecond increase in QTc at 5 days compared with COVID-19-negative status (mean QTc, with COVID-19: 450.45 [95% CI, 441.6 to 459.3] milliseconds; without COVID-19: 423.13 [95% CI, 403.25 to 443.01] milliseconds; P = .01). More patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater compared with patients without COVID-19 (34 of 136 [25.0%] vs 17 of 158 [10.8%], P = .002). Multivariable analysis revealed that age 80 years and older compared with those younger than 50 years (mean difference in QTc, 11.91 [SE, 4.69; 95% CI, 2.73 to 21.09]; P = .01), severe chronic kidney disease compared with no chronic kidney disease (mean difference in QTc, 12.20 [SE, 5.26; 95% CI, 1.89 to 22.51; P = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38]; P < .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57]; P = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19. Conclusions and Relevance: In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.


Subject(s)
Azithromycin , COVID-19 , Electrocardiography , Hydroxychloroquine , Long QT Syndrome , Aged, 80 and over , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19 Testing/methods , Drug Therapy, Combination/methods , Drug Therapy, Combination/statistics & numerical data , Electrocardiography/methods , Electrocardiography/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Long QT Syndrome/virology , Male , Middle Aged , New York/epidemiology , Outcome and Process Assessment, Health Care , Risk Factors , SARS-CoV-2 , Time Factors
13.
Pan Afr Med J ; 38: 225, 2021.
Article in English | MEDLINE | ID: covidwho-1175756

ABSTRACT

Liver damage during COVID-19 disease has been described in numerous studies. Its mechanism is poorly understood. It is mainly reserved for severe forms and is manifested by abnormalities of the hepatic assessment and more particularly cytolysis. Particular attention must be paid to patients with chronic liver disease, both in terms of follow-up and treatment. We wanted to know the evolution of COVID-19 and its treatment, on the liver function of a 27-year-old patient followed for chronic non-cirrhotic hepatitis B at the Hassan II University Hospital in Fez. Our patient had stopped the antiviral B treatment and presented COVID-19 infection with minimal to moderate impairment. The initial evaluation showed cytolysis at 4 times upper limit of normal (ULN). Management consisted in the immediate resumption of Tenofovir in combination with hydroxychloroquine (HCQ) and azythromycin with good clinical and biological evolution.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/complications , Hepatitis B, Chronic/physiopathology , Adult , Azithromycin/administration & dosage , COVID-19/diagnosis , COVID-19/drug therapy , Hepatitis B, Chronic/drug therapy , Hospitals, University , Humans , Hydroxychloroquine/administration & dosage , Liver Function Tests , Male , Morocco , Tenofovir/administration & dosage
14.
Front Immunol ; 12: 613070, 2021.
Article in English | MEDLINE | ID: covidwho-1170085

ABSTRACT

Lack of specific antiviral treatment for COVID-19 has resulted in long hospitalizations and high mortality rate. By harnessing the regulatory effects of adenosine on inflammatory mediators, we have instituted a new therapeutic treatment with inhaled adenosine in COVID-19 patients, with the aim of reducing inflammation, the onset of cytokine storm, and therefore to improve prognosis. The use of inhaled adenosine in COVID19 patients has allowed reduction of length of stay, on average 6 days. This result is strengthened by the decrease in SARS-CoV-2 positive days. In treated patients compared to control, a clear improvement in PaO2/FiO2 was observed together with a reduction in inflammation parameters, such as the decrease of CRP level. Furthermore, the efficacy of inhaled exogenous adenosine led to an improvement of the prognosis indices, NLR and PLR. The treatment seems to be safe and modulates the immune system, allowing an effective response against the viral infection progression, reducing length of stay and inflammation parameters.


Subject(s)
Adenosine/pharmacology , COVID-19/drug therapy , Adenosine/therapeutic use , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , COVID-19/diagnostic imaging , COVID-19/physiopathology , Case-Control Studies , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytokine Release Syndrome/physiopathology , Enzyme Inhibitors/administration & dosage , Female , Heparin/administration & dosage , Hospitalization , Humans , Hydroxychloroquine/administration & dosage , Inflammation/drug therapy , Lopinavir/administration & dosage , Male , Middle Aged , Prognosis , Tomography, X-Ray Computed
15.
Viruses ; 13(3)2021 03 18.
Article in English | MEDLINE | ID: covidwho-1167756

ABSTRACT

COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/- hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients' T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.


Subject(s)
COVID-19/drug therapy , Clinical Protocols , Receptors, G-Protein-Coupled/metabolism , SARS-CoV-2/physiology , Adult , Azithromycin/administration & dosage , COVID-19/genetics , COVID-19/metabolism , Dexamethasone/administration & dosage , Female , Humans , Male , Middle Aged , Phenotype , Prospective Studies , Receptors, G-Protein-Coupled/genetics , Retrospective Studies , SARS-CoV-2/genetics , Taste
16.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1137930

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Azithromycin/administration & dosage , Azithromycin/adverse effects , Azithromycin/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , SARS-CoV-2
17.
Cardiovasc Ther ; 2021: 6683098, 2021.
Article in English | MEDLINE | ID: covidwho-1124809

ABSTRACT

BACKGROUND: Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. METHODS: This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. RESULTS: 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4.The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference (462.5 ± 43.1 milliseconds vs. 464.3 ± 59.1 milliseconds; p = 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. CONCLUSIONS: Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.


Subject(s)
Arrhythmias, Cardiac/chemically induced , Azithromycin/adverse effects , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , SARS-CoV-2 , Adult , Aged , Azithromycin/administration & dosage , Electrocardiography/drug effects , Female , Humans , Hydroxychloroquine/administration & dosage , Male , Middle Aged , Retrospective Studies
18.
Turk J Med Sci ; 51(1)2021 02 26.
Article in English | MEDLINE | ID: covidwho-1112807

ABSTRACT

Background/aim: New treatment regimens for COVID-19, which has threatened the world recently, continue to be investigated. Although some of the treatments are promising, it is thought to be early to state that there is definitive treatment. Experiences and treatment protocol studies from treatment centers are still important. The aim of this study is to evaluate factors affecting the treatment process of the first cases followed in our clinic. Materials and methods: The consecutive hospitalized patients with COVID-19 pneumonia were analyzed in this retrospective and cross-sectional study. Data were recorded from the electronic and written files of patients. Results: Eighty-three patients were evaluated. The median age was 50 ± 15 years. Forty-eight (57.8%) patients had one or more comorbidities. The most common comorbidity was hypertension. The most common symptom was cough in 58 patients (70%). The overall mortality was 15%, and 85% of the patients were discharged. The time between the onset of symptoms and hospitalization was statistically significantly longer in deceased patients (P = 0.039). Age, D-Dimer, troponin, CK, CK-MB, ferritin, procalcitonin, and neutrophil to lymphocyte ratio were statistically significantly higher in deceased patients than survivor patients. In subgroup analysis, in the patients receiving azithromycin plus hydroxychloroquine and other antibiotics plus hydroxychloroquine, the duration of hospitalization was shorter in the azithromycin group (P = 0.027). Conclusion: Early treatment and early admission to the hospital can be crucial for the better treatment process. Combination therapy with azithromycin may be preferred in the first treatment choice because it can shorten the length of hospital stay.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hospitalization , Hydroxychloroquine/therapeutic use , Age Factors , Aged , Antiviral Agents/administration & dosage , Azithromycin/administration & dosage , COVID-19/mortality , COVID-19/therapy , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Length of Stay , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Turkey
19.
Pathog Glob Health ; 115(4): 243-249, 2021 06.
Article in English | MEDLINE | ID: covidwho-1109109

ABSTRACT

Data on the clinical features and outcomes of COVID-19 patients from countries with low disease burden are rare. Greece, however, presented a low burden of COVID-19 disease during the first pandemic outbreak. This is a retrospective study of COVID-19 hospitalized patients in Greece. Clinical data were extracted from medical records using univariable and multivariable logistic regression analyses to assess the factors associated with Intensive Care Unit (ICU) admission and in-hospital death. Eighty-five patients were included in this study, 49 (57.7%) male with median (25th-75th) age 60 (49-72) years old. Sixty-one (72%) of them had at least one comorbidity with hypertension being the most common (45,6%). More than half (56%) had severe or critical disease, 20% required ICU care (14% received invasive ventilation) and 10.7% died. Solid tumor (p = 0.021) and NEWS score (p = 0.048), thrombocytopenia (p = 0.036) or involvement of all lung fields in chest x-ray (p = 0.002) on admission were independent risk factors for ICU admission. Immunosuppression (p = 0.032) and thrombocytopenia (p = 0.049) were independent predictors of death. Hospitalized COVID-19 patients in a European country with a low burden of the disease, in which hospital capacities had not been overwhelmed, had lower mortality rate compared to those reported for patients hospitalized in regions with a high burden of the disease.


Subject(s)
COVID-19/pathology , COVID-19/therapy , SARS-CoV-2 , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones , Adult , Aged , Alanine/administration & dosage , Alanine/analogs & derivatives , Alanine/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antimalarials/administration & dosage , Antimalarials/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Azithromycin/administration & dosage , Azithromycin/therapeutic use , COVID-19/epidemiology , Colchicine/administration & dosage , Colchicine/therapeutic use , Drug Therapy, Combination , Female , Greece/epidemiology , Hospitalization , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
20.
PLoS One ; 16(2): e0245048, 2021.
Article in English | MEDLINE | ID: covidwho-1090566

ABSTRACT

Gautret and colleagues reported the results of a non-randomised case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors reported that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. In light of criticisms regarding how patients were excluded from analyses, we reanalysed the original data to interrogate the main claims of the paper. We applied Bayesian statistics to assess the robustness of the original paper's claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy was effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We found that the statistical evidence was highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ~11), to moderate when including patients who deteriorated (BF+0 ~4.35), to anecdotal when excluding untested patients (BF+0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ~0.6). The fact that the patient inclusions and exclusions are not well justified nor adequately reported raises substantial uncertainty about the interpretation of the evidence obtained from the original paper.


Subject(s)
Antiviral Agents/administration & dosage , Azithromycin/administration & dosage , COVID-19/blood , COVID-19/drug therapy , Hydroxychloroquine/administration & dosage , SARS-CoV-2/metabolism , Viral Load , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged
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