Combination Of Hydroxychloroquine Research Articles

Cutaneous lupus tumidus: An unusual unilateral presentation

Lupus tumidus is a rare subtype of chronic cutaneous lupus erythematosus characterized by erythema and bright urticarial erythematous and violaceous lesions on sun-exposed areas that heal without leaving scars. Lupus tumidus follows a benign and intermittent clinical course and is rarely associated with systemic lupus erythematosus. Treatment involves photoprotection, topical corticosteroids, and antimalarials. We report the case of a 42-year-old patient with an atypical unilateral form of lupus tumidus successfully treated with the administration of hydroxychloroquine in combination with photoprotection and tacrolimus.

Coronavirus disease 2019 (COVID-19) and QTc prolongation

IntroductionThe cause-and-effect relationship of QTc prolongation in Coronavirus disease 2019 (COVID-19) patients has not been studied well.ObjectiveWe attempt to better understand the relationship of QTc prolongation in COVID-19 patients in this study.MethodsThis is a retrospective, hospital-based, observational study. All patients with normal baseline QTc interval who were hospitalized with the diagnosis of COVID-19 infection at two hospitals in Ohio, USA were included in this study.ResultsSixty-nine patients had QTc prolongation, and 210 patients continued to have normal QTc during hospitalization. The baseline QTc intervals were comparable in the two groups. Patients with QTc prolongation were older (mean age 67 vs. 60, P 0.003), more likely to have underlying cardiovascular disease (48% versus 26%, P 0.001), ischemic heart disease (29% versus 17%, P 0.026), congestive heart failure with preserved ejection fraction (16% versus 8%, P 0.042), chronic kidney disease (23% versus 10%, P 0.005), and end-stage renal disease (12% versus 1%, P < 0.001). Patients with QTc prolongation were more likely to have received hydroxychloroquine (75% versus 59%, P 0.018), azithromycin (18% vs. 14%, P 0.034), a combination of hydroxychloroquine and azithromycin (29% vs 7%, P < 0.001), more than 1 QT prolonging agents (59% vs. 32%, P < 0.001). Patients who were on angiotensin-converting enzyme inhibitors (ACEi) were less likely to develop QTc prolongation (11% versus 26%, P 0.014). QTc prolongation was not associated with increased ventricular arrhythmias or mortality.ConclusionOlder age, ESRD, underlying cardiovascular disease, potential virus mediated cardiac injury, and drugs like hydroxychloroquine/azithromycin, contribute to QTc prolongation in COVID-19 patients. The role of ACEi in preventing QTc prolongation in COVID-19 patients needs to be studied further.

COVID-19, A New World Order, Vaccine Safety, Effectiveness and Our Human Rights

This inter-disciplinary paper examines the claims in some secular and religious circles around the world that some global elite have the agenda of foisting a New World Order on the global populace and examines the louder claims, since 2020, that COVID-19 is a man-made pandemic aimed at achieving this aim. The globalists are said to be bent on fostering One World Government, One World Economy and One World Religion on the populace. COVID-19, its second or third wave, attendant lockdowns and restrictions on business activities and religious gatherings are said to be pre-mediated and orchestrated behind the scene to achieve what has since been described by the public and private sectors as “the New Normal.” The World Health Organisation (WHO), United Nations, communists, desperate leftist Western politicians, billionaire investors, big pharmaceutical companies, big media organisations and compromised scientists have been fingered as the New World Order desperadoes. It is alleged that the new waves of the pandemic and the recent predictions of yet a worse pandemic by the WHO and by a prominent globalist are a confirmation that they are desperate to further pursue and achieve their New World Order aim. Such measures as lockdowns, use of facemask, COVID-19 vaccines and restrictions on business activities and religious gatherings are said to be among their tools for achieving a great reset, mind control, social conditioning and/or further damage to the physical, psychological and spiritual health of the people. Those measures as well as the still unsettled or controversial safety and effectiveness of the COVID-19 vaccines are analysed in this paper vis-à-vis the relevant fundamental rights of the people. The growing trend of making the COVID-19 vaccination certificate a requisite to travel overseas or access some public places locally is also examined, more so as this is tantamount to making the COVID-19 vaccination mandatory, not necessarily by law but by policy and not necessarily directly but indirectly. This paper examines whether such measures are in harmony with such fundamental rights as the right to the grant of informed consent, right to personal dignity, right to privacy, freedom of movement and freedom of religion guaranteed by both the municipal law of the nations and the international human rights regime. With the use of indirect, circumstantial and documentary types of evidence available, the paper finds out that the alleged plot to maintain “the New Normal” and foist a New World Order is neither baseless nor unreasonable. To overcome the pandemic and beyond the vaccines which the new variants of the disease may defy, the need to allow the COVID-19 responses to wear human face and comply with human rights, use of the combination of hydroxychloroquine, zinc and azythromycin in the early stage of the disease, exposure to sunlight and eating of certain immunity-boosting fruits and vegetables are recommended. The need for African countries to have a deliberate and purposeful homegrown strategies for fighting the COVID-19 pandemic is also recommended, especially now that it has been established that the pandemic has socio-demographic and cultural dimensions.

Subacute cutaneous lupus erythematosus, and positive anti-MDA5 antibody in clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease: A case report and literature review

BackgroundClinically amyopathic dermatomyositis (CADM) is a subtype of DM with characteristic cutaneous lesion with normal creatinine kinase levels. Presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibody is found to be associated with rapidly progressive interstitial lung disease (RP-ILD). Aim of the work: to report a CADM patient with positive anti-MDA5 antibody and RP-ILD with clinical features of systemic lupus erythematosus (SLE) who clinically responded to a combination of cyclophosphamide and other conventional immunosuppressant. Case presentation: A 44-year-old Indian woman presented with classical cutaneous lesions of DM with normal creatinine kinase levels amongst other clinical features. She was initially diagnosed with SLE before developing RP-ILD and a positive MDA5 antibody. Anti-nuclear antibody, anti-dsDNA and anti-Sm antibody were negative. Serum ferritin level was very high (1599 ng/mL) as compared to C-reactive protein (23.4 mg/L). Anti-Ro-52 and anti-PM-Scl 75 were positive. High resolution computed tomography (HRCT) of the lungs revealed features consistent with ILD. Histology of her skin biopsy was consistent with subacute cutaneous lupus erythematosus (SCLE). Her diagnosis was revised to CADM with overlapping SCLE. She responded to a combination of hydroxychloroquine, cyclosporine-A, mycophenolate mofetil, pulse methylprednisolone and pulse cyclophosphamide 750 mg/month for 6 months. Her cutaneous lesions gradually improved with normalization of serum ferritin level. Repeated HRCT showed no further progression of the pulmonary fibrosis. Conclusion: CADM with positive anti-MDA5 antibody associated with RP-ILD is rare with a high mortality rate. Early recognition and prompt treatment with a combination of immuno-suppressant may improve the outcome of this complex disease.

Multidrug treatment for COVID-19.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which began in Wuhan, China in December 2019, has rapidly spread all over the world. The World Health Organization characterized the disease caused by SARS-CoV-2 (COVID-19) as a pandemic in March 2020. In the absence of specific treatments for the virus, treatment options are being examined. Drug repurposing is a process of identifying new therapeutic uses for approved drugs. It is an effective strategy to discover drug molecules with new therapeutic indications. This strategy is time-saving, low-cost, and has a minimal risk of failure. Several existing approved drugs such as chloroquine, hydroxychloroquine, doxycycline, azithromycin, and ivermectin are currently in use because of their efficacy in inhibiting COVID-19. Multidrug therapy, such as a combination of hydroxychloroquine and azithromycin, a combination of doxycycline and ivermectin, or a combination of ivermectin, doxycycline, and azithromycin, has been successfully administered. Multidrug therapy is efficacious because the mechanisms of action of these drugs differ. Moreover, multidrug therapy may prevent the emergence of drug-resistant SARS-CoV-2.

Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19

ObjectivesTo assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. MethodRetrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. ResultsThe active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47–70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. ConclusionsPatients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Homeopathic Intervention in Health Workers with COVID-19: Case Study

First case - Patient, 35 years old, asthmatic, with psychosomatic condition associated with dysgeusia, anosmia and lymphopenia. He was diagnosed with COVID-19 by means of PCR. A combination of Azithromycin, Hydroxychloroquine, Ivermectin and probioticwas performed with bronchodilator and Phosphorus 30 CH. There was complete remission. Second case - Patient, 56 years old, with comorbidities presented dizziness and headache associated with anxiety and fear of dying. Echocardiogram, two computed tomography scans and PCR were performed, which confirmed positive for COVID-19.

Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?

Since the beginning of the SARS-CoV-2(severe acute respiratory syndrome-coronavirus-2) pandemic, a race to develop a vaccine has been initiated, considering the massive and rather significant economic and healthcare hits that this virus has caused. The pathophysiology occurring following COVID-19(coronavirus disease-2019) infection has given hints regarding the supportive and symptomatic treatments to establish for patients, as no specific anti-SARS-CoV-2 is available yet. Patient symptoms vary greatly and range from mild symptoms to severe fatal complications. Supportive treatments include antipyretics, antiviral therapies, different combinations of broad-spectrum antibiotics, hydroxychloroquine and plasma transfusion. Unfortunately, cancer patients are at higher risk of viral infection and more likely to develop serious complications due to their immunocompromised state, the fact that they are already administering multiple medications, as well as combined comorbidity compared to the general population. It may seem impossible to find a drug that possesses both potent antiviral and anticancer effects specifically against COVID-19 infection and its complications and the existing malignancy, respectively. Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings. In this review, we will discuss the multiple effects of TQ specifically against COVID-19, its beneficial effects against COVID-19 pathophysiology and multiple-organ complications, its use as an adjuvant for supportive COVID-19 therapy and cancer therapy, and finally, its anticancer effects.

Application of unsupervised machine learning to identify and characterise hydroxychloroquine misinformation on Twitter

On July 27, 2020, former US President Donald Trump retweeted to his then 84 million Twitter followers an online video, published by the Breitbart website, promoting misinformation about the anti-malarial drug, hydroxychloroquine.1 The video, featuring Dr Stella Immanuel and a group called America's Frontline Doctors, falsely claimed that the combination of hydroxychloroquine, zinc, and azithromycin (an antibiotic) could cure COVID-19.1 Twitter subsequently removed President Trump's retweet, temporarily suspended and removed tweets from his son, Donald Trump Jr, and removed and suspended other accounts sharing this false information as a violation of its COVID-19 misinformation policy.

MEKiAUTO: A phase I/II open-label study of combination therapy with the MEK inhibitor cobimetinib, Immune-checkpoint blockade with atezolizumab, and the AUTOphagy inhibitor hydroxychloroquine in KRAS-mutated advanced malignancies.

TPS450 Background: Pancreatic ductal adenocarcinoma (PDAC) and colorectal carcinoma (CRC) are aggressive diseases which account for the third and second leading causes of cancer-related death, respectively. Limited progress has been made towards effective treatments or cure. K RAS is mutated or amplified in nearly 30% of all cancers, including up to 95% of PDAC and 45% of CRC. Although no successful KRAS directed therapy has been approved to date, data has emerged demonstrating that inhibition of downstream targets of KRAS, namely MEK/ERK, increases autophagic flux in KRAS-mutated tumors. This catabolic process is used by many tumors to maintain viability and recent preclinical studies have shown that combining MEK/ERK and autophagy inhibitors in KRAS-mutated tumors can synergistically suppress cancer cell proliferation. Inhibition of autophagy has demonstrated an increase in antigen presentation which sensitize tumors to immune checkpoint inhibitors. Presented here is a trial-in-progress that will evaluate combination of cobimetinib (MEK inhibitor), atezolizumab (anti-PDL1), and hydroxychloroquine (autophagy inhibitor) in KRAS-mutated advanced malignancies. Methods: This is a phase 1/2 multicenter, open-label study of combination cobimetinib (40-60mg) orally once daily on days 1-21, hydroxychloroquine (600mg) orally twice daily on days 1-28, and atezolizumab 840 mg IV on days 1 and 15 of each 28 day cycle. Patients with histologically confirmed metastatic or unresectable KRAS-mutant adenocarcinoma for which standard curative or meaningful life-prolonging treatment options do not exist or are no longer effective will be enrolled. The primary objective of the phase I portion of this trial, which seeks to enroll 18 patients, is to estimate the maximum tolerated dose (MTD) of these agents using a two-stage time-to-event continual reassessment method (TITE-CRM). The primary objective of the phase II portion of this trial, which seeks to enroll approximately 66-157 patients, is to evaluate the preliminary efficacy of this combination, based on the objective response by 16 weeks. Secondary endpoints include PFS, OS, and safety. Correlative aims include analyses of pre- and on-treatment biopsies with quantitative multiplex immunofluorescence, RNA-sequencing, reverse phase protein array for association with clinical benefit and to determine mechanisms of action/resistance. An interim analysis will be performed at the conclusion of the phase I portion of the study. This study is open with 4 patients enrolled at the time of submission. Clinical trial information: NCT04214418 . This trial is being conducted as part of the imCORE collaboration. Clinical trial information: NCT04214418.

Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2.

Hydroxychloroquine, used to treat malaria and some autoimmune disorders, potently inhibits viral infection of SARS coronavirus (SARS-CoV-1) and SARS-CoV-2 in cell-culture studies. However, human clinical trials of hydroxychloroquine failed to establish its usefulness as treatment for COVID-19. This compound is known to interfere with endosomal acidification necessary to the proteolytic activity of cathepsins. Following receptor binding and endocytosis, cathepsin L can cleave the SARS-CoV-1 and SARS-CoV-2 spike (S) proteins, thereby activating membrane fusion for cell entry. The plasma membrane-associated protease TMPRSS2 can similarly cleave these S proteins and activate viral entry at the cell surface. Here we show that the SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 expression. This difference can be reversed when the furin-cleavage site of the SARS-CoV-2 S protein is ablated or when it is introduced into the SARS-CoV-1 S protein. We also show that hydroxychloroquine efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of hydroxychloroquine and a clinically-tested TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone. These studies identify functional differences between SARS-CoV-1 and -2 entry processes, and provide a mechanistic explanation for the limited in vivo utility of hydroxychloroquine as a treatment for COVID-19.

Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT): An Open-Label, Multicentre, Randomised, Controlled Trial

Background: No antiviral drug has been proven effective for the treatment of patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Favipiravir and hydroxychloroquine were introduced as potential antiviral agents to treat patients with COVID-19.Methods: We conducted an investigator-initiated, multicentre, open-label, randomised trial involving hospitalised patients with confirmed moderate-to-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at nine hospitals in Saudi Arabia. Eligible patients were adult with moderate-to-severe COVID-19 defined as oxygen saturation (Sao2) of 94% or less while breathing ambient air or significant clinical symptoms with chest X-ray changes requiring hospital admission. Randomisation was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The favipiravir loading dose was 1800 mg twice daily on day 1, then 800mg twice daily for nine days and hydroxychloroquine as 400mg twice daily, followed by 200mg twice daily for days 2-5. The primary outcome was time to clinical improvement of two points (from the status at randomisation) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population of patients to assess the primary and secondary endpoints. The trial is registered at ClinicalTrials.gov (NCT04392973).Findings: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 patients to the combination of favipiravir and hydroxychloroquine. The mean age was 52·65 ±13·06 years, 59·4% were men, and 229 (90·15%) required supplemental oxygen at randomisation (with or without non-invasive ventilation). The time to clinical improvement was not significantly different between the two groups; median of 9 days (95%CI: 8, 12) in the treatment group and 7 days (95%CI: 6, 10) in the control group (HR:0·845; 95% CI 0·617 to 1·157; p-value = 0·29). The median duration of hospitalisation among patients discharged on or before day 14 was 9 days (95%CI: 8, 12) for the treatment group and 8 days (95%CI: 7, 10) for the control group with a p-value of 0·42. The 28-day mortality was not significantly different between the two groups, 9 (7·63%) in the treatment group vs 13 (10·32%) in the control group; p-value=0·45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group.Interpretation: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. No new safety signals were recognised for both medications.Trial Registration: This trial is registered with ClinicalTrials.gov, Identifier: NCT04392973, May 19, 2020.Funding Statement: King Abdullah International Medical Research Center, Saudi Arabia.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This trial was approved by the Saudi Food and Drug Authority (SFDA). Ethical approval was obtained from the Institutional Review Board (IRB) at the Ministry of National Guard-Health Affairs (MNGHA) and Ministry of Health (MOH). The trial was overseen by an independent data and safety monitoring board (DSMB). The trial was done according to the Declaration of Helsinki principles and the International Conference on Harmonization-Good Clinical Practice guidelines.

Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis.

As the underlying pathophysiology of progressive forms of multiple sclerosis (MS) remains unclear, current treatment strategies are inadequate. Progressive MS is associated with increased oxidative stress and neuronal damage in lesions along with an extensive representation of activated microglia/macrophages. To target these disease mechanisms, we tested the novel combination of generic medications, hydroxychloroquine (HCQ), and indapamide, in tissue culture and in mice. HCQ is an anti-malarial medication found to inhibit microglial activation and to ameliorate disease activity in experimental autoimmune encephalomyelitis. We are currently completing a phase II trial of HCQ in primary progressive MS ( ClinicalTrials.gov Identifier: NCT02913157). Indapamide is an antihypertensive previously discovered in our laboratory drug screen to be an anti-oxidant. As these medications have a different spectrum of activities on disease mechanisms relevant to progressive MS, their use in combination may be more effective than either alone. We thus sought preclinical data for the effectiveness of this combination. In vitro, indapamide had robust hydroxyl scavenging activity, while HCQ and indapamide alone and in combination protected against iron-induced neuronal killing; TNF-α levels in activated microglia were reduced by either drug alone, without additional combination effects. In mice with a lysolecithin lesion that manifests demyelination and axonal loss in the spinal cord, the combination but not individual treatment of HCQ and indapamide reduced CD68+ microglia/macrophage representation in lesions, attenuated axonal injury, and lowered levels of lipid peroxidation. Our study supports the combination of indapamide and HCQ as a new treatment strategy targeting multiple facets of progressive MS.

SARS CoV-2: Progression and treatment protocols – An overview

COVID-19 pandemic is a global health crisis which has affected citizens of all nations. With more than a million death cases, this outbreak has already had a significant impact on the physical and mental wellbeing of mankind. Considerable amount of research is going on worldwide to find out effective drugs against the virus. Chloroquine phosphate, an antimalarial drug is currently used for the treatment. Studies on the harmful effects of chloroquine is in progress. India is rich in traditional medical practicing such as Ayurveda, Siddha, Unani etc. Ministry of AYUSH is trying to implement an interdisciplinary treatment encompassing all traditional methodologies. It is proven that Ashwagandha rasayana (Withania sominefera L.Dunal) has better functions than hydroxychloroquine. The ayurvedic formulations such as Sudarshan Ghanvati and Sanshamanivati are also used. The combination of hydroxychloroquine (HCQ) and azithromycin is found to cure COVID-19 more effectively. Use of Tocilizumab is found to cure the respiratory disorders associated with COVID. Favilavir turns out to be yet another effective drug. The alternative medical system has effective prophylaxis and is considered better for the treatment of COVID-19. Ayurveda and yoga improve immunity thus maintaining good health. This review throws light on the mode of progression of the virus along with the various treatment protocols adopted to fight COVID-19.

Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study)

Background: Monotherapy with Remdesivir, Favipiravir, Lopinavir-Ritonavir, or Hydroxychloroquine has been evaluated for the treatment of coronavirus disease 2019 (Covid-19). No antiviral agents have yet been shown to be efficacious in terms of viral clearance and reduction of death in moderate to severe Covid-19 in randomized controlled trials.Methods: We conducted an open-label, randomized, controlled trial of various oral combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, high-dose Oseltamivir, and Hydroxychloroquine in adults who were hospitalized with Covid-19. Ninety patients were randomly assigned to receive either 1) high-dose Oseltamivir and Hydroxychloroquine, 2) Lopinavir-Ritonavir and high-dose Oseltamivir, or 3) Darunavir- Ritonavir, high-dose Oseltamivir, and Hydroxychloroquine, compared to thirty voluntary quarantine patients without antiviral agent for mild Covid-19. In addition, two hundred patients were randomly assigned to receive 1) high-dose Oseltamivir and Lopinavir- Ritonavir, 2) Favipiravir and Lopinavir-Ritonavir, 3) high-dose Oseltamivir and Darunavir-Ritonavir, or 4) Favipiravir and Darunavir-Ritonavir and Hydroxychloroquine for moderate to severe Covid-19.Results: A total of 320 patients were enrolled. Those mild Covid-19 patients who received high-dose Oseltamivir and Hydroxychloroquine had a better median time for negative Polymerase Chain Reaction test (PCR) for SARS-CoV-2 than who were voluntarily quarantined without antiviral agent (ITT: 7.5 days (IQR, 4 to 25) versus 11.5 days (IQR, 8 to 18) (P=0.02), LOCF: 7.5 days (IQR, 4.5 to 14) versus 10 days (IQR, 6.5 to18.5) (P=0.01), and PP 8 days (IQR, 4 to 15) versus 9 days (IQR, 6 to17) (P=0.01).For moderate to severe Covid-19 patients, Favipiravir plus Darunavir-Ritonavir plus Hydroxychloroquine had a better median time to negative PCR for SARS-CoV-2 than who received high-dose Oseltamivir plus Lopinavir-Ritonavir (ITT: 10 days (IQR, 5.5 to 13) versus 12 days (IQR, 7 to 15) (P=0.15), LOCF: 10 days (IQR, 5to 13) versus 11 days (IQR, 6 to 15) (P=0.005), and PP 10 days (IQR, 5 to 13) versus 9.5 days (IQR, 5 to15) (P=0.003). In moderate to severe Covid -19, The Kaplan–Meier estimates of mortality were 16.0% with high-dose Oseltamivir plus Lopinavir-Ritonavir compared to 4.0% with Favipiravir plus Darunavir-Ritonavir plus Hydroxychloroquine (P=0.04), and more patient deaths with high-dose Oseltamivir plus Lopinavir-Ritonavir, and Favipiravir plus Lopinavir-Ritonavir, compared to Favipiravir plus Darunavir-Ritonavir plus Hydroxychloroquine ( P=0.04).Conclusions: High-dose Oseltamivir and Hydroxychloroquine were superior to voluntary quarantine without antiviral agent in terms of viral clearance in mild Covid -19. Favipiravir plus Darunavir-Ritonavir plus Hydroxychloroquine were superior to other antiviral agent combinations in terms viral clearance and death in moderate to severe Covid -19. Clinical Trial Registration Details: ClinicalTrials.gov number NCT04303299.Funding Information: Department of Medical Services of Ministry of Public Health, Health System Research Institute of Ministry of Public Health, and The Office of the National Broadcasting and Telecommunications Commission Institute of Thailand. Declaration of Interests: All authors declare no conflicts of interest, no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: The trial protocol was approved by the institutional review board at each site and the centralized institutional review board of the Ethics Committee of the Ministry of Public Health, Thailand. There were independent data and safety monitoring boards. Written informed consent was obtained from each patient or from the patient’s legally authorized representative if the patient was unable to provide consent.

Emergence of Different Autoimmune Diseases Including a Behçet's disease in a Sibling After tick bites. Remarkable cure of Behcet's disease by a Combination of Antibiotics and Hydroxychloroquine

We report therein the onset of three chronic diseases: Behcet's disease, fibromyalgia and rheumatoid arthritis in three sisters after tick bites. Only Behcet's disease was treated in our department. After failure of the initial treatment including colchicine and corticoids, the patient recovered within a prolonged antibiotic therapy time period of 18 months. A 23-year-old female patient was admitted to hospital in the Infectious Diseases Department as she presented with headache, diffuse inflammatory arthromyalgia, abdominal pain and cutaneous folliculitis, and for the umpteenth time for several past years, meningeal syndrome recurrence. The physical examination was unremarkable. The biological test assessment was normal, as were the ophthalmological and cerebral MRI examinations. The patient’s HLA B5 test was negative. The upper digestive fibroscopy shown digestive ulcerations. The diagnosis of Behcet's disease was made on the following: inflammatory arthralgias, digestive ulcerations, folliculitis lesions; recurrent bipolar aphthosis was found at patient’s interview. The patient was given prednisone 0.5 mg/kg/day and colchicine 1 mg/day. The evolution was characterized by an initial improvement of clinical symptoms followed by further iterative recurrence as soon as the corticosteroid doses were reduced. Upon resuming the interview with the patient’ s mother, clinical symptoms began at the age of 9 years old by the occurrence of a voluminous cutaneous erythema following multiple tick bites. One month later the patient presented with subacute lymphocytic meningitis, which was treated as tuberculosis meningitis without relevant bacteriological evidence. On the same day, the patient's two sisters were also bitten by ticks. A few weeks later on, one of them developed osteomyelitis of the tibia, which was operated on. The bacteriological examination result was negative, the histological examination showed non-specific osteomyelitis. Subsequently, she developed various multiple functional complaints that led to the diagnosis of fibromyalgia. Her other sister concomitantly developed seronegative rheumatoid arthritis. The diagnosis of chronic post-tick bite syndrome was suspected despite the negativity of the Lyme serology. The patient significantly improved thanks to high-dose of intravenous penicillin G, despite an initial exacerbation during the first month of treatment, which could be interpreted as confirmation of an infectious process (Jarisch-Herxheimer reaction). Corticosteroids and colchicine were discontinued ; the patient was given doxycycline for a total duration of 18 months. Antibiotic therapy was associated with hydroxychloroquine, the same way as reported for therapy of chronic Q fever and some types of Lyme disease [1]. In 2004, the patient was in complete remission of Behcet's disease. Ten years later, no recurrence has been observed.

COVID19 pandemic is a «pandemic» of antimicrobial therapy

The article presents a critical analysis of antibiotic usage tactics in the treatment of patients with COVID-19 existing in Russian and foreign healthcare, and discusses the possible causes of unjustified antibiotic aggression in this category of patients. The potential negative consequences of the widespread use of antibiotics in patients carrying a new coronavirus infection are analyzed: life-threatening cardiotoxicity in patients with the simultaneous administration of such a «popular» candidate etiologic therapy as a combination of azithromycin and hydroxychloroquine, the potential development of other serious adverse drug reactions (in particular, the development of an antibiotic-associated pseudomembranous colitis, etc.), the expected dramatic increase in the secondary drug resistance of potentially pathogenic microorganisms to widely and often prescribed antibiotics.

The effect of hydroxychloroquine and azithromycin combination treatment on T peak-end, QT, corrected QT intervals and T peak-end/QT and T peak-end/corrected QT ratios in patients with COVID-19

Background: Hydroxychloroquine and azithromycin are frequently used agents in the treatment of COVID-19. We aimed to investigate the effect of hydroxychloroquine and azithromycin combination therapy on repolarization markers of malignant ventricular arrhythmia. Methods: A total of 107 patients, 54 males, and 53 females, who was positive for COVID-19 in terms of the Polymerase Chain Reaction test (PCR) and had typical viral pneumonia on thoracic computed tomography included in the study. These patients were given a combination of 5-day hydroxychloroquine and azithromycin therapy. Electrocardiograms (ECG) were taken before and after this treatment. T peak-end (Tp-e) interval, QT interval, corrected QT (QTc) interval, Tp-e / QT, and Tp-e / QTc values were calculated in the recorded ECGs. Results: Tp-e, QT, QTc intervals, and Tp-e / QT and Tp-e / QTc ratios increased significantly after treatment in both men and women compared to before the treatment. Conclusions: Superficial ECG markers of malignant ventricular arrhythmias were significantly increased in both men and women receiving hydroxychloroquine and azithromycin combination treatment for COVID-19.

Azithromycin and Hydroxychloroquine combination: The future pharmacotherapy of COVID-19

Background: In response to the urgency of increasing death toll due to COVID-19, caused due to SARS CoV-2, various drugs are under clinical trial, as there is no specific drug for its treatment. In an international survey that was recently conducted in which about 7500 physicians participated from all over the world considered that Hydroxychloroquine and Azithromycin were among the most effective ones for the pharmacotherapy of COVID-19. Azithromycin is a macrolide antibiotic whose mechanism of action against COVID-19 is still unknown, but various theories have been postulated. In vitro and in vivo studies have been conducted; however, their results are quite contradictory. Azithromycin is said to increase the risk of QT prolongation in elderly patients and when given in combination with Hydroxychloroquine can increase the risk of Torsade’s de pointes. Therefore, caution has to be paid before prescribing Azithromycin.&#x0D; Conclusion: The mass loss of human lives is regrettable and needs to be stopped as soon as possible. Azithromycin could be the future drug for COVID-19, but such limited data is insufficient to support the drug's safety or efficacy and needs to be reconsidered.

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis.

BackgroundNumerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective.Methods and findingsWe carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527).ConclusionsIn this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.