Hydroxychloroquine and Azithromycin Combination Could Be Lethal to Covid-19 Patients

Abstract

With the advent of COVID-19 or the novel coronavirus and the pandemic outbreak, scientists around the globe are endeavoured to discover therapeutically efficacious drugs against the disease. Initial small-scale trials and studies have demonstrated the possible impact of the antimalarial drug hydroxychloroquine (HCQ) and antibiotic azithromycin (AZM) unaided or together can be productive in the management of coronavirus disease. However, the latest research stretches on serious implications such as irregularities in the heart electrical impulses, polymorphic ventricular tachycardia including torsade de pointes (TdP), and long QT syndrome (LQTS) associated with the use of these drugs. In the worst-case scenario, higher doses have been lethal to the patients treated with these drugs as per recent reports. To have a closer look over the safety considerations, this review is focused on the latest updates, research, and findings of the impact of HCQ and AZM in COVID-19 affected individuals with an emphasis on the pre-existing cardiovascular risk factors. Besides, this review also briefly compiles some of the major clinical trial case reports which can present evident data related to the clinical application of both the drugs along with its abnormal effect on cardiac rhythm. RezumatO dată cu apariția COVID-19 și a focarului de pandemie, oamenii de știință se străduiesc să descopere medicamente eficiente împotriva bolii. Studiile inițiale și studiile la scară mică au arătat efectul hidroxiclorochinei (HCQ) și azitromicinei (AZM), singure sau în combinație, în tratamentul infecției cu SARS-CoV-2. Cu toate acestea, cele mai recente cercetări se referă la implicații grave, cum ar fi dezechilibre în impulsurile electrice ale inimii, tahicardie ventriculară polimorfă, inclusiv torsada vârfurilor și prelungirea intervalului QT. Această lucrare se axează pe cele mai recente actualizări, cercetări și constatări ale impactului hidroxiclorochinei și azitromicinei la pacienții cu COVID-19, cu accent pe factorii de risc cardiovasculari preexistenți. În plus, lucrarea sumarizează câteva dintre raportările majore ale studiilor clinice care prezintă date concrete în contextul utilizării acestor medicamente.

Potential Therapeutic Options for COVID-19: Current Status, Challenges, and Future Perspectives

“…It is noted that the action of this drug is expanded significantly with a wide range of Gram-positive organisms, particularly Haemophilus Influenza -related with respiratory tract infections ( Dunn and Barradell, 1996 ; Călina et al., 2017 ; Ungureanu et al., 2017 ). Most lately, azithromycin (500 mg) oral tablet has experimented as a prophylactic treatment following a randomized, single-blinded, placebo-controlled phase 2 trial (NCT04369365) in cancer patients (n = 200) undergoing antineoplastic therapy during the COVID-19 pandemic ( Tran et al., 2019 ; Mohammad et al., 2020 ; Clinicaltrials.Gov, 2020bh ).…”

Pathophysiology of COVID-19 and its potential therapeutics

“…48 Azithromycin, a broad spectrum macrolide antibiotic effective against various respiratory pathogens is also being experimented as a prophylactic treatment in cancer patients undergoing chemotherapy. 49,50 Doxycycline, a second generation tetracycline, has been reported to act as a potent inhibitor of dengue viral replication and diminish serum IL-6 levels at the time of infection. 51 It is under phase 3 study to evaluate its efficacy in severe COVID-19 patients.…”

Treatment With Hydroxychloroquine in Patients With Covid-19. Experience of a Neurology Department

“…On the other hand, it was also detected that hydroxychloroquine might halt plasmacytoid dendritic cell maturation and inhibit the conversion of perforin to its active state, subsequently diminishing the toxicity of natural killer cells. Due to endosomal pH alteration, hydroxychloroquine may eventually interfere with the selection of naïve antigen specific B cells, in this way decreasing the affinity maturation of previously involved clones and thus reducing the production of neutralizing antibodies [22,25]. It has been also noticed that chloroquine might inhibit T-cell proliferation by diminishing the IL-2 production [14] and responsiveness and since IL-2 appears to have a decisive part in Th-2 cell differentiation [16], which might act via abolishing inflammation in SARS-CoV2 infection, one might speculate that in fact these drugs could have a negative impact on the immune response against the virus [12].…”