Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and antiinflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES 1. HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. 2. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. 3. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.

Francisella tularensis is disseminated in nature by biting arthropods such as mosquitoes. The relationship between mosquitoes and F. tularensis in nature is highly ambiguous, due in part to the fact that mosquitoes have caused significant tularemia outbreaks despite being classified as a mechanical vector of F. tularensis. One possible explanation for mosquitoes being a prominent, yet mechanical vector is that these insects feed on flower nectar between blood meals, allowing for transmission of F. tularensis between mosquitoes. Here, we aimed to assess whether F. tularensis could survive in flower nectar. Moreover, we examined if mosquitoes could interact with or ingest and transmit F. tularensis from one source of nectar to another. F. tularensis exhibited robust survivability in flower nectar with concentrations of viable bacteria remaining consistent with the rich growth medium. Furthermore, F. tularensis was able to survive (albeit to a lesser extent) in 30% sucrose (a nectar surrogate) over a period of time consistent with that of a typical flower bloom. Although we observed diminished bacterial survival in the nectar surrogate, mosquitoes that fed on this material became colonized with F. tularensis. Finally, colonized mosquitoes were capable of transferring F. tularensis to a sterile nectar surrogate. These data suggest that flower nectar may be capable of serving as a temporary source of F. tularensis that could contribute to the amplification of outbreaks. Mosquitoes that feed on an infected mammalian host and subsequently feed on flower nectar could deposit some F. tularensis bacteria into the nectar in the process. Mosquitoes subsequently feeding on this nectar source could potentially become colonized by F. tularensis. Thus, the possibility exists that flower nectar may allow for vector-vector transmission of F. tularensis.

Introduction Colchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate “cytokine storm” and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies. Objective To evaluate the role of colchicine on morbidity and mortality in COVID-19 patients. Methods This systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated for risk of bias (ROB) using the Revised Cochrane ROB tool for randomised controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for case-control and cohort studies. Results Four RCTs and four observational studies were included in the final analysis. One study evaluated colchicine in outpatients, while all others evaluated inpatient use of colchicine. There was significant variability in treatment protocols for colchicine and standard of care in all studies. A statistically significant decrease in all-cause mortality was observed in three observational studies. The risk of mechanical ventilation was significantly reduced only in one observational study. Length of hospitalisation was significantly reduced in two RCTs. Risk for hospitalisation was not significantly decreased in the study evaluating colchicine in outpatients. Very few studies had low risk of bias. Conclusion Based on the available data, colchicine shall not be recommended to treat COVID-19. Further high-quality and multi-center RCTs are required to assess the meaningful impact of this drug in COVID-19. KEY MESSAGES Colchicine, an anti-inflammatory agent has demonstrated anti-viral properties in in-vitro studies by degrading the microtubules, as well as by inhibiting the production of pro-inflammatory cytokines. Colchicine has been studied as a potential therapeutic option for COVID-19, with variable results. Until further research can establish the efficacy of colchicine in COVID-19, the use of colchicine in COVID-19 shall be restricted to clinical trials.

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