This study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR 5-12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37-0.82) p = 0.003. This association remained significant when saturation of oxygen < 90%, and temperature > 37 °C were added to de model with OR 0.54 (0.36-0.82) p = 0.003, and also when all the other drugs were included as covariates OR 0.42 (0.26-0.66) p < 0.001. The association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.

Chloroquine (CQ) and hydroxychloroquine (HCQ) were both employed in the treatment of COVID-19 in China. Based on unpublished anecdotal positive results in China, CQ is now implemented in China and the Netherlands in moderate to severe COVID-19.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.

Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.

Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10% depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50% maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01µM). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.

Around the world, several dose regimens of hydroxychloroquine have been used for COVID-19 infection treatment, with the objective of identifying a short-term course. Hydroxychloroquine was found to decrease the viral replication in a concentration-dependent manner in vitro and to be more active when added prior to the viral challenge. A loading dose is used to rapidly attain a target drug concentration, which is usually considered as approximately the steady-state concentration. With a loading dose, the minimum effective concentration is reached much more rapidly than when using only the maintenance dose from the start. Thus, we propose a hydroxychloroquine sulphate dose regimen of 400 mg twice daily at Day 1 then 400 mg once daily from Day 2 to Day 10. We aim to evaluate this in the C-20-15 DisCoVeRy trial.

Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March-12th until April-4th 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.

Novel Corona-virus Disease 2019 (nCOVID 19) is caused by a novel virulent corona virus and leads to potentially fatal virulent pneumonia and severe respiratory distress syndrome. It was initially declared as public health emergency if international concern by WHO followed by Pandemic on 12th March 2020. As of 10th April 2020, more than 1.5 million people are affected globally with around 95,000 deaths. Vaccines for this deadly virus are currently under development and many drugs used for other indications have been repurposed and investigated for prophylaxis and treatment of COVID 19. As per SOLIDARITY trial by WHO, some of the most promising candidates include chloroquine phosphate and hydroxychloroquine which are anti-malarial medications, Remdesivir, Lopinavir-Ritonavir combination with or without interferon which are anti-HIV drugs and convalescent plasma therapy. The current evidence of efficacy and ongoing research has been elaborated in the article. Besides, there has been evidence regarding inflammatory pathogenesis of this virus leading to cytokine storm in susceptible individuals. Thus, anti-proinflammatory cytokine drugs like Anakinra and Tocilizumab are undergoing multiple trials and some results are encouraging. Similarly, use of anti-inflammatory cytokines like IL-37 and IL-38 is hypothesised to be useful and is under research. The situation is still evolving and hence there is yet no definitive therapy but to conclude the use of repurposed medications can be a boon till a definitive therapy and vaccines are developed.

The widespread coronavirus SARS-CoV-2 has already infected over 4 million people worldwide, with a death toll over 280,000. Current treatment of COVID-19 patients relies mainly on antiviral drugs lopinavir/ritonavir, arbidol, and remdesivir, the anti-malarial drugs hydroxychloroquine and chloroquine, and traditional Chinese medicine. There are over 2118 on-going clinical trials underway, but to date none of these drugs have consistently proven effective. Cathepsin L (CatL) is an endosomal cysteine protease. It mediates the cleavage of the S1 subunit of the coronavirus surface spike glycoprotein. This cleavage is necessary for coronavirus entry into human host cells, virus and host cell endosome membrane fusion, and viral RNA release for next round of replication. Here we summarize data regarding seven CatL-selective inhibitors that block coronavirus entry into cultured host cells and provide a mechanism to block SARS-CoV-2 infection in humans. Given the rapid growth of the SARS-CoV-2-positive population worldwide, ready-to-use CatL inhibitors should be explored as a treatment option. We identify ten US FDA-approved drugs that have CatL inhibitory activity. We provide evidence that supports the combined use of serine protease and CatL inhibitors as a possibly safer and more effective therapy than other available therapeutics to block coronavirus host cell entry and intracellular replication, without compromising the immune system.

The risk of COVID-19 among people living with HIV (PLWH) is largely unknown and there have been very few reported cases in the literature. We report a case series of five PLWH with COVID-19. We identified all patients with a diagnosis of HIV who tested positive for SARS-CoV-2 at University of Chicago Medicine between March 1, 2020, and April 7, 2020. We retrospectively collected data regarding demographics, comorbidities, medications, laboratory test results, radiology results, and outcomes associated with COVID-19. All five PLWH with COVID-19 were African American; 80% (4/5) were cisgender females. The mean age of patients was 48 years old (range 38-53). The majority of patients presented with cough, fever, and shortness of breath. Three patients had diarrhea. One patient presented with predominantly cardiac symptoms. All were taking antiretroviral therapy (ART) with CD4 count >200 cells/mm3 and suppressed HIV viral loads at the time of COVID-19 diagnosis. All five patients were hospitalized, two required supplemental oxygen, and none required mechanical ventilation. Four patients were treated with azithromycin and a cephalosporin and two were also treated with hydroxychloroquine. The median length of stay was 3 days (range 2-7). All patients recovered. More research is needed to understand the risks of COVID-19 among PLWH and the impact of ART on outcomes for patients with COVID-19.