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At present, no proven effective treatment is available for COVID-19 infection, caused by the SARS-CoV-2 virus, while the available data are changing rapidly depending on the results of ongoing clinical trials.

Nevertheless, until new drugs and vaccines are discovered, chloroquine phosphate or its derivative, hydroxychloroquine, is frequently used in hospitals in combination with azithromycin and/or antimicrobial therapy.

These regimens aim to manage the febrile response as well as reduce the viral load.

Chloroquine and hydroxychloroquine, although antimalarial drugs, have also been used in the past for the treatment of various rheumatic diseases, such as lupus erythematosus and rheumatoid arthritis.

These drugs exert their antiviral activity within a short period after administration and induce immunological modulation, as they reduce cytokine production.

Although the optimal dosage of hydroxychloroquine, as well as the required duration of administration for the treatment of COVID-19, have not been determined, various clinical trials (NCT04261517, NCT04307693, Yao 2020) have used different hydroxychloroquine dosage regimens.

The PATCH Trial (a randomized study involving 400 participants), which is currently underway, compares different hydroxychloroquine dosage regimens in terms of their effectiveness against COVID-19.

The National Public Health Organization (EODY) has developed a therapeutic algorithm for the management of patients with COVID-19 infection in the community and in hospital settings.

For patients with renal / hepatic impairment, there are no specific dosage recommendations, other than the recommendation to “use with caution”.

Particular caution is required with the use of chloroquine phosphate, hydroxychloroquine and azithromycin because of their cardiotoxicity and QT prolongation.

For this reason, patients with chronic conditions, e.g. renal failure, liver disease, epilepsy, Myasthenia Gravis, or patients receiving medications containing active substances that are incompatible with these drugs, require close monitoring, as serious arrhythmias may occur.

Other risk factors that may cause arrhythmias (e.g. torsades de pointes) include hypomagnesemia, hypokalemia, bradycardia, heart failure, advanced age, as well as QT> 450-500 msec.

In addition, long-term treatment or high doses of chloroquine / hydroxychloroquine may lead to retinal damage. It is also important that the treating physician checks for possible G6PD enzyme deficiency during administration.

In recent weeks, the administration of colchicine has also been proposed for COVID-19 patients with concomitant cardiovascular disease. This drug has been used for many years for conditions such as gout, Mediterranean fever and pericarditis, as, among its other properties, it also has anti-inflammatory activity.

GRECCO-19 is a randomized clinical trial that began in Greece and aims to investigate the role of colchicine in patients with COVID-19 infection and its potential to prevent or treat cardiovascular complications.

Another important double-blind, multicenter, randomized clinical trial currently underway, in which Greece is also participating (Adaptive COVID-19 Treatment Trial, NCT04280705), concerns remdesivir, an experimental drug that was initially tested against the Ebola virus and is considered a promising treatment for the SARS-CoV-2 coronavirus.

The aim of this study is to evaluate this drug in hospitalized patients with severe COVID-19 symptoms, as well as to determine the viral load in affected patients. Other clinical trials are also underway to evaluate the safety and efficacy of remdesivir (NCT04292730, NCT04292899).

Other treatments under investigation in patients with severe respiratory distress, concerning clinical deterioration and hyperinflammatory syndrome include monoclonal antibodies such as tocilizumab (an IL-6 antagonist) and leronlimab (a CCR5 receptor inhibitor), which have immunomodulatory activity, as well as Janus kinase (JAK) inhibitors. The human IL-1 receptor antagonist, anakinra, constitutes an alternative treatment to tocilizumab, as it has a shorter half-life and therefore fewer side effects.

The combination of lopinavir / ritonavir, although initially appearing sufficiently effective in clinical practice, ultimately proved not to be useful in combating COVID-19 (it was studied by Chinese scientists in a randomized trial, ChiCTR2000029308).

The combination of darunavir/cobicistat is also under investigation (NCT04304053), although at present there is insufficient clinical evidence regarding its activity against the SARS-CoV-2 virus.

Finally, favipiravir, an antiviral drug developed in Japan, was recently approved by the National Medical Products Administration of China as an investigational treatment for COVID-19 because it showed encouraging results in Chinese clinical trials. Specifically, in clinical trials conducted in Wuhan and Shenzhen, China, favipiravir was observed to accelerate the recovery of hospitalized patients and improve lung function.

At present, this drug is not available in Europe, as approval by the EMA and subsequently by the EOF is required.

In conclusion, the therapeutic regimens used to treat COVID-19, based on the most recent protocols, consist of known drugs with activity against other diseases. However, the urgent need to address this deadly pandemic literally necessitates the use of existing drugs, at least until new drugs and vaccines with specific activity against this particular virus are discovered.

Four randomized studies have already begun internationally to identify effective drugs, with the first involving remdesivir (ACTT), two involving the combination of lopinavir – ritonavir (CATCO, REMAP-CAP), and the fourth involving remdesivir, lopinavir – ritonavir, with or without interferon and hydroxychloroquine (DisCoVeRy).

The EMA is in contact with those responsible for the development of twelve potential COVID-19 vaccines, and two vaccines have already entered Phase I clinical trials.

Vaccine development timelines are difficult to predict, but it is estimated that at least one year will be required before a vaccine is ready for approval and available in sufficient quantities to enable widespread use.