Editorial: Drug Repurposing for COVID-19 Therapy

Barcelona Biomedical Research Park (PRBB), University Pompeu Fabra, Barcelona, Spain, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain, Clinical Pharmacology Unit/Regional Pharmacovigilance Centre, University Hospital of Catania, Catania, Italy, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy, Centre for Research and Consultancy in HTA and Drug Regulatory Affairs (CERD), University of Catania, Catania, Italy


Drug Repurposing for COVID-19 Therapy
The rapid emergence in December 2019 of cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in China rapidly expanded to multiple countries leading to a pandemic situation in March 2020 and dramatic changes worldwide. COVID-19 immediately had major health consequences due to its severity, mainly in the population at risk, and to the lack of effective treatment to ameliorate the prognosis of the disease. Indeed, SARS-CoV-2 infection causes respiratory symptoms that range from mild forms to more serious ones, causing pneumonia, and multi-organ damage. Moreover, the sudden appearance and rapid propagation of COVID-19 produced an unexpected socio-economic crisis and major efforts have been devoted by multiple professionals to try to minimize the burden generated by this disease.
From the beginning of the pandemic, the scientific community made enormous efforts in order to rapidly develop vaccines that prevent the propagation of the SARS-CoV-2 infection. These research efforts result into an unprecedented success by reaching to the development of several efficient and secure vaccines in a time record in the history of vaccine development. Standard adenoviral approaches and novel mRNA strategies were used to successfully develop these novel vaccines and now there are still two enormous challenges opened for reaching an efficient vaccination campaign: the rapid distribution of these vaccines worldwide and the needs to raise awareness in the population about the safety and essential requirement of these vaccines to fight the COVID-19 pandemic.
Simultaneously to the vaccine development, multiple scientific groups concentrate their activities in an attempt to identify effective and safe pharmacological treatments against COVID-19. Indeed, both vaccines and pharmacological treatments are complementary to avoid the transmission of the viral infection and to prevent the severe consequences of the disease. In spite of the progress in the vaccination campaigns, pharmacological interventions are still needed to treat patients suffering the disease and to palliate the long-term consequences of the persistent forms of COVID-19. The efforts of the research were mainly devoted to the identification of compounds with anti-SARS-CoV-2 activity as well as drugs able to minimize the dramatic consequences of the exaggerated immune response leading to the most severe forms of the disease. However, due to the urgent need for a rapid development of pharmacological strategies, there was no time to start the long process required to develop novel compounds for such purposes. Therefore, the dominant research strategy was repurposing drugs for COVID-19 that were previously developed for other therapeutic purposes.
Research efforts of the scientific community were quickly translated in a large number of publications, including those devoted to the development of pharmacological approaches. The large majority of these publications met the rigorous criteria required for any prestigious scientific article.
However, some few exceptions led to sound retractions that were largely commented and discussed by the general media, which emphasized once again the needs of the well-known rigorous peer review process in any scientific publication.
In order to collect the best evidence about drugs repurposed for COVID-19, we proposed and coordinated since May 2020 this Research Topic.
Several articles published in this Research Topic are devoted to antimalarial drugs that initially raised high expectancy due to their potential anti-SARS-CoV-2 activity. This initial interest was mainly focused on chloroquine and hydroxychloroquine, although the important risks associated to these treatments prompt overcome their potential benefits, as it is discussed and well- It has been demonstrated that an exacerbated inflammatory and immunological response to SARS-CoV-2 induces the most severe cases of the disease. The excessive production of proinflammatory cytokines may lead to a cytokine storm syndrome that aggravates the respiratory distress. Several drugs have also been repurposed in order to mitigate the dramatic consequences of this cytokine storm syndrome. The efficient repurposing of a particularly potent glucocorticoid drug, dexamethasone, that has already well-demonstrated the efficacy for such a purpose is , have also been proposed as potential therapies for the severe COVID-19 cases associated to this cytokine storm. Due to the high prevalence of thromboembolic complications that often appear mainly in the severe forms of COVID-19, the use of anticoagulants including heparin has been proposed and the current evidence for addressing this novel approach is also discussed in this Research Topic (Gozzo et al.; Drago et al.).
Multiple other cellular and molecular pathways have also been suggested as additional possible targets for the repurposing of drugs for COVID-19 therapy, as discussed in other articles Finally, several articles highlighted how the repurposing process, as well as the approval of COVID-19 therapy in general, has represented an enormous regulatory challenge which forced the regulatory systems to rapidly adapt their rules to the pandemic (Gozzo et al.; Sultana et al.; Andrade et al.).
We believe that drug reuse has been an important attempt as an emergency strategy in a serious situation that could recur in the future. We cannot rule out that similar pandemics still threaten people as long as globalization affects all human activities. Therefore, we must consider the experience of drug reuse for COVID-19 as extremely helpful in enriching our experience in seeking therapeutic solutions when serious global health hazards occur.