Experimental Pharmacotherapy for COVID-19: The Latest Advances

Abstract

The coronavirus infectious disease-2019 (COVID-19) has overwhelmed like a shock wave in a completely unprepared world. Despite coronavirus infections were involved in previous epidemic outbreaks, no antiviral agent was developed for specific treatment. As a consequence, since the beginning of this pandemic, both repositioned and experimental drugs were used to treat the infected patients without evidence of clinical efficacy. Just based on experience coming from the use of antiviral agents to treat other viruses (eg, lopinavir/ritonavir, remdesivir) and supposed antiviral or immunomodulatory activities of drugs with no approved antiviral indications (eg hydroxychloroquine, tocilizumab), clinicians have faced the ongoing pandemic. Currently, after about 9 months from the COVID-19 spread, there is still no antiviral agent capable of ensuring the cure of this syndrome. Clinical trials are beginning to confirm the benefits of some drugs, while for other compounds, efficacy and safety have not yet been confirmed. Randomized clinical trials (RCT) have denied or downsized the beneficial effects attributed to certain molecules, such as aminoquinolines, largely used in clinical practice at the beginning of COVID-19 spread. Conversely, at the same time, they have provided evidence for unexpected effectiveness of other agents that have been underutilized, such as steroids, which were not used in SARS treatment because of the threatened effect on viral replication. Evidence deriving from pathologic studies have demonstrated that the prothrombotic effects of SARS-CoV-2 can be prevented by heparin prophylaxis, underlining the need for personalized treatment for patients with severe disease. The main aim of this review is to synthesize the available information and evidence on both repositioned and experimental drugs for the treatment of COVID-19, focusing on the need to exercise caution on the use of unproven medical therapies.

PD-L1 Dysregulation in COVID-19 Patients

“…COVID-19 manifests a spectrum of signs and symptoms from mild illness to acute pneumonia. Unfortunately, a considerable percentage of patients rapidly worse to acute respiratory distress syndrome (ARDS) requiring intensive care ( 1 , 2 ).…”

The role of high-dose steroid therapy in Covid-19 pneumonia

“…Today most deaths due to COVID-19 are caused by respiratory failure (stage 3) from cytokine storms and there is no effective and specific treatment is not yet for all the stages. A limited effect on the early stages (stage 1-2) with antiviral agents such as remdesivir, favipiravir, darunavir, lopinavir/ritonavir has been shown besides with the randomized controlled studies still continue on (10). Stage 3 is related to cytokine release syndrome which demonstrates high levels of interleukins (IL) (IL-1 β, IL-1RA, IL-6, IL-8, IL-9, IL-10, IL-17), macrophage inflammatory protein, vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-α), and other pro-inflammatory chemokines, cytokines, and signaling proteins (11).…”

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics

“…Studies of the ACTT-1 trial (NCT04280705) showed that Remdesivir shortens the recovery time (median 11 days compared to 15 days in the placebo group) (52, 53) of ventilated COVID-19 patients and was granted EUA for use in severe COVID-19 patients in the US and the EU. Considering the results of other clinical studies, FDA gave full approval of Remdesivir for COVID-19 treatment a few month later in the US (52)(53)(54). However, the WHO SOLIDARITY study reported that Remdesivir had little or no effect on the length of hospitalization, transition to ventilation, or overall mortality and recommended against the use of it for COVID-19 treatment (55).…”