TREATMENT STRATEGIES

Introduction

Most people infected with the SARS-CoV-2 virus develop mild or moderate symptoms of the COVID-19 disease and do not require a special treatment. However, many people develop severe symptoms requiring hospital treatment and in a considerable number of cases COVID-19 leads to death1. Despite COVID-19’s relatively recent emergence, specific vaccines and some targeted antivirals are already available. Other symptomatic therapies display some efficacy, as well2,3,4. Due to the ongoing pandemic character of COVID-195, emerging variants of concern6, the persistent health system strain and the economic burden of the infection7,8, it is critical to identify new drug treatment options with improved efficacy and safety profile.

Vaccines

A high-priority pursuit by scientists from all over the world led to an unprecedentedly fast development of vaccine formulations. Proved to prevent infection and severe disease, COVID-19 vaccines based on diverse technology platforms are available for application for the general public4,9. As of March 3, 2022, 35 vaccines are approved around the world, of which 10 have been granted Emergency Use Listing by the World Health Organization. Even more formulations are in development4.

Antivirals

Early stages of infection can be targeted by several types of antiviral drugs3. Small molecules and antibodies represent the two most prominent classes of anti-COVID-19 drugs. Various approaches for drug development have enabled the identification of the compounds listed in our database. Rational repurposing of existing broad-spectrum antivirals or pan-coronaviral antibodies is a widely adopted strategy. Off-label treatment was used especially in the early period of COVID-19 pandemics. In another approach, a chemical or an antibody library is screened for antiviral efficacy. This process reduces the set of candidate molecules. Lastly, researchers computationally model structures to inhibit key steps in viral infection. Within the next steps of drug development, promising lead compounds can be further studied or optimized. Naturally occurring molecules, which are often constituents of traditional medicine formulations, are analysed this way, as well.

COVID-19-convalescent patients are a valuable resource of information and even biological material used in the development of antiviral therapies. Many antibodies used clinically to neutralize SARS-CoV-2 were identified in sera of convalescent patients. Convalescent plasma transfusion is no longer recommended for the treatment of COVID-19 (outside clinical trials), however2.

Other treatments

Some treatment strategies alleviate life-threatening symptoms without necessarily having an impact on the viral life cycle. The use of a few of these is supported by a substantial amount of scientific evidence and is recommended by various authorities2. Non-antiviral treatment often targets COVID-19-related hyperinflammation or excessive blood clotting. Our database also provides information on novel cell-based approaches for the treatment of COVID-19. These include the administration of (modified) T cells activated by SARS-CoV-2 antigens, which are toxic to the infected cells, or application of mesenchymal stem cell products alleviating inflammation and boosting tissue repair.

Even the state-of-the-art treatment and prevention measures fail to prevent the development of severe symptoms or side effects in certain cases. Supportive care, including high flow oxygen, invasive mechanical ventilation or even extracorporeal membrane oxygenation might be required to prevent hypoxia. Broad spectrum antibiotics can be applied to tackle secondary bacterial infections. Such conditions, even if successfully managed, present a serious strain for the individual and the healthcare system. It is therefore of high interest to develop safe and yet more potent therapies which would retain their efficacy even against the emerging SARS-CoV-2 variants of concern.

References