The role of spike protein entry inhibitors in the treatment of mild-to-moderate covid-19 in nonhospitalized patients

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a deadly pneumonia caused by an enveloped, single-stranded positive-sense RNA (+ssRNA), 29.881 kb betacoronavirus, belonging to the coronaviridae 2B lineage.1 Clinically, about 80% of the patients with Covid-19 develop asymptomatic or mild illness, usually within 12 days, whereas 15-30% progress to severe disease with acute respiratory distress syndrome (ARDS), hypoxaemic respiratory failure, multi-organ failure (MOF), and death.2 Patients with mild or moderate SARD-CoV-2 are individuals who have respiratory symptoms but are not in respiratory distress, and have no multiorgan dysfunction, or other complications of Covid-19 that require hospitalization.3 These patients can easily be treated as outpatients under quarantine. However, these individuals can progress to severe SARS-CoV-2 requiring hospitalization, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) if they are not treated. SARS-CoV-2 gain entry into host cells via its spike protein (S) which attaches to its cognitive receptor angiotensin-converting enzyme 2 (ACE2). Spike protein entry inhibitors (SPIs), such as bamlanivimab-etesevimab, casirivimab plus imdevimab, sotrovimab, and bebtelovimab have the potential to inhibit endocytosis, and replication of SARS-CoV-2 in host cells. However, the evolving mutations of SARS-CoV-2 has led to the emergency of new variants, such as Delta Plus, and Omicron BA.1, BA.1617, and BA.2 which are resistant to bamlanivimab-etesevimab, and casirivimab plus imdevimab. Henceforth, these doublet biologics are no longer used in many countries, including the USA. Sotrovimab and bebtelovimab are potent to most variants of concern, and BA.1, they are recommended for the treatment of non-hospitalized patients with Covid-19 in countries with high prevalence of Omicron BA. 1. However, sotrovimab has lost activity against BA.2, therefore, it is no longer recommended in all the states and territories in the USA. Currently, only bebtelovimab is the recommend SPI for the treatment of non-hospitalized patients in the USA.