Abstract
COVID-19, caused by SARS-CoV2, first described in several cases of pneumonia in Wuhan, China in December 2020 has now become a disease that is now present throughout the world. Multiple evidence-based measures and therapeutics are now available for the prevention and treatment of COVID-19. Many therapeutics have been studied and some even continue to be used without compelling evidence to suggest efficacy. Critical to the prevention and successful identification of treatments for COVID-19 has been an appreciation of the multiple stages of this disease. A previous paper published in February 2021 presented a consensus framework of relevant stages of COVID-19 authored by 35 physicians and scientist from multiple disciplines and countries. This framework included: three periods: the period of pre-exposure, the incubation period, the period of detectable viral replication, and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology has served as a framework to guide COVID-19 therapeutics studied or currently in use. We now have a greater understanding of this disease and an update framework with two preclinical periods, the Pre-exposure Period and the Incubation Period, followed by four clinical phases, the Early Viral Upper Respiratory Non-hypoxic Phase, the Early Inflammatory Lower Respiratory Hypoxic Phase, the Secondary Symptomatic Phase and the Late Phase. We also have more evidence regarding the role of improved ventilation, the effectiveness of different masks, several highly effective vaccines, and a few effective antiviral, immunomodulatory, and supportive therapies. As there has been substantial progress made in understanding this disease and the role of various interventions, both nonpharmacological and pharmacological and changes over time in characteristics of SARS-CoV-2 such as a shorter incubation period and different susceptibility to various therapeutics, it is appropriate to put forth this update.