The COVID-19 pandemic is currently responsible for over 526 million infections and over 6.3 million deaths. As a new disease, the number of papers on the subject is extensive, motivating considerable heterogeneity in its approach. Despite some medicines having sound evidence of benefit, new interventions and strategies continue to be proposed, and some still lack scientific evidence, which hinders a uniform and consensual approach. This article aims to standardize healthcare to adult patients with moderate-to-critical COVID-19, from the emergency department to hospitalization, either in a general ward or in level 2 or level 3 intensive care units, based on the best and most updated scientific evidence available. This protocol presents recommendations for the stratification of adult patients with COVID-19 disease, adequate workup at admission and during hospitalization, inpatient treatment criteria, general treatment measures, pharmacological treatment, management of complications such as organizing pneumonia and bacterial superinfection, thromboprophylaxis, special considerations on pregnancy and breastfeeding and possible future therapies.