the safety and efficacy of potential treatments for COVID-19. However, the Panel also realizes that many patients and providers who cannot access these potential treatments via clinical trials still seek guidance about whether to use them. New data on the treatment of COVID-19 are emerging at a rapid pace. Some of these data are being published in peer-reviewed journals, but some can be found in manuscripts that have not yet been peer reviewed or in press releases. The Panel continuously reviews the available data and assesses their scientific rigor and validity. These sources of data and the clinical experiences of the Panel members are used to determine whether new recommendations or changes to the current recommendations are warranted. Finally, it is important to stress that the rated treatment recommendations in these Guidelines should not be considered mandates. The choice of what to do or not to do for an individual patient is ultimately decided by the patient and their provider. Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 11 Overview of COVID-19 Last Updated: April 29, 2022 Epidemiology The COVID-19 pandemic has exploded since cases were first reported in China in December 2019. As of April 15, 2022, more than 503 million cases of COVID-19—caused by SARS-CoV-2 infection—have been reported globally, including more than 6.2 million deaths.1 Individuals of all ages are at risk for SARS-CoV-2 infection and severe disease. However, the probability of serious COVID-19 disease is higher in people aged ≥60 years, those living in a nursing home or long-term care facility, and those with chronic medical conditions. In an analysis of more than 1.3 million laboratory-confirmed cases of COVID-19 that were reported in the United States between January and May 2020, 14% of patients required hospitalization, 2% were admitted to the intensive care unit, and 5% died.2 The percentage of patients who died was 12 times higher among those with reported medical conditions (19.5%) than among those without medical conditions (1.6%), and the percentage of patients who were hospitalized was 6 times higher among those with reported medical conditions (45.4%) than among those without medical conditions (7.6%). Mortality was highest in patients aged >70 years, regardless of the presence of chronic medical conditions. Data on comorbid health conditions among patients with COVID-19 indicate that 32% had cardiovascular disease, 30% had diabetes, and 18% had chronic lung disease. Other conditions that may lead to a high risk for severe COVID-19 include cancer, kidney disease, liver disease (especially in patients with cirrhosis), obesity, sickle cell disease, and other immunocompromising conditions. Transplant recipients and pregnant people are also at a higher risk of severe COVID-19.3-10 Data from the United States suggest that racial and ethnic minorities experience higher rates of COVID-19, subsequent hospitalization, and death.11-15 However, surveillance data that include race and ethnicity are not available for most reported cases of COVID-19 in the United States.4,16 Factors that contribute to the increased burden of COVID-19 in these populations may include over-representation in work environments that confer higher risks of exposure to COVID-19, economic inequality (which limits people’s ability to protect themselves against COVID-19 exposure), neighborhood disadvantage,17 and a lack of access to health care.16 Structural inequalities in society contribute to health disparities for racial and ethnic minority groups, including higher rates of comorbid conditions (e.g., cardiac disease, diabetes, hypertension, obesity, pulmonary diseases), which further increase the risk of developing severe COVID-19.15 SARS-CoV-2 Variants Like other RNA viruses, SARS-CoV-2 is constantly evolving through random mutations. New mutations can potentially increase or decrease infectiousness and virulence. In addition, mutations can increase the virus’ ability to evade adaptive immune responses from past SARS-CoV-2 infection or vaccination. This viral evolution may increase the risk of reinfection or decrease the efficacy of vaccines.18 There is evidence that some SARS-CoV-2 variants have reduced susceptibility to plasma from people who were previously infected or immunized, as well as to certain monoclonal antibodies (mAbs) that are being considered for prevention and treatment.19-21 Since December 2020, the World Health Organization (WHO) has assigned Greek letter designations to several identified variants. A SARS-CoV-2 variant designated as a variant of concern (VOC) displays certain characteristics, such as increased transmissibility or virulence. In addition, vaccines and therapeutics may have decreased effectiveness against VOCs, and the mutations found in these variants Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 12 may interfere with the targets of diagnostic tests. The variant of interest (VOI) designation has been used for important variants that are not fully characterized; however, organizations do not use the same variant designations, and they may define their variant designations differently.22,23 In September 2021, the