Human coronavirus (HCoV) was first identified in 1965, isolated from a patient with what was described as the common cold [3]. Subsequently, four types of HCoV have been detected frequently in respiratory secretions from children and adults in scattered regions of the globe, labeled HCoV-229E, -NL63, -OC43, and -HKU1. These agents are a common cause of mild-to-moderate upper respiratory illness, including common cold, bronchitis, bronchiolitis in infants and children, and asthma exacerbation. Rarely, HCoVs have been implicated in lower respiratory tract infection (viral pneumonia), a complication more common to persons with underlying cardiopulmonary disease or weakened immune systems.

Human coronavirus (HCoV) was first identified in 1965, isolated from a patient with what was described as the common cold [3]. Subsequently, four types of HCoV have been detected frequently in respiratory secretions from children and adults in scattered regions of the globe, labeled HCoV-229E, -NL63, -OC43, and -HKU1. These agents are a common cause of mild-to-moderate upper respiratory illness, including common cold, bronchitis, bronchiolitis in infants and children, and asthma exacerbation. Rarely, HCoVs have been implicated in lower respiratory tract infection (viral pneumonia), a complication more common to persons with underlying cardiopulmonary disease or weakened immune systems.

In addition to the seasonal infections caused by the ambient, adaptive HCoVs described, widespread outbreaks of novel coronavirus infection have occurred in each of the past two decades, and the 2019–2020 Wuhan, China, outbreak poses the third threat of a severe novel coronavirus epidemic on a global scale [1,4]. The epidemiologic feature common to these outbreaks is an initial point source cluster of zoonotic infection followed by secondary spread of the virus via human-to-human transmission. Among the factors thought to be conducive to the emergence of such outbreaks are the following: genomic recombination in an animal CoV capsid that renders the virus better adapted to human infection (and perhaps more virulent); and dietary practices and cultural determinants that bring humans into close contact with livestock or raw meat and carcasses of wild animals and birds, thereby facilitating transmission from an infected animal host to humans. After infection is established, secondary viral transmission occurs through close person-to-person contact by way of droplet nuclei propelled into the air during coughing and sneezing. The first two known novel coronavirus outbreaks, severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, are considered to be zoonotic in origin and were associated with serious, sometimes fatal illness.

Infection with SARS-CoV was first recognized in China in November 2002, and signs of an outbreak in Asia were evident by February 2003 [3]. Epidemiologic investigation found that early cases of SARS-CoV were zoonotic infection involving transmission from civet cats to humans. Over the next several months, SARS-CoV spread to countries in North America, South America, Europe, and other parts of Asia before the global outbreak was contained later in the same year.

Despite the availability of effective COVID-19 vaccines beginning in December 2020, the pandemic remained undiminished in Europe and the United States throughout the summer and fall of 2021, in part because of a slow rollout and limited acceptance of COVID-19 vaccines and the emergence of new SARS-CoV-2 strains (variants) more infectious than the original. By July 2021, SARS-CoV-2 Delta variant accounted for 99% of all COVID-19 cases reported in the United States; in December 2021, Delta was rapidly supplanted by the less severe but highly infectious Omicron variant [132].

The first description of clinical features in hospitalized patients with COVID-19-related pneumonia in Wuhan City was published online January 24, 2020 [9]. Of 41 patients with laboratory-confirmed SARS-CoV-2 infection; 30 (73%) were men and 27 (66%) had been exposed to the open-air Huanan Seafood Market. The median age was 49 years, and fewer than half of the patients had a history of underlying chronic disease. Common symptoms at onset of illness were fever (98%), cough (76%), and myalgia or fatigue (44%). Dyspnea developed in 22 patients (55%), at a median time of eight days after onset of illness. Common laboratory abnormalities included leukopenia, lymphopenia, and mild hepatic enzyme elevations. All 41 patients were reported to have pneumonia, and in all save one case there was radiographic evidence of bilateral involvement. The typical findings on chest computed tomography (CT) images of intensive care unit (ICU) patients were bilateral multilobar and segmental areas of consolidation. Acute respiratory distress syndrome developed in 12 (32%) patients, 13 (32%) were admitted to an ICU, and 6 died (15%).

For purposes of risk stratification and prioritization of care, adults with COVID-19 can be grouped into the following severity of illness categories:

As of January 2023, there is no highly effective, safe, and easily administered antiviral therapy for routine treatment of COVID-19. Remdesivir, which must be administered intravenously, is the only drug approved by FDA for treatment of COVID-19. Two oral antiviral drugs, ritonavir-boosted nirmatrelvir (Paxlovid) and molnupiravir, have received EUA from the FDA for early treatment in nonhospitalized patients with mild-to-moderate COVID-19 who are at risk of progressing to severe illness. Recommendations for use of antiviral therapies apply to adults and children (of certain age and weight limitations). The NIH Panel guidelines recommend selecting from the following antiviral agents, in order of preference [57]:

COVID-19 mRNA vaccine is the product of a new vaccine technology with important public health advantages. An mRNA vaccine can be produced completely in vitro, which facilitates purification and allows for rapid production of individual vaccine doses. The COVID-19 mRNA vaccine consists of a nucleoside-modified messenger RNA wrapped in a lipid-laden nanoparticle. The vaccine mRNA encodes for SARS-CoV-2 surface spike protein. The lipid envelope facilitates vaccine delivery into host cells, enhances stability, and may also augment the immune response. Following intramuscular inoculation, host myocytes utilize vaccine mRNA to express SARS-CoV-2 antigen on cell surfaces, which in turn elicits neutralizing antibody and cellular immune responses to SARS-CoV-2. Vaccine mRNA does not enter the host cell nucleus and cannot become part of the host's own DNA.

Phase 3 clinical trials demonstrated the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines to be safe and 94% to 95% effective against the original strain of SARS-CoV-2 [98,99]. In the Pfizer-BioNTech vaccine trial, 43,448 adults were randomized to receive vaccine (21,720 participants) or placebo (21,728 participants) in two doses 21 days apart [98]. The primary outcomes were safety and the incidence of symptomatic COVID-19 at least seven days after the second vaccine dose. The interim analysis included the first 170 cases of symptomatic COVID-19 diagnosed in the study population and covered a median of two months of safety data. Of the total, eight cases of COVID-19 were observed in the vaccine group and 162 cases in the placebo group. This corresponds to a vaccine efficacy of 95.0%. Vaccine efficacy was similar across subgroups defined by age, sex, race, body mass index, and coexisting medical conditions. Ten cases of severe COVID-19 occurred with onset after the first dose, of which nine were in placebo recipients. Post-vaccination reactions included mild-to-moderate localized pain at the injection site and transient systemic reactions such as fatigue, fever, and headache. Systemic reactions occurred more commonly in younger vaccine recipients (16 to 55 years of age) and after the second dose [98]. The Moderna phase 3 vaccine trial results were equally favorable [99]. In this trial, 30,420 adult participants were randomly assigned to receive either two doses of vaccine or placebo 28 days apart. Of 196 confirmed cases of symptomatic COVID-19 with onset at least 14 days after the second inoculation, 185 cases were in the placebo group and 11 in the vaccine group, a vaccine efficacy of 94.1%. Severe COVID-19, including one fatality, occurred in 30 participants, all of whom were in the placebo group. Transient local and systemic post-vaccination reactions occurred commonly; no safety concerns were identified [99].

Confirmation of COVID-19 is performed using the RT-PCR assay for SARS-CoV-2 on respiratory specimens (which can include nasopharyngeal or oropharyngeal aspirates or washes, nasopharyngeal or oropharyngeal swabs, bronchoalveolar lavage, tracheal aspirates, or sputum) and serum. The FDA has worked to expedite the availability of tests through emergency authorization of commercial laboratories that have developed SARS-CoV-2 testing capability. Information on specimen collection, handling, and storage is available at https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html. After initial confirmation of COVID-19, additional testing of clinical specimens can help inform clinical management, including discharge planning. Additional guidance for collection, handling, and testing of clinical specimens is available at the CDC website [12].