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Content Update: October 2022

See Management section for current recommendations for Pharmacotherapy, Antivirals, Anticoagulation, and Monoclonal Antibodies

Content Update: COVID-19 February 2022

Contemporary information on COVID-19 is provided in the following sections: Pathophysiology; Monoclonal Antibodies; and Antivirals. New references are added in these areas.

Review current information on treatment guidelines at: https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/

OVERVIEW

On December 31, 2019, public health authorities in Wuhan, China, reported a cluster of cases of severe atypical pneumonia. Over the next 2 months, experts identified and sequenced the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) as the virus responsible, and Coronavirus Disease 2019 (COVID-19) spread across the world, reaching pandemic status.1 COVID-19 was responsible for more than 1.8 million deaths worldwide in 2020, and it was one of the leading causes of death in the United States.2,3  Public health authorities recommended social distancing, widespread testing, travel bans, stay-at-home orders, mask mandates, and restricted commerce to slow the spread of the infection.

PATHOPHYSIOLOGY

SARS-CoV-2 is an enveloped RNA β-coronavirus genetically similar to the virus that causes Severe Acute Respiratory Distress Syndrome (SARS). SARS-CoV-2 has four structural proteins (spike, membrane, envelope, and nucleocapsid) and binds principally to the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the lung and elsewhere.4 SARS-CoV-2 is transmitted between humans primarily through respiratory droplets (large droplets of secretions that can propagate from an infected individual) and close personal contact. The incubation period of COVID-19 is 2–7 days (median 5 in original SARS-CoV-2, but lower in some newer variants), and viral shedding occurs up to 7 days prior to the onset of symptoms with maximal production in the first week after symptom onset (Figure 154b-1).5-8, 8A During the course of the pandemic, SARS-CoV-2 has evolved through genetic mutation into new variants. Each variant has slightly different transmission dynamics, severity, and response to therapeutics. Based on genetic and epidemiologic surveillance, the U.S. Centers for Disease Control and Prevention (CDC) refers to new variants by labels from the Greek alphabet and classifies important new variants into Variants of Concern (VOC) or Variants of High Consequence (VOHC) based on the transmissibility, severity, and effectiveness of vaccines or therapeutics.

FIGURE 154b-1

Time course of SARS-CoV-2 infection. Approximately 2-5 days after the initial exposure, patients develop symptoms, but viral shedding often occurs before symptoms. Viral replication peaks in the first week of infection, with severe illness manifesting during the second week.

(Reproduced with permission from Cevik M, Kuppalli K, Kindrachuk J, et al: Virology, transmission, and pathogenesis of SARS-CoV-2, BMJ 2020 Oct 23;371:m3862. 7

Data from Oberfeld B, Achanta A, Carpenter K, et al: SnapShot: COVID-19, Cell 2020 May 14;181(4):954-954.e1 and McGrath BA, Brenner MJ, Warrillow SJ, et al: Tracheostomy in the COVID-19 era: global and multidisciplinary guidance, Lancet Respir Med 2020 Jul;8(7):717-725.)

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