The Coronavirus Disease (COVID-19) Pandemic

Course #54151-


Study Points

  1. Differentiate between the common, ubiquitous strains of human coronavirus and novel (outbreak) strains with respect to epidemiology, modes of transmission, spectrum of illness, and public health implications.
  2. Recognize clinical manifestations of acute COVID-19 and the "long COVID" syndrome, and anticipate systemic complications of severe disease in those with known risk factors.
  3. Implement guideline recommendations for diagnostic testing and management of patients with recent exposure, newly diagnosed, or suspected COVID-19.
  4. Discuss the dynamics of SARS-CoV-2 transmission and advise patients as to preventive measures (e.g., social distancing, masking) and the role of COVID-19 vaccines, giving special attention to those at risk for severe disease.
  5. Explain public health implications of emerging SARS-CoV-2 variants, including benefits and limitations of natural, vaccine, and hybrid immunity.

    1 . Human coronavirus (CoV) was first identified in
    A) 1906.
    B) 1965.
    C) 1999.
    D) 2019.

    BACKGROUND

    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.

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    2 . Which of the following statements regarding common human coronaviruses is TRUE?
    A) There are about four antigenic strains in frequent circulation.
    B) They are a common cause of mild-to-moderate upper respiratory illness.
    C) Lower respiratory tract complications, such as pleurisy and pneumonia, are rare.
    D) All of the above.

    BACKGROUND

    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.

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    3 . The common epidemiologic feature in novel coronavirus outbreaks is
    A) chronic substance abuse among patients.
    B) vegetarianism or veganism among patients.
    C) viruses can exchange RNA segments during replication and create viruses with new gene combinations.
    D) an initial point source cluster of zoonotic infection followed by secondary spread via human-to-human transmission.

    BACKGROUND

    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.

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    4 . Early cases of severe acute respiratory syndrome coronavirus (SARS-CoV)-2002–2003 represented a zoonotic infection originating in
    A) pigs.
    B) camels.
    C) civet cats.
    D) migratory birds.

    BACKGROUND

    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.

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    5 . By summer 2021, which variant accounted for 99% of COVID-19 cases reported in the United States?
    A) Alpha
    B) Delta
    C) Lambda
    D) Omega

    THE 2019–2020 NOVEL CORONAVIRUS OUTBREAK: A GLOBAL THREAT

    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].

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    6 . In a report of clinical features of patients hospitalized with COVID-19, the most common symptom at the onset of illness was
    A) fever.
    B) cough.
    C) dyspnea.
    D) myalgia or fatigue.

    CLINICAL MANIFESTATIONS OF COVID-19

    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%).

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    7 . Of the following PCR-positive cases, which one most likely has severe COVID-19?
    A) Sick three days with "cold" plus anosmia, fatigue, temperature of 99.2, new-onset cough, and SpO2 97% by pulse oximetry
    B) Sick three days with headache, myalgias, fatigue, temperature 100.4, new-onset cough, and SpO2 97% by pulse oximetry
    C) Sick seven days with fatigue, feverishness, new-onset cough, shortness of breath, and SpO2 92% by pulse oximetry
    D) All of the above

    CLINICAL MANIFESTATIONS OF COVID-19

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

    • Asymptomatic or presymptomatic infection: Individuals who test positive for SARS-CoV-2 using a virologic test but who have no symptoms consistent with COVID-19.

    • Mild illness: Individuals who have any of the signs or symptoms of COVID-19 but who do not have shortness of breath, dyspnea, or abnormal chest imaging.

    • Moderate illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have an oxygen saturation measured by pulse oximetry (SpO2) ≤94% on room air at sea level.

    • Severe illness: Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, a respiratory rate >30 breaths/minute, or lung infiltrates.

    • Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.

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    8 . The preferred first-line antiviral therapy for the treatment of COVID-19 in adults is
    A) remdesivir.
    B) molnupiravir.
    C) hydroxychloroquine.
    D) ritonavir-boosted nirmatrelvir (Paxlovid).

    COVID-19 TREATMENT OPTIONS

    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]:

    • Ritonavir-boosted nirmatrelvir (Paxlovid): Adults and children at least 12 years of age

    • Remdesivir: Adults and children older than 28 days of age and weighing at least 3 kg

    • Molnupiravir as alternative therapy when ritonavir-boosted nirmatrelvir and remdesivir are not available

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    9 . Which of the following statements regarding COVID vaccination is TRUE?
    A) The CDC recommends booster doses for eligible persons.
    B) Natural immunity that follows SARS-CoV-2 infection is enhanced by vaccination.
    C) COVID-19 mRNA vaccine represents a new vaccine technology that has important public health advantages.
    D) All of the above

    COVID-19 VACCINES

    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].

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    10 . The real-time reverse transcription polymerase chain reaction (rRT-PCR) assay for SARS-CoV-2 can be conducted using
    A) serum.
    B) sputum.
    C) broncheoalveolar lavage.
    D) Any of the above

    GLOBAL PUBLIC HEALTH CONCERNS AND WHO RESPONSE

    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].

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