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ACEP COVID-19 Field Guide

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Severity and Progression of Disease

Diagnosis

The median incubation period for COVID-19 is 4 to 5 days; the range is 2 to 14 days (Figure 10.1). Some variants, like Omicron, appear to cause symptoms sooner than the original virus.

Figure 10.1 Proportion of symptomatic cases per day since infection. Credit: ACEP.

Figure_8.1_Proportion_of_symptomatic_cases_per_day_since_infection.png

Studies suggest that illness severity can range from mild to critical:

  • Asymptomatic: Individuals who test positive for SARS-CoV-2 using a virologic test (ie, a nucleic acid amplification test or an antigen test) but never develop symptoms that are consistent with COVID-19. The HLA-B immune system variant is associated with asymptomatic infection but does not explain all cases.
  • Presymptomatic infection: Patients appear to be infectious shortly before they are symptomatic. How infectious they are is unknown.
  • Mild illness: Individuals who have any of the various signs and symptoms of COVID-19 (eg, fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but 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 have an SpO2 ≥94% on room air at sea level.
  • Severe illness: Individuals who have an SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%.
  • Critical illness: Individuals who have respiratory failure, septic shock, or multiple organ dysfunction.

Clinical progression

During the pandemic, some patients with COVID-19 rapidly deteriorated 1 week after illness onset. Among patients who developed severe disease early in the pandemic, the medium time to dyspnea ranged from 5 to 8 days; the median time to acute respiratory distress syndrome (ARDS) ranged from 8 to 12 days; and the median time to ICU admission ranged from 10 to 12 days, with 26% to 32% of patients admitted to the ICU. There have been different reports, but mortality among patients admitted to the ICU ranged from 39% to 72%. The median length of hospitalization among survivors was 10 to 13 days.

Development of ARDS was reported in:

  • 3% to 17% of all patients;
  • 20% to 42% of hospitalized patients; and
  • 67% to 85% of patients admitted to the ICU.

Additional information can be found from the NIH's COVID-19 Treatment Guidelines in the section "Clinical Spectrum of SARS-CoV-2 Infection."

Risk factors for severe illness

As of 2023, the most significant risk factor for severe COVID-19 is a lack of previous immunity from vaccination or infection. Immunity wears off fairly rapidly. Because a high percentage of the public now has some immunity, accurately measuring disease severity as it relates to other factors has become difficult. The best evidence for risk factors for severe illness is historical. The actual risk factors remain the same, however. Age is the second strongest risk factor for severe illness, complications, and death. According to the CDC reports from early in the pandemic, among the 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were of male sex. The hospitalization rate among patients identified through the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network (COVID-NET) during a 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years (Figure 10.2).

Among more than 44,000 confirmed cases of COVID-19 in China, the case fatality rate was highest among older people:

  • ≥80 years: 14.8%;
  • 70 to 79 years: 8.0%;
  • 60 to 69 years: 3.6%;
  • 50 to 59 years: 1.3%;
  • 40 to 49 years: 0.4%; and
  • <40 years: 0.2%.

Patients in China with no reported underlying medical conditions had an overall case fatality of 0.9%, but case fatality was higher for patients with comorbidities:

  • 5% for those with cardiovascular disease;
  • 3% for diabetes;
  • Approximately 6% for chronic respiratory disease;
  • Approximately 6% for hypertension; and
  • Approximately 6% for cancer.

Heart disease, hypertension, prior stroke, diabetes, chronic lung or respiratory disease, cancer, leukemia, chronic kidney disease, and obesity have all been associated with increased illness severity and adverse outcomes.

Figure 10.2. Laboratory-confirmed COVID-19–associated hospitalization rates* by age group — COVID-NET, 14 states, March 1 to March 30, 2020. Credit: Adapted from Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 — COVID-NET, 14 states, March 1-30, 2020. MMWR. 2020 Apr 17;69(15):458-464. doi:10.15585/mmwr.mm6915e3

Figure_8.2_Laboratory-confirmed_coronavirus_disease_2019.png

* Number of patients hospitalized with COVID-19 per 100,000 population

The hospitalization rate among children is shown in Figure 10.3.

Figure 10.3. COVID-19 cases among children (aged <18 years) with known hospitalization status (N = 745),* by age group and hospitalization status — United States, February 12 to April 2, 2020. Credit: Adapted from CDC COVID-19 Response Team. Coronavirus disease 2019 in children — United States, February 12-April 2, 2020. MMWR. 2020 Apr 10;69(14):422-426. doi:10.15585/mmwr.mm6914e4

Figure_8.3_COVID-19_cases_among_children.png

* Number of children missing hospitalization status by age group: <1 year (303/398; 76%); 1-4 years (189/291; 65%); 5-9 years (275/388; 71%); 10-14 years (466/682; 68%); and 15-17 years (594/813; 73%).

Additional readings

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Testing

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