ACEP COVID-19 Field Guide

The median incubation period for COVID-19 is 4 to 5 days; the range is 2 to 14 days (Figure 8.1).

Figure 8.1 Proportion of symptomatic cases per day since infection.

Studies suggest that illness severity can range from mild to critical (Table 8.4):

• Asymptomatic or presymptomatic infection: Individuals who test positive for SARS-CoV-2 using a virologic test (ie, a nucleic acid amplification test or an antigen test) but who have no symptoms that are consistent with COVID-19.
• 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 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 saturation of oxygen (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, respiratory frequency >30 breaths per minute, or lung infiltrates >50%.
• Critical illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.

Table 8.4 Illness Severity for COVID-19.

According to reports from China:

• Deaths occurred among patients with critical illness, and the overall case fatality rate was 2.3%.
• The case fatality rate among patients with critical disease was 49%.
• Among children, illness severity was lower, with:
• 94% having asymptomatic, mild, or moderate disease; 
• 5% having severe disease; and 
• <1% having critical disease.

Clinical Progression

It is important to note that some patients rapidly deteriorate 1 week after illness onset. 

Among patients who developed severe disease, the medium time to dyspnea ranged from 5 to 8 days; the median time to 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.

Persistent Symptoms or Illnesses After Recovery from Acute COVID-19

There have been an increasing number of reports of patients who experience persistent symptoms after recovering from acute COVID-19. At this time, there is limited information for these lingering signs and symptoms. Some of the symptoms overlap with the post-intensive care syndrome that has been described in patients without COVID-19, but prolonged symptoms and disabilities after COVID-19 have also been reported in patients with milder illness, including outpatients.

Some of the persistent symptoms that have been reported include:

• fatigue
• joint pain
• chest pain
• palpitations
• shortness of breath
• worsened quality of life

Neurologic and psychiatric symptoms have also been reported among patients who have recovered from acute COVID-19. High rates of anxiety and depression have been reported in some patients using self-report scales and younger patients have been reported to experience more psychiatric symptoms than patients aged >60 years.

Patients may continue to experience the following for up to 3 months after diagnosis of COVID-19:

• headaches, 
• vision changes, 
• hearing loss, 
• loss of taste or smell,
• impaired mobility, 
• numbness in extremities,
• tremors, 
• myalgia, 
• memory loss,
• cognitive impairment
• mood changes 

Additional information can be found on the NIH Guidance on Clinical Presentation of People with SARS-CoV-2 Infection

Risk factors for severe illness

Age is a strong risk factor for severe illness, complications, and death. According to CDC reports, among the 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years (Figure 8.2).

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

• ≥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: 

• 10.5% for those with cardiovascular disease;
• 7.3% 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/respiratory disease, cancer , and chronic kidney/renal disease and obesity have all been associated with increased illness severity and adverse outcomes.

Figure 8.2 Laboratory-confirmed coronavirus disease 2019 (COVID-19)–associated hospitalization rates,* by age group — COVID-NET, 14 states,^a March 1, 2020, to March 30, 2020 (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 Morb Mortal Wkly Rep. 2020 Apr 17;69(15):458-464. doi:10.15585/mmwr.mm6915e3).

COVID-NET = Coronavirus Disease 2019–Associated Hospitalization Surveillance Network

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

^a Counties included in COVID-NET surveillance: California (Alameda, Contra Costa, and San Francisco counties); Colorado (Adams, Arapahoe, Denver, Douglas, and Jefferson counties); Connecticut (New Haven and Middlesex counties); Georgia (Clayton, Cobb, DeKalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale counties); Iowa (one county represented); Maryland (Allegany, Anne Arundel, Baltimore, Baltimore City, Calvert, Caroline, Carroll, Cecil, Charles, Dorchester, Frederick, Garrett, Harford, Howard, Kent, Montgomery, Prince George’s, Queen Anne’s, St. Mary’s, Somerset, Talbot, Washington, Wicomico, and Worcester counties); Michigan (Clinton, Eaton, Genesee, Ingham, and Washtenaw counties); Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties); New Mexico (Bernalillo, Chaves, Dona Ana, Grant, Luna, San Juan, and Santa Fe counties); New York (Albany, Columbia, Genesee, Greene, Livingston, Monroe, Montgomery, Ontario, Orleans, Rensselaer, Saratoga, Schenectady, Schoharie, Wayne, and Yates counties); Ohio (Delaware, Fairfield, Franklin, Hocking, Licking, Madison, Morrow, Perry, Pickaway and Union counties); Oregon (Clackamas, Multnomah, and Washington counties); Tennessee (Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, and Wilson counties); and Utah (Salt Lake County).

The hospitalization rate among children is shown in Figure 8.3.

Figure 8.3 COVID-19 cases among children* aged <18 years, among those with known hospitalization status (N = 745),^a by age group and hospitalization status — United States, February 12, 2020, to April 2, 2020 (CDC COVID-19 Response Team. Coronavirus disease 2019 in children — United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):422-426. doi:10.15585/mmwr.mm6914e4).

* Includes infants, children, and adolescents.

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

References

1. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China  [published online ahead of print, 2020 Feb 28]. New Eng J Med. 2020;NEJMoa2002032. doi:10.1056/NEJMoa2002032
2. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China [published online ahead of print, 2020 Feb 7]. JAMA. 2020;e201585. doi:10.1001/jama.2020.1585
3. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 13]. JAMA Intern Med. 2020;e200994. doi:10.1001/jamainternmed.2020.0994
4. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published online ahead of print, 2020 Feb 24] [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir Med. 2020. doi:10.1016/S2213-2600(20)30079-5
5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020 Mar 28;395(10229):1038] Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3
6. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention [published online ahead of print, 2020 Feb 24]. JAMA. 2020;10.1001/jama.2020.2648. doi:10.1001/jama.2020.2648
7. CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) — United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12);343-346. doi:10.15585/mmwr.mm6912e2
8. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State [published online ahead of print, 2020 Mar 19]. JAMA. 2020;e204326. doi:10.1001/jama.2020.4326
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10. Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-151. doi:10.3760/cma.j.issn.0254-6450.2020.02.003
11. CDC COVID-19 Response Team. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 — United States, February 12-March 28, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13);382–386. doi:10.15585/mmwr.mm6913e2
12. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020 Apr;e20200702.
13. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China [published correction appears in Lancet. 2020 Jan 30]. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5

Late Sequelae and Long-Term Effects of COVID-19

While most persons with COVID-19 recover and return to normal health, some patients can have symptoms that can last for weeks or even months after recovery from acute illness. Even people who are not hospitalized and who have mild illness can experience persistent or late symptoms. Characterization of the etiology and pathophysiology of late sequelae is currently emerging, and may reflect:

• organ damage from the acute infection phase
• manifestations of a persistent hyperinflammatory state 
• ongoing viral activity associated with a host viral reservoir 
• an inadequate antibody response

Factors in addition to acute disease that may further complicate the picture include physical deconditioning at baseline or after a long disease course, comorbidities, and psychological sequelae following a difficult disease course as well as those relating to lifestyle changes due to the pandemic. 

Though there is limited information on late sequelae of COVID-19, reports of persistent symptoms in persons who recovered from acute COVID-19 illness have emerged and the most commonly reported symptoms include: fatigue, dyspnea, cough, arthralgia, chest pain, myalgia, headache, fever, and palpitations. More serious complications appear to be less common and include:

• myocardial inflammation
• ventricular dysfunction
• pulmonary function abnormalities 
• acute kidney injury 
• rash
• alopecia 
• olfactory and gustatory dysfunction
• sleep dysregulation 
• altered cognition
• memory impairment 
• depression
• anxiety

References

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6. Gemelli Against COVID-19. Post-Acute Care Study Group. Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res. 2020. doi:10.1007/s40520-020-01616-x.
7. Wu F, Wang A, Liu M, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. 2020. https://www.medrxiv.org/content/medrxiv/early/2020/04/06/2020.03.30.20047365.full.pdf
8. O’Keefe JB, Cellai M. Characterization of prolonged COVID-19 symptoms and patient comorbidities in an outpatient telemedicine cohort. medRxiv. 2020. doi:10.1101/2020.07.05.20146886.
9. Galea S, Merchant RM, Lurie N. The mental health consequences of COVID-19 and physical distancing: The need for prevention and early intervention. JAMA Intern Med. 2020;180(6):817–818. doi:10.1001/jamainternmed.2020.1562
10. Assaf G, Davis H, McCorkell L, et al. What does COVID-19 recovery actually look like? An analysis of the prolonged COVID-19 symptoms survey by Patient-Led Research Team. Patient Led Research for COVID-19, 2020.
11. Banda JM, Singh GV, Alser O, et al. Long-term patient-reported symptoms of COVID-19: an analysis of social media data. medRxiv. 2020. doi: 10.1101/2020.07.29.20164418
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13. Peleg Y, Kudose S, D’Agati V, et al. Acute kidney injury due to collapsing glomerulopathy following COVID-19 infection. Kidney Int Rep. 2020;5:940–945
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