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Clinical Presentation of People with SARS-CoV-2 Infection

Last Updated: October 9, 2020

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can experience a range of clinical manifestations, from no symptoms to critical illness. This section of the Guidelines discusses the clinical presentations of patients according to illness severity.

In general, adults with SARS-CoV-2 infection can be grouped into the following severity of illness categories. However, the criteria for each category may overlap or vary across clinical guidelines and clinical trials, and a patient’s clinical status may change over time.

  • Asymptomatic or Presymptomatic Infection: Individuals who test positive for SARS-CoV-2 using a virologic test (i.e., 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 (e.g., 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 mmHg, respiratory frequency >30 breaths per minute, or lung infiltrates >50%.
  • Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.

Patients with certain underlying comorbidities are at a higher risk of progression to severe COVID-19. Some of these comorbidities include being 65 years or older; having cardiovascular disease, chronic lung disease, diabetes, cancer, obesity, or chronic kidney disease; and being a recipient of immunosuppressive therapy.1 Health care providers should monitor such patients closely until clinical recovery is achieved.

The optimal pulmonary imaging technique has not yet been defined for people with symptomatic SARS-CoV-2 infection who present to care. Initial evaluation for these patients may include chest X-ray, ultrasound, or, if indicated, computerized tomography. An electrocardiogram should be performed if indicated. Laboratory testing includes a complete blood count with differential and a metabolic profile, including liver and renal function tests. While not part of standard care, measuring the levels of inflammatory markers such as C-reactive protein (CRP), D-dimer, and ferritin may have prognostic value.2-4

The definitions for the severity of illness categories listed above also apply to pregnant patients. However, the threshold for certain interventions may be different for pregnant patients and nonpregnant patients. For example, oxygen supplementation is recommended for pregnant patients when SpO2 falls below 95% on room air at sea level, to accommodate physiologic changes in oxygen demand during pregnancy and to assure adequate oxygen delivery to the fetus.5 If laboratory parameters are used for monitoring and interventions, clinicians should be aware that normal physiologic changes during pregnancy can alter several laboratory values. In general, leukocyte cell count increases throughout gestation and delivery and peaks during the immediate postpartum period. This is mainly due to neutrophilia.6 D-dimer and CRP levels also increase during pregnancy and are often higher in pregnant patients than in nonpregnant patients.7 Detailed information on treating COVID-19 in pregnant patients can be found in Special Considerations in Pregnancy, as well as in the pregnancy considerations subsection of each individual section of the Guidelines.

In pediatric patients, radiographic abnormalities are common and, for the most part, should not be used as the sole criteria to define the COVID-19 illness category. Normal values for respiratory rate also vary with age in children; thus, hypoxia should be the primary criteria used to define severe illness, especially in younger children. In a small number of children and in some young adults, SARS-CoV-2 infection may be followed by a severe inflammatory condition called multisystem inflammatory syndrome in children (MIS-C).8,9 This syndrome is discussed in detail in Special Considerations in Children.

Asymptomatic or Presymptomatic Infection

Asymptomatic SARS-CoV-2 infection can occur, although the percentage of patients who remain truly asymptomatic throughout the course of infection is variable and incompletely defined. It is unclear at present what percentage of individuals who present with asymptomatic infection may progress to clinical disease. Some asymptomatic individuals have been reported to have objective radiographic findings that are consistent with COVID-19 pneumonia.10,11 The availability of widespread virologic testing for SARS-CoV-2 and the development of reliable serologic assays for antibodies to the virus will help to determine the true prevalence of asymptomatic and presymptomatic infection. See Therapeutic Management of COVID-19 for recommendations regarding SARS-CoV-2-specific therapy.

Mild Illness

Patients with mild illness may exhibit a variety of signs and symptoms (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell). They do not have shortness of breath, dyspnea on exertion, or abnormal imaging. Most mildly ill patients can be managed in an ambulatory setting or at home through telemedicine or telephone visits. No imaging or specific laboratory evaluations are routinely indicated in otherwise healthy patients with mild COVID-19 disease. Older patients and those with underlying comorbidities are at higher risk of disease progression; therefore, health care providers should monitor these patients closely until clinical recovery is achieved. See Therapeutic Management of COVID-19 for recommendations regarding SARS-CoV-2-specific therapy.

Moderate Illness

Moderate COVID-19 illness is defined as evidence of lower respiratory disease during clinical assessment or imaging, with SpO2 ≥94% on room air at sea level. Given that pulmonary disease can progress rapidly in patients with COVID-19, close monitoring of patients with moderate disease is recommended. If bacterial pneumonia or sepsis is strongly suspected, administer empiric antibiotic treatment, re-evaluate the patient daily, and de-escalate or stop antibiotics if there is no evidence of bacterial infection. See Therapeutic Management of COVID-19 for recommendations regarding SARS-CoV-2-specific therapy.

Severe Illness

Patients with COVID-19 are considered to have severe illness if they have SpO2 <94% on room air at sea level, a respiratory rate of >30 breaths/min, PaO2/FiO2 <300 mmHg, or lung infiltrates >50%. These patients may experience rapid clinical deterioration. Oxygen therapy should be administered immediately using a nasal cannula or a high-flow oxygen device. See Therapeutic Management of COVID-19 for recommendations regarding SARS-CoV-2-specific therapy. If secondary bacterial pneumonia or sepsis is suspected, administer empiric antibiotics, re-evaluate the patient daily, and de-escalate or stop antibiotics if there is no evidence of bacterial infection.

Critical Illness

Severe cases of COVID-19 may be associated with acute respiratory distress syndrome, septic shock that may represent virus-induced distributive shock, cardiac dysfunction, elevations in levels of multiple inflammatory cytokines that provoke a cytokine storm, and/or exacerbation of underlying comorbidities. In addition to pulmonary disease, patients with COVID-19 may also experience cardiac, hepatic, renal, central nervous system, or thrombotic disease.

As with any patient in the intensive care unit (ICU), successful clinical management of a patient with COVID-19 includes treating both the medical condition that initially resulted in ICU admission and other comorbidities and nosocomial complications.

For more information, see Care of Critically Ill Patients with COVID-19.

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 on the prevalence, duration, underlying causes, and effective management strategies for these lingering signs and symptoms.12 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.13,14

Some of the persistent symptoms that have been reported include fatigue, joint pain, chest pain, palpitations, shortness of breath, and worsened quality of life.15,16 One study from China found that pulmonary function was still impaired 1 month after hospital discharge.17 A study from the United Kingdom reported that among 100 hospitalized patients (32 received care in the ICU and 68 received care in hospital wards only), 72% of the ICU patients and 60% of the ward patients experienced fatigue and breathlessness at 4 to 8 weeks after hospital discharge. The authors of the study suggest that post-hospital rehabilitation may be necessary for some of these patients.15

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 for psychiatric distress.16,18 Younger patients have been reported to experience more psychiatric symptoms than patients aged >60 years.15,16

Patients may continue to experience headaches, vision changes, hearing loss, loss of taste or smell, impaired mobility, numbness in extremities, tremors, myalgia, memory loss, cognitive impairment, and mood changes for up to 3 months after diagnosis of COVID-19.19,20 More research is needed to better understand the pathophysiology and clinical course of these post-infection sequelae and to identify management strategies for patients.

References

  1. Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19): people with certain medical conditions. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Accessed September 22, 2020.
  2. Tan C, Huang Y, Shi F, et al. C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol. 2020;92(7):856-862. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32281668.
  3. Berger JS, Kunichoff D, Adhikari S, et al. Prevalence and outcomes of d-dimer elevation in hospitalized patients with COVID-19. Arterioscler Thromb Vasc Biol. 2020;40(10):2539-2547. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32840379.
  4. Casas-Rojo JM, Anton-Santos JM, Millan-Nunez-Cortes J, et al. Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry. Rev Clin Esp. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32762922.
  5. Society for Maternal Fetal Medicine. Management considerations for pregnant patients with COVID-19. 2020. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2336/SMFM_COVID_Management_of_COVID_pos_preg_patients_4-30-20_final.pdf. Accessed: May 20, 2020.
  6. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326-1331. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19935037.
  7. Anderson BL, Mendez-Figueroa H, Dahlke JD, Raker C, Hillier SL, Cu-Uvin S. Pregnancy-induced changes in immune protection of the genital tract: defining normal. Am J Obstet Gynecol. 2013;208(4):321 e321-329. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23313311.
  8. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607-1608. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32386565.
  9. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771-1778. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32410760.
  10. Zhang R, Ouyang H, Fu L, et al. CT features of SARS-CoV-2 pneumonia according to clinical presentation: a retrospective analysis of 120 consecutive patients from Wuhan city. Eur Radiol. 2020;30(8):4417-4426. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32279115.
  11. Inui S, Fujikawa A, Jitsu M, et al. Chest CT findings in cases from the cruise ship “Diamond Princess” with coronavirus disease 2019 (COVID-19). Radiology: Cardiothoracic Imaging. 2020;2. Available at: https://pubs.rsna.org/doi/10.1148/ryct.2020200110.
  12. Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020;585(7825):339-341. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32929257.
  13. Rawal G, Yadav S, Kumar R. Post-intensive Care Syndrome: an Overview. J Transl Int Med. 2017;5(2):90-92. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28721340.
  14. Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March-June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993-998. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32730238.
  15. Halpin SJ, McIvor C, Whyatt G, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32729939.
  16. Cai X, Hu X, Ekumi IO, et al. Psychological distress and its correlates among COVID-19 survivors during early convalescence across age groups. Am J Geriatr Psychiatry. 2020;28(10):1030-1039. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32753338.
  17. Huang Y, Tan C, Wu J, et al. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res. 2020;21(1):163. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32600344.
  18. Mazza MG, De Lorenzo R, Conte C, et al. Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors. Brain Behav Immun. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32738287.
  19. Lu Y, Li X, Geng D, et al. Cerebral micro-structuralchanges in COVID-19 patients - an MRI-based 3-month follow-up study. EClinicalMedicine. 2020;25:100484. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32838240.
  20. Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther. 2020;12(1):69. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32498691.