Clinical Spectrum of SARS-CoV-2 Infection

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 [NAAT] 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 an oxygen saturation (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/min, 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 progressing to severe COVID-19. These comorbidities include being aged 65 years or older; having cardiovascular disease, chronic lung disease, sickle cell disease, diabetes, cancer, obesity, or chronic kidney disease; being pregnant; being a cigarette smoker; and being a recipient of transplant or 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. Initial evaluation for these patients may include chest X-ray, ultrasound, or, if indicated, computed 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. Although inflammatory markers such as C-reactive protein (CRP), D-dimer, and ferritin are not routinely measured as part of standard care, results from such measurements 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 ensure adequate oxygen delivery to the fetus.⁵ If laboratory parameters are used for monitoring pregnant patients and making decisions about 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 increase is mainly due to neutrophilia.⁶ D-dimer and CRP levels also increase during pregnancy and are often higher in pregnant patients than nonpregnant patients.⁷ Detailed information on treating COVID-19 in pregnant patients can be found in Special Considerations in Pregnancy and 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 the only criteria used to determine the severity of illness. The normal values for respiratory rate also vary with age in children; thus, hypoxia should be the primary criterion used to define severe COVID-19, 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 what percentage of individuals who present with asymptomatic infection 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 determine the true prevalence of asymptomatic and presymptomatic infection. See Therapeutic Management of Nonhospitalized Adults With 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. 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 Nonhospitalized Adults With COVID-19 for recommendations regarding SARS-CoV-2-specific therapy.

Moderate Illness

Moderate 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, patients with moderate disease should be closely monitored. If bacterial pneumonia or sepsis is 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 Nonhospitalized Adults With 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 >30 breaths/min, PaO₂/FiO₂ <300 mm Hg, 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 Hospitalized Adults With 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

Critically ill patients may have acute respiratory distress syndrome, septic shock that may represent virus-induced distributive shock, cardiac dysfunction, an exaggerated inflammatory response, and/or exacerbation of underlying comorbidities. In addition to pulmonary disease, patients with critical illness 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.

SOURCE: NIH : COVID-19 Treatment Guidelines