Prevention and Diagnosis
The estimated incubation period for COVID-19 is up to 14 days from the time of exposure, with a median incubation period of 4 to 5 days. Patients with COVID-19 often have clinical manifestations of fever (85–89%), cough (68–86%), and shortness of breath (19–80%). In a study of 1,099 confirmed cases hospitalized with COVID-19, fever was present in 43.8% of patients at admission but ultimately developed in 88.7% of patients during hospitalization.1
Less common symptoms are nausea (24%), muscle ache (11–15%), confusion (9%), headache (8–14%), sore throat (5–18%), nasal congestion/rhinorrhea (5–16%), chest pain (2%), and diarrhea (2–27%). Other reported symptoms have included anosmia, dysgeusia, sputum production, dizziness, abdominal pain, anorexia, and vomiting. 1-3
The clinical spectrum of COVID-19 ranges from asymptomatic to respiratory failure to multiorgan and systemic manifestations. A large study of 44,672 confirmed COVID-19 cases identified by the Chinese Centers for Disease Control and Prevention found that4:
- 81% of cases were mild (e.g., non-pneumonia and mild pneumonia)
- 14% of cases were severe (e.g., dyspnea, respiratory frequency ≥30/min, blood-oxygen saturation ≤93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 mm Hg, and/or lung infiltrates >50% within 24 to 48 hours)
- 5% of cases were critical (e.g., respiratory failure, septic shock, and/or multiple organ dysfunction or failure)
The overall case-fatality rate (CFR) identified in this study was 2.3%. No deaths were reported among mild and severe cases, but the CFR was 49.0% among critical cases.4
In Italy, up to 12% of all positive COVID-19 cases required admission to the intensive care unit (ICU).5 A study of hospitalized patients in China found that 32% were admitted to the ICU.6 The median time from symptom onset to the development of pneumonia is 5 days, and the median time from symptom onset to severe hypoxemia and ICU admission is 7–12 days. Acute hypoxemic respiratory failure from acute respiratory distress syndrome (ARDS) is the most common complication, found in 60–70% of patients admitted to the ICU. Shock (30%), myocardial dysfunction (20–30%), and acute kidney injury (10–30%) also account for a substantial number of complications related to COVID-19.5
Risk Factors for Severe Illness
In a study of 44,672 confirmed COVID-19 cases in China, the CFR was elevated among those with preexisting comorbid conditions, including cardiovascular disease (10.5%), diabetes (7.3%), chronic respiratory disease (6.3%), hypertension (6.0%), and cancer (5.6%).4 A study of 1482 patients hospitalized with COVID-19 in the United States (US) found that 89.3% had one or more underlying conditions, the most common being hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%).
Age is another important factor impacting disease severity. Compared with the overall CFR of 2.3% in the study in China, the CFR was elevated in patients ≥80 years of age (14.8%) and in those aged 70–79 years (8.0%). A preliminary analysis of the mortality rate in the US between February 12 and March 16, 2020 found that the fatality of COVID-19 ranges from 10% to 27% in persons aged ≥85, followed by 3% to 11% in persons aged 65–84 years, 1% to 3% among persons aged 55–64 years, and <1% in persons aged 20–54 years.7
A retrospective study of 150 patients in Wuhan, China identified several predictors of fatal outcome in COVID-19 cases, including older age, the presence of underlying diseases or secondary infections, and elevated inflammatory indicators in the blood. Laboratory results showed significant differences in white blood cell counts and platelets, cardiac troponin, myoglobin, C-reactive protein (CRP), and interleukin-6 (IL-6) between patients who recovered from COVID-19 and those who died from viral complications.8 A meta-analysis found the most frequent laboratory abnormalities with COVID-19 were lymphopenia (35–75% of cases) and increased CRP levels (75–93% of cases), lactate dehydrogenase (LDH) (27–92% of cases), erythrocyte sedimentation rate (ESR) (up to 85% of cases), and D-dimer (36–43% of cases), as well as low concentrations of serum albumin (50–98% of cases) and hemoglobin (41–50%). Laboratory abnormalities that were predictive of adverse outcome included lymphopenia, neutrophilia, and elevated levels of LDH, CRP, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).9
COVID-19 patients with ARDS showed abundant interstitial mononuclear inflammatory infiltrate in the lungs, particularly lymphocytes, implying that immune hyperactivation may be at least partially responsible for the severity of COVID-19 in these patients.10 These laboratory features, combined with the fever and confusion commonly found in critically ill patients infected with COVID-19, suggest the presence of a cytokine storm syndrome (CSS) that results in ARDS and multiorgan failure. 2,11,12 CSS is believed to be a consequence of an accentuated immune response to various triggers, including certain viral infections.
In the early phase of pneumonia induced by COVID-19, the main computed tomography (CT) findings include multifocal peripheral and basal ground-glass opacities, crazy-paving patterns, traction bronchiectasis, and air bronchogram signs. A progressive transition to consolidation, together with pleural effusion, extensive small lung nodules, irregular interlobular or septal thickening, and adenopathies characterize the more advanced phase of the disease.13
In a recent report of 41 patients with COVID-19, abnormal chest imaging findings were observed in all patients, with 40 individuals having bilateral disease at initial imaging. ICU patients commonly exhibit bilateral subsegmental areas of air-space consolidation. Non-ICU patients typically show transient areas of subsegmental consolidation early, with bilateral ground-glass opacities predominating in later stages of the disease.6 Another study of 99 confirmed COVID-19 cases in a hospital in Wuhan, China found bilateral lung involvement in 75% of patients and unilateral pneumonia in 25% of cases. Multiple mottling and ground-glass opacity were found in 14% of cases. Additionally, pneumothorax occurred in one patient in this report.2 No pleural effusion or cavitation has been reported so far in confirmed cases of COVID-19-associated pneumonia. Overall, the imaging findings are highly nonspecific and may overlap with the symptoms of H1N1 influenza, cytomegalovirus pneumonia, or atypical pneumonia.14
COVID-19 is extremely transmissible, with every case seeding more than two secondary cases. The WHO-China Joint Mission report found that healthcare workers accounted for 3.7% of cases with laboratory-confirmed COVID-19 in China.5 A large study of confirmed COVID-19 cases in Wuhan, China found that 14.8% of cases among healthcare workers were classified as severe or critical.4
During the COVID-19 pandemic, aerosol-generating procedures increase the risk of infection among healthcare workers. To minimize the spread of COVID-19 within healthcare facilities and to reduce the risk of infection for healthcare workers, the following recommendations have been issued:
- N95 respirators or powered air-purifying respirators should be used when performing aerosol-generating procedures, in addition to other personal protective equipment (PPE) (i.e., gloves, gowns, face shield or safety goggles).
- Surgical masks are less effective in blocking aerosols and should not be used during aerosol-generating procedures. Surgical masks may be used when providing usual care for non-ventilated COVID-19 patients or when performing nonaerosol-generating procedures on mechanically ventilated COVID-19 patients.
- Aerosol-generating procedures on COVID-19 patients should be performed in a negative-pressure room, or airborne infection isolation room (AIIR), when possible. Examples of aerosol-generating procedures include endotracheal intubation and extubation; bronchoscopy; open suctioning; high-flow nasal cannula (HFNC) or face mask; nebulizer treatment; manual ventilation; physical proning of the patient; disconnecting a patient from a ventilator; mini-bronchoalveolar lavage; noninvasive positive pressure ventilation (NIPPV); tracheostomy; or cardiopulmonary resuscitation.15
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-1720.
- Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-513.
- 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;69:458-464.
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239-1242.
- Phua J, Weng L, Ling L, et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med. 2020;8:506-517.
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.
- Centers for Disease Control and Prevention (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;69:343-346.
- Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;3:1-3.
- Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-19 infection. Clin Chem Lab Med. 2020;March 3: Epub ahead of print.
- Bersanelli M. Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors. Immunotherapy. 2020;12:269-273.
- Chen L, Liu HG, Liu W, et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Chin J Tuberc Respir Dis.2020;43:E005 [Abstract in English].
- Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061-1069.
- Calabrò L, Peters S, Soria JC, et al. Challenges in lung cancer therapy during the COVID-19 pandemic. Lancet Resp Med. 2020;April 9:Epub ahead of print.
- Kooraki S, Hosseiny M, Myers L, Gholamrezanezhad A. Coronavirus (COVID-19) outbreak: what the department of radiology should know. J Am Coll Radiol. 2020;17:447-451.
- National Institutes of Health (NIH). Infection Control. Available at https://covid19treatmentguidelines.nih.gov/critical-care/infection-control/.
- Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433.