COVID-19
(Coronavirus disease 2019)

Abstract: COVID-19, also known as Coronavirus disease, is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2). Transmission mainly occurs via direct contact or aerosol droplets. The infection may present asymptomatically or with fever and dry cough. Individuals who are over 65 years of age, immunosuppressed, or have preexisting conditions have a higher risk of developing severe symptoms and complications. Management is based on supportive care.

Updated April 7, 2020

1. Nasopharyngeal swab: Insert swab into a nostril parallel to the palate, and carefully slide it forward until a soft resistance is felt. Swab should reach a depth equal to distance from nostrils to outer opening of the ear. Rotate for several seconds to absorb secretions, and then slowly remove. 1. Oropharyngeal swab: Insert swab into the oral cavity without touching the gums, teeth, and tongue. A tongue depressor may be used. Swab the posterior pharyngeal wall using a rotatory motion. 2. Place swabs immediately into sterile tubes containing 2-3 ml of viral transport media. If both swabs are collected, they should be combined into a single vial. 3. Carefully leverage the swab against the tube rim to break the shaft at the scoreline. 4. Store specimens at 2-8°C for up to 72 hours after collection. If a delay in testing/shipping is expected, store specimens at -70°C or below. Use only synthetic fiber swabs with plastic shafts. Calcium alginate swabs or swabs with wooden shafts may inactivate the virus and inhibit PCR testing.

During an ongoing COVID-19 outbreak, laboratory testing should be prioritized as follows according to the CDC:

Hospitalized patients with compatible signs and symptoms (especially those presenting with unexplained viral pneumonia or respiratory failure)
Healthcare professionals with compatible signs and symptoms
Symptomatic individuals who are at high risk of developing a severe form of the disease or a complication (e.g., patients who are elderly, immunocompromised, or have chronic conditions)
Critical infrastructure workers with compatible signs and symptoms
Any individual, including healthcare professionals, who had close contact with a suspect or laboratory-confirmed COVID-19 patient within 2 weeks of their symptom onset, or has a history of travel from affected geographic areas in the last 2 weeks.
Individuals without symptoms

All persons under investigation (PUI) and confirmed cases should be reported according to regulations set forth by local health authorities and the national surveillance center.

Patients with COVID-19 present with the following laboratory and radiological findings. These are more pronounced and common in severe cases but can be present even in mild infections.

WBC count: leukopenia, leukocytosis, and lymphopenia (most common)
Inflammatory markers: ↑ LDH and ferritin
Liver markers: ↑ AST and ALT
Chest x-ray and CT: non-specific imaging findings most commonly found in atypical or organizing pneumonia, with a bilateral, peripheral, and/or basal distribution
- Multiple areas of consolidation
- Ground-glass opacities (GGOs)
- Crazy paving appearance (GGOs + inter-/intralobular septal thickening)
- Bronchovascular thickening

In hospitalized COVID-19 patients with severe infections, regular laboratory testing and imaging are necessary for the assessment of disease progression and complications.

CBC: severe cases present with advanced lymphocytopenia and thrombocytopenia
ABG: to assess levels of hypoxia and acid-base balance
- ARDS presents initially as hypoxemic respiratory failure with low PaO2 and respiratory alkalosis, later progressing into hypercapnic respiratory failure.
Inflammatory markers:
- ↑ IL-6 and C-reactive protein in severe cases
- ↑ procalcitonin in bacterial coinfection with pneumonia and/or sepsis
- ↑ lactate in sepsis and septic shock
Hemostasis tests:
- Prolonged PT and PTT times
- ↑ D-dimer in cardiac injury and septic shock
Assessment of organ function: abnormal findings may indicate multi-organ failure
- Creatinine, urea, and BUN used to assess renal function
- AST, ALT, GGT, and bilirubin used to assess hepatic function
- Troponin and ECG used to assess cardiac function
Chest X-ray and CT: severe infections may also present
- Pleural thickening and effusion
- Lymphadenopathy
- Air bronchograms and atelectasis
- Solid white consolidation

Causes of death in COVID-19 patients include progressive hypoxia, multi-organ failure, and hypotensive shock.

Differential Diagnoses

	COVID-19	Influenza	Common cold
Incubation period	2–14 days	1–4 days	<3 days
Onset	Gradual	Sudden	Sudden
Fever	Very common	Very common	Rare
Dry cough	Very common (mild to severe)	Very common (mild to severe)	Common (usually mild, can be productive)
Fatigue	Common	Very Common	Rare or mild
Myalgia	Common	Very Common	Mild
Sneezing	Sometimes	Rare or mild	Very common
Nasal congestion	Rare or mild	Common	Very common
Headache	Sometimes	Very common	Rare or mild
Sore throat	Sometimes	Sometimes	Very common
Diarrhea	Sometimes	Sometimes	Rare
Dyspnea	Common	Rare	Never

Management

No specific treatment for COVID-19 is currently available. As a healthcare professional, one must always implement practices for infection prevention and control (IPC) whenever dealing with a PUI or laboratory-confirmed COVID-19 case.

Patients with mild symptoms and no risk factors do not require hospitalization and are recommended to begin supportive at-home care. In the case of antipyretics, the use of ibuprofen is now considered safe according to the latest WHO advice (March 17, 2020). In the outpatient setting, one must seek professional medical assistance if any of the following emergency warning signs develop:

Difficulty breathing or shortness of breath
Persistent pain or pressure in the chest
Confusion or inability to arouse
Cyanosis (bluish-tint to lips or face)

The decision to monitor a patient in the inpatient setting should be made on a case-by-case basis. Once hospitalized, supportive care and acute measures should be applied as necessary for complications, such as:

Oxygen therapy for patients who develop respiratory distress, hypoxemia, or shock
Empiric antimicrobials in the case of sepsis or secondary pneumonia
Glucocorticoids have been associated with an increased risk for mortality or severe forms of illness in patients with influenza and MERS-CoV infection. Therefore, the WHO and CDC recommend glucocorticoids not be used in patients with COVID-19 pneumonia unless there are indications related to underlying chronic conditions.
Advanced oxygen therapy, ventilatory support, and conservative fluid management in the case of acute respiratory distress syndrome
Fluid bolus and vasopressors in the case of septic shock

For the latest step-by-step management guidelines, see the “

The mortality rate of COVID-19 varies across different nations and age groups, with a global average of 5.6%; with 1,279,722 cumulative cases and 72,614 deaths according to the WHO Situation Report-78 on April 7, 2020. Patients >80 years of age have a mortality rate of 15%.

The ongoing pandemic makes it difficult to determine an accurate mortality rate at this time. The mortality rate is assumed to be lower due to many undetected cases (lack of widespread testing in many countries and asymptomatic individuals not seeking to be tested).

Investigational therapies

Several clinical trials are currently being performed to further the development and research of antiviral drugs against SARS-CoV 2. However, it’s important to note that there is no available data as of April 6, 2020, to support the recommendation of any of the following investigational therapeutics for patients with confirmed/suspected COVID-19:

Remdesivir is reported to have in-vitro activity against SARS-CoV and MERS-CoV by incorporating into nascent viral RNA chains and producing pre-mature termination.
Chloroquine and hydroxychloroquine, widely-used antimalarial drugs, are reported to block viral entry by inhibiting virus/cell fusion.
- The combined use of hydroxychloroquine and azithromycin, a macrolide antibiotic, was reported to reduce the detection of SARS-CoV-2 RNA in upper respiratory tract specimens. Caution is advised when administering these drugs in patients with chronic medical conditions as both are associated with QT prolongation and may lead to life-threatening arrhythmia or sudden death.
Lopinavir-ritonavir, a combined protease inhibitor usually used for HIV infection, was reported as having in vitro inhibitory activity against SARS-CoV. However, no benefit was observed in hospitalized adult patients with severe Covid-19 in trials conducted in China.
Tocilizumab is an anti-IL-6 receptor agent used for rheumatoid arthritis. It is currently being investigated in patients with severe COVID-19 presenting with high IL-6 levels.
Camostat mesilate (CM): a TMPRSS2 inhibitor, is reported to block viral entry by inhibiting S protein priming.

For more information on international clinical trials, see the WHO website and clinicaltrials.gov.

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Prevention

Individuals who live within an area undergoing an outbreak are advised to prevent the spread of COVID-19 infection. General recommendations include:

Home isolation and/or avoiding public/crowded areas whenever possible to minimize the chance for exposure
Covering coughs and sneezes with a tissue or the inner elbow
Washing hands regularly for at least 20 seconds with soap and water or with an alcohol-based hand sanitizer that contains at least 60% alcohol
Maintain 1–2 m (~3–6 ft) distance from other people, “social distancing”
Regular cleaning of all ‘high-touch’ surfaces within the home
Wearing a facemask if one is a healthcare professional, begins to present with symptoms, or when caring for a sick individual. The use of facemasks is not recommended for the general population.

Isolation and quarantine can be discontinued only after the following criteria has been met:

For hospitalized patients: negative results of PCR testing from at least 2 consecutive sets of paired nasopharyngeal and throat swab specimens collected ≥ 24 hours apart (total of 4 specimens: 2 nasopharyngeal and 2 throat)
For at-home patients: negative results of PCR testing from at least 2 consecutive nasopharyngeal swab specimens collected ≥ 24 hours apart OR
- At least 3 days have passed since the resolution of fever without the use of antipyretics and improvement in respiratory symptoms AND
- At least 7 days have passed since the onset of symptoms

For more detailed guidelines on how to prevent infection, see the Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings (CDC).

Vaccine:

There is no FDA-approved vaccine yet available to prevent COVID-19. A Phase 1 clinical trial evaluating an investigational vaccine began on March 16, 2020, in the Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle, WA, USA. The vaccine is called mRNA-1273, and is designed to encode for a prefusion-stabilized form of the S protein. The trial will enroll 45 healthy adult volunteers aged 18 to 55 years over approximately 6 weeks.

References:

www.who.int/health-topics/coronavirus
www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html
coronavirus.jhu.edu/map.html
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