Since Coronavirus has become an epidemic, physicians all over the world should be well-versed with the clinical features and lab tests that may help in the diagnosis and risk stratification of the Virus. The Coronavirus lab tests include ancillary tests that may help in the diagnosis and confirmatory tests that are used to diagnose the infection. Since the sensitivity of the diagnostic tests is low, physicians should not rely on a single test and should interpret the lab tests in light of the clinical presentations and epidemiological data of the patient.

The incubation period of Coronavirus:

The incubation period of the COVID-19 Coronavirus is 1 - 14 days. In the first five days, the disease is mild however, it is most contagious during the first five days.

Most patients start to deteriorate after the 10th day of the illness.

It is similar to SARS and MERs-CoV, however, it has a greater affinity for the ACE-2 receptors than the other coronaviruses.

Swabs from the nasopharynx and the throat have high viral loads. Patients with symptoms and those without symptoms can both spread the illness.

It has similar viral shedding as the influenza viruses.

What are the clinical features of Coronavirus infection?

The clinical features of Coronavirus infection are similar to any viral pneumonia. 80% of the patients develop a mild disease, 14% develop severe disease, and 5% of the patients develop a critical illness.

Most patients have:

• Cough
• Shortness of breath
• Fever
• Myalgias
• Fatigue

Less common symptoms may include:

• Sputum production
• Flu
• Nausea
• Vomiting
• Aiarrhea
• Chest pain
• Dizziness
• Confusion
• Headache
• Anorexia
• Abdominal pain
• Sore throat

Occasionally, and especially in children, patients may not develop any symptoms but they have radiological evidence of the infection.

Which individuals are at risk of severe illness?

Patients who fall into the following categories are more likely to experience serious illness and need to be identified:

• Long-term kidney disease
• People who have already had cardiovascular disease
• Those taking biologics
• A1c level of more than 7.6% in diabetics
• Those who have experienced hypertension
• Utilization of other immunosuppressive medications or a transplant history
• Older than 55 years old
• Those who already have a pulmonary illness
• All HIV-positive individuals, regardless of CD4 count

Note: It is also believed that antimalarial medications (such as hydroxychloroquine and chloroquine) can prevent pneumonia linked to COVID-19 and keep the illness to the upper respiratory tract. Thus, the prevention of Coronavirus infection involves the use of antimalarial medications.

Clinical signs that are suggestive of severe Coronavirus illness:

• Patients with a respiratory rate exceeding 24 breaths/min
• Heart rate greater than 125 beats/min, and
• SpO2 less than 90% on room air

Lab tests that suggest severe coronavirus infection:

• D-dimers exceeding 1000 ng/mL
• Elevated troponin
• Admission absolute lymphocyte count of less than 800/ul
• Ferritin greater than 300 ug/L
• CPK exceeding twice the upper limit of normal
• LDH greater than 245 U/L
• CRP exceeding 100

Age more than 70 and a high SOFA score is associated with poor prognosis.

Which laboratory tests should be run on individuals who have a coronavirus infection, whether they are suspects or not?

The following investigations may be ordered in the patients with Coronavirus infection [Ref]:

• Pulse oximetry:

  • It is advised for individuals with severe illnesses, cyanosis, and respiratory distress.
  • Pulse oximetry may show hypoxemia (SpO2 of less than 90%)

• ABGs (Arterial blood gases):

  • It is recommended in patients with severe disease as manifested by respiratory distress and cyanosis who have hypoxemia of pulse oximetry.
  • It will detect hypoxemia, hypercarbia, and acidosis.

• CBC (Complete Blood Counts):

  • All hospitalised patients and those with mild to moderate illness should have it.
  • The most common findings that may be seen in patients with Coronavirus infection include leukopenia, lymphopenia, and thrombocytopenia.
  • It is also done to rule out the possibility of a bacterial infection as indicated by a high leukocyte count.

Lymphopenia with normal WBC count is common in 80%

• Coagulation screen

  • It is ordered in patients with severe illness.
  • According to one study, patients who did not survive had considerably higher D-dimers, Prothrombin times, and activated partial thromboplastin times than those who did.
  • Patients with severe disease may have a prolonged prothrombin time and elevated D dimers.
  • D-dimers exceeding 1000 is associated with poor prognosis.

• Metabolic profile

  • In patients with serious illnesses, it is prescribed.
  • Renal impairment, low albumin, and elevated liver enzymes are frequently observed in individuals.

• Serum procalcitonin

  • In patients with serious illnesses, it is prescribed.
  • Patients who experience a subsequent bacterial infection typically have increased levels.

• Serum C-reactive protein

  • It is less specific but may be raised in patients with a subsequent bacterial illness.
  • In patients with serious illnesses, it is prescribed.

A high CRP is a marker of disease severity.

• Serum creatine kinase

  • It is ordered in patients with severe illness.
  • 13% to 33% of the patients may develop elevated levels of CK.
  • Elevated levels indicate injury to the myocardium.
•  

• Serum lactate dehydrogenase

  • It is ordered in patients with severe illness.
  • 73% to 76% of the patients had elevated levels of LDH.
  • It may indicate hemolysis and liver injury.

• Serum troponin levels

  • In patients who are critically unwell, troponin levels are ordered.
  • When someone has myocarditis, they might have increased levels.

Elevated troponin levels were found in half of the dead patients! It is considered as a marker for poor prognosis.

• Blood and sputum cultures

  • Before starting empiric antibiotics in any patient, blood and sputum samples for culture should be sent to rule out any other reasons for lower respiratory tract infection.

• Polymerase chain reaction with real-time reverse transcription (RTPCR)

  • Coronavirus infection must be verified using rt-PCR molecular testing.
  • In patients with a strong suspicion of coronavirus infection and negative initial testing, repeat sampling from multiple sites should be taken including the nose, sputum, and endotracheal aspirate is recommended after 48 - 72 hours.
  • Wherever possible, lower respiratory tract specimens should be acquired; however, if lower respiratory tract specimens cannot be obtained, nasopharyngeal and oropharyngeal specimens may be taken.
  • In some situations, the patient's blood, urine, and stools may be tested for the virus.

RT-PCR for COVID19 is only 70% sensitive and may be negative initially.

• Chest x-ray

  • A chest X-ray may reveal bilateral or unilateral lung infiltrates in 75% or 25% of patients, respectively.
  • In all patients with a suspected case of pneumonia, it should be requested.

• Computed tomography (CT) of the chest

  • In certain cases, CT abnormalities could be present before a SARS-CoV-2 RT-PCR test is positive.
  • Patients with a history of probable pneumonia and a normal chest X-ray should think about getting a CT scan of their chest.
  • Coronavirus infection does not cause lymphadenopathy, pulmonary nodules, effusions, or cavitation of the lungs.
  • Ground-glass pacification, numerous mottling, crazy-paving, and tiny nodular ground-glass pacification are among the CT findings (in children).

CT-scan of the chest has a very high sensitivity (97% of cases) and should be ordered in patients with strong suspicion and an initial negative PCR.

Coronavirus Lab Tests recommended for hospitalized patients:

Recommended daily lab tests:

• A whole metabolic panel
• CPK (creatine kinase)
• Differential counts on the CBC (Watch for the trend of absolute lymphocyte count)

Viral Serologies on admission:

• HIV1/2 antigens and antibodies (It is significant to note that Kaletra, which contains lopinavir and ritonavir, should not be administered to patients who are HIV/Covid-19 positive as a monotherapy.)
• HBV (Hepatitis B viral serologies including HepBsAg, HepBsAb, and HepBcAb
• HCV (Hepatitis C virus antibody

Coronavirus lab tests for risk-stratification:

• D-dimer
• Ferritin
• CRP (C-reactive protein)
• Troponin (Elevated troponin levels of more than twice the upper limits of normal in asymptomatic patients should be repeated after 48 hours. All symptomatic patients and those with rising levels should undergo an echocardiogram).
• ESR (erythrocyte sedimentation rate)
• Baseline ECG (Monitor for QT interval. If QT interval is prolonged >500 msec, consider stopping drugs that prolong the QT interval such as azithromycin and hydroxychloroquine).
• LDH (Lactate dehydrogenase)

Coronavirus lab tests to be done if clinically indicated:

• Routine two sets of blood cultures
• Send urinalysis and spot urine protein: creatinine in patients with acute kidney injury (i.e. serum creatinine of more than 0.3 above the baseline)
• Procalcitonin
• IL-6 concentrations in patients with a cytokine storm before receiving the first dose of tocilizumab.

Radiology in Coronavirus infection:

• CXR portable at entry
• Only if a non-contrast CT scan of the chest is likely to alter management or the status of the PUI (person under investigation), should it be considered.
• Only if there is a very low likelihood that a patient is carrying COVID-19 should a high threshold for PA and lateral view be taken into consideration.

Following up-to-date infection control guidelines and appropriate PPE:

• Test for SARS-CoV-2, if not already done.
• Send respiratory viral panel on all patients if available
• Send an influenza A/B and RSV (Respiratory syncytial virus) test if they are available.
• Only if clinically necessary should routine sputum for Legionella/Strep pneumonia urine antigen, bacterial gramme stain, and culture be ordered.

Suggested Coronavirus Lab tests for immunocompromised patients:

Pneumocystis DFA (direct fluorescein assay) from sputum should be sent, if possible. Consider submitting serum beta-d-glucan instead of sputum if the patient is unable to send any. If clinically necessary, send fungus cultures as well as AFB sputum smears and cultures.