COVID-19 laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2] Shakiba Hassanzadeh, MD[3]

Overview

Laboratory tests can be done to confirm whether illness may be caused by human coronaviruses. Specific laboratory tests include serology for viral antigen, molecular testing and viral culture. All these tests can be used to confirm infection with coronavirus. Non-specific laboratory findings in COVID-19 include lymphocytopenia, thrombocytopenia, elevated C-Reactive protein, elevated liver function tests (ALT, AST), increased creatine kinase, increased D-Dimer and an increase in the levels of markers of cell damage e.g. troponin, lactate dehydrogenase, interleukin-4, procalcitonin.

Tests to be Performed for Patients Meeting COVID-19 Case Definition

Antigen tests

Abbott BinaxNOW Ag Card detects the SARS-CoV-2 nucleocapsid protein antigen but does not differentiate between SARS-CoV and SARS-CoV2.

Molecular tests

Molecular tests are used to diagnose active infection (presence of COVID-19) in people who are thought to be infected with COVID-19 based on their clinical symptoms and having links to places where COVID-19 has been reported.

Real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays are molecular tests that can be used to detect viral RNA in clinical samples.

Nucleic acid amplification test

• The importance of the need for confirmation of results of testing with pan-coronavirus primers is underscored by the fact that four human coronaviruses (HcoVs) are endemic globally: HCoV-229E, HCoV-NL63, HCoV-HKU1 as well as HCoV-OC43. The latter two are betacoronaviruses. Two other betacoronaviruses that cause zoonotic infection in humans are MERS-CoV, acquired by contact with dromedary camels and SARS arising from civets and cave-dwelling horseshoe bats.

• The accuracy of nucleic acid amplification tests have been systematically reviewed.
• PCR has been used to test salivary specimens.

Serological testing

• Serological testing may be useful to confirm immunologic response to a pathogen from a specific viral group, e.g. coronavirus.
• Best results from serologic testing requires the collection of paired serum samples (in the acute and convalescent phase) from cases under investigation.
• The accuracy of serologic tests have been systematically reviewed.

Tests to be performed for patients meeting case definition
Laboratory Test	Source of Specimen	Additional Comments
In laboratories that have validated broad coronavirus RT-PCR assays it is advised to check the primers against the published 2019-nCoV sequence and check if primers are overlapping and have the capacity to detect the 2019-nCoV. On a positive results sequencing should be performed to determine the precise virus detected (e.g. on an amplicon of a non-conserved region).	Respiratory secretions	Collect on presentation. Done by an expert laboratory.
NAAT for 2019n-CoV when it becomes available (assays currently under validation)	Respiratory secretions	Collect on presentation. Done by an expert laboratory until validation has been finalized.
Serology, broad corona virus serology on paired samples if available.	Respiratory secretions	Paired samples necessary for confirmation, the first sample collected in week 1 of illness, and the second collected 3-4 weeks later. If a single serum sample can be collected, collect at least 3 weeks after onset of symptoms. Done by the expert laboratory until more information on the performance of available assays.

Laboratory Findings

Complete Blood Count

Complete blood count may show the following:

• Anemia

• Leukocytosis
  • Leukocytosis is seen in 11.4% of patients with severe COVID-19 infection compared to 4.8% of patients with non-severe infection.
  • In patients with COVID-19 infection, leukocytosis may be an indication of a bacterial infection or superinfection.

• Neutrophilia

• Lymphocytopenia

• Increase in monocyte distribution width (MDW)
  • MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.

• Thrombocytosis
  • Thrombocytosis has been reported in 4% of patients with COVID-19 infection.

• Thrombocytopenia

Acute Phase Reactants

The following inflammatory markers may be altered:

• Increased C-reactive protein
  • Increase in CRP is seen in 81.5% of patients with severe COVID-19 infection compared to 56.4% of patients with non-severe infection.
  • CRP is an acute phase reactant that increases in conditions with inflammation.
  • In patients with COVID-19 infection, increase in CRP may be an indication of severe viral infection or sepsis and viremia.

• Increased IL-6
  • Increase in IL-6 has been reported to be associated with death in COVID-19 infection.
  • Increased level of IL-6 is an indicator of COVID-19-associated cytokine storm.

• Increased procalcitonin
  • Increase in procalcitonin is seen in 13.7% of patients with severe COVID-19 infection compared to 3.7% of patients with non-severe infection.
  • In sepsis, the activation and adherence of monocytes increase procalcitonin, therefore procalcitonin in a biomarker for sepsis and septic shock.
  • In patients with COVID-19 infection, increase in procalcitonin may be an indication of bacterial infection or superinfection.

• Increased ferritin
  • There have been different reports regarding the association of increase in ferritin with death in COVID-19 infection; for example, there has been a report that increase in ferritin is associated with acute respiratory distress syndrome (ARDS) but not death, while another one reports an association between increase in ferritin and death in COVID-19 infection.
• Decreased albumin
  • As a negative acute‐phase reactant, circulatory level of albumin may fall as a result of increased transcapillary leakage or reduced hepatic synthesis mediated by inflammatory cytokines such as interleukin‐6 and tumor necrosis factor alpha. Consequently, hypoalbuminemia may indicate a hyperinflammatory status associated with COVID-19.
  • Albumin may be decreased in many conditions such as sepsis, renal disease or malnutrition.
  • In patients with COVID-19 infection, decrease in albumin may indicate liver function abnormality.

Liver Function Tests

The following abnormalities may be observed on LFTs:

• Increased aspartate aminotrasnferase (AST):
  • Increase in AST is seen in 39.4% of patients with severe COVID-19 infection compared to 18.2% of patients with non-severe infection.
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.
• Increased alanine aminotransferase (ALT):
  • Increase in ALT is seen in 28.1% of patients with severe COVID-19 infection compared to 19.8% of patients with non-severe infection.
  • ALT is produced by liver cells and is increased in liver conditions.
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.
• Increase in total bilirubin
  • Increase in total bilirubin is seen in 13.3% of patients with severe COVID-19 infection compared to 9.9% of patients with non-severe infection.
  • Bilirubin  is produced by liver cells and increases in liver and biliary conditions.
  • In patients with COVID-19 infection, increase in total bilirubin may indicate injury to the liver.

Renal Function Tests

Renal function tests may show the following:

• Increased BUN
• Increased creatinine
  • Increase in creatinine is seen in 4.3% of patients with severe COVID-19 infection compared to 1% of patients with non-severe infection.
  • Creatinin is produced in the liver and excreted by the kidneys; creatinine increases when there is decrease in glomerular filtration rate.
  • In patients with COVID-19 infection, increase in creatinine may indicate injury to the kidneys.

Markers of Cell Damage

The following markers of cellular damage may be altered:

• Increased troponin
  • In myocardial infarction and acute coronary syndrome are used for diagnosis.
  • In patients with COVID-19 infection, increase in cardiac troponins may indicate cardiac injury.
• Increased myoglobin
• Increased lactate dehydrogenase (LDH)
  • Increase in LDH is seen in 58.1% of patients with severe COVID-19 infection compared to 37.2% of patients with non-severe infection.
  • LDH is expressed in almost all cells and an increase in LDH could be seen in damage to any of the cell types.
  • In patients with COVID-19 infection, increase in LDH may indicate injury to the lungs or multi-system damage.
• Increased creatine kinase