Simple laboratory tests are playing an important role in risk stratification of COVID-19

SARS-CoV-2 continues to baffle medical experts with its presentations. It is crucial for clinicians to identify early, those who are at risk. This will aid them in recognizing the future need for admission to ICU, improve allocation of patients for specific therapies and initiation of preventive strategies.  

While initially it was assumed that the virus damages only the lungs, studies have concluded its impact on various other organs too. Routine parameters in blood and urine are useful to provide novel insights in the patho-physiology of COVID-19 and its severity. 

Significant reduction in Absolute Lymphocyte Count and Hemoglobin, is associated with increase in total WBC count, absolute Neutrophil count, ESR, Prothrombin Time and Pro-calcitonin. These lab findings, especially elevated Ferritin, suggest an imminent ‘Cytokine Storm’ which might lead to complications like Acute Respiratory Distress Syndrome (ARDS), Pneumonia and Multi-organ Failure (MOD).

Important laboratory parameters in COVID-19 patients:

Neutrophil-to-Lymphocyte Ratio (NLR)
Neutrophils and lymphocytes are types of white blood cells (WBC) that form an essential part of the body’s immune system. NLR is a simple parameter to assess the inflammatory status of a patient. The normal NLR values in an adult is between 0.78 - 3.53. In a study it was concluded that patients ≥50 years with a NLR ≥3.13 are at risk of severe illness, and should get rapid access to ICU, if needed.

Hematologic Microscopic Parameters
Lymphopenia (reduced lymphocytes in blood) is an important marker to indicate worsening of COVID-19, particularly in younger patients. Microscopic review of blood shows a higher number of patients who are lymphopenic with few reactive lymphocytes.

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Lactate Dehydrogenase (LDH)
LDH is an enzyme found in the heart, kidney, liver, muscle and body tissues and it catalyzes the conversion of sugar into energy. An increase in the serum levels of LDH (>200 U/L) is an indication of tissue damage. LDH is proving to be a marker of interest in determining the prognosis of patients with COVID-19. An elevated LDH in COVID-19 signifies a potential pulmonary injury or wide spread tissue damage. 

Experts have observed significant differences in LDH levels in patients with mild and severe infections. Several studies have indicated that elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. In fact, elevated LDH levels were found in >95% of non-survivors compared to <60% of survivors. 

C-Reactive Protein (CRP)
According to the IFCC guidelines, CRP is one of the markers to evaluate the severity of infection, prognostics, and therapeutic monitoring of COVID 19.

CRP is produced in the liver and released into blood in response to inflammation. Inflammation is the body’s way of protecting the tissues from damages due to autoimmunity, infection and other causes. Therefore, a high level of CRP in the blood is an indication of infection.

Patients with severe COVID-19, are prone to a cytokine storm, that can be fatal. A cytokine storm in an uncontrollable secretion of pro-inflammatory cytokines (small proteins secreted by the immune system to control the spread of infection) in a short span of time. A cytokine storm can thus trigger inflammation, leading to high levels of CRP in the blood. 

In COVID-19 patients, clinical deterioration occurs 7-10 days after the onset of symptoms. Interestingly, this is the time when viral titres decline, suggesting that deterioration is driven by inflammation rather than viral load. Thus, disease worsening has been more strongly linked to elevation of inflammatory markers such as CRP rather than age or co-morbidity.  

A CRP level of >50 mg/L, indicates severity of disease related to lung damage and worse prognosis. 

D Dimer
Evolving clinical resources confirm a convoluted role of abnormal blood clotting in COVID-19. D Dimer, a small protein left floating in the blood when a clot is degraded, is playing an important role in early identification of complications due to blood clotting (coagulation) in severe COVID-19 cases.

Inflammation caused due to a cytokine storm in a COVID-19 patient leads to narrowing of the blood vessels and an overactive coagulative system. 

Also, immobility and restricted activity during the course of treatment is causing an increase in the prevalence of Pulmonary Embolism (clotting in lungs). There is a disturbing trend that indicates that many people who have recovered from COVID-19 are getting re-admitted with breathing problems due to lung damage caused by PE.

Medical experts are relying on elevated D Dimer levels as an indicator of major clots. A D Dimer value >1000 ng/mL is alarming for a COVID-19 patient. A four-fold increase is a strong indicator of mortality in those suffering from COVID-19.

Urinalysis
SARS-CoV-2 affects not only lungs but also kidneys, and that too at an early stage of infection. COVID-19 associated kidney complications can be easily screened with a simple, inexpensive urine test that can reveal a wide range of abnormalities such as Proteinuria (increased protein in urine), Hematuria (blood in urine) and Leucocytouria (WBC in urine) days before rapid worsening of the COVID-19 infection.  

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Antibody tests
Antibodies are specialized proteins that destroy pathogens such as bacteria and virus in the body. Presence of antibodies against SARS-CoV-2 could be an indication of an asymptomatic infection or a past infection.

The presentation of symptoms and a positive RT-PCR test gives a confirmation of COVID-19 infection. However, there is a large population that remains asymptomatic and hence undiagnosed. Obviously, this can lead to a spread in the infection, if these asymptomatic carriers remain untraced. 

This is where antibody testing plays an important role. While RT-PCR and antigen tests assess the viral load in infected patients; antibody test helps in identifying asymptomatic individuals. 

Choosing the right tests
Today the market is flooded with assays for the above mentioned parameters. It is important to keep in mind certain key points while selecting a suitable kit. A kit that offers an excellent precision over a wide measuring range is preferred as it is more accurate. A test kit in varying pack sizes allows the pathologists flexibility to select the size depending on their workload, making the tests cost-effective for patients. Needless to say, the assay protocol should be based on the gold standard method for consistency in reporting. Also, laboratories prefer a kit that offers a long shelf life and remains stable in ambient conditions. A kit with ready-to-use reagents doesn’t require reconstitution and dilution and thus makes it user-friendly. 

The last and most important point is the after-sales application support. Manufacturers often supply test kits but do not provide after-sales support. In such a scenario, pathologists are often in a dilemma when they may need some technical assistance with calibration for running the assay. It is important to select a manufacturer with a wide network of well trained experts for round-the-clock assistance, especially in tier II-IV cities and towns.

With the right panel of analytes and appropriate testing kits, clinicians are able to effectively use risk stratification models for disease progression.