Dr Barnali Das, consultant, biochemistry & immunology, Kokilaben Dhirubhai Ambani Hospital, Mumbai analyses the importance of biomarker monitoring in admitted COVID-19 patients as they play an essential role in patient admission protocol, assessment of staging of disease according to severity, prognostication, patient monitoring and therapeutic guide
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection originating from Wuhan in China, has infected over sixteen million people (WHO dashboard; 8:00 AM CEST, July 28th, 2020: 16,301,736 confirmed cases) worldwide, and led to deaths of over 6,50,069 people across the globe.
In India the total active cases estimated now is 4,96,988 and 33,425 people have already died from the highly contagious virus. National capital Delhi and financial capital Mumbai account for 40 per cent of the total number of deaths reported in India. The number of recoveries continues to be more than the number of active cases in India. As the number of individuals infected with COVID-19 continues to rise worldwide, as well as in India, it is clear that the routine laboratory will play an essential role in this crisis, contributing to patient monitoring/ treatment, as well as prognostication.
We have evaluated the role of routine laboratory biomarkers and observed statistically significant abnormal values of biochemical and immunoassay parameters: C Reactive Protein (CRP), Procalcitonin (PCT), Lactate Dehydrogenase (LDH), D-Dimer, Interleukin 6 (IL6), Ferritin, Blood Gases, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Serum Albumin, Total Bilirubin (T Bil), and Creatinine in COVID 19 patients, who are admitted with rRT-PCR positive test results of SARS-CoV-2 in nasopharyngeal or oropharyngeal samples in Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute at Mumbai.
The critical role of laboratory medicine in this pandemic extends far more than etiological diagnosis of COVID-19. Biochemical monitoring of COVID-19 patients through testing is critical for assessing disease severity and progression, as well as monitoring therapeutic intervention. In addition to more common laboratory tests like, LFT, KFT, blood gas etc., new evidence suggests that patients with severe COVID-19 could be at risk of cytokine storm syndrome. Cytokine tests, particularly IL-6, should be used to assess severe patients, suspected of hyper inflammation. Severe COVID-19 associated pneumonia patients, with features of systemic hyper-inflammation, are designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm.
These markers play an essential role in patient admission protocol, assessment of staging of disease according to severity, prognostication, patient monitoring and therapeutic guide.
We analysed the retrospective routine laboratory data of the COVID-19 cases admitted in Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute. Amongst the total patients that carried out Interleukin-6 (IL-6) and NtProBNP test, 100 per cent of the patients showed an increase. Elevated levels of CRP were seen in 86.274 per cent patients, PCT in 69.23 per cent patients, D-Dimer in 92 per cent patients, Ferritin in 80.952 per cent patients, LDH in 90 per cent of patients, White blood cells (WBC) IN 67.273 per cent patients, Neutrophils in 67.273 per cent patients, Blood urea nitrogen (BUN) in 52.778 per cent patients, Aspartate aminotransferase (AST) in 50 per cent patients and creatinine in 41.025 per cent patients.
On the other hand, decreasing levels of PO2 were seen in 82.353 per cent patients, SO2 in 82.352 per cent patients, albumin in 86.363 per cent patients, total protein in 59.259 per cent patients, lymphocytes in 83.636 per cent patients and eosinophils in 83.636 per cent patients. To explain the role of routine laboratory parameters in disease monitoring, let’s demonstrate the routine lab parameters of one case.
An elderly male who was known case of diabetes, hypertension and chronic kidney disease on maintenance haemodialysis was presented to the hospital with a complaint of very high grade fever since three days along with breathing difficulty and generalised weakness.
The patient had no travel or contact history. The patient tested positive for SARS-CoV-2 by reverse transcriptase polymerase chain reaction (rRT-PCR) using nasopharyngeal swab. Chest X-ray showed bilateral lung infiltrates. The routine laboratory findings supported the diagnosis with elevated levels of Interleukin-6 (650.5 pg/ml), C Reactive Protein (17.3 ng/ml), Procalcitonin (2.02 ng/ml), High Sensitive Tropinin I (45.9 pg/ml), D Dimer (3298.31 ng/ml), Ferritin (>40000 ng/ml), LDH (745.2 U/L), Creatinine (4.5 mg/dl), Blood Urea Nitrogen (29.5 mg/dl), Neutrophil count (85.7 per cent), Absolute Neutrophil count (11 X 103/microL) Lactate (3.3 mmol/L) and decreased levels of Albumin (3.62 g/dl), Total Protein (6.3 g/dl), SO2% (85.2 per cent), Lymphocyte count (6.2 per cent), Absolute Lymphocyte count (0.8 X 103/microL) and Platelet count ( 132 X 103/microL).
Here, we are giving example of importance of biomarker monitoring in admitted patients. For example, if we consider IL6, CRP, PCT, D-Dimer, Ferritin and LDH in one critical patient admitted patient, we can see sequential rise of those markers in cytokine storm.
The ongoing pandemic of COVID-19 is characterised by respiratory illness and diverse systemic clinical presentations, which in turn are reflected by routine laboratory abnormalities, based on severity of disease presentation. The main laboratory changes encompass an array of increased inflammatory biomarkers, coagulation parameters, tissue-specific tissue injury indicators (liver, kidney, cardiac) and derangement of the complete blood count. Based on severity of disease, host inflammatory response to virus may lead to cytokine storm that can cause multi-organ damage. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly deranged in patients in the critical stage of COVID-19. In hospitalised patients, there should be close monitoring of C Reactive Protein (CRP), Procalcitonin (PCT), Lactate Dehydrogenase (LDH), D-Dimer, Interleukin 6 (IL6), Ferritin, Blood Gases, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Albumin, Total Bilirubin (T Bil), and Creatinine, WBC count, Neutrophil Count, Lymphocyte count and Platelet count, as markers for potential progression to critical stage of the illness and fatality.
Of the many challenges in COVID-19 pandemic, understanding the pathogenesis of the disease is formidable. The clinical picture of COVID-19 spans many organ systems but the respiratory failure is the most serious clinical feature. We need to understand in greater detail what determines the disease severity and disruption of the immune system. The surges in IL-6, IL-10 and TNFɑ and decreased levels of CD4+ and CD8+ cells contribute largely to the pneumonia. Studies like the one carried out by Dr. Barnali Das are important to understand the pathogenesis of the disease and more importantly, to design therapeutic strategies.