The study reviewed 100 adults and 33 COVID positive children. The children were all asymptomatic and admitted to the covid ward for observation, however showed no signs of clinical or haematological deterioration. All the haematological parameters were well within normal physiological limits.
We limit our discussion to basic haematological parameters, coagulation screen and inflammatory biomarkers in Covid 19 positive adults upon hospital admission. Peak age of presentation was 55 to 60 years, with male to female ratio of 3:1. There was no significant difference in mean age and sex between the two groups (p>0.05).
Lymphocytopenia was a prominent and the most consistent feature in all affected patients, although ICU patients suffered from greater lymphocytopenia; thus significantly associated with severity. Lymphocytopenia has been conventionally known to occur in viral diseases. Affinity for the virus for lymphocytic ACE receptors may attribute to its direct cytopathic effect. While lymphocyteapoptosis due to increased granulopoiesis seen as an exaggerated inflammatory response could be another reason. Studies are of the opinion that lymphopenia can be an effective predictor severity in COVID 19, our findings supports this claim.
Additionally rise in TLC with high absolute neutrophil count was seen significant (p<0.05) and hence a high NLR and PLR was found. High NLR may be indicative of the patient’s response to inflammatory insult, with neutrophils rising in response to stress, which, when overwhelming, induces lymphocyte apoptosis[ 4–7]. Neutrophilshere seems act as a double edged sword. There are hypothesis that Neutrophil Extracellular Traps (NETs) released by neutrophils contribute to organ damage and death in COVID–19 patients. Also that development of Acute Respiratory Distress Syndrome (ARDS), thick mucus secretions in the airways and the development of blood clots, were similar to the symptoms of diseases already known to the researchers as being caused by NETs . Fox et al, Yao et al have documented neutrophil infiltration in the pulmonary capillaries of the three autopsy samples of COVID–19 patients further supports the theory that neutrophils may be responsible for mortality in these severe coronavirus cases [9,10]. Taken together, the high ANC with associated lymphocytopenia and hence a high NLR, seems to be an affirmation of dysregulated immune system which identify patients who have lesser physiological reserve to compete the inflammatory insult. In our study, NLR was found to have the most efficient screening parameter with AUC of 0.901 with maximum sensitivity (91%) and specificity (85%) at cut off at 6.9 to identify patients likely to have severe progression. Our results are in concordance with findings of other researchers who analysed NLR as a diagnostic/prognostic /predictor of severity in Covid 19 positive patients .
The inflammatory markers studied (wherever possible), like CRP, Ferritin and LDH also showed a markedly increased mean value in ICU patients but did not show statistical correlation (p>0.05). Researcher from China assessed the usefulness of CRP levels in the early stage of COVID–19 and found that it positively correlated with lung lesions and could reflect disease severity . Meta-analysis of reports from China have also detailed C-reactive along with D-dimers, coagulation times, and lactate dehydrogenase; with lower platelet and lymphocyte counts a common finding in "Cytokine Storm Syndrome" in hospitalized patients with COVID–19 . Others have also analysed CRP to look for association with the disease aggravation showed that CRP was significantly associated with aggravation of nonsevere COVID–19 patients . Elevated levels of these inflammatory markers found in the our study group concur to these hypothesis. However, presence of chronic comorbid conditions in many of these patients act as major confounder to establish their role in clinical worsening due to SARS-CoV 2 virus.
The mean values of Pt, aPTT, PT-Fg were not found to be significantly higher in ICU patients. D-dimer was found statistically significant in ICU group (p<0.05), when compared with HDU admissions. We refrain to compare D-dimer value of ICU patients with ward patients since most of the ward patients minimally symptomatic and were not tested.
Similar to us, results published from various studies from Wuhan, China reported elevated aPTT, elevated PT, elevated D-dimer, increased biomarkers of inflammation including interleukin–6 (Il–6), ESR, and CRP from first 99 patients hospitalized in Wuhan .
Report from another Wuhan hospital on the first 138 patients found minimal elevations in PT and normal aPTT, rising D-dimer in 5 non-survivors compared to 28 survivors . In contrary, Tang et al studied survivor status from admission of 183 COVID–19 positive patients analyzed over 14 days, and found that over their hospitalization, non-survivors had evidence of progressive DIC with decreased fibrinogen, increased D-dimer, and increased PT, occurring 10 days after admission, although information regarding evidence of sepsis was not provided .
We observed no thrombocytopenia in either ICU/HDU admissions or ward patients in our study. Together with no significant rise noted in ICU admissions supports the fact that “COVID–19 associated coagulopathy” proposed to be occurring early in infection, reflects abnormalities in tests but does not fulfill the usual definition of a clinical coagulopathy where impaired ability to clot results in bleeding. The development of coagulation test abnormalities seen in SARS-CoV–2 infected patients is most likely a result of the profound inflammatory response than intrinsic procoagulant effect of virus itself. The inflammation associated with COVID–19 might subsequently activate coagulation and is the probable cause for the elevated D-dimer levels, as increased levels have been associated with many conditions other than thromboembolism, with infection an important etiology [18–20]. The acronym COVID–19 associated coagulopathy (CAC) is being used to describe the coagulation changes in infected patients, although it needs even more evidence and research to establish its exact pathology and further, its role in treatment.
Procalcitonin was also studied as a sepsis marker in these patients, though it showed a higher mean value in ICU patients but did not show statistical significance in these patients.
Considering this disease as highly contagious and pestilent, we could not correlate the coagulation profile with clinical severity of the patients. The study has a limitation that no asymptomatic carrier was included. We could not analyze and study the prognosis of the included cases. Severity of the patients was assumed on the basis of admission to ICU, and not correlated clinically.
Our study suggests that in adults, TLC, ANC and NLR can be used as a screening tool to identify patients requiring intensive care and thus enable risk stratification, guide intervention.