COVID-19 pandemic has affected all age groups, breached geo-political barriers, stunned the healthcare, economic and social systems of countries across the globe. The death toll is over a million till date. The unpredictable course of COVID 19 mandates the need for early clinical and laboratory markers of outcome. In resource limited settings triage could prioritize patients who need hospitalization and intensive monitoring. To date, the search for such specific and cost effective biomarker is elusive to the scientific community . Accumulating body of evidence suggest that inflammatory mediators like IL-6, ferritin, LDH and CRP play a critical role in the progression of COVID-19 . Therefore, these biomarkers play an indispensable role in not just clinical management but timely screening of patients who are on the trajectory to severe disease. Though measurement of inflammatory markers can bear prognostic implications, uncertainties exist on the optimal timing and right combination. Whether their cumulative validity is additive is another grey area. We studied the association between one time measured biomarkers like ferritin, LDH, CRP and D-dimer on the 7-10 th day illness and the observed mortality.
It is common knowledge that underlying organ damage occurs due to activation of the complement system, inflammatory cascades and proinflammatory cytokines in severe COVID 19. Circulating levels of free thrombin activate platelets and dysregulated fibrinolysis portrayed by elevated D-dimer levels were observed to associate with severe COVID disease in previous research work. Moreover they were instrumental in guiding anticoagulant therapy among COVID patients. Akin to other published reports, we observed a significant rise in D-dimer levels in our patients as well who suffered severe COVID [OR 1.020, p<0.001]. Interestingly we also found out that performing D-dimer for all admitted patients was not cost effective and the productivity was enhanced when done approximately 7th – 10th day of symptoms and on those requiring oxygen therapy to maintain SpO2 of > 94%.
CRP is a sensitive marker of acute-phase response in inflammation, infection, and tissue damage  whose potential has been exploited in COVID as well. In the study by Chen et al., although no statistically significant difference was found in the level of CRP between the nonsevere and the severe group, the mean level of CRP was higher in the latter . Henry et al also reported significant increases in ferritin and CRP levels in patients with severe COVID-19, consistent with the earlier findings . In our case series we measured CRP only by qualitative method however documented statistically significant CRP positivity with severe COVID 19 disease [p <0.001]. Two other pertinent findings surfaced in our study, firstly, qualitative method of CRP was sufficient to triage patients which could considerably reduce the cost burden. Secondly, internal comparison among the study participants revealed that one-time performance of the test had the same prognostic accuracy as repeat measurements done on day 15 and 20 of symptoms.
Markers such as ferritin and CRP have an important role to play in a country like India, where IL-6 cannot be so widely estimated due to high cost. The elevated ferritin levels are probably due to secondary phagocytic lymphohistiocytosis and severe cytokine release syndrome [19, 20]. Pastora J et al. in a systematic review on the utility of ferritin in COVID-19 found that ferritin concentrations of COVID-19 patients were generally within the normal range of less than 400 ng/ml in non-severe disease  .However, hyperferritinemia (ferritin level > 400 µg/L), was observed in patients with severe disease on admission, precisely between 1.5 and 5.3 times higher. The author evaluated studies comparing ferritin levels on admission between COVID-19 survivors and non-survivors and demonstrated that non-survivors showed ferritin levels on admission around 1400 ng/mL, which is between 3 and 4 times higher than survivors. Our observations parallel that of other researchers with a mean ferritin value of 1199.50 ng/mL in severe group. The unadjusted odds for patients suffering severe covid was 1.007 in patients with elevated ferritin levels. The finding provides clinicians with a cost effective, point of care triage tool to optimize outcomes in resource limited settings.
A previous study found significantly higher levels of LDH in ICU patients than non-ICU patients (248 U/L vs 151 U/L, p=0.002). Since high levels of LDH continued in the ICU patients for a number of days post-admission (160 U/L vs 218 U/L, p=0.002), LDH was speculated to predict mortality. However, this being a single centre study was prone to selection bias with doubtful validity. A multi-centric study involving 1099 patients reported strong evidence correlating extent of tissue damage and inflammation with increasing levels of LDH which corroborated well with CT scan scoring of severe COVID 19 pneumonia. In our study LDH charted a significant rise among patients with severe COVID 19 [OR 1.004/p<0.001]. This increase observed in our series is consistent with the findings of Liu who correlated LDH, lymphocyte, neutrophil, and CRP abnormalities with severe COVID pneumonia .
The viral particles spread through the respiratory mucosa, first using the ACE2 receptor at the level of ciliated bronchial epithelial cells and then infecting other cells. Cytotoxic lymphocytes and natural killers play a key role in controlling the spread of infection which becomes relentless if lymphocyte count deplete. The number of lymphocytes particularly CD4 type can serve as a surrogate marker of severity and mortality in COVID 19 disease . Lymphocytopenia directly correlates with disease severity and death with three-fold higher risk of poor outcome, in younger patients compared to older . Other hematological markers of significance are high Neutrophil Lymphocyte Ratio and thrombocytopenia which have been associated with adverse outcomes in COVID 19 patients. Elevated NLR is conducive to a dysregulated cytokine elaboration whereas low platelet counts resulted from microthombi and vascular occlusion of pulmonary vessels (27). In our study, we documented a strong predilection between high NLR and poor outcome of COVID 19, however thrombocytopenia was not statistically significant.
Other relevant findings in our study included an older age and longer hospital duration being predictive of COVID mortality. Similar relevance to age factor has been reiterated in research work both regional and global .