Several human-tropic coronaviruses (CoVs) constantly circulate in the human population and usually cause mild respiratory disease. Two of these RNA viruses—SARS-CoV-1 and MERS-CoV—had been discovered in 2002 and 2012, respectively, as the cause of severe acute respiratory syndromes.

In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. The disease, termed coronavirus disease 19 (COVID-19), rapidly spread from China as a global devastating pandemic

SARS-CoV-2 and SARS-COV-1 are almost 79% identically similar in sequence. SARS-COV-1, SARS-COV-2 and Middle East respiratory syndrome viruses in the Coronaviridae family, with its positive-sense single-stranded RNA genome containing a surface glycoprotein, and viral envelope is coated by spike (S) glycoprotein, envelope (E), and membrane (M) protein.

S glycoprotein has 2 sub-units S1 and S2, N-terminal S1 subunit contains the receptor-binding domain that binds to the peptidase domain of angiotensin 1 converting enzyme 2 (ACE 2) and membrane-proximal S2 subunit helps in membrane fusion highly preserved and is considered a potential antiviral target.

It has been almost a year since the first case of SARS-COV-2 has been reported, and the pathogenesis is still based on cytokine storm, and as the SARS-COV-2 has the greater affinity to bind to ACE-2 receptors. On the airway epithelial cells and vascular endothelial cells a transmembrane cell surface protein (serine protease 2) the virus bind to ACE 2 receptor which is in synergy with the host's transmembrane serine protease 2 receptor.

Predicting the prognosis and outcome is a bit challenging for physicians. COVID‐19 causes high mortality with widespread inflammation and cytokine storm, excessive activation of the immune system and monocyte‐macrophage system activation, damage occurs in many organs, especially the lungs.

At present day, there are 104 million cases and Indian stats say around 11 million cases have been reported till the day, with an average of 8,000 news cases per day with a significant reduction in the death rate of an average 100 per day in India.

Graphical representation of data: MS Excel and MS word was used to obtain various types of graphs such as bar diagram.

p-value (Probability that the result is true) of <0.05 was considered as statistically significant after assuming all the rules of statistical tests.

Statistical software: MS Excel, SPSS version 22 (IBM SPSS Statistics, Somers NY, USA) was used to analyze data.

Table 1: D Dimer levels concerning the outcome.

In the study there was no significant difference in mean D Dimer levels concerning the outcome. Mean D dimer was high among subjects who required NIV and low among subjects who required O2.

Table 2: Serum LDH levels concerning the outcome.

In the study there was a significant difference in mean serum LDH levels concerning Outcome. Mean Serum LDH was high among subjects who required NIV and low among subjects who required Room air.

Table 3: Serum Ferritin levels concerning the Outcome.

In the study there was a significant association between Outcome and Serum Ferritin levels. Among subjects with normal Ferritin levels, 32.5% required O2, 12.5% were required NIV and 2.5% were intubated, were as among subjects with increased Ferritin levels, 49.3% required O2, 28.4% required NIV and 6% were intubated.

Our study show's that elevated levels of serum ferritin, serum LDH and D-dimer had shown to be requiring higher O2 support and some of the patient requiring non-invasive ventilatory support. The effect of D-dimer, serum LDH and serum ferritin individually and combinedly showed in our study there was no significant difference between D-dimer and the outcome however there was a significant p-value of <0.001 with serum LDH and the outcome, and p-value of 0.016 with serum ferritin and outcome.

In our study there was a significant association between D-dimer and the outcome which showed, increase in D dimer levels there was a need for O2, NIV and Intubation compared to those with normal D Dimer levels. Among subjects with normal LDH levels, 21.1% required O2 and 5.3% were intubated, were as among subjects with increased LDH levels, 47.7% required O2, 27.3% required NIV and 4.5% were intubated.

Among subjects with normal Ferritin levels, 32.5% required O2, 12.5% were required NIV and 2.5% were intubated, were as among subjects with increased Ferritin levels, 49.3% required O2, 28.4% required NIV and 6% were intubated.

As SARS-CoV-2 has spread globally it has accumulated some mutations in the viral genome, which contains geographic signatures [7]. even though the virus had attributed some mutations but does not affect the pathogenicity and transmissibility [8]. Spike glycoprotein helps in the binding which is the first step of infection to the host, such binding triggers a cascade of events leading to the fusion between the host cell and viral membranes entry of the virus into the host cell.

There are many different variants out of which the newer one G614 variant has been hypothesized to increase infectivity and transmissibility of the virus. With the G614 variant higher viral load was observed although no association was made with severity in outcomes, These findings have yet to be confirmed with regards to natural infection.

In our study, the elevated levels of serum ferritin show a higher requirement of o2 support or even requiring mechanical ventilator support.

Elevated Serum LDH levels along with elevated ferritin levels in patients who have widespread inflammation are observed leading to ARDS.

Lactate dehydrogenase (LDH) is an enzyme that helps in the conversion of lactate to pyruvate in the cells and LDH is elevated when there is increased tissue breakdown and involved in the various pathophysiological process.

Elevated serum LDH is observed in many various clinical conditions, such as hemolysis, cancer, severe infections and sepsis, liver diseases, hematologic malignancies, and many others. Some studies suggesting that the serum LDH levels serves as a non-specific indicator of cellular death.

LDH is released from cells upon damage to their cytoplasmic membrane and is not only a metabolic but also an immune surveillance prognostic biomarker [19],[20]. LDH increases the production of lactate, which leads to the enhancement of immune-suppressive cells and inhibition of cytolytic cells [21]. These changes could weaken the immune response mounted against the viral infection, resulting in more severe disease in patients with elevated LDH.

LDH is validated for its potential usefulness as biochemical markers for assessing clinical severity and to monitor treatment response in COVID-19 pneumonia increase in LDH has a high specificity for disease progression inflammatory responses reflected the nonspecific responses to hypoxia, tissue injury, and necrosis, indicating a correlation between infectious cells, immune system and inflammatory response variable studies have shown that an elevated serum LDH is an indicator for poor prognosis.

Cytokines normally mediate and regulate immunity, inflammation, and hematopoiesis; however, further exacerbation of immune reaction and accumulation of cytokines in other organs in some patients may cause extensive tissue damage, or a cytokine release syndrome (cytokine storm), resulting in the capillary leak, thrombus formation, and organ dysfunction.[22,23].

There is strong evidence that dysregulated and excessive cytokine release is responsible for rapid progression and high mortality [24,25].

Activation of host defence systems results in subsequent activation of coagulation and thrombin generation as critical communication components among humoral and cellular amplification pathways, a term called thromboinflammation or immunothrombosis.

During infections and sepsis increased fibrinolysis have been reported these changes might be due to reductions in coagulation factors which is considered as a fibrinolytic phase of DIC, which may be a late step with advanced disease, and might explain why high D-dimers are associated with the progression of the disease and worse outcomes.

Some patients appear to have a more pronounced inflammatory response to infection with SARS-CoV-2, such as seen with systemic inflammatory response syndrome or cytokine storm, which may explain more dramatic changes in coagulation tests, including significantly elevated D-dimer, especially as the disease progresses

As discussed earlier inflammatory effects of cytokines leading to vascular endothelial dysfunction with SIC, an endothelioma appears to contribute to the pathophysiology of microcirculatory changes in SARS-CoV-2 infections.

Viral replication in the host target cells causing inflammatory cell infiltration, endothelial cell apoptosis, and microvascular prothrombotic effects.

Microcirculatory changes (or) dysfunction contributes to the clinical sequelae in patients with COVID-19.

From a clinical perspective, in addition to the systemic hypercoagulability and potential threat for thromboembolic complications, the described microvascular endothelial injury with microcirculatory clot formation noted, In severe cases of COVID -19 Infection induced coagulopathy and secondary hyperfibrinolysis had been identified. Higher D-dimer levels at the time of admission are suggestive of a worse prognosis of COVID-19. The presence of the SARS-CoV-2 virus within endothelial cells suggests that direct viral effects, as well as perivascular inflammation, may contribute to endothelial cell injury. Likely, endotheliosis, endothelial injury, endothelial cell dysfunction and impaired microcirculatory function in different vascular beds contribute markedly to life-threatening complications. Pulmonary thrombosis is mostly responsible for the elevation of D-dimer in severe case although more studies required.