Review, upgrade current clinical Covid-19 guidelines: Satish Ranjan

The alarming rise in Covid-19 cases in India indicates that the current virus variant has breached the higher degree of naturally acquired immunity as revealed by the previous sero-prevalence study in many cities. Emerging evidence among people getting infected post vaccinations suggests that the immunity induced even by a vaccination is being compromised, says Dr Satish Ranjan, PhD, an immunobiologist based in Germany and a Covid-19 scientific consultant.

With diagnosis and treatment becoming even more challenging, there is an urgent need to review the current clinical guidelines for upgradation andget it implemented in hospitals across India, Ranjan told BusinessLine .

Three main approaches

The clinical management of Covid-19 now hinges around three approaches, namely the reduction of viral load, managing the ‘cytokine storm’ and the risk of thrombocytopenia and thrombosis.

A focussed effort should be made to reduce the viral load with available drugs while use of multiple antibiotics in the absence of confirmed bacterial infection should be avoided. Use of antiviral drugs and convalescent plasma therapy should be judged on a case-by-case basis.

“One of the prime reasons for the increasing fatality rate is the cytokine storm leading to systemic inflammation and multiple organ failure,” says Ranjan.

What's a cytokine storm?

A Cytokine storm is most commonly used to describe an uncontrollable inflammatory response by the immune system. They are small glycoproteins produced by various types of cells throughout the body.

Upon release, they promote a wide range of functions, some of which involve the control of cell-proliferation and differentiation processes, autocrine, paracrine and/or endocrine activity, as well as regulating immune and inflammatory responses.

During such storms, various inflammatory cytokines are produced at a much higher rate than normal. This causes a positive feedback on other immune cells to occur, which allows for more immune cells to be recruited to the site of injury that can lead to organ damage.

One of the most notable clinical conditions associated with cytokine storms includes acute respiratory distress syndrome (ARDS) that has accounted for a significant number of deaths from SARS-CoV-2.

Elevated cytokine levels

Early detection of elevated levels of pro-inflammatory cytokines and early administration of pro-inflammatory cytokines inhibitors/blockers can save many precious lives, Satish Ranjan pointed out.

Currently, only the IL-6 level is detected to determine the cytokine storm. The cytokine profiling needs to be expanded to include the more pro-inflammatory ones associated with severe Covid-19, namely Tumor Necrosis Factor-α (TNF-α), Interleukin-8 (IL-8) and IL-1β, he opined.

With emerging scientific evidence that elevated levels of these cytokines are associated with severe Covid-19, likely resulting in higher fatality rate, it is a no-brainer that these are also included in the recommended profiling while prescribing specific inhibitors as well.

Common co-morbidities

The most prevalent co-morbidities among Covid-19 patients requiring hospitalisation are hypertension and diabetes, explains Ranjan. Several scientific studies suggest that in these patients and others, cytokine storm can lead to cardiac injury measured by elevated levels of Troponin I.

Elevated levels of Troponin I have been found to be associated with elevated levels of inflammatory markers including IL-6, CRP, ferritin and leukocytosis (increased WBC), demonstrating an important correlation between cardiac injury and hyper inflammation triggered by the viral infection.

Timely determination of increased levels of pro-inflammatory cytokines and administration of specific steroids/inhibitors can prevent cardiac injury and malfunctioning of other vital organs leading to multiple organ failure.

Low platelets count

Another major risk factor triggered by the viral infection is high risk of thrombocytopenia (low platelets count) and thrombosis diagnosed by elevated levels of D-dimer.

Suspected evidence of the vaccine (especially Covishield) inducing rare side effects of thrombosis and thrombocytopenia in rare cases and association of heparin with these events warrants use of non-heparin anticoagulants (Rivaroxaban or Apixaban) especially in those who have had infection post vaccination.

In the absence of proper classification of patients into vaccinated and non-vaccinated groups, it is advisable to review the use of current heparin (both unfractionated and low molecular weight-heparin) anticoagulant in all Covid-19 patients for managing the risk of thrombosis.

Treatment protocol details

Detailed guidelines need to be made available in each and every hospital regarding treatment protocol for different patients with different existing co-morbidities.

Clinical guidance must be frequently revised based on emerging scientific evidence to provide best and safer therapies to save lives. Healthcare facilities (diagnosis and treatment) should be expanded on a war footing so that even at primary/district level hospitals, severe cases can be managed.

Lack of complete diagnosis and corresponding treatment are likely adding to increasing case fatality rate. In the current situation, a treatment based on emerging facts and scientific evidence should be strictly adopted backed by expert consultations with immunologists and other subject matter experts.

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