Shalendra Singh Its costly but a good drug to stop cytokine storm.

Is not a magic drug, latest one drug dose enough to control il6

Yesterday Maharashtra govt issued a guideline to give toci only one dose bw 5 to 9th day only when indicated

Shalendra Singh Its costly but a good drug to stop cytokine storm.

SARS-CoV-2 silences many of its host's immune defenses particularly during the first week of infection. The body is late in its responses and responds massively with a strong production of inflammatory cytokines to oppose the virus. Thus, the cytokine storm is a massive production of many cytokines. Cytokines always work in groups therefore attacking IL-6 alone does not lead to appreciable results. Tocilizumab is just an example of these drug effects.

The organism's inflammatory responses are of various types with the use of many pathways. Shooting in the pile on a single cytokine does not lead to effective results. Dexamethasone works best because it is non-specific and is much less expensive. All this also suggests that the body does not have feedback mechanisms to control inflammatory processes, which proceed without limits.

What about IL 6 level in ARDS pre- COVID era

Some small studies found that a plasma IL-6 level >400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival. In Italy, we have performed a wide study. AIFA (Italian drug agency), at the end of phase III of a national study, stated that "Tocilizumab reduces discharge times in treated patients" but "has not shown a statistically significant advantage in reducing mortality four weeks after its use and clinical improvement in patients with COVID-19". So in phase III, they found doubts about mortality. But the coordinator (Dr. Ascierto) says that the study suggests that there is no benefit in non-serious patients but does not rule out that there may be a subset of severe patients who could benefit from treatment with tocilizumab. Therefore, the knowledge of the plasma values ​​of some biomarkers, such as the basal values ​​of IL-6, CRP, Ferritin, D Dimer of individual patients is necessary to allow us to identify the subgroup of patients who could benefit from the drug. But the limit is that, if there is really a drug-sensitive subgroup, to know the basal values ​​of the markers of these specific patients, it is necessary to refer to their values ​​when healthy, which is almost impossible. Baseline values ​​for many of these markers differ from individual to individual. The limit of many markers, such as D-Dimer for example, is linked to their low specificity in the many physiological and pathological conditions associated with an increase. The baseline value may change according to age, sex, instrumentation in use, and methods, so the concentration of the D-dimer increases in all circumstances, specific or non-specific, associated with or characterized by fibrin formation and fibrinolysis. The same happens for IL-6 which in some situations is pro-inflammatory, in others it is anti-inflammatory.

The international Phase III CoVacta study achieved similar results. In fact, the efficacy of using tocilizumab compared with placebo did not show a statistically significant advantage in reducing mortality at 4 weeks and in clinical improvement in patients with COVID-19 ". While a Spanish national study says the drug would have had significant effects on a group of more severe patients connected to mechanical ventilators or who need oxygen, reaching similar conclusions to Ascierto.

Thank you sir @Giovanni Colonna

In recent study published in LANCET journal observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. However Results of ongoing randomised controlled trials are awaited.

Hay especies de plantas nativas que ayudan a mejorar el sistema inmune de las personas, asi como a mejorar el periodo convaleciente

It act by blocking IL-6 receptors and some clinicians felt inspiring clinical results including temperature returned to normal quickly and respiratory function improved.

General public think it is magic drug n is effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.

Avoid in liverdysfunction cases

Slightly lower trend of using it in my state

Tocilizumab is expected to decrease the mortality of severe COVID-19 patients. Preprint papers uploaded to medRxiv show it reduces mortality by only 3.8% – which becomes even less impressive when side effects listed by manufacturer are accounted for. They include risk of reactivation of tuberculosis along with other latent and bacterial, fungal and viral infections.

New data on covid are clearly showing that the aggressiveness of the virus is based both on the silencing of innate immunity and on the immunological deficiencies of individual patients. Many of the severe patients (around 15%) have immunological deficits because genetic causes (low levels of interferon I), others have a deficit in the immune response caused by an uncoordinated response of the adaptative immune defenses to the virus. Still, some immunotypes lack adequate feedback to control the cytokine storm. All of this suggests why different anti-inflammatory drugs give different and often only partial responses. The virus acts mainly by silencing innate immunity and using genetic alterations of adaptive immunity in its favor. Comorbidities no longer appear to be the primary target of the virus but only a critical complication in severe cases when the body begins to fail.

Furthermore, it must not be forgotten that cytokines never act alone but in very numerous and functionally independent groups, as has been demonstrated with multiplexing techniques where about 90 different cytokines were analyzed simultaneously in covid patients. Focusing on one or a few cytokines doesn't make much sense (and all the partial results show it). The real problem is the knowledge of the initial molecular strategies implemented by the virus on the immune defenses of the infected person. In the first 6 to 8 days, the virus silences the defenses and massively invades the body (already in the first 72 hours) without apparent symptoms. Waiting longer means relying on the chance and individual genetics because there are no effective and elective drugs to stop the virus. In the serious patients, we only try to alleviate some symptoms, and nothing more. Interferon I (which is a cytokine) should trigger the immune alarm in the first few hours, but it does not. We need to discuss and focus on this to save even more people.

Only symptomatic relief