COVID-19 infection affecting every one of us from last one year and continue to affecting so far through various new strains. Recently, new variant i.e.Omicron of COVID-19 is emerged and start spreading across the globe.The major objective today is to save the patients as we can from lethal effect of this virus. Reports have shown the massive increase in various inflammatory mediators of COVID-19 patients resulting in cytokine storm and death. Steroids are well known powerful anti-inflammatory agents available in the market for the management of various diseases. Thus, use of steroids in COVID-19 patients could have the potential to reduce mortality. However, there is lot of confusion regarding use of steroids in COVID-19 patients as unnecessary use of these agents could results in various adverse drug reactions (ADRs). This article briefly present role of immune system and the importance of steroids in COVID-19 patients. Further, the main findings of recent meta-analysis done by our team is also summarized.
COVID-19 is already declared as pandemic by World Health Organization and various new strains are also emergning across the globe and creating havoc. Vaccines are developed and showing a promising results in the prevention of this infection. The role of vaccine against new strains is complelty unclear so far. Further, till now, no specific drug is available for its treatment.Various classes of drugs such as specific antibiotics like doxycycline, azithromycin, etc, anthelmintics like ivermectin, anti-gout agents like cholchicine, anti-viral agents like remedesivir, favipiravir, etc, monoclonal antibodies like trastuzumab, antimalariral like hydroxychoroquinin, anti-inflammatory agents like indomethacin, Analgesics and antipyretics like paracetamolare being used in the management of COVID-19 patients depending upon the condition of the individual. Researchers across the globe working hard to come up with a specific molecule against this infection.
The SARS-Cov-2 enters into body and spike protein specifically attached to the angiotensin converting ezyme (ACE-2) of the host followed by entry of the virus inside the cell. The SARS-Cov-2 is a single stranded RNA virus which uses the machinery of the host cell and make millions of copies. As we know that immune system play a significant role in protection of body against exogenous agents. Immune system is broadly divided into two parts i.e. innate immune system and adaptive immune system. The skin, mucous membranes, white blood cells (WBCs) are part of innate immune system whereas T and B cells are parts of the adaptive immune system. Normally, skin protects us against harmful agents through keratin protein but if exogenous agents enter through mouth, nose etc, the mucous membrane contains specific enzymes which do degradation of these agents. Further, if exogenous agents entersinto blood circulation, WBCs will do the degradation and removal through the process of phagocytosis. The most important feature of immune system is to distinguish between self and non-self. The specific type of receptors called pattern recognition receptors (PRRs) act as a sensor for pathogen associated molecular pattern (PAMPs) of exogenous agents. The Toll like receptors (TLRs) is well known example of PRRs. If innate immune system is unable to handle as in case of SARS-Cov-2 infection, adapative immune system is activated. The activation of adaptive immune system usually take 5-7 days for activation and is activated through innate immune system. The antigen presenting cells (APCs) like dendritic cells, WBCs etc present the processed viral protein to T cell (adaptive immune system). The presenation of antigen is done through specific protein i.e. major histocompatibility complex (MHCs) and co-stimulatory signals. The activation of T cells release various cytokines which result in the clonal expansion. The released cytokines kill the antigen as well as activate cytotoxic T cells. The released cytokines also activates the B cells to produce antibodies. Unfortunatley, in case of SARS-Cov-2 infection, in some of cases, the immune system is unable to handle and result in overactivation which result in release of excessive cytokines. The excess release of cytokines could result in the death of patients also.
Steroids are well known powerful anti-inflammatory agents which are being used in the management of various diseases. Emergning studies have highlighted the importance of steroids in the management of COVID-19 patients. The regulatory authorities across the globe such as World Health Organization (WHO), National Institute of Health (NIH), Indian Council of Medical Research (ICMR)also recommended the use of steroids in COVID-19 patients under medical supervision as inappropriate use could results in various adverse drug reactions. The mechanism of action of steroids is well known, it act on the nuclear receptors and decrease the hyperactivation of immune response. The role of steroids in COVID-19 patients is unclear so far as well as there is a confusion among physicians.
Recently, we have analysed the available clinical data regarding use of steroids in reduction of mortality of COVID-19 patients. The study was conducted as per standard guidelines and registered with the International prospective register of systematic reviewsProspectively register of systematic reviews (PROSPERO). The studies were screened as per inclusion and exclusion criteria. A total of 21 studies (13 RCTs, 5CTs, 3 observational) were found suitable andanalysed using suitable software. The studies were also assessed for quality using standard scale. A total of 9,922 COVID-19 cases were found in 21 studies. The random effect model was used due to variation among studies. The odd ratio (OR) was calculated as overall estimate with 95% confidence interval (C.I.). The heterogeneity among studies was calculated by chochrane Q test and I2stastics. The publication bias was assessed qualitatively through funnel plot.
The results have shown a significant role of steroids in the reductions of deaths of COVID-19 patients. However, the publication bias was involved as indicated by funnel plot. The sensitivity analysis results also have shown no effect of outliers on the conclusion of the study. The heterogeneity among studies was found to be higher which was reduced after removal of outliers. We have also checked the effect of invidual steroids on the deaths of COVID-19 patients and found significant effect with methyl-prednisolone. However, more evidence is required for dexamethasone and hydrocortisone. Steroids are found to be life saving drugs in the COVID-19 patients.
In conclusion, steroids are useful in reduction of mortality of COVID-19 patients till further evidence. However, steroids should be used in supervision of physician only as unnecessary and overuse of steroids could results in various adverse drug reactions.
Thakur, M., Datusalia, A. K., & Kumar, A. (2021). Use of steroids in COVID-19 patients: A meta-analysis. European Journal of Pharmacology, 174579. DOI: https://doi.org/10.1016/j.ejphar.2021.174579.