Major severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccine-associated adverse effects; benefits outweigh the risks.

INTRODUCTION: Since its emergence, there have been huge efforts to design vaccines against coronavirus disease 2019 (COVID-19) to inhibit its interpersonal spread. Global vaccine development is the most promising cost-effective method for overcoming the epidemic. However, following reports of post-vaccination thromboembolic adverse effects, there have been raising concerns about the safety profile of the COVID-19 vaccine. AREAS COVERED: We aimed to review the recent Food and Drug Administration (FDA)-approved vaccines and identify the organ-based major complications of COVID-19 vaccines based on reliable published studies. To find high-quality and large-scale observational, clinical trial, and cohort studies, PubMED, Scholar, Embase, and Web of Science were searched using keywords: COVID-19, SARS-CoV-2, vaccine, Pfizer (BNT162b2), Johnson and Johnson (Ad26.COV2), Moderna (mRNA-1273), Oxford AstraZeneca (ChAdOx1nCoV19), Coronavac (Sinovac), BBIBP-CorV (Sinopharm), adverse effect, and complication. To include all relevant articles, backward searching was also done on similar article citations. Case reports, studies including less than 10 participants, and biased articles were excluded. EXPERT OPINION: Based on data from high-quality and population-based studies, major adverse effects are divided into four major organ-specific groups, including cardiovascular, neurologic, hematologic, and immune-allergic side effects. The incidence of most of these side effects is not different between vaccinated and normal populations, and currently, the benefits of vaccination against COVID-19 are greater than the mortality and morbidity risks of COVID-19 infection. However, further studies, specifically systematic review and meta-analysis, are still indicated to investigate further unknown side effects of these vaccines and the existence of causality between the vaccine and reported adverse events.

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19).

Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung damage in COVID-19. This article aims to review the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL-6 signaling blockade at different levels, including IL-6 soluble and membrane receptor pathways, IL-6 downstream signaling (such as JAK-STAT) inhibition, and non-specific anti-inflammatory therapeutic approaches. Recent clinical data of each method, with specific concentration on tocilizumab, along with other new drugs, such as sarilumab and siltuximab, have been discussed. Challenges of IL-6 signaling inhibition, such as the risk of superinfection and hepatic injury, and possible solutions have also been explained. Moreover, to achieve the highest efficacy, ongoing clinical trials and special clinical considerations of using different IL-6 inhibitors have been discussed in detail. Special considerations, including the appropriate timing and dosage, monotherapy or combination therapy, and proper side effect managment must be noticed regarding the clinical administration of these drugs. Future studies are still necessary to improve the productivity and unknown aspects of IL-6 signaling blockade for personalized treatment of severe COVID-19.