Introduction
COVID-19 vaccines are considered of utmost importance to stem SARS CoV-2 current pandemic, with 48 candidates in clinical evaluation, including seven adenovirus, five messenger RNA (mRNA) and one self-amplifying RNA based vaccines encoding spike protein of SARS CoV-2 as declared by the WHO on the 12th of November 2020[1, 2]. However, the unprecedent accelerated timelines to develop some of COVID-19 vaccines have necessitated a call for active pre and post-licensure safety surveillance systems to properly investigate potential adverse effects or toxicities [1, 3]. Importantly, two adenovirus vector-based SARS CoV-2 vaccine global phase III clinical trials were temporarily paused due to reports of serious adverse medical events of autoimmune complications including multiple sclerosis and transverse myelitis which were ultimately deemed to be unrelated to the SARS CoV-2 vaccine. However, lack of transparency concerns have been raised as the involved companies declined the release of the thorough details of these serious adverse events claiming privacy issues [4-7] and a sharp criticism of the analysis of the results of one trial including a serious dose mistake that involved thousands of patients has also been raised[8]. Notably, adenovirus vector SARS CoV-2 vaccine has been first commercially approved in humans in Russia and is undergoing a mass vaccination program[9, 10].
RNA based vaccines potential hazards
 On the other hand, RNA based vaccines, recently first approved in UK for COVID-19 as a first ever approval for this novel type of vaccination in a western country [11], possess multiple theoretical and manufacturing advantages over traditional subunit, live attenuated and killed virus vaccines[12-14]. However, in practice the results of two previous clinical trials using mRNA vaccines to prevent H10N8, H7N9 influenza viruses and rabies have been lower than what was expected when compared to those of their preclinical studies[13]. Similarly, though mRNA vaccines encoding HIV and CMV antigens elicited antigen-specific CD4+ and CD8+ T cell immune responses; no reduction in viral load was observed[12].
Similar to adenovirus vector-based vaccines, potential risks of mRNA and saRNA based vaccines also include risk of potential autoimmunity with possible development of autoreactive antibodies of any non-native nucleotides and delivery system components [13, 15, 16]. All SARS CoV-2 adenovirus vector and RNA vaccines phase III clinical trials involved only tens of thousands of patients and this risk cannot be fully excluded until post marketing safety data prove their safety. Notably, soon after its mRNA based SARS CoV-2 vaccine approval, the UK Medicines and Healthcare products Regulatory Agency advised people with a history of significant allergic reactions to medicines, food or vaccines not to have the jab [17] and the identification of individuals at an increased risk of autoimmune reactions before mRNA vaccination was advised[13]. We would like to explore some groups of individuals who are potentially more vulnerable to autoimmune diseases, aiming to recommend a personalized risk benefit ratio to be considered before a decision to be immunized by adenovirus and RNA based SARS CoV-2 vaccine until encouraging post marketing safety data are revealed for all SARS CoV-2 types of vaccines.
Who are the higher-risk groups, and could we lower their chances to develop autoimmune diseases?
The first higher-risk group are smokers; cigarette smoke has been reported to lead to an enhanced risk of inflammatory and autoimmune diseases[18]. Smokers are more likely to develop critical COVID-19 requiring mechanical ventilation [19] that might lead to a higher mortality rate [20, 21]. Interestingly, alarms about the danger of misreading non-significant or inconclusive frequentist results containing several possible biases of a contradictory hypotheses have been raised [22, 23].
Two other important groups that might be closely monitored include obese and diabetic individuals; obesity was suggested to be a major environmental factor contributing to the onset and progression of autoimmune diseases[24] and a concomitant autoimmune disease was encountered as 1 in 4 of 179,248 people diagnosed with type 1 diabetes[25]. Notably, a meta-analysis has showed diabetes, but not obesity, to be linked to a higher COVID-19 mortality[26]. However, increasing risks of COVID-19 hospital death were noticed to be associated with increasing levels of obesity (BMI >40 fully adjusted HR 2.27, 95% CI 1.99-2.58)[27].
Interestingly, quitting smoking at diagnosis was recently shown to decrease the risk of death in cancer patients[28], and quitting smoking was suggested to alleviate its impact in patients with pneumonia and other COVID-19 associated infections[21, 23, 29], thus a beneficial advice to quit smoking together with another to lose overweight and to control the blood glucose levels might also help to lower the chances of SARS CoV-2 adenovirus and RNA-based vaccine potential autoimmunity in those individuals. Most importantly, we would like to stress the utmost importance to remind the participants to report all experienced adverse effects to a well-prepared post marketing surveillance system. Further, the search to improve methods that help to develop nucleic acid based vaccines with minimal autoimmune potential risk should continue and until more reassuring post marketing safety data are released, we recommend considering an individualized risk benefit ratio especially for those higher risk groups of patients.
Conflict of interests
the author declares he has no conflict of interest
Funding/Financial disclosure
None
References:
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