Why is it so hard to investigate the rare side effects of COVID vaccines?

An Overview of Vaccines against SARS-CoV-2 in the COVID-19 Pandemic Era

“…Consequently, in most cases, events are only linked by their timing: a vaccine is administered and, at some point afterward, the person experiences the adverse effect. This makes it particularly challenging to establish causality between the medical problem and the vaccine, especially when the reaction occurs in the middle term after the immunization [ 99 ].…”

“…To establish the causal relationship of adverse events following immunization, several organizations, such as EMA, FDA and WHO conduct studies to determine the probability of having an adverse event after receiving the vaccine compared with the probability of having the same adverse effect in people who did not receive the vaccine. They also need to determine the mechanism that could have caused the reaction [ 99 ].…”

“…However, clinical trials are not designed to detect extremely rare side effects, which might occur in fewer than one case per 10,000 vaccinations. As a result, very rare events, such as severe allergic reactions or thromboembolisms, are not reported until hundreds of millions of people have been vaccinated [ 99 , 105 ]. The main goal of these reports and the clinical challenge now is to work out which of these events are linked to the vaccine.…”

COVID-19 vaccine induced rhabdomyolysis: Case report with literature review

“…Studies have shown a high prevalence of COVID-19 vaccine reluctance and misinformation through mass media, and therefore policy efforts must acknowledge this discrepancy [ 7 ]. This increase in uncertainty is coupled with the need for accurate information on the short-term and long-term side effects of the COVID-19 vaccines, as there is a definitive gap in the literature for this topic area [ 8 ].…”

Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for an Ambispective study

“…Our data will be compared to local and systemic reactions (reactogenicity) of the COVID-19 vaccines reported by participants of clinical trials [7][8][9][10][11][12][13][14] and participants of vsafe or other prospective studies [15,16] 0 to 7 days after the injection. We will take into account confounding factors [17][18][19][20][21][22], previously proposed approaches [22][23][24] and will also review reports from social media and clinical case studies. Literature reviews of long-term and unusual side effects of COVID-19 vaccines will be performed continuously, including evaluation of dynamically evolving Adverse Events of Special Interest (AESI) and establishing background rates for these AESI [25][26][27][28][29][30][31][32][33][34][35][36].…”