Newly emerged Covid-19 variants are of great concern since they can be highly transmissible, severe, or fatal. The mutations can also help evade detection or reduce the effectiveness of treatments or vaccines . Vaccination in the COVID-19 pandemic is the only known effective means to prevent COVID-19 spread and prospect mutations; however, any fully vaccinated subject may experience COVID-19 infection yet. Thus, understanding the complications and effectiveness of the available vaccines will aid us in developing better policies. This study was conducted on healthcare students more exposed to COVID-19 infection. The study was performed during the most violent peak of COVID-19 in Summer in Iran, with 30,519 reported fatalities and 71,297 excess deaths,  while only 16.2% of the general population were fully vaccinated by the end of summer .
Among the 3591 medical and paramedical students, our study reported a PCR-confirmed vaccine breakthrough of 5.13%, which is significantly higher than most previous studies. High exposure risk of participants, low vaccine coverage, administrated types of vaccines, dominancy of delta variant, or coincidence with pandemic wave may explain some extent of this high vaccine breakthrough infection rate.
This study was performed on the earliest fully vaccinated population and coincided with the emergence of the Delta variant and the greatest COVID-19 waves in Iran. The estimated initiation time of the follow-up period was mid-April, when only 0.12% of the national population were fully vaccinated . At that time, countries with mostly unvaccinated populations (such as Iran and India) experienced a brutal coronavirus wave. As in a single-center study in India, 13.3% of healthcare workers experienced breakthrough infections during a massive COVID-19 wave with the Alpha and Delta dominancy period . At the time of Delta variant dominancy in the USA, when 50.2% of the population were immunized, the weekly incidence rate of breakthrough infections rose from 6.94 to 130.23 per 100000 fully vaccinated . Therefore, the effect of the Delta variant on delineating vaccine effectiveness is indisputable [4, 5]. Although not enough data is available regarding the share of variants in Iran, the immune escape by Delta variant may play a role in the high breakthrough infection rate in countries with low vaccination rates.
In the latest official available data, the efficacy of Gam-COVID-Vac, ChAdOx1-S, and BIBP-CorV were reported to be 91.6%, 72%, and 79%, respectively [12–14]. Our study observed the lowest breakthrough infection rate in participants vaccinated with Gam-COVID-Vac. Vaccines have been proven to prevent contracting severe COVID-19 effectively. Despite administering the BIBP-CorV vaccine to less exposed healthcare students, ChAdOx1-S and Gam-COVID-Vac were significantly more effective in preventing severe COVID-19. In addition, COVID-19 infection after the first dose was significantly more prevalent among participants vaccinated with ChAdOx1-S than other vaccines. This can be justified by the long interval between its first and second dose (8 to 12 weeks for ChAdOx1-S relative to 4 weeks for other vaccines). The best vaccine in pandemic waves should be decided based on the efficacy and shortest time to reach maximum effectiveness.
Recent studies suggested a history of COVID-19 infection and healthcare jobs as factors for breakthrough infections. Higher breakthrough rates were reported in participants with higher neutralizing antibody titers [15, 16]. Vaccine breakthrough was less common in our participants experiencing COVID-19 infection before vaccination which is in line with previous studies . According to serological studies, individuals with a history of COVID-19 infection have significantly high anti-spike antibody levels . In our study, about 29% of the participants had a history of COVID-19 infection, yet the breakthrough infection rates were high. A study on 126,586 vaccine recipients reported that working in healthcare centers is associated with a higher risk of breakthrough infection . Although exposure is an essential factor, our study’s rate of 5.13% breakthrough cases is very high compared to previous studies on healthcare workers [15, 19].
Since no study has assessed the side effects of different types of vaccines in Iran, we also studied this issue. The most commonly reported side effects were fever, lethargy/fatigue, weakness, myalgia, and pain at the injection site. Inconsistent with previous studies, vaccines without adjuvant (Gam-COVID-Vac and ChAdOx1-S) were accompanied by a higher incidence of systemic adverse events, while vaccines with excipients consisting of Aluminum compounds (COVIran Barekat, BBV152, and BIBP-CorV) caused local reactions . In our study, fever was the most reported adverse event of the COVID-19 vaccine and most probable in the first dose administration. Severe post-vaccination adverse events were present in 0.25% (n = 9) of our population, in which ChAdOx1-S and Gam-COVID-Vac were more likely to develop such events. A previous report on 1954 healthcare workers showed a 0.4% (n = 9) severe post-vaccination adverse incident leading to hospital attendance; BIBP-CorV (n = 1), Gam-COVID-Vac V (n = 3), and ChAdOx1-S (n = 5) . Overall, among vaccine recipients, adverse events were rare and non-life-threatening.
This study investigated breakthrough infection and adverse events at young ages. There are some significant limitations to this study. This was a retrospective study with no control group, and investigation of vaccine effectiveness was impossible. In addition, this study does not include asymptomatic COVID-19 breakthrough infections; hence, underestimating breakthrough infection cases is possible. Comparison between the types of vaccines should be avoided since the time and administration settings were not similar. At first, Gam-Cov-Vac and ChAdOx1-S were more available for administration to front-line medical interns whereas BIBP-CorV was mainly administered to students with less exposure. Also, our study may miss a fatality ratio because of its retrospective nature. However, we checked authorities for any mortality report, which was found to be zero. Further prospective cohorts and active surveillance programs are warranted to investigate complications of COVID-19 vaccines.