Archives of Academic Emergency Medicine. 2022; 10(1): e54 REV I EW ART I C L E Safety and Adverse Events Related to Inactivated COVID- 19 Vaccines and Novavax; a Systematic Review Omid Dadras1,2, Esmaeil Mehraeen3, Amirali Karimi4, Marcarious M. Tantuoyir4,5, Arian Afzalian4, Newsha Nazarian6, Hengameh Mojdeganlou7, Pegah Mirzapour1, Ahmadreza Shamsabadi8, Mohsen Dashti9, Afsaneh Ghasemzadeh9, Farzin Vahedi4, Parnian Shobeiri4, Zahra Pashaei1, SeyedAhmad SeyedAlinaghi1∗ 1. Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran. 2. School of Public Health, Walailak University, Nakhon Si Thammarat, Thailand. 3. Department of Health Information Technology, Khalkhal University of Medical Sciences, Khalkhal, Iran. 4. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Biomedical Engineering Unit, University of Ghana Medical Center (UGMC), Accra, Ghana. 6. School of Medicine, Islamic Azad University, Tehran, Iran. 7. Department of Pathology, Urmia University of Medical Sciences, Urmia, Iran. 8. Department of Health Information Technology, Esfarayen Faculty of Medical Sciences, Esfarayen, Iran. 9. Department of Radiology, Tabriz University of Medical Sciences, Tabriz, Iran. Received: April 2022; Accepted: May 2022; Published online: 7 July2022 Abstract: Introduction: Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to systematically review the adverse events reported for inactivated vaccines and Novavax. Methods: In this systematic review, the databases of PubMed, Scopus, Cochrane, and Web of Science were searched on September 15, 2021. Then we identified the eligible studies using a two-step title/abstract and full-text screening process. Data on the subjects, studies, and types of adverse events were extracted and entered in a word table, including serious, mild, local, and systemic adverse events as well as the timing of side effects’ appearance. Results: Adverse effects of inactivated coronavirus vac- cines side effects were reported from phases 1, 2, and 3 of the vaccine trials. The most common local side effects included injection site pain and swelling, redness, and pruritus. Meanwhile, fatigue, headache, muscle pain, fever, and gastrointestinal symptoms including abdominal pain and diarrhea were among the most common systemic adverse effects. Conclusion: This systematic review indicates that inactivated COVID-19 vaccines, including Sinovac, Sinopharm, and Bharat Biotech, as well as the protein subunit vaccines (Novavax) can be considered as safe choices due to having milder side effects and fewer severe life-threatening adverse events. Keywords: Adverse Effects; BBV152 COVID-19 vaccine; COVID-19; COVID-19 vaccines; recombinant SARS-CoV-2 vaccine NVX-cov2373; Safety; SARS-CoV-2; sinovac COVID-19 vaccine; Vaccines, Inactivated Cite this article as: Dadras O, Mehraeen E, Karimi A, Tantuoyir M.M, Afzalian A, Nazarian N, et al. Safety and Adverse Events Related to Inactivated COVID-19 Vaccines and Novavax; a Systematic Review. Arch Acad Emerg Med. 2022; 10(1): e54. https://doi.org/10.22037/aaem.v10i1.1585. ∗Corresponding Author: SeyedAhmad SeyedAlinaghi, Iranian Re- search Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran. Email:s_a_alinaghi@yahoo.com, Tel: 0098 (021) 66581583, ORCID: http://orcid.org/0000-0003-3210-7905. 1. Introduction COVID-19 was first found in Wuhan, China, in December of 2019. It is caused by a new coronavirus, called SARS-COV-2. The virus is similar to the other two coronaviruses, SARS-CoV and MERS-CoV (1, 2). COVID-19 manifestations are cough- ing, fever or chills, and shortness of breath; thus, it may be challenging to distinguish it from influenza (3-5). COVID- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 2 19 spreads more easily through droplets and aerosols than SARS, MERS, and influenza (5). Given these characteristics, it quickly spread from its source to other areas and countries, causing a pandemic across the world. This has been a huge problem for health systems around the world. It is still im- portant to curb the virus by wearing masks and avoiding pub- lic gatherings or closing schools, even though these measures have had a big impact on daily life and the world economy (6). Because there is not yet a standard treatment for COVID- 19, vaccines must be administered quickly to stop the global pandemic. Influenza and poliovirus vaccines have been demonstrated to be safe and efficacious when made from inactivated viruses (7). Having been used for a long time gives them sev- eral benefits, such as well-developed manufacturing meth- ods and the ability to easily scale production and storage up and down. Inactivated SARS-CoV-2 vaccines have been shown to generate significant levels of neutralizing anti- body titers in mice, rats, guinea pigs, rabbits, and non- human primates (8-10). SARS-CoV-2 vaccines have shown strong neutralizing antibody responses and effectiveness against COVID-19 during clinical studies conducted in differ- ent countries (11-15). SARS-CoV-2 vaccines manufactured by Sinovac Life Sciences/CoronaVac (China) and Beijing Insti- tute of Biological Products/Sinopharm (China) have received conditional marketing approval from the China National Medical Products Administration and have been placed on WHO’s Emergency Use Listing (16, 17) so far. NVX-CoV2373 (Novavax, USA) and ZF2001 (Longcom, China), two COVID- 19 protein subunit vaccines, are now undergoing phase-3 clinical studies (18, 19). An early study found that the vac- cines, NVX-CoV2373 (Novavax, USA) and ZF2001 (Longcom, China), both of which imitate the receptor-binding domain (RBD) of the SARS-COV-2 S protein, successfully prevent in- fection and generate high antibody titers against the SARS- COV-2 S protein (18, 19). Evidence to assist in selection of vaccines for population- based immunization in diverse areas is limited. To give ad- ditional data to optimize the use of the COVID-19 vaccines, we performed a systematic review of the adverse events of the existing inactivated vaccines and Novavax to determine their safety. 2. Methods This review was conducted according to the Preferred Re- porting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of relevant records was carried out in the online databases using selected key- words on September 15th, 2021. 2.1. Study objective The aim of the present study was to evaluate the safety and side effects of the inactivated vaccines of COVID-19 and No- vavax. 2.2. Databases Consistent with the Cochrane handbook of systematic re- views, PubMed, Scopus, Web of Science, and Cochrane were selected databases in this study. 2.3. Search Terms We designed our search strategy using the keywords from previous articles and the medical subject headings (MeSH) terms. The search was conducted on September 15, 2021. Supplementary material 1 includes the search strategy for all the databases. The following query demonstrates the PubMed search strategy: ((((((COVID-19[Title]) OR (SARS-CoV-2[Title])) OR (SARS- CoV2[Title])) OR (2019-nCoV[Title])) OR (Novel Coronavirus [Title])) AND ((((Vaccine*[Title]) OR (Vaccination[Title])) OR (Vaccinated[Title])) OR (Immunization[Title]))) AND (((((Safety[Title]) OR (Side effect*[Title])) OR (Adverse event*[Title])) OR (Adverse effect*[Title])) OR (Adverse reaction*[Title])) 2.4. Inclusion/exclusion criteria We included the original studies that assessed the safety and adverse events related to inactivated COVID-19 vaccines and Novavax. The following were the exclusion criteria: 1) Non-original studies, including review articles, meta- analyses, and editorials without original data 2) Abstracts/conference abstracts or unavailability of full texts 3) Protocols of clinical trials or ongoing clinical trials with un- published results 4) Studies on types of vaccines rather than inactivated vac- cines and Novavax or the studies that only reported the effi- cacy of inactivated vaccines and Novavax without reporting their adverse events 5) Case reports 2.5. Screening and data screening Records from the start until September 15, 2021, were down- loaded into the Endnote software. A two-phase screening was done. Firstly, after removing duplicates, the title and ab- stract of articles were assessed against the inclusion and ex- clusion criteria. Then, a full-text screening was completed by two reviewers. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e54 2.6. Data extraction This study aimed to evaluate the safety and adverse events related to inactivated COVID-19 vaccines and Novavax. To achieve this goal, data for the following variables were ex- tracted for further analysis: the name of the first author, year of publication, country / ethnic group, type of study, manu- facturer, phase of the study, sample population, age, gender, serious side effects, time from injection to adverse effects, lo- cal side effects, as well as systemic adverse effects. 2.7. Quality assessment We assessed the quality of the studies using the Newcastle- Ottawa scale (NOS) checklist, which allocates a score of 0-9 to each study based on selection, comparability, and expo- sure/outcome(20). Studies that scored 4 or below were con- sidered of poor quality (Table 2). 3. Results We initially identified a total of 1062 relevant records; how- ever, only 515 remained after duplicate removal. Of the re- maining records, 171 and 325 were removed in title/abstract and full-text screenings, respectively. Therefore, 19 studies appeared to be eligible and entered the qualitative synthesis (Figure 1). Analysis of the included studies identified inactivated coron- avirus vaccines including Bharat Biotech (Covaxin), Sinovac (CoronaVac), and Sinopharm. Sinopharm was the most com- monly reported inactivated vaccine. Perfusion S vaccine was also reported in one study. Sinovac (CoronaVac) vaccine had most of its clinical trials in China and a few other countries like Turkey, Brazil, Indonesia, and the Philippines. Bharat Biotech (Covaxin) on the other hand was only clinically tri- aled in India, while Sinopharm went through trials mostly in China, the USA, and United Arab Emirates. Perfusion S vac- cine was also trialed in the US. These studies reported ad- verse effects from phases 1, 2, and 3 of the vaccine trials. Most of these reported trials involved subjects that were 18 years and above with very few trials conducted in all age groups. The most common local side effects included pain, redness, pruritus, induration, urticaria, stiffness, and swelling at the site of the injection; while fatigue, body pain, headache, skin rashes, sleepiness, systemic reactogenicity, anorexia, cough, edema, joint pain, chills, muscle pain, fever, malaise, and gastrointestinal symptoms like diarrhea and constipa- tion were the most common systemic side effects (Table 1). The majority of the studies reported no serious side effects for the vaccines. Nevertheless, very few studies reported se- rious adverse effects like hypertension, chest pain, thrombo- cytopenia, acute macular neuroretinopathy, limb weakness, limb shaking, menstruation, as well as episcleritis, anterior scleritis, paracentral acute middle maculopathy, and subreti- nal fluid. There was no documented death in our analysis (Table 1). None of the studies were of poor quality. The mean score of the studies was 7.9 (Table 2). The most commonly encoun- tered problem based on the NOS checklist was the lack of ad- equate matching of cases and controls, present in some of the observational studies. 4. Discussion This study only focused on inactivated COVID-19 vaccines that have been approved by the WHO including Sino- vac (CoronaVac), Sinopharm (BBIP-CorV (Vero Cells)), and Bharat Biotech (Covaxin) as well as a protein subunit vaccine (Novavax). Bharat has been trialed 7 times in only one coun- try (India) and it is being used and approved in 12 countries, while Sinovac has been trailed 27 times in 8 countries and approved in 48 countries. Sinopharm, on the other hand, had 19 trials in 10 countries and is widely used in 80 coun- tries (21). Clinical trials have been conducted under uncon- ventional swift circumstances, hence necessitating the ex- treme care for patient safety to gain the trust of the public and the medical community in procedures used to develop the vaccine, as the safety concerns regarding the COVID-19 vaccines are major obstacles to scaling up the vaccine up- take (22, 23). Reporting these events is of paramount im- portance in tackling vaccine hesitancy and ultimately curtail- ing the pandemic (24). A multinational study conducted on adverse effects of the COVID-19 vaccines hypothesizes that there could be a huge variety in side effects due to diversity in age groups and gender as well as high heterogeneity in populations. Consequently, single studies should be inter- preted with extreme caution and account for the effect of po- tential confounders (25). Serious adverse events (SAEs) after vaccine injection include life-threatening events, congenital anomaly or birth defect, death, inpatient hospitalization, sig- nificant disruption of the ability to carry out usual life activ- ities, as well as an event that may require medical interven- tion. On the other hand, common or mild adverse events en- compass local and systemic side effects that are considered non-life-threatening and often spontaneously resolve with- out any medications (26). 4.1. Sinopharm From our study, this vaccine was found to be the most commonly used inactivated COVID-19 vaccine. This phe- nomenon has been attributed to the higher number of coun- tries that have approved the Sinopharm vaccine to be used within their boundaries. Furthermore, Sinopharm has been widely reported to be safe with barely any serious side effects except for some mild to moderate complications such as the pain and firmness at the This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 4 point of injection regardless of the number of doses taken (27-29). Although some studies reported no adverse effects at all, the most common local side effects from this vaccine reported in various studies include redness (erythema), ur- ticaria, swelling, induration, pain, and skin itching at the in- jection site (30-32). Concerning systemic side effects, fatigue, fever, inappetence, headache, dizziness, muscle and body pain, nausea, vomiting, joint pain as well as gastrointesti- nal complications like constipation and diarrhea were mostly associated with this type of vaccine(31, 33). Interestingly, a study found that this vaccine could be associated with a sore or dry throat, clogged nose, and runny nose as compared to other types of vaccines (34). Despite most reports suggest- ing that the Sinopharm vaccine presents mild side effects, the duration of these side effects and the time from injec- tion to the appearance of the side effects varied depending on the dose. The time taken for side effects to appear typi- cally ranges from 9 hours after to about 15 days after the first dose. The second dose and booster doses could take a longer duration up to 28 days for the side effects to appear. However, these adverse effects have been reported to be self-limiting and usually resolve within 1-3 days (27, 28, 30, 32-37). These features exhibited by the Sinopharm vaccine may reflect on the safety profile of the Sinopharm vaccine; however, long- term side effects should also not be ignored (29). Contrary to the numerous reports of Sinopharm being a quiet vaccine with no serious adverse events (27-30, 32, 38), very few studies have reported serious adverse effects. A study reported ocular complications 5.2 days post-vaccination that presented in the form of uveitis, central serous chori- oretinopathy, chronic serous pigment epithelial detachment, blurry vision, sudden paracentral scotoma & hemorrhage, episcleritis, anterior scleritis, acute macular neuroretinopa- thy, paracentral acute middle maculopathy, and subretinal fluid. Nevertheless, there was no causal relationship estab- lished in this study (37). Thrombocytopenia, irregular heart- beats, abnormal blood pressure, chest distress, palpitation, shortness of breath, limb weakness, and limb shaking were also reported as SAEs in some studies (34, 35). This may be similar to the findings of Fan Y et al. in their study describing inactivated vaccines to be associated with serious metabolic, musculoskeletal, immune system, and renal disorders (39). However, most of these SAEs appeared to be unrelated to the vaccine and resolved with appropriate treatment with no mortality (27, 35). These adverse effects may be influenced by the age group and gender as suggested by Li et al. (25) and Saeed et al. with females experiencing more SEs in their study (40), but Aga et al. and Guo et al. stipulated that these adverse effects are not dependent on gender, dose, or age (27, 28, 39). Therefore, further multinational studies are recom- mended to explore the potential side effects of the vaccine in populations with different demographic backgrounds. 4.2. Sinovac (CoronaVac) Another commonly used inactivated COVID vaccine is Sino- vac (CoronaVac) vaccine. Various studies have reported this type of vaccine to induce mild to moderate side effects. All the studies analyzed in this study reported injection site pain to be the most common local side effect of the Sinovac- vaccine (41-45). It has been well documented that Sino- vac shots are associated with injection site pain, which oc- curs more often after the second dose as compared to the first dose. Other local adverse events include swelling, dis- coloration, induration, itching, pruritus, erythema (redness), abdominal pain, and paranesthesia at the injection site (41- 47). These local side effects are self-limiting; hence, they re- solve in a short period. Though these SEs do not last long, the systemic side effects may take a longer time to resolve. The most common systemic side effects are fever, sleepi- ness, fatigue, muscle pain, headache, diarrhea, vomiting, allergy, arthralgia, rash, mucocutaneous eruption, oral hy- poesthesia, hypoesthesia, peripheral edema, abdominal dis- tention, drowsiness, joint pain, hypersensitivity, runny and stuffy nose, lymphadenopathy, cough, and loss of appetite. Among these symptoms, fatigue is the most frequent sys- temic adverse reaction to the Sinovac vaccine (33, 41, 43, 44). Additionally, there is no significant variation in symp- tom presentation among different age groups (42). Notably, Sinovac injection is associated with no life- threatening adverse events. The evidence from phases 1 and 2 trials reported no vaccine-related mortality or grade 4 ad- verse events so far (41, 46). However, sporadic serious ad- verse events were reported in separate studies conducted by Zhang et al. and Wu et al. (43, 47). They reported pneumo- nia, numbness of limbs, chest pain, palpitation, hyperten- sion, and menstruation as serious side effects that occurred in people after Sinovac vaccination; however, these SAEs ap- peared to be vaccine-unrelated (42, 47). Adverse events of the Sinovac vaccine are expected to occur within 7 days after the first dose of the vaccine but it may take up to 28 days as reported by some studies (42, 45). Additionally, the second dose may elicit side effects from 1- 4 days post-vaccination. The safety profile of this vaccine from clinical trials in phases 1 and 2 postulates that it is safe and well-tolerated in various age groups. 4.3. Bharat Biotech The Bharat Biotech vaccine was found to be the least used inactivated corona vaccine. Its clinical trials are comparable to the extent to which it is being used, but this may not im- ply its efficacy and safety profile. From the phase 1 and 2 tri- als, this vaccine has been reported to be well-tolerated by all the subjects with no significant differences in safety for vari- ous age groups (48). Ella et al. reported that the most com- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2022; 10(1): e54 mon adverse events that were deemed mild to moderate in- cluded pain at the injection site, redness at the injection site, itching, stiffness in the upper arm, and weakness in the in- jection arm as local side effects. Furthermore, they reported the systemic side effects to entail body ache, fever, headache, malaise, weakness, and rashes (48). The time of SEs appear- ance was not significantly different from other vaccines like Sinopharm, Sinovac, Moderna, and AstraZeneca (34). In the first shot, the Covaxin produces SEs within 0-7 days after in- jection, while the second dose was reported to elicit SEs 7 days after receiving the vaccine. The Covaxin produced no severe or life-threatening adverse effects in trials (48). How- ever, these findings may as well require multi-site surveil- lance studies to ascertain the long-term effects and popula- tion heterogeneity effects since the current data may be in- sufficient to make a definitive conclusion. 4.4. Novavax The Novavax vaccine, which is a recombinant protein sub- unit vaccine, was reported by a single study in our analy- sis. Despite concerns about the reactogenicity and side ef- fects caused by the adjuvant in these vaccines, their desirable safety profiles due to the absence of live viral components, the addition of adjuvant to increase immunogenicity, and the ease of scalability of the recombinant protein serve as advan- tages for this type of vaccine. As a result, vaccine developers are drawn to this sort of vaccine. Goepfert et al. reported no vaccine-related unintended adverse events or severe ad- verse events of special interest in phase 1 and 2 trials of the Perfusion S (preS) protein vaccine. Solicited side effects may appear after 7 days of taking the first dose. Local side ef- fects include pain, swelling, erythema, and grade 3 reaction; while systemic side effects include myalgia, malaise, fever, and headache. It was observed that systemic adverse events usually appeared on the second day after the second dose of the Perfusion S (preS) protein vaccine. Furthermore, im- mune responses in the elderly seem to be lower than younger age group independent of the number of doses (49). Emerg- ing clinical evidence from investigations of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine, re- vealed that it is safe and associated with a significant immune response in healthy adult participants. The majority of the time, reactogenicity is modest and brief. The frequency of significant adverse events seems to be minimal and compa- rable in all age groups (50). 4.5. Limitations and Recommendations The results of the present review may be limited in various aspects, as there is no specific system for the registration of COVID-19 vaccine side effects in different countries. It is also limited in the aspect of data retrieval, since some stud- ies were incomplete and their results had not been published yet. Additionally, study subjects in the analyzed articles may have given biased reports of their adverse effects. This may be due to the difference in their level of education. Conse- quently, the included studies may have had reporting bias; hence, there is an influence on the reliability of reported side effects. There are no scales for the severity of common side effects like pain and fatigue; hence, these reported side ef- fects are patient-dependent, so mild ones may be neglected. Also, we have no scale for comparison of these effects be- tween studies and some reported adverse effects (e.g cardio- vascular events) may be due to the co-existence of patients’ underlying diseases and vaccination. Considering that the COVID-19 vaccine rollout is relatively new, all of the adverse effects may not be well-known and the long-term effects are still undetermined. Consequently, there is not sufficient evi- dence to affirm that these complications are solely due to the vaccines. Therefore, multinational studies are recommended to address the influence of demographic heterogeneity on the manifestation of vaccines’ adverse effects as well as to determine the long-term adverse events of the inactivated COVID vaccines. 5. Conclusion This systematic review investigated the adverse effects of WHO-approved inactivated vaccines including Sinovac (CoronaVac), Sinopharm (BBIP-CorV ), and Bharat Biotech (Covaxin) as well as a protein subunit vaccine (Novavax). Sinopharm followed by Sinovac, and Bharat were the most common inactivated vaccines trialed and used globally. The most common local side effects are pain, redness, and swelling at the injection site; while fatigue, body pain, headache, muscle pain, fever, and malaise were the most common systemic side effects. Almost all these local and systemic adverse effects were self-limiting. Therefore, they resolved within minutes to days post-vaccination. Although few SAEs were reported after injecting inactivated and pro- tein subunit vaccines, particularly with the Sinopharm vac- cine, no statistically significant relation was found between the vaccines and these side effects or any related mortal- ity. Hence, inactivated vaccines seem to be a safe choice due to their mild side effects and few life-threatening adverse events. 6. Declarations 6.1. Acknowledgments The present study was conducted in collaboration with Khalkhal University of Medical Sciences, Iranian Research Center for HIV/AIDS, Tehran University of Medical Sciences, and Walailak University. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 6 6.2. Authors’ contributions (1) The conception and design of the study: Esmaeil Mehraeen, SeyedAhmad SeyedAlinaghi (2) Acquisition of data: Amirali Karimi, Marcarious M. Tan- tuoyir (3) Analysis and interpretation of data: Arian Afzalian, New- sha Nazarian, Hengameh Mojdeganlou (4) Drafting the article: Pegah Mirzapour, Ahmadreza Shamsabadi, Mohsen Dashti, Afsaneh Ghasemzadeh, Farzin Vahedi, Parnian Shobeiri, Zahra Pashaei, Omid Dadras (5) Revising it critically for important intellectual con- tent: SeyedAhmad SeyedAlinaghi, Esmaeil Mehraeen, Omid Dadras (6) Final approval of the version to be submitted: all authors 6.3. Funding and supports This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 6.4. Competing interests The authors declare that there is no conflict of interest re- garding the publication of this manuscript. 6.5. Ethics approval and consent to participate Not applicable 6.6. Availability of data and material The authors stated that all information provided in this arti- cle could be shared. References 1. Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related? Clinical microbiology and infection. 2020;26(6):729-34. 2. Dadras O, Alinaghi SAS, Karimi A, MohsseniPour M, Barzegary A, Vahedi F, et al. Effects of COVID-19 pre- vention procedures on other common infections: a sys- tematic review. European journal of medical research. 2021;26(1):67. 3. Qin C, Liu F, Yen T-C, Lan X. 18F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases. Eu- ropean journal of nuclear medicine and molecular imag- ing. 2020;47(5):1281-6. 4. Sanie Jahromi MS, Aghaei K, Taheri L, Kalani N, Hatami N, Rahmanian Z. Intensive Care Unit of COVID-19 dur- ing the Different Waves of Outbreaks in Jahrom, South of Iran. Journal of Medicinal and Chemical Sciences. 2022;5(5):734-42. 5. Sheikhbahaei E, Mirghaderi SP, Moharrami A, Habibi D, Motififard M, Mortazavi SMJ. Incidence of Symptomatic COVID-19 in Unvaccinated Patients Within One Month After Elective Total Joint Arthroplasty: A Multicenter Study. Arthroplast Today. 2022;14:110-5. 6. Wilder-Smith A, Freedman DO. Isolation, quarantine, so- cial distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV ) outbreak. Journal of travel medicine. 2020. 7. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine. 2009;27(15):2114-20. 8. Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, et al. De- velopment of an inactivated vaccine candidate for SARS- CoV-2. Science. 2020;369(6499):77-81. 9. Wang Z-J, Zhang H-J, Lu J, Xu K-W, Peng C, Guo J, et al. Low toxicity and high immunogenicity of an inactivated vaccine candidate against COVID-19 in different animal models. Emerging microbes & infections. 2020;9(1):2606- 18. 10. Wang H, Zhang Y, Huang B, Deng W, Quan Y, Wang W, et al. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell. 2020;182(3):713-21. e9. 11. Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS- CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo- controlled, phase 1/2 clinical trial. The Lancet Infectious Diseases. 2021;21(6):803-12. 12. Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, et al. Safety and immunogenicity of an inacti- vated SARS-CoV-2 vaccine, BBV152: a double-blind, ran- domised, phase 1 trial. The Lancet Infectious Diseases. 2021;21(5):637-46. 13. Zhao J, Zhao S, Ou J, Zhang J, Lan W, Guan W, et al. COVID-19: coronavirus vaccine development updates. Frontiers in immunology. 2020;11:3435. 14. Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. Jama. 2020;324(10):951- 60. 15. Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV- 2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. The Lancet Infec- tious Diseases. 2021;21(1):39-51. 16. Sudharsanan N, Favaretti C, Hachaturyan V, Bärnighausen T, Vandormael A. The effect of fram- ing and communicating COVID-19 vaccine side-effect risks on vaccine intentions for adults in the UK and the USA: A structured summary of a study protocol for a This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 7 Archives of Academic Emergency Medicine. 2022; 10(1): e54 randomized controlled trial. Trials. 2021;22(1):592. 17. Hoffman Y, Palgi Y, Goodwin R, Ben-Ezra M, Greenblatt- Kimron L. A storm in a teacup: older adults’ low preva- lence of COVID-19 vaccine side-effects and their link with vaccination anxiety. International psychogeriatrics. 2021;33(12):1335-7. 18. Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. New England Journal of Medicine. 2020;383(24):2320-32. 19. Yang S, Li Y, Dai L, Wang J, He P, Li C, et al. Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double- blind, placebo-controlled, phase 1 and 2 trials. The Lancet Infectious Diseases. 2021;21(8):1107-19. 20. Meira CM, Jr., Meneguelli KS, Leopoldo MPG, Florindo AA. Anxiety and Leisure-Domain Physical Activity Fre- quency, Duration, and Intensity During Covid-19 Pan- demic. Frontiers in psychology. 2020;11:603770. 21. (WHO) WHO. 10 Vaccines Approved for Use by WHO 2021 [updated 27 December 2021; cited 2021 28 December]. Available from: https://covid19.trackvaccines.org/agency/who/. 22. Panda DS, Giri RK, Nagarajappa AK, Basha S. Covid-19 vaccine, acceptance, and concern of safety from public perspective in the state of Odisha, India. Human vaccines & immunotherapeutics. 2021;17(10):3333-7. 23. Joffe S, Babiker A, Ellenberg SS, Fix A, Griffin MR, Huns- berger S, et al. Data and Safety Monitoring of COVID-19 Vaccine Clinical Trials. The Journal of infectious diseases. 2021;224(12):1995-2000. 24. Riad A, Schünemann H, Attia S, Peričić TP, Žuljević MF, Jürisson M, et al. COVID-19 Vaccines Safety Tracking (CoVaST): Protocol of a Multi-Center Prospective Cohort Study for Active Surveillance of COVID-19 Vaccines’ Side Effects. International journal of environmental research and public health. 2021;18(15):7859. 25. Li X, Ostropolets A, Makadia R, Shoaibi A, Rao G, Sena AG, et al. Characterising the background incidence rates of adverse events of special interest for covid-19 vaccines in eight countries: multinational network cohort study. BMJ (Clinical research ed). 2021;373:n1435. 26. Karayeva E, Kim HW, Bandy U, Clyne A, Marak TP. Monitoring Vaccine Adverse Event Reporting System (VAERS) Reports Related to COVID-19 Vaccination Ef- forts in Rhode Island. Rhode Island medical journal (2013). 2021;104(7):64-6. 27. Guo W, Duan K, Zhang Y, Yuan Z, Zhang YB, Wang Z, et al. Safety and immunogenicity of an inactivated SARS- CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial. EClinicalMedicine. 2021;38:101010. 28. Al Khames Aga QA, Alkhaffaf WH, Hatem TH, Nassir KF, Batineh Y, Dahham AT, et al. Safety of COVID-19 vaccines. Journal of medical virology. 2021;93(12):6588-94. 29. Abu-Hammad O, Alduraidi H, Abu-Hammad S, Alnaz- zawi A, Babkair H, Abu-Hammad A, et al. Side Effects Re- ported by Jordanian Healthcare Workers Who Received COVID-19 Vaccines. Vaccines. 2021;9(6):577. 30. Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. Jama. 2020;324(10):951- 60. 31. Niebel D, Novak N, Wilhelmi J, Ziob J, Wilsmann-Theis D, Bieber T, et al. Cutaneous Adverse Reactions to COVID- 19 Vaccines: Insights from an Immuno-Dermatological Perspective. Vaccines. 2021;9(9):944. 32. Abu-Halaweh S, Alqassieh R, Suleiman A, Al-Sabbagh MQ, AbuHalaweh M, AlKhader D, et al. Qualitative As- sessment of Early Adverse Effects of Pfizer-BioNTech and Sinopharm COVID-19 Vaccines by Telephone Interviews. Vaccines. 2021;9(9):950. 33. Kaur RJ, Dutta S, Bhardwaj P, Charan J, Dhingra S, Mi- tra P, et al. Adverse Events Reported From COVID-19 Vac- cine Trials: A Systematic Review. Indian J Clin Biochem. 2021;36(4):427-39. 34. Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Hatmal M, Alhaj-Qasem DM, Olaimat TM, et al. Side Effects and Per- ceptions Following COVID-19 Vaccination in Jordan: A Randomized, Cross-Sectional Study Implementing Ma- chine Learning for Predicting Severity of Side Effects. Vaccines. 2021;9(6):556. 35. Wang G, Zhu L, Zhu Y, Ye Q, Yu X, Fu M, et al. Safety survey by clinical pharmacists on COVID-19 vaccination from a single center in China. Human vaccines & immunother- apeutics. 2021;17(9):2863-7. 36. Pu J, Yu Q, Yin Z, Zhang Y, Li X, Yin Q, et al. The safety and immunogenicity of an inactivated SARS-CoV- 2 vaccine in Chinese adults aged 18-59 years: A phase I randomized, double-blinded, controlled trial. Vaccine. 2021;39(20):2746-54. 37. Pichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG. Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi. JAMA ophthalmology. 2021;139(10):1131-5. 38. Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV- 2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. The Lancet Infec- tious diseases. 2021;21(1):39-51. 39. Fan YJ, Chan KH, Hung IF. Safety and Efficacy of COVID- 19 Vaccines: A Systematic Review and Meta-Analysis of This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 8 Different Vaccines at Phase 3. Vaccines. 2021;9(9):989. 40. Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side effects and perceptions following Sinopharm COVID-19 vaccination. International journal of infec- tious diseases : IJID : official publication of the Interna- tional Society for Infectious Diseases. 2021;111:219-26. 41. Tanriover MD, Doğanay HL, Akova M, Güner HR, Azap A, Akhan S, et al. Efficacy and safety of an inacti- vated whole-virion SARS-CoV-2 vaccine (CoronaVac): in- terim results of a double-blind, randomised, placebo- controlled, phase 3 trial in Turkey. Lancet (London, Eng- land). 2021;398(10296):213-22. 42. SeyedAlinaghi S, Mirzapour P, Dadras O, Pashaei Z, Karimi A, MohsseniPour M, et al. Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review. European journal of med- ical research. 2021;26(1):51. 43. Zhang MX, Zhang TT, Shi GF, Cheng FM, Zheng YM, Tung TH, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Expert review of vaccines. 2021;20(7):891-8. 44. Yang ZN, Zhao YY, Li L, Gao HD, Cai Q, Sun XX, et al. [Evaluation of safety of two inactivated COVID-19 vaccines in a large-scale emergency use]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. 2021;42:1-6. 45. Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. Safety, tolerability, and immunogenicity of an inacti- vated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet Infectious diseases. 2021;21(2):181-92. 46. Kaya F, Pirincci E. Determining the frequency of serious adverse reactions of inactive SARS-COV-2 vaccine. Work (Reading, Mass). 2021;69(3):735-9. 47. Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS- CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo- controlled, phase 1/2 clinical trial. The Lancet Infectious diseases. 2021;21(6):803-12. 48. Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, et al. Safety and immunogenicity of an in- activated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, ran- domised phase 1 trial. The Lancet Infectious diseases. 2021;21(7):950-61. 49. Goepfert PA, Fu B, Chabanon AL, Bonaparte MI, Davis MG, Essink BJ, et al. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. The Lancet Infectious diseases. 2021;21(9):1257-70. 50. Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. The New England journal of medicine. 2021;385(13):1172-83. 51. Han B, Song Y, Li C, Yang W, Ma Q, Jiang Z, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial. The Lancet Infectious diseases. 2021;21(12):1645-53. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 9 Archives of Academic Emergency Medicine. 2022; 10(1): e54 Figure 1: PRISMA 2020 flow diagram of this systematic review. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 10 Table 1: Characteristics of various inactivated and protein subunit COVID-19 vaccines and their adverse effects ID First Author Year Country Type Vaccine name Phase Sample Age Gender Serious adverse event Time Side effects Local Systemic 1 Abu- Halaweh, S. (32) 2021 USA Cohort Sinopharm N/A 513 par- ticipants ≥70 Male (67%), female (33%) No serious adverse reaction N/A Pain Fever Headache 2 Abu- Hammad, O. (29) 2021 USA CS Sinopharm N/A 409 health- care personnel N/A N/A No serious adverse reaction N/A Pain, Redness Headache 3 Al Khames Aga, Q. A. (28) 2021 USA CS Sinopharm N/A 340 par- ticipants 18–35, 36–55, >55 Males (51.61%), female (48.39%) No serious adverse reaction 1.733±1.258, 1.405±0.916, 2.080±2.120 duration of signs and symptoms (days) Pain, Redness, Urticaria, and swelling at the site of the injection Fatigue, body Pain, Headache, Muscle Pain, Fever, and gastroin- testinal effects 4 Ella, R. (48) 2021 India RCT Bharat I/II 190 par- ticipants 12–65 Male: (74%), female: (26%) No serious adverse reaction First dose: (days 0–7), Second dose: At 7 days after the injection Pain at the injection site, redness at the injection site, Itching, Stiffness in the upper arm, Weakness in the injection arm Body ache, Fever, Headache, Malaise, Weakness, Rashes 5 Goepfert, P.A. (49) 2021 USA RCT Perfusion S (preS) protein vaccine I/II 439 par- ticipants 18-49 & ≥50 N/A No serious adverse reaction Systemic & local adverse events appeared 7 days after vaccination (first dose) Pain, swelling & erythema & grade 3 reaction Myalgia, malaise Fever & headache, 6 Guo, W. (27) 2021 China RCT Vero Cells (Sinopharm) I/II 784 par- ticipants ≥18 Female: 58.9%(18- 49y), female: 40.55% (≥60 y) No serious adverse reaction During 7 days of the first dose Pain Fever Headache Fatigue nausea 7 Han, B. (51) 2021 China RCT CoronaVac (Sinovac) I/II 72 partici- pants for phase I & 480 par- ticipant for phase II 3-17 Female: (57.7%) (phase I), female: (44.2%) (phase II) No vaccine- related serious adverse reaction During 7 days of the first dose Pain Swelling Pruritus Erythema Fever Headache Cough Anorexia Diarrhea Vomiting Fatigue 8 Hatmal, MM. (34) 2021 USA CS Sinopharm (38.2% of partici- pants received Sinopharm 3.46% received Moderna, N/A 2213 par- ticipants N/A N/A Among Sinopharm receivers: 2.5% showed severe adverse effects (e.g.,thro- mbocy- topenia, Mostly appeared within 9-12 h after injection Pain Swelling Fatigue Headache Sleepiness Chills Myalgia Joints pain Fever Dizziness Nausea Sweatin This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 11 Archives of Academic Emergency Medicine. 2022; 10(1): e54 Table 1: Characteristics of various inactivated and protein subunit COVID-19 vaccines and their adverse effects ID First Author Year Country Type Vaccine name Phase Sample Age Gender Serious adverse event Time Side effects Local Systemic Sputnik, Covaxin& Johnson & Johnson Other 58.34% received As- traZeneca &Pfizer) irregular heartbeats, abnormal blood pressure,) 9 Kaya, F. (46) 2021 Turkey CS CoronaVac (Sinovac) III 329 par- ticipants Mean age: 35.77 ±9.07 Male: (51.5%), female: (48.5%) 33.2% No life-threatening adverse reaction was determined During 1.14 ±4 days after injection of the second dose Pain Redness Swelling Nausea Vomiting Fever Headache Fatigue Allergy myalgia 10 Pichi, F. (37) 2021 UAE CS Sinopharm III 7 partici- pants Mean age: 41.4 Male: (42.86%), female: (57.14%) 9 eyes of 7 patients presented with Ocular Adverse events: (e.g. Uveitis, central serous chorioretinopathy, chronic serous pigment epithelial detachment, blurry vision, sudden paracen- tralscotoma& hemorrhage), Episcleritis Anterior scleritis Acute macular neuroretinopathy Paracentral acute middle maculopathy Subretinal fluid Within 15 days after injection of first dose N/A N/A 11 Pu, J. (36) 2021 China RCT Sinopharm I 294 par- ticipants 18-59 Male: (45%), female: (55%) No severe adverse event day 7 and 28 after booster Pain, Redness, Swelling, and Itch Fatigue, Rash, Diarrhea, and Fever 12 Saeed, B. Q. (40) 2021 U CS Sinopharm N/A 1102 par- ticipants 18-80 Male: (29%), Female: (71%) N/A N/A Pain, Redness, Tender- ness, Indura- tion, and pruritus at the vacci- nation site Fatigue, Fever, Nausea, Diarrhea, Cough, Allergy, Muscle pain, lethargy, Abdomi- nal pain, Back pain, and headache This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 12 Table 1: Characteristics of various inactivated and protein subunit COVID-19 vaccines and their adverse effects ID First Author Year Country Type Vaccine name Phase Sample Age Gender Serious adverse event Time Side effects Local Systemic 13 Tanriover, M. D. (41) 2021 Turkey RCT CoronaVac I/II 11303 partici- pants 18–59 Male: (57.4%), Female: (42.6%) N/A day 14 Pain, Pruritus, Swelling, Induration, Paranesthe- sia, and Erythema Allergic reaction, Rash, Fatigue, Headache, Myalgia, Vomiting, Nausea, Chill, Fever, Arthralgia, Cough, and Diarrhea 14 Wang, G. (35) 2021 China RCT Sinopharm (Aikewei) III 11303 partici- pants N/A N/A Chest distress, palpita- tion, shortness of breath, limb weakness, limb shaking, general anesthe- sia, and transient vague 0–28 days Local pain, Skin itching, Hand anesthesia, local induration, Muscle soreness, and Local rash Dizziness, Headache, Fatigue, Cough, Nausea, Dry mouth, Low-grade fever, and Chill 15 Wu, Z. (47) 2021 Hebei, China RCT CoronaVac I/II Phase I: 72 partici- pants and phase II: 349 par- ticipants ≥60 Phase I: (Male: 51.3%, fe- male:48.7%) Phase II: (Male: 48.42%, female: 51.58%) Palpitation Hyper- tension days 0 and 28 Pain Pruritus Erythema Swelling Abdominal pain Dizziness Fever Mucocutaneous eruption Oral hypoesthesia Fatigue Diarrhea Muscle pain Rash Hypoesthesia Peripheral edema Cough Headache Nausea Anorexia Abdominal distention Vomiting Drowsiness Joint pains Hy- persensitivity 16 Xia, S. (30) 2020 China RCT Sinopharm I/II Total: 481 partici- pants, phase I: 96 partici- pants were included and phase II: 224 par- ticipants 18-59 Phase I: (Male: 39.5%, female: 60.5%) Phase II: (Male: 36.6%, female: 63.4%) N/A Days 0 and 28 Itching, Redness, Swelling, and Pain Coughing Headache, Fatigue Diarrhea Fever, Nausea, Pruritus, and vomiting This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 13 Archives of Academic Emergency Medicine. 2022; 10(1): e54 Table 1: Characteristics of various inactivated and protein subunit COVID-19 vaccines and their adverse effects ID First Author Year Country Type Vaccine name Phase Sample Age Gender Serious adverse event Time Side effects Local Systemic 17 Xia, S. (38) 2021 China RCT Sinopharm (BBIBP- CorV ) I/II Phase I: 192 par- ticipants and phase II: 448 par- ticipants 18–80 Phase I (Male: 47%, female: 53% ) Phase II: (male: 45%, female: 55%) N/A Days 0 and 28 Pain Swelling Itch Redness Induration Fatigue, Fever Inappetence Headache Muscle pain Nausea Diarrhea, Joint pain 18 Zhang, M. X. (43) 2021 China CS CoronaVac N/A 1526 par- ticipants 18–60 Male: (20.7%), female: (79.3%) Numbness of limbs, Chest pain, and Menstru- ation Days 0 and 28 Pain, Redness, Swelling, Induration, and Itch Muscle pain, Fatigue Stuffy, Rash, Headache, Dizziness, Vomiting, Diarrhea, Appetite impaired, runny nose, Nausea, Fever, Cough, Throat pain, Allergic reaction, urticarial, Lym- phadenopa- thy 19 Zhang, Y. (45) 2021 China RCT CoronaVac I/II Phase I: 144 par- ticipants Phase II: 600 par- ticipants 18–59 Days 0 and 14 vaccina- tion Male: (44%), female: (56%) Days 0 and 28 vaccina- tions Male: (49%), female: (51%) N/A Days 0 and 28 Pain Pain Swelling Redness, Discoloration Pruritus, Fatigue Diarrhea, Fever, Headache, Nausea, Cough Hyper- sensitivity, Muscle pain, and Decreased appetite *Time from injection to the appearance of adverse events. RCT: randomized clinical trial; CS: cross sectional. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem O. Dadras et al. 14 Table 2: The results of quality assessment of included studies using Newcastle-Ottawa scale (NOS) tool The first author (refer- ence) Selection (Out of 4) Comparability (Out of 2) Exposure/outcome (Out of 3) Total score (Out of 9) Abu-Halaweh, S.(32) **** - ** 6 Abu-Hammad, O. (29) **** - ** 6 Al Khames Aga, Q. A. (28) **** ** *** 9 Ella, R. (48) **** ** *** 9 Goepfert,P.A. (49) **** ** *** 9 Guo, W. (27) **** ** *** 9 Han, B. (51) **** ** *** 9 Hatmal, MM. (34) **** - ** 6 Kaya, F. (46) **** - *** 7 Pichi, F. (37) **** - *** 7 Pu, J. (36) **** ** *** 9 Saeed, B. Q. (40) **** - ** 6 Tanriover, M. D. (41) **** ** *** 9 Wang, G. (35) **** - *** 7 Wu, Z. (47) **** ** *** 9 Xia, S. (30) **** ** *** 9 Xia, S. (38) **** ** *** 9 Zhang, M. X. (43) **** - ** 6 Zhang, Y. (45) **** ** *** 9 This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Conclusion Declarations References