Comparison of Biological, Pharmacological Characteristics, Indications, Contraindications, Efficacy, and Adverse Effects of Inactivated Whole-Virus COVID-19 Vaccines Sinopharm, CoronaVac, and Covaxin: An Observational Study

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging viral zoonotic illness that has developed a distinctive and threatening situation globally. Worldwide, many vaccines were introduced to fight against the COVID-19 pandemic. The present study aims to compare the bio-pharmacological characteristics, indications, contraindications, efficacy, and adverse effects of inactivated whole-virus COVID-19 vaccines, Sinopharm, CoronaVac, and Covaxin. Initially, 262 documents and 6 international organizations were selected. Finally, 41 articles, fact sheets, and international organizations were included. The data were recorded from the World Health Organization (WHO), Food and Drug Administration (FDA) USA, Web of Science, PubMed, EMBASE, and Scopus. The results demonstrated that these three inactivated whole-virus COVID-19 vaccines, Sinopharm, CoronaVac, and Covaxin, received emergency approval from the FDA/WHO, and all three of these vaccines are beneficial for the prevention of the COVID-19 pandemic. The Sinopharm vaccine has been recommended during pregnancy and for people of all age groups, and the CoronaVac and Covaxin vaccines are recommended for people over 18 years of age and older. These three vaccines have recommended intramuscular doses of 0.5 mL each, with a 3–4 week interval. These three vaccines can be stored in a refrigerator at +2 to +8 °C. The common adverse effects of these vaccines are pain at the injection site, redness, fatigue, headache, myalgias, general lethargy, body ache, arthralgia, nausea, chills, fever, and dizziness. The overall mean efficiency for the prevention of the COVID-19 disease is 73.78% for Sinopharm, 70.96% for CoronaVac, and 61.80% for Covaxin. In conclusion, all three inactivated whole-virus COVID-19 vaccines, Sinopharm, CoronaVac, and Covaxin, are beneficial for the prevention of the COVID-19 pandemic. However, evidence suggests that the overall impact of Sinopharm is slightly better than that of CoronaVac and Covaxin.


Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed a highly threatening situation worldwide. The swift spread of the disease is due to its numerous epidemiological and transmission trends. A SARS-CoV-2 infection is extremely contagious and provokes extensive health and socio-economic harm [1]. From 19 December 2019 to 25 March 2023, the virus swiftly spread all around the world and infected 761,402,282 people, resulting in 6,887,000 deaths with a fatality rate of 0.90% [2].
The global epidemiological and transmission trends of the disease are linked to various factors, including social gathering, travel, close contact, body fluids, respiratory droplets,  Table 1 shows the biological and pharmacological characteristics of the inac whole-virus COVID-19 vaccines Sinopharm, CoronaVac, and Covaxin. The FDA h vided emergency authorization for the administration of the Sinopharm, CoronaV Covaxin COVID-19 vaccines. FDA approval was granted for Sinopharm on 7 Ma updated 14 October 2021; 15 March 2022; CoronaVac/Sinovac was approved on 2021; and Covaxin on 3 November 2021. The dose of all of these vaccines is two do mL each) intramuscularly with an interval of 3-4 weeks and a booster dose 4-6 following the primary series vaccination. The approximate cost of Sinopharm wa USD 30  per dose, the cost of CoronaVac was USD 5-14 per dose, and of the Covaxin COVID-19 vaccine was about USD 2 per dose (Table 1).   Table 1 shows the biological and pharmacological characteristics of the inactivated whole-virus COVID-19 vaccines Sinopharm, CoronaVac, and Covaxin. The FDA has provided emergency authorization for the administration of the Sinopharm, CoronaVac, and Covaxin COVID-19 vaccines. FDA approval was granted for Sinopharm on 7 May 2021, updated 14 October 2021; 15 March 2022; CoronaVac/Sinovac was approved on 24 May 2021; and Covaxin on 3 November 2021. The dose of all of these vaccines is two doses (0.5 mL each) intramuscularly with an interval of 3-4 weeks and a booster dose 4-6 months following the primary series vaccination. The approximate cost of Sinopharm was about USD 30 (GBP 22-26) per dose, the cost of CoronaVac was USD 5-14 per dose, and the cost of the Covaxin COVID-19 vaccine was about USD 2 per dose ( Table 1).

Results
The major local complaints of Sinopharm may include pain or redness at the injection site, fatigue, headache, myalgias, general lethargy, body ache, arthralgia, nausea, chills, fever, and dizziness ( Table 2).
The common adverse effects of the CoronaVac/Sinovac vaccine can include injection site pain, fatigue, headache, muscle pain, and joint pain. Moreover, it can cause thromboembolism (Table 2). Finally, the adverse effects of the Covaxin vaccine can include local injection site pain, swelling, redness, and itching. The systemic effects can include headache, fever, malaise, body aches, nausea, and vomiting. The overall adverse effects were mild or moderate and common after the first dose. However, a severe allergic reaction may very rarely occur after the first dose of the COVAXIN vaccine (Table 2).

Contraindications
Known history of anaphylaxis, if developed after the first dose should not receive a second dose and acute symptoms [10,11] Known history of anaphylaxis, if developed anaphylaxis after the first dose and should not receive a second dose [12,13] Known history of anaphylaxis, if developed, should not receive a second dose, and acute infection or fever [14,15]. Table 3 demonstrates the efficacy of the three different inactivated whole-virus COVID-19 vaccines, Sinopharm, CoronaVac, and Covaxin. Based on the available data, it was determined that after the two doses of Sinopharm, with an interval of 21 days, efficacy was 73.78%, and it was effective against new virus variants and for persons aged 60 years and above with comorbidities. Two doses of CoronaVac/Sinovac at an interval of 14 days (2-4 weeks) has an efficacy of 70.96 against SARS-CoV-2 symptomatic patients. Moreover, the mean efficacy of Covaxin is 61.80% against all variants of COVID-19 (Table 3; Figures 2 and 3). Table 2. Comparison of immunogenicity and adverse effects between the Sinopharm, CoronaVac, and Covaxin vaccines against COVID-19 infection.

Discussion
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a highly distinctive, challenging, and threatening situation. Vaccines are the best strategy to protect people from this pandemic. Worldwide, people have received vaccinations, but there is a need to gather evidence about the safety and adverse effects of these vaccines. The immunity induced by these vaccines not only depends on the host factors but also is determined by vaccine components. Therefore, it is vital to understand the biological and pharmacological characteristics, efficacy, and adverse effects of various vaccines. We studied all three vaccines of this inactivated group (Sinopharm, CoronaVac, and Covaxin) because the three vaccines are used in many countries by people with diverse socio-economical, genetic, and environmental conditions.
The Sinopharm vaccine was prepared in China and was added to the WHO emergency use list. The Sinopharm vaccine has been widely distributed, and some clinical trials were conducted in various regions worldwide. The clinical trials in children showed this vaccine to be safe and demonstrated robust humoral responses against the SARS-CoV-2 infection after two doses of the vaccine [51].
AlHosani et al., 2022 [29] investigated the efficacy of the Sinopharm vaccine among people in Abu Dhabi, UAE. The study population was people 14 days post-vaccination who were either fully or partially vaccinated. The efficacy of the Sinopharm vaccine among fully vaccinated people was 80% against hospitalization, 92% against severe diseases, and 97% against death [29]. In another study also conducted in the United Arab Emirates, the Sinopharm vaccine demonstrated disease prevention and hospitalizations due to the SARS-CoV-2 Delta variant with an effectiveness of about 95% (95% CI, 94% to 97%) [30].
These studies of the efficacy of Sinopharm vaccines demonstrate satisfactory effectiveness. For further understanding of the effectiveness of the Sinopharm vaccine, clinical trials were organized during the first wave of the pandemic and demonstrated that the Sinopharm vaccine offered satisfactory effectiveness in preventing SARS-CoV-2 cases and deaths. The estimated disease efficacy was 78.89% (95% CI, 65.79%-86.97%). Moreover, the vaccine efficacy estimates were similar in males at 78.4% and females at 75.6% [52]

Discussion
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a highly distinctive, challenging, and threatening situation. Vaccines are the best strategy to protect people from this pandemic. Worldwide, people have received vaccinations, but there is a need to gather evidence about the safety and adverse effects of these vaccines. The immunity induced by these vaccines not only depends on the host factors but also is determined by vaccine components. Therefore, it is vital to understand the biological and pharmacological characteristics, efficacy, and adverse effects of various vaccines. We studied all three vaccines of this inactivated group (Sinopharm, CoronaVac, and Covaxin) because the three vaccines are used in many countries by people with diverse socioeconomical, genetic, and environmental conditions.
The Sinopharm vaccine was prepared in China and was added to the WHO emergency use list. The Sinopharm vaccine has been widely distributed, and some clinical trials were conducted in various regions worldwide. The clinical trials in children showed this vaccine to be safe and demonstrated robust humoral responses against the SARS-CoV-2 infection after two doses of the vaccine [51].
AlHosani et al., 2022 [29] investigated the efficacy of the Sinopharm vaccine among people in Abu Dhabi, UAE. The study population was people 14 days post-vaccination who were either fully or partially vaccinated. The efficacy of the Sinopharm vaccine among fully vaccinated people was 80% against hospitalization, 92% against severe diseases, and 97% against death [29]. In another study also conducted in the United Arab Emirates, the Sinopharm vaccine demonstrated disease prevention and hospitalizations due to the SARS-CoV-2 Delta variant with an effectiveness of about 95% (95% CI, 94% to 97%) [30].
These studies of the efficacy of Sinopharm vaccines demonstrate satisfactory effectiveness. For further understanding of the effectiveness of the Sinopharm vaccine, clinical trials were organized during the first wave of the pandemic and demonstrated that the Sinopharm vaccine offered satisfactory effectiveness in preventing SARS-CoV-2 cases and deaths. The estimated disease efficacy was 78.89% (95% CI, 65.79%-86.97%). Moreover, the vaccine efficacy estimates were similar in males at 78.4% and females at 75.6% [52]. A study conducted in Peru reported a similar efficacy in preventing both cases and COVID-19-specified mortality. These protections were, respectively, 90.5% and 93.9% [35].
Phase three clinical trials in the literature from various countries have shown that the two doses, with a 21-day interval, have an efficacy of 79% (CI: 66-87%) against SARS-CoV-2 symptomatic cases and an efficacy of 79% (95% CI: 26-94%) against hospitalization [32]. Jara [20] studied the adverse effects of the first and second doses of the Sinopharm vaccine among vaccinated medical students and healthcare workers. The common side effects were pain at the injection site, general lethargy, myalgia/body pain, low-grade fever, and headache. The adverse effects were mild in intensity for both doses but slightly more common and severe after the first dose than the second dose of the vaccine [20].
In another study conducted on Sinopharm in Iran, Almufty et al., 2021 [53] found that with both doses of vaccines, females reported more adverse effects compared to males. These adverse effects were similar to those identified in a study conducted in the United Arab Emirates [54]. The most frequently reported adverse effects were fatigue, chill, fever, headache, and injection site reactions. Babaee et al., 2022 [55] performed a study in Iran among persons who received the Sinopharm vaccine. Among the 979 participants, 62.6% of the Sinopharm recipients did not report adverse effects after the first or second doses. The commonly reported adverse effects of the Sinopharm vaccine were fatigue, chill, fever, dizziness, headache, and local reactions.
The Covaxin (BBV152) vaccine is also a whole-virion-inactivated SARS-CoV-2 vaccine against the COVID-19 pandemic. It enhances the human body's immune system without the risk of causing the disease. The mechanism of action is based on the principle that once inactivated viruses enter the body, they enhance antibody production and ensure that the body is ready to respond to an infection with live SARS-CoV-2. This vaccine contains Vaccines 2023, 11, 826 9 of 12 an aluminum-based adjuvant to enhance the immune system's response [British Society of Immunology] [58].
A study by Ella et al., 2021 [48] reported the Covaxin vaccine's efficacy among Indian people who were vaccinated two weeks after their second vaccination to be 77.8%. In another study, Singh et al. [18] investigated the antibody response after the Covaxin vaccine among healthcare workers in India. The authors reported that participants showed seropositivity after vaccination, which was almost 70%. Similarly, Kumar et al., 2021 [59] completed a study on the antibody responses to the BBV152 vaccine among healthcare professionals. The investigators found that about 76% of participants showed seropositivity after vaccination [59].
The literature demonstrates that the efficacy of the Covaxin vaccine was 63% in asymptomatic people, 78% for mild, moderate, and severe cases, 65% for the Delta variant, and 93% for severe COVID-19 cases. The Covaxin vaccine was also found to be effective in neutralizing this Alpha strain, and the vaccine was found to have a neutralizing capacity regarding the Beta and Delta variants [60]

Study Strengths and Limitations
This study establishes a comparison between various characteristics, efficacies, and adverse effects of three inactivated whole-virus COVID-19 vaccines, Sinopharm, CoronaVac, and Covaxin. This article provides a detailed comparison for a better understanding of these three vaccines in the prevention of COVID-19 disease. Moreover, the analysis of the findings is based on reputable evidence-based documents. The insights of this study are important for policymakers. The limitations of the present study include a limited amount of evidence about, first, the efficacy and adverse effects of these vaccines, and second, the specific virus variants-based information that could not be determined. Third, little is known about the vaccine in regions with low-income and middle-income countries, and this information might be missed despite a search for data from every country about responses to these vaccines. The above limitations must be considered when interpreting our reported vaccine outcomes.

Conclusions
The FDA has granted emergency use of the Sinopharm, CoronaVac, and Covaxin COVID-19 vaccines in adults 18 years of age and older. All these vaccines are inactivated vaccines and contain the killed virus. The Sinopharm, CoronaVac, and Covaxin COVID-19 vaccines are effective in reducing rates of infection and hospitalization and are thus beneficial for the prevention of the COVID-19 pandemic. The common adverse effects of these three vaccines are pain and redness at the injection site, fatigue, headache, myalgia, general lethargy, body ache, arthralgia, nausea, chills, fever, and dizziness. Furthermore, the CoronaVac/Sinovac vaccine may also cause thromboembolism. The evidence supports the conclusion that the overall benefit of Sinopharm is slightly greater than that of Coron-aVac and Covaxin. This research emphasizes the importance of continuously monitoring vaccine efficacy and adverse events. This study encourages future studies on Sinopharm, CoronaVac, and Covaxin vaccines and will lead to making a comparison between different vaccines to establish a better understanding of the vaccination outcomes. Institutional Review Board Statement: Data was obtained from publicly available databases hence ethical approval was not required.

Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.