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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: José Eduardo Riceto Loyola Junior, M.D.[2]


On December 11, 2020, the F.D.A. authorized Pfizer's vaccine for emergency use for the prevention of COVID-19. Since then, many other vaccines have been developed, such as the ones from Pfizer, Moderna, AstraZeneca, Janssen, Sinovac, Sinopharm and Gamaleya. Efficacy, side effects and safety profiles vary dramatically between them, as they are produced using different strategies. Fully vaccinated persons with a negative recent COVID-19 test are now being accepted for entering the U.S.

Most Used Vaccines

  • All following vaccines, except for Covaxin and Sputnik are currently being accepted for entering in the U.S. for tourists. The chosen criteria was to accept FDA and WHO-approved vaccines.
  • Latest studies have shown that some vaccines have waning protection against COVID-19 infection after 5-7 months, reaching 20% efficacy. Effectiveness preventing critical disease, deaths and hospitalization has remained unaltered after 7 months.[1]

Pfizer/BioNtech Comirnaty - BNT162b2

- Mechanism of action: mRNA-based; PEGylated lipid nanoparticles vector.
It was approved for emergency use on December 11, 2020. It has been shown to have an efficacy of 95% at preventing COVID-19 in persons 16 years of age or older.[2] Its protection against severe COVID-19 was shown to be of approximately 97%. New analysis showed that after six months its efficacy fell to 84%, which is not known if this is due to the vaccine and immune system themselves of if the emergence of variants are affecting the efficacy of the vaccine. As for side effects, the vaccine has been reported to cause mostly mild symptoms such as myalgia, headaches and soreness in the location where it was applied. Allergic reactions have also been reported in a few patients, and they all recovered quickly after an epinephrine shot. It has been theorized that the allergic reactions were mediated by the PEGylated lipid nanoparticles in which the mRNA is stabilized. [3] It has also been reported to be associated with myocarditis and pericarditis, especially in young men, but the cases reported so far were mild and recovered.[4][5] An Israeli study found out that the most common age and gender for the occurrence of myocarditis is men between 16 and 19 years of age, after the second dose.[6] Efficacy against the Delta variant is of about 88%, while against the alpha variant, in the same study, it was about 93.7%.[7] Another recent study published in NEJM showed that Pfizer's vaccine was associated with myocarditis and lymphadenopathy which occurred in 11 and 78.4 persons per 100.000 respectively. Despite that, the incidence of myocarditis in COVID-19 has been shown to be much bigger. The vaccine also showed a protective effect against pulmonary thromboembolism and anemia possibly due to many undiagnosed infections among the control group which eventually complicated with such events.[8]

  • Dose regimen:
    • Application of 2 doses, spaced by 21 days between shots.
    • A third shot was recently recommended by the F.D.A. for adults 6 months after their second dose. A different israeli study showed that immunity against the delta variant of SARS-CoV-2 seemed to wane in all age groups a few months after the second dose of vaccine.[9] It was found that a third dose of this vaccine was associated with significantly increased antibody titers after 10 to 19 days. It also developed response in 49% of the transplant patients who previously did not have seroconversion.[10]
  • Must be kept at very low temperatures to preserve its substrate, between -80 and -60C. Undiluted vials must be kept in the refrigerator at 2 to 8C for up to 5 days, and it must not be kept at room temperature for more than 30 minutes during its administration.[11]

Moderna - mRNA-1273

- Mechanism of action: mRNA-based; lipid nanoparticles vector.
Approved for emergency use by the F.D.A. on December 18, 2020. The clinical trials produced by Moderna showed that its vaccine has an efficacy of 90% against symptomatic COVID-19 and 95% efficacy against severe disease after six months. Side-effects include: arthralgia, myalgia, fever, chills, headache, nausea or induration/pain at application site.[12]. No allergic reactions has been described with Moderna's vaccine so far, in comparison to Pfizer's, but it has been associated with a bigger occurrence of mild side-effects in comparison to the latter.[11] It has also been associated with pericarditis and myocarditis, but these were mild cases, as was the case with the Pfizer's one, but cases were mild and recovered.[4][5] Efficacy against the Delta variant is of about 88%, while against the alpha variant, in the same study, it was about 93.7%.[7]

  • Dose regimen:
    • Application of 2 doses, spaced by 28 days between shots.
  • Must be kept in temperatures of -25 to -15C in order to conserve its substrate. Vials can be kept in the refrigerator at 2 to 8C for up to 30 days. After first application, vial must be discarded after 6 hours.[11]

Janssen - Ad26.COV2.S

- Mechanism of action: adenoviral vector Ad26.
Authorized for emergency use by the F.D.A. on February 27, 2021.[13] According to the CDC, its efficacy has been estimated to be at approximately 67% in preventing moderate to severe COVID-19 after at least 14 days after vaccination and 66% after at least 28 days. Regarding only severe cases, its efficacy has been of approximately 77% at least 14 days after vaccination ad 85% at least 28 days after vaccination. According to the CDC, the most common side effects are: headache, fatigue, nausea, pain at the injection site and muscle aches, lasting 1-2 days after injection. It was also associated with Guillain-Barré syndrome and also with vaccine-induced thrombocytopenia and thrombosis.

  • Dose regimen: single dose
  • Must be kept at temperatures between 2 to 8C in order to conserve its substrate. Unpunctured vials may be kept between 9 to 25C for up to 12 hours.

AstraZeneca/Oxford - ChAdOx1 nCoV-19

- Mechanism of action: adenoviral vector - chimpanzee adenovirus (ChAdOx).
Not F.D.A. approved. Efficacy of preventing COVID-19 infection was first estimated to be of 70.4% with a curious stark difference between two groups of patients.[14]. Efficacy against Delta variant is 67% after two doses, in comparison to an estimate of 74.5% against the alpha variant.[7] Patients that received first a low dose and then a standard dose had a much higher efficacy (90%) in comparison to those who got two standard doses. The trial was interrupted twice due to two cases of transverse myelitis.[14]. Efficacy against Delta variant is 67% after two doses, in comparison to an estimate of 74.5% against the alpha variant.[7]. It was associated with Guillain-Barré syndrome, which occurred very rarely, and also with vaccine-induced thrombocytopenia and thrombosis. Many studies have documented the association of this vaccine with venous thromboembolism, stating that it increases the occurrence of this event in about 20 times. Despite that, the absolute occurrence is still very rare, and researchers have concluded that the benefits far outweigh the risks.[15]

  • Dose regimen:
    • Two doses spaced 8 to 12 weeks between doses.
  • Must be kept at temperatures between 2 to 8C in order to conserve its substrate.

Vaccine-induced Thrombocytopenia and Thrombosis

Diagnostic criteria - must have all four:[16][17][18]

Signs and symptoms
Headache, visual abnormalities, nausea and vomiting, back pain, leg pain and swelling, abdominal pain, shortness of breath, petechiae, bruising or bleeding.
Imaging to screen for thrombosis + cell blood count to assess thrombocytopenia, PF4-ELISA (HIT assay), fibrinogen and D-dimer.
If confirmed: start intravenous immune immunoglobin and nonheparin anticoagulation.

SinoVac - CoronaVac

- Mechanism of action: inactivated virion.
Not F.D.A. approved. Most widely used vaccine in the world against SARS-CoV2, according to Airfinity. A Chilean cohort study. stated that its efficacy is at approximately 65.9% for preventing COVID-19 in fully immunized patients, 87.5% for prevention of hospitalization and 90.3% for prevention of ICU admission. Its efficacy for prevention of COVID-19-related death was estimated at 86.3%.[19]. A study performed by Butantan Institute reported an efficacy for prevention of COVID-19 infection of 50.4%, 77% for prevention of mild disease and 100% efficacy on prevention of severe disease, but the numbers were not statistically significant. Despite these results, some deaths of fully vaccinated patients in the country have been reported, specially for its elderly population, which was the one that was vaccinated with CoronaVac. A non-peer reviewed study reported that it had a real-world efficacy of only 42% in the elderly population and that its efficacy decreases with age. In June, due to a reduction in its previous efficacy estimate, Chile started to give to its population older than 55 years old that were fully vaccinated with Coronavac a shot of AstraZeneca's vaccine. Lastly, another Brazilian study showed that despite its efficacy, many patients still developed COVID-19 disease after the second shot and concluded that social distancing should be maintained during the vaccination campaign.[20] Regarding side effects, the vaccine has a low incidence of adverse effects in comparison to the others, presenting with injection site pain, fatigue, headache, muscle pain and joint pain.[21] The most severe being an allergic reaction to a component of the vaccine that required hospitalization.[22]. Despite that, there are a few cases reports of Guillain Barré syndrome after its administration.

  • Dose regimen:
    • Application of two doses spaced by at least 4 weeks.


- Mechanism of action: inactivated virion.
Not F.D.A. approved. Its efficacy and safety was assessed in a phase I study, in which all subjects developed elevated antibody response.[23] Nonpublished data of ongoing phase III studies done by Bharat Biotech claimed an efficacy of 81%. It was approved for use in India before phase III studies were completed, which caused widespread criticism.

  • Dose regimen:
    • Application of 2 doses, spaced by 28 days between shots.
  • Must be kept at temperatures between 2 to 8C in order to conserve its substrate.

Gamaleya - Sputnik

- Mechanism of action: heterologous recombinant adenovirus approach using adenovirus 26 and adenovirus 5 as vectors.[24]
This vaccine uses two different adenoviral vectors in order to expand the immune response against the SARS-CoV2 Spike protein, which is inserted into these vectors. It's efficacy has been estimated to be at 91.6% and disease severity was reduced after the first dose was taken.[24][25] with Gamaleya institute stating that their vaccine achieved 97.6% in real world assessment. Many criticisms were done to the vaccine's efficacy as it lacked transparency and seemed to be done at haste. Brazil's regulatory agency, ANVISA, first refused the vaccine stating that there was evidence of presence of adenovirus that "could reproduce", which would be a serious defect for the agency. It was later approved with a very restricted use and only on healthy adults. Most common side effects were: injection site reactions, headache, asthenia and flu-like illness. In the same study, 122 rare serious adverse reactions were not considered to be due to the vaccination.[25] It didn't show any significant differences in sera neutralizing activity against B.1.1.7, B.1.617.3 and local russian genetic lineages B.1.1.141 , B.1.1.317, but it had a reduction of neutralizing activity against B.1.351, P.1, and B.1.617.2 of 3.1-, 2.8-, and 2.5-fold, respectively.[26]

  • Dose regimen:
    • Application of 2 doses, spaced by 21 days between shots.

Promising Vaccines

Novavax - NVX-CoV2373

- Mechanism of action: protein-based vaccine.

A phase II clinical trial found out that the vaccine had a 89%.7% efficacy. Most common side effect was injection-site tenderness or pain followed by headache, fatigue and nausea. Later data analysis showed an efficacy of 86.3% against the B.1.1.7 (or alpha) variant and 96.4% against non-B.1.1.7 variants.[27] Another study found out that the vaccine had an efficacy against B.1.351 of 51%.[28] It is still in development and has not been approved for use in any country.

  • Dose regimen:
    • Application of 2 doses, spacing yet to be determined.


  1. Chemaitelly H, Tang P, Hasan MR, AlMukdad S, Yassine HM, Benslimane FM; et al. (2021). "Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar". N Engl J Med. doi:10.1056/NEJMoa2114114. PMID 34614327 Check |pmid= value (help).
  2. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S; et al. (2020). "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine". N Engl J Med. 383 (27): 2603–2615. doi:10.1056/NEJMoa2034577. PMC 7745181 Check |pmc= value (help). PMID 33301246 Check |pmid= value (help). Review in: Ann Intern Med. 2021 Feb;174(2):JC15
  3. Kleine-Tebbe J, Klimek L, Hamelmann E, Pfaar O, Taube C, Wagenmann M; et al. (2021). "Severe allergic reactions to the COVID-19 vaccine - statement and practical consequences". Allergol Select. 5: 26–28. doi:10.5414/ALX02215E. PMC 7787363 Check |pmc= value (help). PMID 33426427 Check |pmid= value (help).
  4. 4.0 4.1 Singh B, Kaur P, Cedeno L, Brahimi T, Patel P, Virk H; et al. (2021). "COVID-19 mRNA Vaccine and Myocarditis". Eur J Case Rep Intern Med. 8 (7): 002681. doi:10.12890/2021_002681. PMC 8276934 Check |pmc= value (help). PMID 34268277 Check |pmid= value (help).
  5. 5.0 5.1 Tano E, San Martin S, Girgis S, Martinez-Fernandez Y, Sanchez Vegas C (2021). "Perimyocarditis in Adolescents After Pfizer-BioNTech COVID-19 Vaccine". J Pediatric Infect Dis Soc. doi:10.1093/jpids/piab060. PMC 8344528 Check |pmc= value (help). PMID 34319393 Check |pmid= value (help).
  6. Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E; et al. (2021). "Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel". N Engl J Med. doi:10.1056/NEJMoa2109730. PMID 34614328 Check |pmid= value (help).
  7. 7.0 7.1 7.2 7.3 Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S; et al. (2021). "Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant". N Engl J Med. 385 (7): 585–594. doi:10.1056/NEJMoa2108891. PMC 8314739 Check |pmc= value (help). PMID 34289274 Check |pmid= value (help).
  8. Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernán MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD (August 2021). "Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting". N Engl J Med. doi:10.1056/NEJMoa2110475. PMID 34432976 Check |pmid= value (help).
  9. Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman L, Haas EJ; et al. (2021). "Waning Immunity after the BNT162b2 Vaccine in Israel". N Engl J Med. doi:10.1056/NEJMoa2114228. PMID 34706170 Check |pmid= value (help).
  10. Eliakim-Raz N, Leibovici-Weisman Y, Stemmer A, Ness A, Awwad M, Ghantous N; et al. (2021). "Antibody Titers Before and After a Third Dose of the SARS-CoV-2 BNT162b2 Vaccine in Adults Aged ≥60 Years". JAMA. doi:10.1001/jama.2021.19885. PMID 34739043 Check |pmid= value (help).
  11. 11.0 11.1 11.2 Meo SA, Bukhari IA, Akram J, Meo AS, Klonoff DC (2021). "COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines". Eur Rev Med Pharmacol Sci. 25 (3): 1663–1669. doi:10.26355/eurrev_202102_24877. PMID 33629336 Check |pmid= value (help).
  12. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M; et al. (2020). "Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults". N Engl J Med. 383 (25): 2427–2438. doi:10.1056/NEJMoa2028436. PMC 7556339 Check |pmc= value (help). PMID 32991794 Check |pmid= value (help).
  13. Barouch DH, Stephenson KE, Sadoff J, Yu J, Chang A, Gebre M; et al. (2021). "Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination". N Engl J Med. doi:10.1056/NEJMc2108829. PMC 8314733 Check |pmc= value (help). PMID 34260834 Check |pmid= value (help).
  14. 14.0 14.1 Knoll MD, Wonodi C (2021). "Oxford-AstraZeneca COVID-19 vaccine efficacy". Lancet. 397 (10269): 72–74. doi:10.1016/S0140-6736(20)32623-4. PMC 7832220 Check |pmc= value (help). PMID 33306990 Check |pmid= value (help).
  15. Perera R, Fletcher J (2021). "Thromboembolism and the Oxford-AstraZeneca vaccine". BMJ. 373: n1159. doi:10.1136/bmj.n1159. PMID 33952506 Check |pmid= value (help).
  16. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S (2021). "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination". N Engl J Med. 384 (22): 2092–2101. doi:10.1056/NEJMoa2104840. PMC 8095372 Check |pmc= value (help). PMID 33835769 Check |pmid= value (help).
  17. Muir KL, Kallam A, Koepsell SA, Gundabolu K (2021). "Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination". N Engl J Med. 384 (20): 1964–1965. doi:10.1056/NEJMc2105869. PMC 8063883 Check |pmc= value (help). PMID 33852795 Check |pmid= value (help).
  18. Tiede A, Sachs UJ, Czwalinna A, Werwitzke S, Bikker R, Krauss JK; et al. (2021). "Prothrombotic immune thrombocytopenia after COVID-19 vaccination". Blood. 138 (4): 350–353. doi:10.1182/blood.2021011958. PMC 8084604 Check |pmc= value (help). PMID 34323939 Check |pmid= value (help).
  19. Jara A, Undurraga EA, González C, Paredes F, Fontecilla T, Jara G; et al. (2021). "Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile". N Engl J Med. doi:10.1056/NEJMoa2107715. PMC 8279092 Check |pmc= value (help). PMID 34233097 Check |pmid= value (help).
  20. Hitchings MDT, Ranzani OT, Torres MSS, de Oliveira SB, Almiron M, Said R; et al. (2021). "Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study". Lancet Reg Health Am: 100025. doi:10.1016/j.lana.2021.100025. PMC 8310555 Check |pmc= value (help). PMID 34386791 Check |pmid= value (help).
  21. Riad A, Sağıroğlu D, Üstün B, Pokorná A, Klugarová J, Attia S; et al. (2021). "Prevalence and Risk Factors of CoronaVac Side Effects: An Independent Cross-Sectional Study among Healthcare Workers in Turkey". J Clin Med. 10 (12). doi:10.3390/jcm10122629. PMC 8232682 Check |pmc= value (help). PMID 34203769 Check |pmid= value (help).
  22. Tanriover MD, Doğanay HL, Akova M, Güner HR, Azap A, Akhan S; et al. (2021). "Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey". Lancet. 398 (10296): 213–222. doi:10.1016/S0140-6736(21)01429-X. PMC 8266301 Check |pmc= value (help). PMID 34246358 Check |pmid= value (help).
  23. "Correction to Lancet Infect Dis 2021; published online Jan 21.". Lancet Infect Dis. 21 (4): e81. 2021. doi:10.1016/S1473-3099(21)00131-6. PMID 33636147 Check |pmid= value (help). External link in |title= (help)
  24. 24.0 24.1 Jones I, Roy P (2021). "Sputnik V COVID-19 vaccine candidate appears safe and effective". Lancet. 397 (10275): 642–643. doi:10.1016/S0140-6736(21)00191-4. PMC 7906719 Check |pmc= value (help). PMID 33545098 Check |pmid= value (help).
  25. 25.0 25.1 Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS; et al. (2021). "Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia". Lancet. 397 (10275): 671–681. doi:10.1016/S0140-6736(21)00234-8. PMC 7852454 Check |pmc= value (help). PMID 33545094 Check |pmid= value (help).
  26. Gushchin VA, Dolzhikova IV, Shchetinin AM, Odintsova AS, Siniavin AE, Nikiforova MA; et al. (2021). "Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants". Vaccines (Basel). 9 (7). doi:10.3390/vaccines9070779. PMC 8310330 Check |pmc= value (help). PMID 34358195 Check |pmid= value (help).
  27. Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F; et al. (2021). "Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine". N Engl J Med. doi:10.1056/NEJMoa2107659. PMC 8262625 Check |pmc= value (help). PMID 34192426 Check |pmid= value (help).
  28. Ikeme MM, Adelaja AO (1990). "Effects of the timing of antigen stimulation on parasitaemia profile and subsequent immunodepression in an experimentally induced Trypanosoma brucei infection". Rev Elev Med Vet Pays Trop. 43 (3): 331–6. PMID 0.1056/NEJMoa2103055 Check |pmid= value (help).