Comparison of constitutional and dermatologic side effects between COVID-19 and non–COVID-19 vaccines: Review of a publicly available database of vaccine side effects
Authors: Stephanie R. Cohen, David X. Gao, Jared S. Kahn, David Rosmarin
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: In December 2020, the US Food and Drug Administration authorized the emergency use of 2 COVID-19 vaccines. The rapid development and authorization of these vaccines raised safety concerns among the general population.1Many remain doubtful about getting COVID-19 vaccine. AP-NORC Center for Public Affairs Research.https://apnorc.org/projects/many-remain-doubtful-about-getting-covid-19-vaccine/Date accessed: March 15, 2021Google Scholar In the Pfizer/BioNTech BNT162b2 messenger RNA (Pfizer/BioNTech) and Moderna messenger RNA-1273 SARS-CoV-2 (Moderna) COVID-19 vaccines phase 3 clinical trials, local and systemic reactions were reported.2Baden L.R. El Sahly H.M. Essink B. et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021; 384: 403-416Crossref PubMed Scopus (6722) Google Scholar,3Polack F.P. Thomas S.J. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9728) Google Scholar We sought to compare constitutional and dermatologic postimmunization side effects of the COVID-19 vaccines versus the hepatitis B virus (HBV) and seasonal influenza (Flu) vaccines on the Vaccine Adverse Event Reporting System (VAERS), a national, self-reported surveillance database.4VAERS Data. US Department of Health and Human Services.https://vaers.hhs.gov/data.htmlDate accessed: March 5, 2021Google Scholar HBV and Flu (seasonal flu recombinant and inactivated) vaccines were selected because they are 2 established nonlive vaccines that have been administered to the general population for decades. For both COVID-19 vaccines, data were obtained from their rollout in December 2020 until February 26, 2021, whereas for the HBV and Flu vaccines, data were obtained from 1990 until February 26, 2021. Only constitutional and dermatologic side effects with reported rates ≥1% for all 4 vaccines were included. Data were analyzed using the χ2 test in R-4.0.3. At the time the data from VAERS were obtained, Pfizer/BioNTech and Moderna vaccines were approved for adults aged ≥16 and 18 years, respectively. The HBV and Flu vaccines are approved for infants since birth and for ages of ≥6 months old, respectively. In our research, reported constitutional side effects were higher for the Moderna and Pfizer/BioNTech when compared with the HBV and Flu vaccines. The dermatologic side effects reported for Moderna were greater than that of HBV but not Flu. However, Pfizer/BioNTech did not have a statistically significantly higher percentage of dermatologic side effects when compared with HBV or Flu. When comparing Moderna and Pfizer/BioNTech, the majority of constitutional and dermatologic side effects were higher for Moderna in terms of percent of cases reported (Table I).Table IComparison among Pfizer/BioNTech BNT162b2 messenger RNA COVID-19 vaccine, Moderna messenger RNA-1273 SARS-CoV-2 vaccine, hepatitis B virus vaccine, and seasonal influenza vaccineVaccinesP vaccineM vaccineHBV vaccineFlu vaccineVaccine comparison14,64910,40358,063152,627P-MP-HBVP-FluM-HBVM-FluTotal number of patients reporting SENumber of reported SE (%)Number of reported SE (%)Number of reported SE (%)Number of reported SE (%)Constitutional SE Headache2932 (20.02)2242 (21.55)3641 (6.27)11,594 (7.60).003<.001<.001<.001<.001 Fatigue2188 (14.94)1537 (14.77)1124 (1.94)6305 (4.13).736<.001<.001<.001<.001 Pyrexia2003 (13.67)1853 (17.81)9473 (16.32)19,880 (13.03)<.001<.001.027<.001<.001 Chills1985 (13.55)1763 (16.95)1291 (2.22)9890 (6.48)<.001<.001<.001<.001<.001 Pain1853 (12.65)1622 (15.59)3335 (5.74)18,395 (12.05)<.001<.001.035<.001<.001 Nausea1794 (12.25)1458 (14.02)3602 (6.20)9141 (5.99)<.001<.001<.001<.001<.001 Myalgia940 (6.42)721 (6.93)2669 (4.60)7004 (4.59).113<.001<.001<.001<.001 Arthralgia754 (5.15)593 (5.70)2363 (4.07)4477 (2.93).059<.001<.001<.001<.001 Malaise659 (4.50)290 (2.79)1683 (2.90)5246 (3.44)<.001<.001<.001.554<.001 Asthenia621 (4.24)433 (4.16)2645 (4.56)6407 (4.20).789.103.828.079.881Dermatologic SE Pruritus785 (5.36)678 (6.52)3651 (6.29)9197 (6.03)<.001<.001.001.388.044 Rash779 (5.32)528 (5.08)4954 (8.53)8305 (5.44).411<.001.540<.001.115 Urticaria571 (3.90)403 (3.87)3715 (6.40)8424 (5.52).949<.001<.001<.001<.001 Hyperhidrosis474 (3.24)314 (3.02)1190 (2.05)3225 (2.11).350<.001<.001<.001<.001 Erythema416 (2.84)498 (4.79)1388 (2.39)12,426 (8.14)<.001.001<.001<.001<.001Injection Site Pain1192 (8.14)1269 (12.20)3102 (5.34)18,140 (11.89)<.001<.001<.001<.001.347Injection site erythema323 (2.20)1104 (10.61)2175 (3.75)17,523 (11.48)<.001<.001<.001<.001.007Injection site swelling291 (1.99)839 (8.06)1358 (2.34)12,759 (8.36)<.001.011<.001<.001.301Injection site warmth153 (1.04)576 (5.54)802 (1.38)7831 (5.13)<.001.001<.001<.001.073Values in bold are values that are statistically significant (P value <.05). Cutoff value for statistical significance ≤.05.Flu, Seasonal influenza vaccine; HBV, hepatitis B virus vaccine; M, Moderna messenger RNA-1273 SARS-CoV-2 vaccine; P, Pfizer/BioNTech BNT162b2 messenger RNA COVID-19 vaccine; SE, side effect. Open table in a new tab Values in bold are values that are statistically significant (P value <.05). Cutoff value for statistical significance ≤.05. Flu, Seasonal influenza vaccine; HBV, hepatitis B virus vaccine; M, Moderna messenger RNA-1273 SARS-CoV-2 vaccine; P, Pfizer/BioNTech BNT162b2 messenger RNA COVID-19 vaccine; SE, side effect. Of note, Moderna had a significantly higher percentage of injection site reactions (ie, pain, erythema, swelling, and warmth) compared with Pfizer/BioNTech and HBV but not Flu. For the Pfizer/BioNTech vaccine, injection site reactions were lower than for the other vaccines. In both Pfizer/BioNTech and Moderna trials, younger patients (16-55 and 18 to <65 years old, respectively) experienced more frequent and severe side effects, possibly due to their having a more robust immune system and consequently a higher degree of reactogenicity.2Baden L.R. El Sahly H.M. Essink B. et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021; 384: 403-416Crossref PubMed Scopus (6722) Google Scholar,3Polack F.P. Thomas S.J. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9728) Google Scholar Overall, both COVID-19 vaccines have favorable safety profiles and proven efficacy.2Baden L.R. El Sahly H.M. Essink B. et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021; 384: 403-416Crossref PubMed Scopus (6722) Google Scholar,3Polack F.P. Thomas S.J. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (9728) Google Scholar It is vital for physicians to encourage appropriate vaccination of our patients. Our study may help address patients' concerns regarding the COVID-19 vaccines. Future studies should assess whether similar results are observed in children in whom the vaccine was approved recently. Limitations to our study are the incomplete capture and reporting from the VAERS database, which is self-reported and voluntary, although VAERS has previously successfully detected safety signals for other vaccines such as intussusception for the rotavirus vaccine.5Shimabukuro T.T. Nguyen M. Martin D. DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS).Vaccine. 2015; 33: 4398-4405Crossref PubMed Scopus (398) Google Scholar Finally, the population receiving the COVID-19 vaccine may not match those getting the Flu and HBV vaccines.4VAERS Data. US Department of Health and Human Services.https://vaers.hhs.gov/data.htmlDate accessed: March 5, 2021Google Scholar Dr Rosmarin has received honoraria as a consultant for AbbVie, Celgene, Dermavant, Dermira, Janssen, Lilly, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; has received research support from AbbVie, Bristol Meyers Squibb, Celgene, Dermira, Incyte, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; and has served as a paid speaker for AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc, and Sanofi. Dr Cohen and Authors Gao and Kahn have no conflicts of interest to declare.