Many are questioning whether they should receive the COVID-19 vaccination, especially since it is relatively new and mRNA vaccinations, while they have been in use, have not been widely used in the population. Below is an attempt to provide a comparison, as much as possible, to assist in rational decision-making. Medicine is very much an attempt at weighing the rewards with the risks to achieve the best possible outcome under the circumstances. Most physicians recognize that this does not always yield the ideal result.
Despite what would appear to be inherent risks of COVID-19 vaccination, it should be appreciated that both Moderna and Pfizer attempted to include low-risk as well as high-risk patients in their vaccination studies. In most cases, the adverse events did not appear to occur at a rate higher than that which occurs in the population at large.
Table I reviews the common adverse events with the vaccine compared with the same effect during natural COVID-19 infection.
Table II compares rates of more severe side effects of COVID-19 infection with the same side effects of COVID-19 vaccination and the rate in the general population.
Table I: Common adverse events of COVID-19 vaccination v. infection.
|Statistic||Without vaccination||After COVID-19 Vaccination|
|Rate of contracting severe COVID-19 in Pfizer trial (7 d after 2nd dose)4||.08%
Rate of contracting severe COVID-19 (Moderna)3
|Severity of infection with COVID-199||80% asymptomatic or mild
15% severe, requiring oxygen.
5% critical, requiring ventilation.
|95% effective at preventing COVID-193,4
0% severe, requiring oxygen.
0% critical, requiring ventilation.
|Number of patients with fever||80% of symptomatic COVID -19 patients10||14.8% of vaccinated patients (from vaccine, compared with 0.6% of placebo) in Moderna trial1; 14.2% in Pfizer trial4, 12|
|Number of patients with chills||63% of symptomatic COVID -19 patients10||43.4% of vaccinated patients (from vaccine, compared with 9.58 % of placebo) in Moderna trial1; 31.9% in Pfizer trial4, 12|
|Number of patients with fatigue||62% of symptomatic COVID -19 patients10||68.5 % of vaccinated patients (from vaccine, compared with 36.1 % of placebo) in Moderna trial1; 62.9% in Pfizer trial4, 12|
|Number of patients with headache||59% of symptomatic COVID -19 patients10||63 % of vaccinated patients (from vaccine, compared with 36.5 % of placebo) in Moderna trial1; 55.1% in Pfizer trial4, 12|
|Number of patients with shortness of breath||57% of symptomatic COVID-19 patients10||1 patient of vaccine group in Moderna trial (noted as resolving), otherwise noted in the placebo group3; shortness of breath was only noted in placebo group of Pfizer trial12|
Table II: Comparison of the more severe side effects of COVID-19 infection v. COVID-19 vaccination v. rate of occurrence in the general population.
|Statistic||During COVID-19 infection||After COVID-19 Vaccination||Rate in general population|
|Number of patients that develop blood clots5||31% of hospitalized COVID patients (81% of which are pulmonary emboli)5||Unknown but in none noted in trials3,4||1 in 1000/year in adults18|
|Number of patients with ischemic stroke6, 15||0.4-2.7 % of hospitalized COVID patient6, 15
As high as 6% in hospitalized COVID patients requiring intensive care16
|Unknown. One patient hospitalized 32 days after 2nd vaccine of Moderna trial but in 0 % in trials3, 4, 12; one patient with known pre-existing history of artherosclerosis died in Pfizer trial of arteriosclerosis 3 days after first vaccination and rate of non-fatal stroke was .02%12||Prevalence is approximately 3% of adult population19|
|Number of patients with hemorrhagic stroke||0.2-0.9% of hospitalized COVID patients6, 15||Unknown but in 0 % in trial3, 4, 12||Prevalence is 13% of stroke20|
|Neurologic manifestations||Covid‐19 onset in 419 of 509 patients hospitalized with covid (82.3%) at any time during disease2. Of these, rate of myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%)2||Headache occurred in 63% of vaccinated patients (from vaccine, compared with 36.5 % of placebo) in Moderna trial1 and 55.1% in Pfizer trial4, 12 but long-term unknown unknown long-term||1-year prevalence of headache is 46% and 64% lifetime prevalence32; Musculoskeletal pain prevalence in 13.5-47% of population with chronic widespread pain in 11.4-24%33; 12-month prevalence of dizziness in US is 14.8%34|
|Number of patients with Guillain-Barre Syndrome||2-4/816 patients hospitalized with COVID14||Unknown but not seen in trials3, 4, 12
|Number of patients with Bell’s palsy||Case reports11||.0091-.009% in trials3, 4, 12||25-35/100,000/year13|
|Number of patients with cardiac issues||In patients observed for a median time of 71 days: 78% demonstrate some cardiac involvement.
60% demonstrate ongoing myocardial inflammation.
7% fulminant myocarditis was likely cause of death7
|In Pfizer trial 1 patient had cardiac arrest 62 days after 2nd vaccination and died 3 days later12; rate of nonfatal acute Myocardial infarction was .02%12||American adults diagnosed with heart disease is 12.1%35|
|Risk of ARDS from COVID-19||14.8% of patients hospitalized for COVID-19 (52.4% of which die from ARDS)8||0 % in vaccine groups of trials3, 4, 12||10-15% of hospitalized patients; 23% of mechanically ventilated patients26|
|Risk of Gastrointestinal disorders||>50% (loss of appetite, nausea, vomiting, and diarrhea)10||Diarrhea or vomiting was noted in 3% vaccinated and 2% placebo patients in Pfizer trial 12; gastrointestinal disorder or diarrhea was noted in 2.8% and 1.2% of vaccinated patients (2.6% and 1.0% of placebo recipients), respectively in Moderna trial3||Incidence was 0.14 episodes per person-year in high income North America39|
|Acute respiratory distress syndrome||41.8% of 201 patients hospitalized with COVID, 52.4 % of whom died24||Unknown but 0 % in trials in vaccinated group3, 4, 12||10-15% of patients admitted to the intensive care unit40|
|Post-COVID pulmonary fibrosis||4% of patients with ARDS and a disease duration of less than 1 week, 24% of patients with a disease duration of between weeks 1 and 3, and 61% of patients with a disease duration of greater than 3 weeks, developed fibrosis23||Unknown; not noted in trials3, 4, 12||Incidence is 10.7 per 100,000/year for men and 7.4/100,000/year for women; prevalence is 20/100,000/ year for men and 13/ 100,000/ year for women27|
|Risk of Brain fog||Of 120 patients hospitalized with COVID, 34% developed memory loss, 27% had concentration problems months later25||Unknown; not noted in trials3, 4, 12||25% of people over 75 years of age28|
|Lingering cough, shortness of breath, and chest pain||Of 120 patients hospitalized with COVID-19, 17% had cough, 42% had shortness of breath, and 11% had chest pain months later7, 25||Unknown; not noted in trials3, 4, 12||Prevalence of shortness 27% globally29|
|Lingering fatigue||Of 120 patients hospitalized with COVID, 55% developed lingering fatigue25||Unknown; not noted in trials3, 4, 12||71.34/100,000 persons30|
|Incidence of Multisystem Inflammatory Syndrome in Children||1659 cases from mid-May-October 1, 2020; 99% of which had COVID21||Unknown. Children were excluded from initial trial||Kawasaki syndrome-associated hospitalization rate in 2006 was 28.0/100,000 in children < 5yo22|
|Cases of anaphylaxis||N/A||21 cases out of 1,893,360 people who received the Pfizer vaccine26; in Pfizer trial 0.63% (vs. 0.51% in control group)12; no vaccine-associated anaphylaxis in Moderna trial3||Incidence 1.6-5.1 % and prevalence is 42/100,000-person-years31|
|Death||Globally 2,115,125 deaths/ 98,529,820 cases (2.1%); U.S. 416,289 deaths/ 24,934,941 cases (1.7%)38||In Moderna trial, 6 deaths in vaccine group (7 in placebo group)3 In Pfizer trial, 2 deaths in vaccine group (4 in placebo group)12||867.8 deaths per 100,000 people in the U.S.37|
In conclusion, the course of COVID-19 infection is complex and unpredictable. Its interaction with the infected patient’s immune system is quite variable. The infection itself can be challenging to overcome and many patients are laden with prolonged side effects. In absence of previous history or likelihood of adverse reaction to the vaccine, while it may not be perfect and long-term side effects may come to light in the future, the risk versus reward ratio seems to be weighted in favor of vaccination.
2Liotta, EM, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients; Annals of Clinical and Translational Neurology 2020; 7(11): 2221–2230.
5Klok, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19; J Thromb Res 2020; 191: 145-147.
6Merkler, AE, et al. Risk of Ischemic Stroke in Patients with Coronavirus Disease 2019 (COVID-19) vs Patients with Influenza; JAMA Neurol 2020; 77: 1366-1372.
7Valentina, O, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered from Coronavirus Disease 2019 (COVID-19); JAMA Cardiol 2020; 5: 1265-1273.
8Sun P, et al. Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: A single arm meta-analysis. J Med Virol 2020; 92: 612-617.
9Shi, S, et al. Association of Cardiac Injury with Mortality in Hospitalized Patient with COVID-19 in Wuhan, China. JAMA Cardiol 2020; 5: 802-810.
10Burke, RM, Killerby, ME, Newton, S, et al. Symptom Profiles of a Convenience Sample of Patient with COVID-19—United States, January-April 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 904-908.
11Lima, MA, et al. Peripheral facial nerve palsy associated with COVID-19. J Neurovirol 2020; Oct 2: 104. doi: 10.1007/s13365-020-00912-6.
14Toscano, G, et al. Guillain-Barre Syndrome Associated with SARS-CoV-2. N Engl J Med 2020; 382: 2574-2576
15Elkind, MSV, et al. Coronavirus diseases 2019 (COVID-19): Neurologic complications and management of neurologic conditions; UpToDate; accessed January 23, 2021.
16Li, Y, et al. acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke & Vascular Neurology 2020: 5: e000431. Doi: 10.1136/svn-2020-000431.
17Winer, JB, et al. Guillain Barre syndrome. Mol Pathol 2001; 54: 381-385.
18Cushman, M. Epidemiology and Risk Factors for Venous Thrombosis. Semin Hematol 2007; 44: 62–69.
19Ovbiagele, B and Nguyen-Huynh, MN. Stroke Epidemiology: Advancing Our Understanding of Disease Mechanism and Therapy. Neurotherapeutics 2011; 8: 319–329.
20Habibi-koolaee, M, et al. Prevalence of Stroke Risk Factors and Their Distribution Based on Stroke Subtypes in Gorgan: A Retropective Hospital-Based Study—2015-2016. Neurol Res Int. 2018; 2018: 2709654. doi: 10.1155/2018/2709654
22Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB. Hospitalizations for Kawasaki syndrome among children in the United States, 1997-2007. Pediatr Infect Dis J. 2010; 29:483–8.
23Deependra, KR et al. Post covid 19 pulmonary firbrosis—Is it reversible? Indian J Tuberc 2020; Nov 10. doi: 10.1016/j.ijtb.2020.11.003.
24Wu C., Chen X., Cai Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–943.
25Garrigues, E, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect 2020; 81: e4-e6.
26Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020. MMWR Morb Mortal Wkly Rep 2021; 70: 46–5.
27Kim, DS, et al. Classification and Natural History of the Idiopathic Interstitial Pneumonias. Proc Am Thorac Soc. 2006; 3: 285–292.
28Fillit, HM, et al. Achieving and Maintaining Cognitive Vitality with Aging. Mayo Clin Proc 2002; 77: 681-696.
29Grønseth, R, et al. Predictors of dyspnea prevalence: Results from the BOLD study. Eur Respir J. 2014; 43: 1610–1620.
30Vincent, A, et al. Prevalence, Incidence, and Classification of Chronic Fatigue Syndrome in Olmsted County, Minnesota, as Estimated Using the Rochester Epidemiology Project. Mayo Clin Proc 2012; 87: 1145–1152.
31Shaker, MD, Wallace, DV, et al. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis; J Allergy Clin Immunol 2020;145:1082-123.
32 Manzoni, GC, Stoyner, LJ, Epidemiology of headache. Handb Clin Neurol 2010; 97: 3-22.
33Cimmino, MA, Ferrone, C, and Cutolo, M. Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 2011; 25: 173-83.
34Kerber, KA, et al. Dizziness Symptom Type Prevalence and Overlap: A US Nationally Representative Survey. The American J of Medicine 2017; 130: 1465.e1-1465.e9.35
36Siegel, MD, et al. Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults. UpToDate. Accessed January 23, 2021.
39Troeger, C, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis 2018; 18: 1211–2.
40Seigel, MD, et al. Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults; UpToDate accessed January 23, 2021.