What are the pros and cons of the COVID-19 (Coronavirus Disease 2019) vaccine, including Pfizer-BioNTech (Comirnaty), Moderna (mRNA-1273), and Johnson & Johnson (Ad26.COV2.S)?

COVID-19 Vaccination: Benefits Substantially Outweigh Risks

The benefits of COVID-19 vaccination far outweigh the risks across all age groups and populations, including those with cancer, pregnancy, chronic diseases, and the elderly, with vaccines demonstrating 91-98% effectiveness against hospitalization and 92-98% effectiveness against mortality. 1

Major Benefits of COVID-19 Vaccination

Prevention of Severe Disease and Death

• COVID-19 vaccines reduce mortality by 84% (odds ratio 0.16) in elderly populations, with significant protection against SARS-CoV-2 infection (odds ratio 0.38). 2
• Vaccination reduces hospitalization and death by 56% in cancer patients with COVID-19, making it critical for this vulnerable population. 1
• Protection against critical illness remains durable at 69% effectiveness at 7-59 days post-vaccination, declining to 32% at 120-179 days, but protection against severe outcomes remains substantially higher than protection against infection. 1

Effectiveness Across Populations

• mRNA vaccines (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) demonstrate >90% efficacy in preventing symptomatic COVID-19 in phase III trials. 3
• Real-world data from 90,000 pregnant women showed no safety signals, and vaccination is particularly critical as symptomatic pregnant women have 2-3 fold higher rates of ICU admission, invasive ventilation, and mortality compared to non-pregnant women. 4, 1
• Vaccination is recommended for all special populations including diabetes, obesity, cardiovascular disease, HIV, COPD, chronic liver disease, and cancer patients. 4

Protection Against Variants

• mRNA vaccines, AZD1222, and CoronaVac effectively prevent symptomatic COVID-19 and severe infections against Alpha, Beta, Gamma, and Delta variants, though with reduced effectiveness against Delta. 3
• Vaccination after natural infection enhances immunity and provides more robust protection against variants that may evade natural immunity alone. 5

Risks and Adverse Events (Rare and Generally Mild)

Common Side Effects (Mild to Moderate)

• The most common adverse events are injection site pain, fatigue, myalgia, headache, and fever, which are usually mild or moderate (grade 1-2). 4, 6
• Local and systemic adverse events occur but are generally well-tolerated across all age groups. 2

Rare Serious Adverse Events

• Myocarditis/pericarditis risk is highest after the second mRNA vaccine dose in young males aged 12-29 years, with 39-47 cases expected per 1 million vaccinated, but this risk is substantially outweighed by benefits. 1
• Anaphylaxis occurs in 2.5-4.7 cases per million doses, similar to influenza vaccines (1.4 cases per million), pneumococcal vaccines (2.5 cases per million), and shingles vaccines (9.6 cases per million). 4
• Myocarditis incidence is approximately 1-4 cases per 100,000 vaccinated persons, with 95% of patients showing rapid resolution of symptoms within days. 7
• Cardiovascular adverse events occur in <0.05% of vaccine recipients, with rates of hypertension, atrial fibrillation, acute coronary syndrome, and heart failure similar between vaccine and placebo groups. 1

Risk-Benefit Analysis in High-Risk Groups

• Even in the highest-risk subgroup (males 16-17 years old), modeling predicts 13,577 prevented COVID cases, 127 prevented hospitalizations, 41 prevented ICU admissions, and 1 prevented death, while excess myocarditis cases range from 98-196 with zero predicted deaths. 8
• The clinical implications of hospitalization due to COVID-19 infection are far more severe than vaccine-attributable myocarditis/pericarditis cases, making the benefits clearly outweigh risks even in this high-risk subgroup. 8

Specific Recommendations by Population

Cancer Patients

• Vaccination should be given preferably 2-4 weeks prior to initiation of cancer treatment when feasible, but should still be strongly advised early in treatment even if this timing cannot be achieved. 4
• mRNA vaccine efficacy in cancer patients is 83% for solid tumors and 72% for hematological malignancies. 4
• Patients should not have to choose between enrolling in oncology clinical trials and receiving COVID-19 vaccination. 4

Pregnant and Breastfeeding Women

• The CDC and WHO recommend COVID-19 vaccination for all pregnant women, as the benefits outweigh potential risks. 4
• Placental transfer of vaccine-specific anti-SARS-CoV-2 IgG antibodies occurs, and antibodies are detected in breast milk for up to 6 weeks after first dose. 4
• For Janssen vaccine, individualized risk/benefit assessment should be performed before vaccination in pregnancy. 4

Elderly (≥65 Years)

• Elderly individuals are at significantly higher risk of severe COVID-19 due to comorbidities, malnutrition, impaired immunity, and decreased organ function. 6
• Despite potentially weaker immune responses, COVID-19 vaccines remain effective in preventing mortality in this age group. 6
• All currently approved COVID-19 vaccines are safe and effective for the elderly population. 6

Immunocompromised Patients

• Patients receiving immunosuppressive therapy should receive additional vaccine doses after a 2-month interval, as they may have weakened vaccine responses. 1
• Early studies show immune-related adverse events are not significantly higher in patients undergoing immunotherapy including immune checkpoint inhibitors. 4

Timing Considerations

Optimal Vaccination Timing

• Vaccination should occur preferably 2-4 weeks before starting immunosuppressive cancer therapy when feasible. 4
• For individuals who recently had COVID-19 infection, postpone vaccination for 2-3 months after infection to allow immune system recovery and potentially enhance vaccine response. 6, 5
• An interval of at least 2-3 days between surgery and vaccination is recommended to determine which is responsible for symptoms such as fever. 4

Current Recommendations

• The Advisory Committee on Immunization Practices (ACIP) recommends 2024-2025 COVID-19 vaccination for all persons aged ≥6 months to target currently circulating strains. 1
• At least one dose of the updated 2023-2024 COVID-19 vaccine is recommended for previously vaccinated individuals. 1

Critical Pitfalls to Avoid

• Do not delay urgent vaccination in high-risk individuals due to concerns about suboptimal timing relative to immunosuppressive therapy—the benefits of vaccination outweigh concerns about reduced immune response. 1
• Do not withhold vaccination from patients with allergic diseases unless there is prior history of allergy to polyethylene glycol (PEG) for mRNA vaccines or polysorbate for adenoviral vector vaccines, or positive skin test for these agents. 4
• Evaluate chest pain occurring early after mRNA vaccination with ECG, cardiac troponin, and echocardiogram to assess for myocarditis. 1
• Recognize that vaccine effectiveness against infection declines at 6 months for BNT162b2 and AZD1222, but protection against severe outcomes remains substantially higher. 3

Bottom Line

COVID-19 vaccination is recommended for all eligible individuals regardless of prior COVID-19 infection, as vaccination provides additional protection beyond natural immunity and the benefits vastly outweigh the rare risks across all populations. 5, 9, 3