What are the efficacy and risks of Covid-19 vaccines, such as Pfizer (mRNA vaccine) and Johnson & Johnson (viral vector vaccine), in preventing severe illness and death from Covid-19, particularly for individuals with a history of severe allergic reactions or other underlying medical conditions?

COVID-19 Vaccine Efficacy and Safety

COVID-19 vaccines are highly effective and safe, with mRNA vaccines achieving 91-98% effectiveness against hospitalization and 92-98% effectiveness against death, and the benefits overwhelmingly outweigh the risks even in populations at highest risk for rare adverse events like myocarditis. 1

Vaccine Effectiveness Against Severe Outcomes

Overall Protection

• Two-dose mRNA vaccine regimens provide 98% effectiveness against both hospitalization and death from COVID-19 1, 2
• Protection against critical illness remains more durable than protection against infection: 69% effectiveness at 7-59 days declining to 32% at 120-179 days post-vaccination 1
• Vaccine effectiveness against hospitalization starts at 49% at 7-59 days, declining to 14% at 120-179 days, but protection against severe outcomes (ICU admission, death) remains substantially higher throughout 1

Variant Coverage

• Two doses provide excellent protection against Alpha, Gamma, and Delta variants, with both homologous and heterologous vaccine schedules showing comparable effectiveness 2
• The 2024-2025 bivalent formulations target currently circulating Omicron sublineages 3

Safety Profile and Adverse Events

Cardiovascular Safety

• Cardiovascular adverse events occur in less than 0.05% of vaccine recipients, with rates of hypertension, atrial fibrillation, acute coronary syndrome, cerebrovascular events, and heart failure similar between vaccine and placebo groups 3, 1

Myocarditis/Pericarditis Risk

• Myocarditis risk is highest in young males aged 12-29 years after the second mRNA dose, with 39-47 cases expected per 1 million vaccinated 3, 1
• Based on 2023-2024 data, myocarditis/pericarditis rates are approximately 8 cases per million doses in persons 6 months through 64 years, and 27 cases per million in males 12-24 years 4
• Most myocarditis cases are mild, with symptoms resolving within days after anti-inflammatory treatment 3
• Follow-up heart MRIs commonly show signs of injury with improvement over time in most people, though long-term effects are still being studied 4
• Seek immediate medical attention for chest pain, shortness of breath, or palpitations within 2 weeks of vaccination 4

Benefit-Risk Analysis

• For every 1 million males aged 12-29 years receiving a second mRNA dose, vaccination prevents 560 hospitalizations, 138 ICU admissions, and 6 deaths, while causing 39-47 myocarditis cases 3, 1
• This represents an overwhelmingly favorable benefit-risk ratio even in the highest-risk demographic for myocarditis 3

Overall Mortality

• Among 1.2 million vaccinated persons, severe outcomes occurred in only 1.5 per 10,000, with 0.3 deaths per 10,000 5
• Early mortality surveillance showed 8.2 deaths per million population overall, with deaths occurring primarily in elderly individuals with multiple comorbidities 6

Contraindications and Precautions

Absolute Contraindications

• History of severe allergic reaction (anaphylaxis) to any vaccine component 4
• Previous severe allergic reaction to any dose of mRNA COVID-19 vaccine 4

Severe Allergic Reaction Management

• Severe allergic reactions typically occur within minutes to 1 hour after vaccination 4
• Signs include: difficulty breathing, facial/throat swelling, rapid heartbeat, widespread rash, dizziness, and weakness 4
• Healthcare providers should observe vaccine recipients for a short period post-vaccination 4

Special Considerations for Timing

• Patients with Guillain-Barré syndrome history should receive mRNA vaccines (not viral vector vaccines) if not contraindicated 3
• Persons who recently had SARS-CoV-2 infection may consider delaying vaccination by 3 months from symptom onset or positive test 3, 7

Special Populations

Immunocompromised Patients

• Cancer patients show 56% reduction in hospitalization and death (OR 0.44) with vaccination 1, 8
• mRNA vaccine efficacy is 83% in solid tumors but only 72% in hematological malignancies due to anti-CD20 therapies and cytotoxic chemotherapy reducing antibody responses 3, 8
• Despite suboptimal antibody responses, T-cell responses remain strong enough to recommend vaccination in all cancer patients except during intensive chemotherapy phases 3
• Additional booster doses should be considered in immunocompromised patients who fail to mount adequate responses 8

Patients on Immunosuppressive Therapy

• For patients on anti-CD20 therapy (rituximab), ideally vaccinate 4-6 weeks before starting treatment or wait 4-6 months after the last infusion 3
• Patients on immune-reconstitution therapies (alemtuzumab, cladribine) should delay vaccination until at least 6 months after the last treatment course 3
• Those on high-dose or long-term corticosteroids should delay vaccination 4-6 weeks after treatment completion 3
• If disease is active, immunosuppressive therapy takes priority over vaccination, though disease relapse after vaccination is rare 3

Neurological Disorders

• Patients with MS, Parkinson's, Alzheimer's, myasthenia gravis, and Guillain-Barré syndrome are at increased risk for severe COVID-19 and should be prioritized for vaccination 3
• Disease-modifying therapies for MS may reduce antibody response but vaccination should proceed 3
• Patients on β-interferons, glatiramer acetate, teriflunomide, natalizumab can be vaccinated anytime during treatment 3
• For ocrelizumab, complete two-dose vaccine series 4-6 weeks before starting therapy or 4-6 months after last infusion 3

Pregnant Women

• Symptomatic pregnant women have 2-3 fold higher rates of ICU admission, invasive ventilation, and mortality compared to non-pregnant women, making vaccination particularly critical 1

Autoimmune and Rheumatologic Conditions

• The American College of Rheumatology recommends vaccination in all eligible rheumatologic patients, as benefits outweigh risks of disease exacerbation 3
• Vaccines may trigger autoimmunity through immune-activating or adjuvant effects, but such events are rare 3

Current Vaccination Recommendations

Primary Series

• Two doses of mRNA vaccine (Pfizer-BioNTech or Moderna) or single dose of Janssen (Johnson & Johnson) 5
• For cancer patients planning cytotoxic chemotherapy, administer first dose at least 2 weeks before starting treatment 3
• For those already on chemotherapy, administer between cycles 3

Booster Doses

• Bivalent mRNA booster recommended for all persons aged ≥5 years, administered ≥2 months after completing primary series or previous monovalent booster 3
• 2024-2025 COVID-19 vaccination recommended for all persons aged ≥6 months 3, 1
• Monovalent Novavax booster may be used in limited situations for adults ≥18 years unable or unwilling to receive mRNA vaccine 3

Immunocompromised Patients

• Consider preexposure prophylaxis with Evusheld (tixagevimab/cilgavimab) every 6 months for moderately or severely immunocompromised persons to supplement vaccine protection 3

Clinical Pitfalls to Avoid

• Do not delay urgent vaccination in high-risk individuals due to suboptimal timing relative to immunosuppressive therapy—benefits outweigh concerns about reduced immune response 1, 7
• Do not confuse exposure with infection—exposure alone is not a reason to delay vaccination 7
• Do not discontinue immunosuppressive medications solely to achieve better vaccine response, as this risks disease complications 7
• Do not assume natural immunity is sufficient—vaccination after infection provides enhanced and broader protection 7
• Evaluate any chest pain occurring early after mRNA vaccination with ECG, cardiac troponin, and echocardiogram to assess for myocarditis 1
• For patients on checkpoint inhibitors, avoid vaccination on the same day as immunotherapy infusions to distinguish adverse events 8
• Monitor for immune-related adverse events in the 2-3 days following vaccination in cancer patients on immunotherapy 8

Adverse Event Reporting

• Report vaccine administration errors, serious adverse events, multisystem inflammatory syndrome, myocarditis, pericarditis, and COVID-19 resulting in hospitalization or death to VAERS at 1-800-822-7967 or https://vaers.hhs.gov 3
• Enroll in v-safe smartphone-based surveillance system for active monitoring of adverse events 3