COVID -19 Vaccine

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Population

Inclusion: Healthy adults or those with stable medical conditions including human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection were eligible. United States, 130 sites; Argentina, 1; Brazil, 2; South Africa, 4; Germany, 6; and Turkey, 9

Exclusion: Previous history of Covid-19, treatment with immuno-suppressive therapy, or diagnosis with an immunocompromising condition.

Design

Randomized controlled trial using an interactive Web-based system

Intervention

30 μg of BNT162b2 (0.3 ml volume per dose) into the deltoid muscle. Two 30 mcg doses of the vaccine administered 21 days apart

Control

Saline placebo

Post-vaccination monitoring at site

Participants were monitored for 30 minutes for any adverse reactions.

Outcomes

Demographics: similar

Safety outcomes

• Specific local or systemic adverse events and use of antipyretic or pain medication within 7 days after the receipt of each dose of vaccine or placebo

• Unsolicited adverse events (those reported by the participants without prompts from the electronic diary) through 1 month after the second dose and unsolicited serious adverse events through 6 months after the second dose
• Adverse event data through approximately 14 weeks after the second dose are reported 
• Number assessed for safety (2 months data after second dose): 37,706

Local

Mild to moderate injection site pain: 70-80%; more among patients older than 55 years. Resolved in 1–2 days.

Systemic

More in subjects less than 55-year-old; more often after the second dose.

Fatigue (59 vs. 52: young vs. old)

Headache (51 vs. 39: young vs. old)

Fever (temperature more than 38 C or 100.4 F):

0.2 vs. 0.1% (vaccine vs. placebo) after first dose

0.8 vs. 0.1% after second dose

Chills, vomiting, diarrhea, muscle and joint pain more with vaccine

Adverse events

Any adverse event: 27 vs. 12%

Related adverse event: 21% vs. 5%

Lymphadenopathy: 0.3% vs. less than 0.1%

Four related adverse events with vaccine: shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia

Death: 2 in the vaccine group (one from arteriosclerosis, one from cardiac arrest)

4 in the placebo group (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). All deaths considered unrelated. No Covid-19–associated deaths.

Efficacy outcomes

First primary endpoint efficacy of the vaccine to prevent Covid-19 as confirmed by FDA criteria. Onset of protective effect assessed from at least 7 days after the second dose. Participants had no serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose. Number assessed: 36,523

Second primary endpoint efficacy of the vaccine in participants with and in participants without evidence of prior infection up to 7 days after the second dose. Number assessed: 40,137

Confirmed Covid-19 was defined according to the Food and Drug Administration (FDA) criteria as the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting, combined with a respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-COV-2 by nucleic acid amplification–based testing, either at the central laboratory or at a local testing facility (using a protocol-defined acceptable test).

Efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a comorbidities was similar to overall efficacy

Infection rate between the first dose and the second dose: 39 cases vs. 82 cases resulting in a vaccine efficacy of 52% (95% CI, 29.5 to 68.4). Protection may start from 12 days after the first dose. Full efficacy from 7 days after second dose.

Secondary endpoint: Major secondary end points included the protective effect of the vaccine against severe Covid-19. Severe Covid-19 is defined by the FDA as confirmed Covid-19 with one of the following additional features: clinical signs at rest that are indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; or death.

Severe infection: 1 vs. 9

Limitations

Sample size not large enough to identify rare adverse events

Follow-up is limited to 2 months after second dose; however adverse event screening for long periods is unethical as the placebo group remains unprotected

Duration of protection needs to be evaluated

Does it prevent asymptomatic infection?

The study did not include children, pregnant women

Very cold temperatures are required for shipping and longer storage

Summary – 

All 3 vaccines – Pfizer, Moderna and Oxford are safe to use.

Long term protection with these vaccines still remains unknown.

Efficacy of these vaccines against newly emerging UK strain remains uncertain at this point in time.