Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants: Systematic review

Table 1 Characteristic of studies included for vaccine effectiveness

Ref.	Study design	Location	Purpose	Age of study group	Vaccine type	Number of doses received	Variant of concern
Baum et al[33], 2022	Cohort study	Finland	To estimate VE against severe COVID-19 among the elderly	Adult population including ≥ 70 yr old	Pfizer-BioNTech	2 doses	Omicron
Grewal et al[34], 2022	Case control design	Canada	To estimate vaccine effectiveness of mRNA vaccines among aged ≥ 60 yr who were tested for SARS-CoV-2	≥ 60 yr old	Pfizer-BioNTech and Moderna	Booster	Omicron
Rosenberg et al[35], 2021	Cohort study	USA (NY)	To describe vaccine efficacy in NY	Adult population including ≥ 50 yr old	Pfizer-BioNTech and Moderna	2 doses	Delta
Rosero-Bixby[36], 2021	Cross-sectional study	Costa Rica	To estimate the dose-dependent effectiveness of coronavirus disease (COVID-19) vaccines to prevent severe illness in real-world conditions	Adult population including ≥ 58 yr old	Pfizer-BioNTech	2 doses	Delta
Rane et al[37], 2022	Case control study	USA (NY)	To monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups	Adult population including ≥ 50 yr old	Pfizer-BioNTech	2 doses	Delta
Chemaitelly et al[38], 2021	Case control study	Qatar	To estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of COVID-19	Adult population including ≥ 50 yr old	Pfizer-BioNTech	2 doses	Delta
Lytras et al[39], 2022	Cohort study	Greece	To estimate COVID-19 effectiveness against disease and death	Adult population including ≥ 60 yr old	Pfizer-BioNTech and Moderna	2 doses and booster	Delta
Ranzani et al[40], 2022	Case control study	Brazil	To evaluate vaccine effectiveness against symptomatic COVID-19 and severe COVID-19 (hospital admission or deaths)	Adult population including ≥ 70 yr old	Pfizer-BioNTech	2 doses and booster	Omicron

COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; USA (NY): United States of America (New York); VE: Vaccine effectiveness.

Table 2 Characteristic of participants included for vaccine effectiveness

Ref.	Study population (n)	Age of study population	mRNA vaccinated elderly participants with 2 doses	mRNA vaccinated participants with 2 doses according to vaccine type		mRNA vaccinated elderly participants with 2 doses according to age		Unvaccinated elderly participants	Unvaccinated elderly participants according to age
				Pfizer-BioNTech	Moderna	Pfizer-BioNTech	Moderna
Baum et al[33], 2022	897932	Adult population including ≥ 70 yr old	241630	-	-	70-79 yr old: 171816; 80-89 yr old: 57024; 90-115 yr old: 12790		747486	70-79 yr old: 480532; 80-89 yr old: 223267; 90-115 yr old: 43687
Grewal et al[34], 2022	46849	≥ 60 yr old	45345	-	-	-	-	1272	-
Rosenberg et al[35], 2021	8834604	Adult population including ≥ 50 yr old	3479102	-	-	50-64 yr old: 846664; ≥ 65 yr old: 984464	50-64 yr old: 624226; ≥ 65 yr old: 1023748	976536	50-64 yr old: 606411; ≥ 65 yr old: 370125
Rosero-Bixby[36], 2021	3670000	Adult population including ≥ 58 yr old	741474	-	-	741474		58887	58887
Rane et al[37], 2022	1058493	Adult population including ≥ 50 yr old	143104	-	-	50-59 yr old: 64806; 60-69 yr old: 48260; 70-79 yr old: 22997; ≥ 80 yr old: 7041		27362	50-59 yr old: 14936; 60-69 yr old: 8352; 70-79 yr old: 3066; ≥ 80 yr old: 1008
Chemaitelly et al[38], 2021	-	Adult population including ≥ 50 yr old	1402622	907763	494859	-	-	8043	50-59 yr old: 6350; 60-69 yr old: 1326; ≥ 70 yr old: 367
Lytras et al[39], 2022	9200000	Adult population including ≥ 60 yr old	2380402	2128913	251492	-		-	8138482
Ranzani et al[40], 2022	1417149	Adult population including ≥ 60 yr old	306883	-	-	60-79 yr old: 258306; ≥ 80 yr old: 48577		306588	60-79 yr old: 265073; ≥ 80 yr old: 41515

Table 3 ROBINS-I risk of bias assessment of observational studies

Ref.	Confounding	Selection of participants	Classification of interventions	Deviations from interventions	Missing data	Measurement of outcomes	Reported result	Overall bias
Baum et al[33], 2022	Moderate	Low	Moderate	Moderate	Low	Low	Low	Moderate
Grewal et al[34], 2022	Moderate	Moderate	Low	Low	Low	Low	Low	Moderate
Rosenberg et al[35], 2021	Moderate	Moderate	Low	Low	Moderate	Low	Low	Moderate
Rosero-Bixby[36], 2021	Moderate	Low	Low	Low	Moderate	Moderate	Low	Moderate
Rane et al[37], 2022	Low	Low	Low	Low	Moderate	Low	Low	Low
Chemaitelly et al[38], 2021	Moderate	Low	Low	Low	Moderate	Low	Low	Moderate
Lytras et al[39], 2022	Moderate	Low	Low	Low	Moderate	Moderate	Low	Moderate
Ranzani et al[40], 2022	Low	Low	Low	Low	Low	Moderate	Low	Moderate

Low risk: Comparable to a well-performed randomised trial; Moderate risk: Sound for a non-randomised study but cannot be compared to a well performed randomised trial; Serious risk: Study has some important problems; Critical risk: Study is too problematic to provide any useful evidence.

Table 4 Outcomes of studies included for vaccine effectiveness

Ref.	Outcome measurements					Vaccine effectiveness
	Infection (n/%)	Hospitalization (n/%)	ICU admission (n/%)	Intubation (n/%)	Death (n/%)
Baum et al[33], 2022	-	2 doses of Pfizer (within 3 mo): 30/5.64%; 2 doses of Pfizer (within 6 mo): 193/36.28%; 2 doses of Pfizer (≥ 6 mo): 148/27.82%; 3 doses of Pfizer (within 3 mo): 95/17.86%; 3 doses of Pfizer (≥ 6 mo): 66/12.41%	2 doses of Pfizer (within 3 mo): 5/8.33%; 2 doses of Pfizer (within 6 mo): 24/40%; 2 doses of Pfizer (≥ 6 mo): 14/23.33%; 3 doses of Pfizer (within 3 mo): 9/15%; 3 doses of Pfizer (≥ 6 mo): 8/13.33%	-	-	Hospitalization: 2 doses of Pfizer (within 3 mo): 90%; 2 doses of Pfizer (within 6 mo): 85%; 2 doses of Pfizer (≥ 6 mo): 72%; 3 doses of Pfizer (within 3 mo): 95%; 3 doses of Pfizer (≥ 6 mo): 88%; ICU Admission: 2 doses of Pfizer (within 3 mo): 98%; 2 doses of Pfizer (within 6 mo): 95%; 2 doses of Pfizer (≥ 6 mo): 82%; 3 doses of Pfizer (within 3 mo): 98%; 3 doses of Pfizer (≥ 6 mo): 85%
Grewal et al[34], 2022	Infection: 3 doses of Pfizer: 2691/42.43%; 3 doses of Moderna: 3651/57.57%; Symptomatic Infection: 3 doses of Pfizer: 395/38.69%; 3 doses of Moderna: 626/61.31%	3 doses of Pfizer: 214/58.79%; 3 doses of Moderna: 150/41.21%	-	-	3 doses of Pfizer: 214/58.79%; 3 doses of Moderna: 150/41.21%	Infection: 3 doses of Pfizer: 31%; 3 doses of Moderna: 51%; Symptomatic Infection: 3 doses of Pfizer: 61%; 3 doses of Moderna: 73%; Hospitalization or Death: 3 doses of Pfizer: 87%; 3 doses of Moderna: 77%
Rosenberg et al[35], 2021	≥ 65 yr old (2 doses of Pfizer): 5302/61.70%; ≥ 65 yr old (2 doses of Moderna): 3291/38.30%	≥ 65 yr old (2 doses of Pfizer): 972/64.07%; ≥ 65 yr old (2 doses of Moderna): 545/35.93%	-	-	-	Infection: ≥ 65 yr old (2 doses of Pfizer): 83.0%; ≥ 65 yr old (2 doses of Moderna): 89.2%; Hospitalization: ≥ 65 yr old (2 doses of Pfizer): 91.9%; ≥ 65 yr old (2 doses of Moderna): 95.7%
Rosero-Bixby[36], 2021		40-57 yr old: 37/0.006%; ≥ 58 yr old: 65/0.009%	-	-	-	Hospitalization: 40-57 yr old: 94%; ≥ 58 yr old: 92%
Rane et al[37], 2022	60-69 yr old: 3232/5.8%; 70-79 yr old: 1221/2.2%; ≥ 80 yr old: 468/0.8%	-	-	-	-	Infection: 51-64 yr old: 60%; 65 80 yr old: 55%; ≥ 80 yr old: 51%
Chemaitelly et al[38], 2021	2 doses of Pfizer (within 1 mo): 2915/2.51%; 2 doses of Pfizer (within 2 mo): 1450/1.28%; 2 doses of Pfizer (within 3 mo): 800/0.71%; 2 doses of Pfizer (within 4 mo): 492/0.44%; 2 doses of Pfizer (within 5 mo): 548/0.49%; 2 doses of Pfizer (within 6 mo): 460/0.41%; 2 doses of Pfizer (≥ 7 mo): 135/0.12%	2 doses of Pfizer (within 1 mo): 32/0.78%; 2 doses of Pfizer (within 2 mo): 23/0.56%; 2 doses of Pfizer (within 3 mo): 17/0.42%; 2 doses of Pfizer (within 4 mo): 10/0.25%; 2 doses of Pfizer (within 5 mo): 0/0; 2 doses of Pfizer (within 6 mo): 8/0.20%; 2 doses of Pfizer (≥ 7 mo): 6/0.15%			2 doses of Pfizer (within 1 mo): 32/0.78%; 2 doses of Pfizer (within 2 mo): 23/0.56%; 2 doses of Pfizer (within 3 mo): 17/0.42%; 2 doses of Pfizer (within 4 mo): 10/0.25%; 2 doses of Pfizer (within 5 mo): 0/0; 2 doses of Pfizer (within 6 mo): 8/0.20%; 2 doses of Pfizer (≥ 7 mo): 6/0.15%	Infection: 2 doses of Pfizer (within 1 mo): 75.8%; 2 doses of Pfizer (within 2 mo): 69.7%; 2 doses of Pfizer (within 3 mo): 63.7%; 2 doses of Pfizer (within 4 mo): 39.1%; 2 doses of Pfizer (within 5 mo): 11.4%; 2 doses of Pfizer (within 6 mo): 9.2%; 2 doses of Pfizer (≥ 7 mo): -4.4%; Hospitalization and Death: 2 doses of Pfizer (within 1 mo): 95.9%; 2 doses of Pfizer (within 2 mo): 96.3%; 2 doses of Pfizer (within 3 mo): 93.4%; 2 doses of Pfizer (within 4 mo): 80.8%; 2 doses of Pfizer (within 5 mo): 100%; 2 doses of Pfizer (within 6 mo): 81.8%; 2 doses of Pfizer (≥ 7 mo): 44.1%
Lytras et al[39], 2022				2 doses of Pfizer: 548/90.28%; 2 doses of Moderna: 35/5.77%; 3 doses of Pfizer: 24/0.04%	2 doses of Pfizer: 1629/64.60%; 2 doses of Moderna: 42/2.44%; 3 doses of Pfizer: 51/5.96%	Intubation: 60-79 yr old (2 doses): 96.9%; ≥ 80 yr old (2 doses): 94.4%; ≥ 80 yr old (2 doses, within 6 mo): 86.0%; ≥ 80 yr old (3 doses): 97.6%; Death: 60-79 yr old (2 doses): 94.6%; ≥ 80 yr old (2 doses): 91.0%; ≥ 80 yr old (2 doses, within 6 mo): 84.1%; ≥ 80 yr old (3 doses): 98.4%
Ranzani et al[40], 2022	Symptomatic Infection: 60-74 yr old (2 doses): 34077/86.93%; ≥ 75 yr old (2 doses): 15539/79.84%; 60-74 yr old (3 doses, within 2 mo): 15053/64%; 60-74 yr old (3 doses, after 2 mo): 3273/66.36%; ≥ 75 yr old (3 doses, within 2 mo): 116955/89.86%; ≥ 75 yr old (3 doses, after 2 mo): 64495/99.36%				60-74 yr old (2 doses): 2035/63.3%; ≥ 75 yr old (2 doses): 2750/52.81%; 60-74 yr old (3 doses, within 2 mo): 50/68.50%; 60-74 yr old (3 doses, after 2 mo): 51/96.01%; ≥ 75 yr old (3 doses, within 2 mo): 511/90.41%; ≥ 75 yr old (3 doses, after 2 mo): 2964/72.40%	Infection: 60-74 yr old (2 doses): 63.4%; ≥ 75 yr old (2 doses): 40.7%; 60-74 yr old (3 doses, within 2 mo): 88.4%; 60-74 yr old (3 doses, after 2 mo): 90.4%; ≥ 75 yr old (3 doses, within 2 mo): 77.3%; ≥ 75 yr old (3 doses, after 2 mo): 78.5%; Hospitalization or death: 60-74 yr old (2 doses): 63.4%; ≥ 75 yr old (2 doses): 40.7%; 60-74 yr old (3 doses, within 2 mo): 88.4%; 60-74 yr old (3 doses, after 2 mo): 90.4%; ≥ 75 yr old (3 doses, within 2 mo): 77.3%; ≥ 75 yr old (3 doses, after 2 mo): 78.5%