COVID-19 vaccine effectiveness among immunocompromised populations: a targeted literature review of real-world studies

Figures & data

Table 1. Study characteristics

Study/Peer-reviewed	Country	Vaccines included in analyses	Study period	Study design	Data source
Young-Xu Y, et al./Yes [17]	United States	Pfizer-BioNTech BNT162b2 mRNA vaccine Moderna mRNA-1273 vaccine	Pre-Delta: Dec 14 2020– Mar 14, 2021	Matched test negative case–control analysis for infection Matched case–control analysis for hospitalization and death	EMR data from VHA Corporate Data Warehouse
Tenforde MW, et al./Yes [18]	United States	Pfizer-BioNTech BNT162b2 mRNA vaccine Moderna mRNA-1273 vaccine	Intermediate: Mar 11 – May 5, 2021	Case-control analysis	Hospital admission logs and EMRs (18 academic hospitals/16 states)
Tenforde MW, et al./Yes [19]	United States	Pfizer-BioNTech BNT162b2 mRNA vaccine Moderna mRNA-1273 vaccine	Including Delta: Mar 11 – Jul 14, 2021	Case-control analysis	Hospital admission logs and EMRs (21 academic hospitals/18 states)
Khan N & Mahmud N/Yes [20]	United States	Pfizer-BioNTech BNT162b2 mRNA vaccine Moderna mRNA-1273 vaccine	Pre-Delta: Dec 18 2020 – Apr 20, 2021	Retrospective cohort analysis	VHA data sources, including VHA Corporate Data Warehouse
Polinski JM, et al./No, medRxiv preprint [21]	United States	Janssen Ad26.COV2.S vaccine	Including Delta: Mar 1 – Jul 31, 2021	Matched control analysis	Administrative insurance claims in Health Verity database
Dagan N, et al.; Barda N, et al./Yes [22,23]	Israel	Pfizer-BioNTech BNT162b2 vaccine	Pre-Delta: Dec 20 2020 – Feb 1, 2021	Matched control analysis	EMR data from Clalit Health Services data repositories
Chodick G, et al./Yes [24]	Israel	Pfizer-BioNTech BNT162b2 vaccine	Pre-Delta: Dec 19 2020 – Feb 20, 2021	Retrospective cohort analysis	EMR data from Maccabi Healthcare Services databases
Yelin I, et al./No, medRxiv preprint [25]	Israel	Pfizer-BioNTech BNT162b2 vaccine	Pre-Delta: Dec 1 2020– Feb 25, 2021	Prospective Patient-level analysis	EMR data from Maccabi Healthcare Services databases
Whitaker HJ, et al./No, Khub preprint [26]	England	Pfizer-BioNTech BNT162b2 mRNA vaccine Oxford/AstraZeneca ChAdOx1 nCoV-19 vaccine	Including Delta: Dec 7 2020– Jun 13, 2021	Nested test-negative case-control analysis	EMR data of 718 general practices
Chemaitelly H, et al./No, medRxiv preprint [27]	Qatar	Pfizer-BioNTech BNT162b2 mRNA vaccine Moderna mRNA-1273 vaccine	Including Delta ^a: Feb 1 2021– Jul 21, 2021	Retrospective cohort analysis with cross-over design	Hamad Medical Corporation: integrated nationwide digital-health information platform

EMR: Electronic medical record; mRNA: messenger ribonucleic acid; VHA: Veterans Health Administration.

Covariant predominance period was defined as Pre-Delta, Intermediate, and Including Delta (when the study period extended to months when the Delta variant was predominant) for countries referring to [36; https://covariants.org/per-country] as below.

US: Dec 2020-April 2021 as Pre-delta; May 2021-June 2021: Intermediate; July 2021-Sept 2021: Delta.

Israel: Dec 2020 – Feb 2021 was Alpha, which was defined as Pre-delta.

England: Dec 2020 – April 2021 was Alpha (Pre-delta), May 2021: Intermediate, June 2021 was during Delta variant, hence defined as including Delta.

Qatar: Feb–Apr 2021 was Beta (Pre-delta), May 2021: Intermediate, and June–July 2021 was Delta, hence as defined as including Delta.

^aIn Qatar, the Delta variant was preceded by the Beta variant, as opposed to the Alpha variant in the US, Israel, and England. Authors reported that as of 28 July 2021 Delta was at low incidence in Qatar.

Table 2. General characteristics of the overall study populations

Study	Count	Follow-up duration	Proportion fully vaccinated	Age	Sex distribution
Young-Xu Y, et al. [17]	Overall: N = 6,647,733 in VHA cohort SARS-CoV-2 positive cases: N = 15,110 Controls: N = 60,436	≥14 days after 2^nd dose up to 3 months	Positive cases: N = 41 (0%) Controls: N = 3,711 (6%)	Median age not reported. Positive cases: 66% were 45–74 yrs of age Controls: 78% were 45–74 yrs of age	Positive cases: 90% male Controls: 90% male
Tenforde MW, et al. [18]	Overall: N = 1,212 in general hospitalized population Hospitalized COVID-19 cases: N = 593 Controls: N = 619	Median: 43 days; maximum: 113 days	Cases: N = 45 (8%) Controls: N = 215 (35%)	Median age of cases: 56 yrs Median age of controls: 61 yrs	Cases: 48% female Controls: 51% female
Tenforde MW, et al. [19]	Overall: N = 3,089 in general hospitalized population Hospitalized COVID-19 cases: N = 1,194 Controls: N = 1,895	Up to 24 weeks	Cases: N = 141 (12%) Controls: N = 988 (52%)	Median age of cases: 56 yrs Median age of controls: 62 yrs	Cases: 49% female Controls: 49% female
Khan N & Mahmud N. [20]	Overall: N = 14,697 in VHA cohort with IBD Vaccinated: N = 7,321 Unvaccinated: N = 7,376	Vaccinated: median of 38 days Unvaccinated: median of 123 days	91% of Pfizer (N = 3,017) and 89% of Moderna (N = 3,561) patients received both vaccine doses during full study period	Median age of vaccinated: 71 yrs Median age of unvaccinated: 64 yrs	Vaccinated: 93% male Unvaccinated: 92% male
Polinski JM, et al. [21]	General population cohort Vaccinated: N = 390,517 Unvaccinated: N = 1,524,153	≥14 days after single dose and up to 5 months	100% of vaccinated cohort	Median age of vaccinated: 55 yrs Median age of unvaccinated: 55 yrs	Vaccinated: 56% female Unvaccinated: 56% female
Dagan N, et al.; Barda N, et al. [22,23]	General population cohort Vaccinated: N = 596,618 Unvaccinated: N = 596,618	Mean follow-up: 15 days Subgroup analyses: mean follow-up 18 days	Among those with ≥21 days of follow-up, 96% received a 2nd dose	Median age of vaccinated: 45 yrs Median age of unvaccinated: 45 yrs	Vaccinated: 50% male Unvaccinated: 50% male
Chodick G, et al. [24]	Overall: N = 1,178,597 in general population Protection period group: N = 872,454 Reference period group: N = 1,178,597	Days 1–7 after 1^st dose Days 7–27 after 2^nd dose	N = 872,454 (74%)	Median age of protection period group: 52 yrs Median age of reference period group: 48 yrs	Protection period group: 48% male Reference period group: 48% male
Yelin I, et al. [25]	Overall in general population: 1.8 million/ 1.3 million were vaccinated	67 days, >93 million observations after exclusion	>98% of patients administered with the 1^st dose administered with 2^nd dose; 1,721,377 vaccinated	Not included in preprint	Not included in preprint
Whitaker HJ, et al. [26]	Overall: N = 5,642,687 in general population Clinical risk groups: N = 1,054,510	≥14 days after 2^nd dose up to 6.5 months	Data not available; to be published in Supplementary material S2.	Data not available; to be published in Supplementary material S2.	Data not available; to be published in Supplementary material S2.
Chemaitelly H, et al. [27]	N = 782 kidney transplant recipients Vaccinated ≥14 days after 2^nd dose through study period: N = 506; 248 crossed over from unvaccinated cohort Unvaccinated: N = 423	≥14 days after 2^nd dose up to ~6 months	N = 601 (77% of 782 with ≥1^st dose)	Median age of vaccinated: 52 yrs Median age of unvaccinated: 49 yrs	Vaccinated: 70% male Unvaccinated: 63% male

COVID-19: Coronavirus disease 2019; IBD: Inflammatory bowel disease; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; Yrs: Years; VHA: Veterans Health Administration.

Table 3. Comparison of IC definitions and populations across studies

Study	IC definition	Study population with IC condition (% of overall population or case/control cohort)
Young-Xu Y, et al. [17]	HIV, asymptomatic HIV, pneumocystosis, retrovirus disease, post-transplant lymphoproliferative disorder, neutropenia, functional disorders of polymorphonuclear neutrophils, white blood cell disorders, spleen diseases, other diseases with lymphoreticular and reticulohistiocytic tissue, immunodeficiencies, other disorders involving immune mechanisms, rheumatoid arthritis, enteropathic arthropathies, juvenile arthritis, polyarteritis nodosa and related conditions, other necrotizing vasculopathies, systemic lupus erythematosus, dermatopolymyositis, systemic sclerosis, Sjögren syndrome, systemic connective tissue disorders, absence/malformation of spleen, antineoplastic and immunosuppressive drug unintentional poisoning, organ transplant, antineoplastic radiation therapy, antineoplastic chemotherapy and immunotherapy	N = 16,315 (22%) Positive cases: N = 2,236 (15%) Controls: N = 14,079 (23%)
Tenforde MW, et al. [18]	Active solid organ cancer with or without metastases (active cancer defined as treatment for the cancer or newly diagnosed cancer in the past 6 months), active hematologic cancer (such as leukemia/lymphoma/myeloma) or active cancer defined as treatment for the cancer or newly diagnosed cancer in the past 6 months, HIV infection without AIDS, AIDS, congenital immunodeficiency syndrome, prior splenectomy, prior solid organ transplant, immunosuppressive medication usage, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, scleroderma, IBD including Crohn’s disease or ulcerative colitis	N = 254 (21%) Cases: N = 99 (17%) Controls: N = 155 (25%)
Tenforde MW, et al. [19]	Active solid organ cancer (active cancer defined as treatment for the cancer or newly diagnosed cancer in the past 6 months), active hematologic cancer (such as leukemia, lymphoma, or myeloma), HIV infection without AIDS, AIDS, congenital immunodeficiency syndrome, previous splenectomy, previous solid organ transplant, immunosuppressive medication usage, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, scleroderma, or inflammatory bowel disease, including Crohn’s disease or ulcerative colitis	N = 652 (21%) Cases: N = 205 (17%) Controls: N = 447 (24%)
Khan N & Mahmud N. [20]	IBD diagnosis w/ IBD medication exposure (mesalamine, thiopurines, anti-tumor necrosis factor biologic agents, vedolizumab, ustekinumab, tofacitinib, methotrexate, and corticosteroid use)	N = 14,697 (100%)
Polinski JM, et al. [21]	Any diagnosis for active cancer, history of organ/stem cell transplant, primary immunodeficiency (e.g. DiGeorge syndrome, Wiskott-Aldrich syndrome), or HIV infection, AND/OR recent use (within 60 days of index) of immunosuppressive medications including high-dose corticosteroids (i.e. ≥20 mg prednisone or equivalent per day), transplant-related immunosuppressives, antimetabolites, alkylating agents, and other severely immunosuppressive cancer chemotherapeutics, tumor necrosis factor blockers, and other immunosuppressive biologics. IC subgroup definitions were based on CDC vaccine guidance for moderately to severely immunocompromised status [10].	N = 131,820 (7%) Vaccinated: N = 26,720 (7%) Unvaccinated: N = 105,100 (7%)
Dagan N, et al.; Barda N, et al. [22,23]	HIV, asymptomatic HIV, organ transplant, bone marrow or hematopoietic stem cell transplant, immunosuppressive medication usage	N = 1,674 (0.5% of full study population with 7–28 days after 2^nd dose: N = 310,696)
Chodick G, et al. [24]	Hematopoietic cell or solid organs transplant, immunosuppressive medication usage, asplenia, and chronic renal failure (advanced kidney disease, dialysis, or nephrotic syndrome)	N = 27,822 (2%)
Yelin I, et al. [25]	Not included in preprint	Not included in preprint
Whitaker HJ, et al. [26]	Data not available; to be published in Supplementary material S2.	Data not available; to be published in Supplementary material S2.
Chemaitelly H, et al. [27]	Kidney transplant recipients with maintenance immunosuppressive medication usage	N = 782 (100%)

Bolded text shows the only 2 common conditions across six of the studies included in this review.

AIDS: Acquired immunodeficiency syndrome; CDC: Centers for Disease Control and Prevention; HIV: Human immunodeficiency virus; IBD: Inflammatory bowel disease; IC: Immunocompromised.

Figure 1. VE against SARS-CoV-2 infection, symptomatic COVID-19 illness, and COVID-19-related hospitalization in IC populations versus general populations^a.

^a See Table 5 for VE including 95% CIs.

^b Dagan et al.; Barda et al. [22,23] reported a BNT162b2 VE against COVID-19-related hospitalization of 100% in their IC population; however, only two such events occurred in the unvaccinated IC group and none in the vaccinated group.

CI: Confidence interval; COVID-19: Coronavirus disease 2019; IC: Immunocompromised; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; VE: Vaccine effectiveness

Table 4. Details of the study outcome measures related to COVID-19 VE

Study	Outcome measures	Controls	VE follow-up duration	VE calculation	Analysis method
Young-Xu Y, et al. [17]	VE: SARS-CoV-2 infection (positive RT-PCR or antigen test) VE: COVID-19-related hospitalization (admission/discharge diagnosis of COVID-19); not assessed in IC VE: COVID-19-related death; not assessed in IC	For SARS-CoV-2 infection, controls were patients with a negative SARS-CoV-2 RT-PCR test For endpoints 2 & 3, controls were patients with a positive SARS-CoV-2 RT-PCR test who were not hospitalized for COVID-19 or died during the study period	≥14 days after 2^nd dose up to 3 months	(1− OR) X 100 OR: SARS-CoV-2 infection in vaccinated vs. unvaccinated	Logistic regression
Tenforde MW, et al. [18]	VE: Odds of prior SARS-CoV-2 vaccination in hospitalized cases with COVID-19 (symptoms and a positive RT-PCR/clinical test) vs. controls	Test-negative controls: Hospitalized patients who tested negative for SARS-CoV-2, but with acute respiratory illness (ARI) symptoms ARI syndrome-negative controls: Hospitalized patients who tested negative for SARS-CoV-2 and without ARI signs and symptoms	≥14 days before reference date (date of hospitalization for cases)	(1‒OR) X 100 OR: Prior vaccination in cases vs. controls	Logistic regression
Tenforde MW, et al. [19]	VE: Odds of prior SARS-CoV-2 vaccination in hospitalized cases with COVID-19 (symptoms and a positive RT-PCR/clinical test) vs. controls	Test-negative controls: Hospitalized patients who tested negative for SARS-CoV-2, but had COVID-19-like illness COVID-19-like illness-negative controls: Hospitalized patients who tested negative for SARS-CoV-2 and did not have COVID-19-like illness	≥14 days before reference date (date of hospitalization for cases) Full surveillance period and separately for March–May and June–July 2021, because of increased circulation of Delta variant in the US	(1‒OR) X 100 OR: Prior vaccination in cases vs. controls	Logistic regression
Khan N & Mahmud N. [20]	VE: SARS-CoV-2 infection (positive RT-PCR test) VE: Severe COVID-19 (hospitalization or death) VE: All-cause mortality (extracted from vital status file in VHA dataset)	Unvaccinated controls	≥7 days after 2^nd dose Median fully vaccinated: 38 days Median unvaccinated: 123 days	(1 – incidence vaccinated/incidence unvaccinated) X 100	Inverse probability weighted (IPW) adjusted models Cox proportional hazards regression
Polinski JM, et al. [21]	VE: SARS-CoV-2 infection (medical claim with COVID-19 diagnosis code and/or a positive RT-PCR test) VE: COVID-19-related hospitalization (discharge diagnosis of COVID-19 or a recorded infection within 21 days before admission)	Unvaccinated controls	≥14 days after single dose up to 5 months	(1-HR) X 100 HR: COVID-19 infection/hospitalization in vaccinated vs. unvaccinated	Propensity score matching Incidence rates calculated per 1,000 person-years Cox regression models used to calculate hazard ratios VE estimates were corrected for under-recording in data source
Dagan N, et al.; Barda N, et al. [22,23]	VE: SARS-CoV-2 infection (positive RT-PCR test) VE: Symptomatic COVID-19 (documented in EMR) VE: Severe COVID-19 illness (according to NIH criteria [37]) VE: COVID-19-related hospitalization (admission records) VE: COVID-19-related death (admission records); not assessed in IC	Matched unvaccinated controls	7 days after 2^nd dose up to 28 days: mean follow-up: 18 days in subgroup analyses	1 – RR RR: vaccinated vs. unvaccinated	Matching analysis Kaplan-Meier analysis to compute risk of outcomes and then calculated risk ratios
Chodick G, et al. [24]	VE: SARS-CoV-2 infection (≥1 positive RT-PCR test) VE: Symptomatic COVID-19 (documented in EMRs) VE: Risk of COVID-19-related hospitalization/death among infected (extracted from EMRs); VE not reported in IC	Between 7 to 27 days after 2^nd dose (protection-period) vs. days 1 to 7 after the 1^st dose (reference period)	Days 7–27 after 2^nd dose vs. days 1–7 after 1^st dose	(1 – Relative Risk) X 100 Relative Risk: Protection-period vs. reference-period	Logistic regression was used to estimate odds ratios for symptomatic COVID-19 among infected cases Cox proportional hazards model were used to calculate adjusted hazard ratios for COVID-19-related hospitalization/death.
Yelin I, et al. [25]	VE: SARS-CoV-2 infection (positive RT-PCR test) VE: Symptomatic COVID-19; not assessed in IC	Unvaccinated controls	1–11 days 12–28 days 29–50 days (IC) All post-vaccination	(1-OR) X 100 OR: Positive test/symptomatic infection in vaccinated vs. unvaccinated	Logistic regression
Whitaker HJ, et al. [26]	VE: Symptomatic COVID-19 (diagnosis of COVID-19 or clinical illness consistent with COVID-19 within 10 days before or after a positive RT-PCR test)	Test-negative controls: Patients with symptoms within 10 days of SARS-CoV-2 negative test	≥14 days after 2^nd dose up to ~6.5 months	Adjusted VE OR OR: Cases in vaccinated vs. unvaccinated	Logistic regression
Chemaitelly H, et al. [27]	VE: SARS-CoV-2 infection (positive RT-PCR test) VE: Severe COVID-19 illness (according to WHO criteria [38])	Unvaccinated controls	≥14 days after 2^nd dose ≥42 days after 2^nd dose ≥56 days after 2^nd dose	1 – HR HR: vaccinated vs. unvaccinated	A proportional hazards model was used to calculate adjusted hazard ratios

COVID-19: Coronavirus disease 2019; EMR: Electronic medical records; HR: Hazard ratio; IC: Immunocompromised; NIH: National Institutes of Health; OR: Odds ratio; RR: Risk ratio; RT-PCR: Reverse transcription polymerase chain reaction; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; VE: Vaccine effectiveness; VHA: Veterans Health Administration; WHO: World Health Organization.

Table 5. Vaccine effectiveness against SARS-CoV-2 infection, symptomatic COVID-19 illness, severe COVID-19 illness, and COVID-19-related hospitalization across studies

Study	Vaccine	Outcome	Patient group	VE	95% CI Lower	95% CI Upper
Young-Xu Y, et al. [17]	mRNA vaccines	Infection	IC	87%	79%	92%
Young-Xu Y, et al. [17]	mRNA vaccines	Infection	Overall population	95%	93%	96%
Khan N & Mahmud N. [20]	mRNA vaccines	Infection	IC: IBD	80%	NR	NR
Polinski JM, et al. [21]	Ad26.COV2.S	Infection	IC	64%	57%	70%
Polinski JM, et al. [21]	Ad26.COV2.S	Infection	Overall population	79%	77%	80%
Polinski JM, et al. [21]	Ad26.COV2.S	Infection	Non-IC	79%	78%	81%
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Infection	IC	90%	49%	100%
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Infection	Overall population	93%	91%	94%
Chodick G, et al. [24]	BNT162b2	Infection	IC	71%	37%	87%
Chodick G, et al. [24]	BNT162b2	Infection	IC ≥65 yrs	52%	26%	82%
Chodick G, et al. [24]	BNT162b2	Infection	Overall population	90%	79%	95%
Yelin I, et al. [25]	BNT162b2	Infection	IC	OR:0.67	0.53	0.83
Yelin I, et al. [25]	BNT162b2	Infection	Overall population	95%	93%	96%
Chemaitelly H, et al. [27]	mRNA vaccines	Infection	Kidney transplant recipients ≥14 days after 2^nd dose	47%	0%	74%
Chemaitelly H, et al. [27]	mRNA vaccines	Infection	Kidney transplant recipients ≥42 days after 2^nd dose	66%	21%	85%
Chemaitelly H, et al. [27]	mRNA vaccines	Infection	Kidney transplant recipients ≥56 days after 2^nd dose	74%	33%	90%
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Symptomatic illness	IC	84%	19%	100%
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Symptomatic illness	Overall population	96%	94%	97%
Chodick G, et al. [24]	BNT162b2	Symptomatic illness	IC	75%	44%	88%
Chodick G, et al. [24]	BNT162b2	Symptomatic illness	Overall population	94%	88%	97%
Whitaker HJ, et al. [26]	BNT162b2	Symptomatic illness	IC; age range not provided	73%	34%	89%
Whitaker HJ, et al. [26]	ChAdOx1 nCoV-19	Symptomatic illness	IC; age range not provided	75%	19%	92%
Whitaker HJ, et al. [26]	BNT162b2	Symptomatic illness	Overall population 16–64 yrs	93%	86%	97%
Whitaker HJ, et al. [26]	ChAdOx1 nCoV-19	Symptomatic illness	Overall population 16–64 yrs	78%	70%	84%
Whitaker HJ, et al. [26]	BNT162b2	Symptomatic illness	Overall population ≥65 yrs	87%	80%	91%
Whitaker HJ, et al. [26]	ChAdOx1 nCoV-19	Symptomatic illness	Overall population ≥65 yrs	76%	59%	86.5%
Khan N & Mahmud N. [20]	mRNA vaccines	Severe illness^a	IC: IBD	70%	NR	NR
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Severe illness^b	IC	100%	1 vs. 0^c
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Severe illness^b	Overall population	95%	89%	99%
Chemaitelly H, et al. [27]	mRNA vaccines	Severe illness^d	Kidney transplant recipients ≥14 days after 2^nd dose	72%	0%	91%
Chemaitelly H, et al. [27]	mRNA vaccines	Severe illness^d	Kidney transplant recipients ≥42 days after 2^nd dose	85%	36%	96.5%
Chemaitelly H, et al. [27]	mRNA vaccines	Severe illness^d	Kidney transplant recipients ≥56 days after 2^nd dose	84%	31%	96%
Tenforde MW, et al. [18]	mRNA vaccines	Hospitalization	IC	63%	21%	83%
Tenforde MW, et al. [18]	mRNA vaccines	Hospitalization	IC subgroup: solid organ or hematologic malignancy or solid organ transplant	51%	−31%	82%
Tenforde MW, et al. [18]	mRNA vaccines	Hospitalization	Overall population	87%	81%	91%
Tenforde MW, et al. [18]	mRNA vaccines	Hospitalization	Non-IC	91%	86%	95%
Tenforde MW, et al. [19]	mRNA vaccines	Hospitalization	IC	63%	44%	76%
Tenforde MW, et al. [19]	mRNA vaccines	Hospitalization	Overall population	86%	82%	88%
Tenforde MW, et al. [19]	mRNA vaccines	Hospitalization	Non-IC	90%	87%	92%
Polinski JM, et al. [21]	Ad26.COV2.S	Hospitalization	IC	68%	54%	77%
Polinski JM, et al. [21]	Ad26.COV2.S	Hospitalization	Overall population	81%	79%	84%
Polinski JM, et al. [21]	Ad26.COV2.S	Hospitalization	Non-IC	83%	80%	85%
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Hospitalization	IC	100%	2 vs. 0^c
Dagan N, et al.;Barda N, et al. [22,23]	BNT162b2	Hospitalization	Overall population	92%	85%	97%

^aHospitalization or death [20].

^bAccording to National Institutes of Health criteria [37]: Individuals who have SpO₂ < 94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO₂/FiO₂) <300 mmHg, respiratory frequency >30 breaths/min, or lung infiltrates >50%; critical illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.

^cNumber of events in unvaccinated vs. vaccinated.

^dSevere disease (acute-care hospitalization) and critical disease (intensive care unit hospitalization) were defined per World Health Organization guidelines [38]: Oxygen saturation of <90% on room air, and/or respiratory rate of >30 breaths/minute in adults and children >5 years old (or ≥60 breaths/minute in children <2 months old or ≥50 breaths/minute in children 2–11 months old or ≥40 breaths/minute in children 1–5 years old), and/or signs of severe respiratory distress (accessory muscle use and inability to complete full sentences, and, in children, very severe chest wall indrawing, grunting, central cyanosis, or presence of any other general danger signs).

aHR: Adjusted hazard ratio; CI: Confidence interval; COVID-19: Coronavirus disease 2019; IBD: Inflammatory bowel disease; IC: Immunocompromised; mRNA: messenger ribonucleic acid; OR: Odds ratio; NR: Not reported; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; yrs: Years; VE: Vaccine effectiveness

Young-Xu Y, Korves C, Powell EI, et al. Coverage and effectiveness of mRNA SARS-CoV-2 vaccines among United States veterans. JAMA Network Open. 2021;4(10):e2128391.

 PubMed Web of Science ®Google Scholar

Tenforde MW, Patel MM, Ginde AA, et al. Effectiveness of SARS-CoV-2 mRNA vaccines for preventing Covid-19 hospitalizations in the United States. Clin Infect Dis. 2021 Aug 6; ciab687. doi: https://doi.org/10.1093/cid/ciab687. Online ahead of print.

 Google Scholar

Tenforde MW, Self WH, Naioti EA, et al. Sustained effectiveness of Pfizer-BioNTech and moderna vaccines against COVID-19 associated hospitalizations among adults — United States, March–July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(34):1156–1162.

 PubMed Web of Science ®Google Scholar

Khan N, Mahmud N. Effectiveness of SARS-CoV-2 vaccination in a veterans affairs cohort of patients with inflammatory bowel disease with diverse exposure to immunosuppressive medications. Gastroenterology. 2021;161(3):827–836.

 PubMed Web of Science ®Google Scholar

Polinski JM, Weckstein AR, Batech M, et al. Effectiveness of the single-dose Ad26.COV2.S COVID vaccine. medRxiv. 2021 Sep 10. DOI:https://doi.org/10.1101/2021.09.10.21263385. Preprint.

 Google Scholar

Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412–1423.

 PubMed Web of Science ®Google Scholar

Barda N, Dagan N, Balicer RD. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting: reply. N Engl J Med. 2021;384:1970.

 PubMed Web of Science ®Google Scholar

Chodick G, Tene L, Rotem RS, et al. The effectiveness of the two-dose BNT162b2 vaccine: analysis of real-world data. Clin Infect Dis. 2021 May 17; ciab438. doi: https://doi.org/10.1093/cid/ciab438. Online ahead of print.

 Google Scholar

Yelin I, Katz R, Herzel E, et al. Associations of the BNT162b2 COVID-19 vaccine effectiveness with patient age and comorbidities. medRxiv. 2021 May 24. DOI:https://doi.org/10.1101/2021.03.16.21253686. Preprint.

 Google Scholar

Whitaker HJ, Tsang RSM, Byford R, et al. Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response among individuals in clinical risk groups. Khub.net. Posted July 2021. Preprint.

 Google Scholar

Chemaitelly H, AlMukdad S, Paravila J, et al. SARS-CoV-2 vaccine effectiveness in immunosuppressed kidney transplant recipients. medRxiv. 2021 Aug 9. DOI:https://doi.org/10.1101/2021.08.07.21261578. Preprint.

 Google Scholar

Covariants.org [Internet]. Munich (Germany): GISAID; Overview of variants in countries. [cited 2021 Dec 30]. Available from: https://covariants.org/per-country

 Google Scholar

Cdc.gov [Internet]. COVID-19 vaccines for moderately to severely immunocompromised people. Atlanta (GA): Centers for Disease Control and Prevention;. Updated. 2021 Sep 2 [cited 2021 Sep 30]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html. ** Of considerable importance: provides definition of moderately to severely immunocompromised individuals.

 Google Scholar

Nih.gov [Internet]. Coronavirus disease 2019 (COVID-19) treatment guidelines. Bethesda (MD): National Institutes of Health; 2021. [cited 2021 Dec 30]. Available from: https://www.covid19treatmentguidelines.nih.gov

 Google Scholar

Who.int [Internet]. COVID-19 clinical management: living guidance. Geneva (Switzerland): World Health Organization; [cited 2021 Dec 30]. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1

 Google Scholar

Data availability statement

All data contained within this review were extracted from the published/preprint referenced articles and are available to the public.