Table 1.
Summary of characteristics of studies included in the systematic literature review.
| First author, year, location | COVID-19 vaccine | Study design/D&B score (max score 28) | Study duration [dates] | Number of patients [immunocompromised vs. healthy controls] | Total or% participants with neutralizing antibodies [immunocompromised vs. healthy controls] |
Mean (SD) or median [IQR] antibody titers [immunocompromised vs. healthy control] |
Immunocompromised patients: Symptomatic COVID-19 (N) /No symptomatic COVID-19 (N) [vaccinated vs. unvaccinated] |
Immunosuppressive therapy | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| After 1st dose | After 2nd dose | After 1st dose | After 2nd dose | After 1st dose | After 2nd dose | ||||||
| Achiron, 2021, Israel | Pfizer/ BioNTech |
Retrospective cohort 18 |
NR | 93 on treatment for MS Vs. 32 with untreated MS Vs. 47 healthy controls |
NR | 34 (32.3%) treatment for MS Vs. 32 (100%) with untreated MS Vs. 46 (97.9%) healthy controls |
NR | 7 (6.5–8.1) on cladribine, 0.27 (0.12–0.45) on Fingolimod and 0.29 (0.006–0.89) on Ocrelizum Vs. 8.1 (7.5–8.4) for untreated MS Vs. 7.4 (6.4–8.1) for healthy controls |
NR | NR | Claribine, Fingolimod, Ocrelizumab |
| Ammitzbøll, 2021, Aarhus, Denmark | Pfizer/ BioNTech |
Prospective cohort 21 |
4 months [Dec, 2020 Apr, 2021] | 61 patients with SLE Vs. 73 patients with RA |
NR | SLE patents: 89% (54/61) Vs. RA patients: 67% (49/73) |
NR | NR | NR | NR | Prednisone, Hydroxychloroquine, MMF, Azathioprine Rituximab |
| Barriere 2021, Nice, France |
Pfizer/ BioNTech |
Prospective cohort 18 |
2 months [Jan 18, 2021 - Mar 15, 2021] | 122 immunocompromised patients (solid tumors) Vs. 29 healthy controls |
58/122 Vs. 13/13 |
40/42 Vs. 24/24 |
0.52 UI/mL Vs. 21.6 UI/mL |
245.2 UI/mL Vs 2517 UI/mL |
NR | NR | NR |
| Bertrand, 2021, France | Pfizer/ BioNTech |
Retrospective cohort 17 |
2 months [Jan 2021 – Mar 2021] | 45 kidney transplant recipients Vs. 10 hemodialysis patients |
NR | NR | 311 AU/mL for kidney transplant recipients Vs. 178.9 AU/mL for HD patients |
671 AU/mL (IQR: 172–1523) for kidney transplant recipients Vs. 1052 AU/mL (IQR: 515–2689) for HD patients |
NR | NR | Tacrolimus, Belatacept |
| Braun-Moscovici, 2021, Israel | Pfizer/ BioNTech |
Prospective Cohort 22 |
NR | NR | NR | 227 (86%) immunocompromised [rheumatic inflammatory disease] who took the vaccine Vs. 24 (92.3%) - COVID19 recovered immunocompromised |
NR | 6764.27 AU/mL (9291.61) immunocompromised who took the vaccine Vs. 2044.8 AU/mL (4944.8) - COVID19 recovered immunocompromised |
NR | NR | conventional DMARDs, colchicine, nintedanib, biological/targeted DMARDs, and corticosteroids |
| Broseta, 2021, Spain | Pfizer/ BioNTech and Moderna |
Prospective cohort 21 |
11 weeks [Feb 3, 2021 – Apr 2021] |
10 HD patients on immunosuppression Vs. 165 HD patients without immunosuppression |
NR | 6 (60%) for patients on immunosuppression Vs. 161 (97.6%) for patients without immunosuppression |
NR | NR | NR | NR | Tacrolimus, eclizumab |
| Chodick,2021, Israel | Pfizer/ BioNTech |
Retrospective Cohort 21 |
2 months [Dec 19,2020 – Feb 20, 2021] |
25,459 immunocompromised patients with 2 doses Vs. 27,822 immunocompromised patients with 1 dose |
NR | NR | NR | NR | NR | 56/25,403 [vaccinated] Vs. 79/27,743 [unvaccinated] |
NR |
| Danthu, 2021, France | Pfizer/ BioNTech |
Prospective cohort 17 |
14 weeks [vaccine time: Feb 2, 2021 – Mar, 15, 2021; and 58 days of follow-up] |
74 kidney transplant patients Vs. 78 patients on HD Vs. 7 healthy controls |
NR | 3 (4.1%) for patients after kidney transplant, 59 (85.5%) for patients on HD, and 7 (100%) for healthy control | NR | 6.6 AU/mL (2.1–19) for patients on HD, 1082 AU/mL (735–1662) for healthy control. Titer not shown for transplant patients (only 3 were positive) | NR | NR | Antimetabolite, Steroid |
| Furer, 2021, Tel Aviv, Israel |
Pfizer/ BioNTech |
Prospective cohort 22 |
3 months [Dec 2020 – Mar 2021] | 686 patients with AIIRD Vs. 121 healthy controls |
NR | Immunocompromised: 86% (590/686) Vs. Healthy control: 100% (121/121) |
NR | Immunocompromised: S1/S2 IgG: 132.9 (+/- 91.7) BAU/mL Vs. Healthy controls S1/S2 IgG: 218.6 (+/- 82.06) BAU/mL |
NR | NR | Anti-CD20, Methotrexate, MMF, Interleukin 6 inhibitor, Janus kinase inhibitor, Glucocorticoids, Abatacept |
| Geisen, 2021, Kiel,,Germany. |
Pfizer/ BioNTech and Moderna |
Prospective cohort 19 |
6 weeks [NR] | 26 immunocompromised (patients with chronic inflammatory conditions, and immunosuppressive therapy) Vs. 42 healthy controls |
NR | Immunocompromised: 26(100% ) Vs. Healthy controls 42 (100%) |
NR | Immunocompromised: Anti-SARS-COV-2 IgG: 2053 BAU/mL (+- 1218); Neutralizing antibodies: 87.42% (+−17.94); IgA: 24.52 U/mL (+- 30.48) Vs. Healthy controls: Anti-SARS-COV-2 IgG: 2685 BAU/mL (+−1102);Neutralizing antibodies: 96.04% (+−1551); IgA: 47.65 U/mL (+−45.12) |
NR | NR | Biological DMARD; Conventional DMARD; Steroids (prednisolone) |
| Ghione, 2021, Buffalo, NY, United States |
Pfizer/ BioNTech and Moderna |
Prospective cohort 20 |
2 months [NR] |
65 lymphoma patients with treatment Vs. 21 Lymphoma patients without treatment Vs. 194 healthy controls |
NR | 36/86 Vs. 197/201 |
NR | 0.13 in patients with recent treatment 20.7 in patients with prior treatment |
NR | NR | Anti-CD20, Bruton tyrosine kinase, inhibitors based therapied, chimeric antigen receptor (CAR) T cell therapy |
| Grupper, 2021, Israel | Pfizer/ BioNTech |
Prospective cohort 23 |
NR | 136 kidney transplant patients Vs. 25 healthy controls |
NR | NR | NR | 5.9 (3.8–4.2) for kidney transplants Vs. 189 (141.1–248) for healthy controls |
NR | NR | Methylprednisolone + Basiliximab for induction; Calcineurin inhibitors + Mycophenolate mofetil + Prednisone for maintenance |
| Haberman, 2021, United States | Pfizer/ BioNTech |
Prospective cohort 19 |
4 months [Dec 23, 2020 – Mar 31, 2021] |
101 with immunemediated inflammatory diseases Vs. 26 healthy controls |
NR | NR | NR | 46,90125-694,528 units for Metothrexate group. 113,60825-737,310 units for the imunossupressed without metothrexate and 104,354 units (141–601,185) for healthy controls | NR | NR | disease-modifying antirheumatic drugs (TNF inhibitor) with or without Methotrexate |
| Havlin, 2021, Prague Czech Republic | Pfizer/ BioNTech |
Prospective cohort 19 |
NR | 48 LTR patients Vs. 33 LTR patients post-COVID-19 infection Vs. 10 healthy controls |
NR | LTR patients: 0% (0/48) Vs. LTR patients post-COVID-19: 85% (28/33) Vs. Healthy control: 100% (10/10) |
NR | NR | NR | 3/43 [vaccinated] Vs. 1/1 [unvaccinated] |
NR |
| Herishanu 2021 Tel-Aviv, Israel |
Pfizer/ BioNTech |
Prospective cohort 22 |
3 months [Dec 2020 – Feb 2021] |
167 immunocompromised (chronic lymphocytic leukemia) Vs. 52 healthy controls |
NR | Immunocompromised:39.5% (66/167) patients with CLL Vs. Healthy controls: 52 (100%) |
NR | Immunocompromised: Median: 0.824 U/ml (IQR: 0.4–167.3) Vs. Healthy controls: Median: 1084 U/mL (IQR: 128.9–1879) |
NR | NR | Anti-CD20 (rituximab or obinutuzumab), Venetoclax |
| Herzog Tzarfati, 2021, Israel | Pfizer/ BioNTech |
Retrospective cohort 21 |
NR | 315 immunocompromised (hematologic CA) Vs. 108 healthy controls |
NR | 74.6% for hematologic CA Vs. CIT (29%); single agent anti CD20 Ab (0%); BCL2i (25%); BTKi (40%), JAK2i (42%) Vs. 99.1% for controls |
85 (10.7–172) AU/mL - median | 157 (130–221) AU/mL - median | NR | NR | Chemotherapy, chemo-immunotherapy (CIT), single agent anti CD20, proteasome inhibitors, IMIDs, BCR-ABL TKI, BCL2 inhibitors, JAK2 inhibitors, BTK inhibitors |
| Iacono, 2021, Italy | Pfizer/ BioNTech |
Prospective Cohort 16 |
NR |
36 hematologic CA Vs. 72 healthy controls |
NR | NR |
NR |
2369.1 (0–3276.3) AU/mL in the immunosuppressed Vs. 8737.49 (398.9–967,280) AU/mL for healthy controls |
NR | NR | Rituximab, Paclitaxel + Transtuzumab, Corticosteroids |
| Khan, 2021, VA across the United States |
Pfizer/ BioNTech and Moderna |
Retrospective cohort 21 |
4 months [Dec 18, 2020 – April 20, 2021] |
7376 immunocomprimised patients [IBD] with vaccines Vs. 7211 immunocomprmised patients without vaccine |
NR | NR | NR | NR | NR | 14/7098 [vaccinated] Vs. 197/14,500 [unvaccinated] |
Mesalamine Thiopurine Anti TNF Vedolizumab Ustekinumab Tofacitinib Methotrexate steroid |
| Korth 2021 Kronach Germany |
Pfizer/ BioNTech |
Prospective cohort 19 |
2 months [Jan 2021 – Feb 2021] |
23 Immunocompromised: (KTR) Vs. 23 healthy controls |
NR | Immunocompromised: 22% (5/23) Vs. Healthy controls: 100% (23/23) |
NR | Immunocompromised: IgG: 50.9 (+/- 138.7) AU/mL Vs. Healthy controls IgG: 727.7 (+/- 151.3) AU/mL |
NR | NR | Tacrolimus, MMF, corticosteroids |
| Lim, 2021, UK | Pfizer/ BioNTech; AstraZeneca |
Prospective Cohort 18 |
NR | 119 immunocompromised patients: 44% (52/119) with lymphoma on treatment Vs. 150 healthy controls |
Immuno compromised: 9/31 (28%) Vs. healthy control: - |
Immuno compromised: 13/33 (39%) Vs. not on treatment: Hodgkin lymphoma (100%); aggressive B-cell non-Hodgkin lymphoma (81%); indolent B-cell non-Hodgkin lymphoma (89%) |
Immuno compromised: Vs. healthy control: Pfizer/ BioNTech: 172 BAU/mL (95% CI 109–272) AstraZeneca: 67 BAU/mL40-111 |
Immunocompromised: on treatment: 2.5 BAU/mL (95% CI 1.1–5.8) Vs. not on treatment: 141.8 BAU/mL (75.6–266.0); Hodgkin lymphoma: 652.2 BAU/mL (95% CI 604.7–703.4); aggressive B-cell non-Hodgkin lymphoma: 244.6 BAU/mL (31.12–1923); Vs. healthy control: Pfizer/ BioNTech: 2339 BAU/mL1,923-2,844 AstraZeneca: 199 BAU/mL (140–282) |
NR | NR | Anti-lymphoma therapy |
| Longlune, 2021, France | Pfizer/ BioNTech |
Prospective cohort 21 |
NR | 20 HD patients on immunosuppression, Vs. 92 HD patients without immunosuppression |
5 (4.5%) in total | 10 (58.8%) for patients on immunosuppression Vs. 76 (95.0%) for patients without immunosuppression |
NR | NR | NR | NR | mTOR inhibitor, Mycophenolic acid, steroid |
| Maneikis, 2021, Lithuania | Pfizer/ BioNTech |
Prospective cohort 21 |
3.5 months [Jan 8, 2021 – April 21, 2021] |
857 patients with hematologic CA Vs. 68 healthy controls |
NR | NR | NR | 6961 AU/mL (IQR: 1292–20,672) for hematologic CA Vs. 21,395 AU/mL (IQR: 14,831–33,553) for healthy controls |
NR | NR | Anti-CD20, Tyrosine kinase inhibitors, Nivolumab, Ruxolitinib, Venetoclax, Aregrelide or interferon |
| Miele, 2021, Palermo, Italy | Pfizer/ BioNTech |
Prospective cohort 18 |
4 months [Dec 2020 – Mar 2021] |
16 SOT patients Vs. 23 healthy controls |
NR | Immunocompromised:37% (6/16) Vs. Healthy control: 100% (23/23) |
NR | Mean: 87.32 AU/mL for SOT patients Vs. Mean: 233 AU/mL for healthy controls |
NR | NR | Tacrolimus, Everolimus, MMF, Corticosteroids |
| Monin 2021 London, UK |
Pfizer/ BioNTech |
Prospective cohort 21 |
2 months [Dec 8, 2020 – Feb 18, 2021] |
151 immunocompromised (solid and hematologic CA) Vs. 54 healthy controls |
Solid CA: Week 3: 21; 28%26-51; Week 5: 10; 30%17-47 Vs. Hematologic CA: Week 3: 8; 18%10-32 Week 5: 4; 11%4-25 Vs. Healthy controls: Week 3: 32; 94% (81–98); Week 5:18; 86%65-95 |
Solid CA: 18; 95% (75–99) Vs. Hematological CA:; 60%23-88 Vs. Healthy controls: 12; 100% (76–100) |
NR | NR | NR | NR | NR |
| Peled, 2021, Israel | Pfizer/ BioNTech |
Prospective cohort 16 |
NR | 77 patients after heart transplant Vs. 136 healthy controls |
NR | 8 (10.4%) for heart transplant patients Vs. 127 (93.4%) for healthy controls |
NR | NR | NR | NR | Calcineurin inhibitor, prednisone |
| Rabinowich, 2021, Tel Aviv-Yafo, Israel |
Pfizer/ BioNTech |
Prospective cohort 20 |
6 weeks [Dec 2020 – Jan 2021] |
80 in immunocompromised patients (liver transplant recipients) Vs. 25 healthy controls |
NR | (47.5%) 38/80 in immunocompromised patients Vs. (100%) 25/25 in healthy controls |
NR | Immunocompromised: 95.4 AU/ml (+- 92.4) Vs. 200.5 AU/ml (+−65.1) in healthy controls |
NR | NR | Prednisone, Tacrolimus/cyclosporin, Everlolimus, Azathioprine, MMF |
| Rincon-Arevalo, 2021, Berlin, Germany | Pfizer/ BioNTech |
Prospective cohort 18 |
7 weeks [NR] |
44 on dialysis Vs. 40 in kidney transplant patients Vs. 34 healthy controls |
NR | 30/44 in dialysis group Vs. 0/10 in transplant group |
NR | NR | NR | NR | MMF, Steroid, Calcineurin inhibitor |
| Sattler, 2021, Germany |
Pfizer/ BioNTech |
Prospective Cohort 17 |
NR | 39 immunocompromised (KTR) Vs. 26 patients with kidney failure on HD Vs. 39 healthy controls |
NR | Immunocompromised:IgG: 1 (2.6%); IgA: 4 (10.26%); Neutralizing antibodies: 0 Vs. Patients with kidney failure on hemodialysis: IgG: 22 (84.62%); IgA: 22 (84.62%); Neutralizing antibodies: 20 (76.92%) Vs. Healthy patients: IgG: 39 (100%); IgA: 38 (97.44%); Neutralizing antibodies: 39 (100%) |
NR | NR | NR | NR | Cyclosporin, Tacrolimus MMF, corticosteroids |
| Schramm, 2021, Germany | Pfizer/ BioNTech |
Prospective Cohort 19 |
NR | 50 cardiothoracic transplant recipients Vs. 50 healthy controls |
NR | NR | 96% below the cut off in the immunosuppressed group Vs. Abbott: 8241-149; Roche: 3312-75; Euroimmun: 62 27-100 in healthy controls |
90% below the cut off in the immunosuppressed group Vs. Abbott 1417 (732-2,589); Roche: >250; Euroimmun: >100 in healthy controls |
NR | NR | Calcineurin inhibitor, MMF |
| Seyahi, 2021, Instabul, Turkey |
Coronavac | Prospective cohort 22 |
15 weeks [Jan 14, 2021 – May 2, 2021] | Elderly immunocompromised [inflammatory rheumatic disease]: 22 elderly healthy control: 47 Vs. immunocompromised [inflammatory rheumatic disease]: hospital workers: 82 Vs. healthy controls (health care workers): 300 |
NR | 1 (14.3%) for RTX Vs. 22 (88%) for non-RTX biological agents Vs. 25 (92.6%) for conventional DMARDs- Vs. 16 (100%) for colchicine Vs. 29 (100%) for no treatment |
NR | NR | NR | NR | RTX, non-RTX biological agents-based regimen, conventional DMARDs-based regimen, colchicine |
| Tenforde,2021, United States |
Pfizer/ BioNTech and Moderna |
Prospective cohort 19 |
4 months [Mar 11, 2021 – May 5, 2021] |
254 in immunocompimised patients Vs. 958 healthy controls |
NR | NR | NR | NR | NR | 20/59 [vaccinated] Vs. 62/60 [unvaccinated] |
NR but definition for immunocompromised active solid organ CA (treated or newly diagnosed in the past 6 months), active hematologic CA (e.g., leukemia, lymphoma, myeloma), HIV infection without AIDS, AIDS, congenital immunodeficiency syndrome, previous splenectomy, SOT, immunosuppressive medication, SLE, RA, psoriasis, scleroderma, or IBD |
| Woldemeskel, 2021, United States | Pfizer/ BioNTech |
Prospective cohort 14 |
NR | 12 patients with HIV Vs. 17 healthy controls |
NR | NR | NR | median 8.84 for HIV patients Vs. median 9.49 for healthy controls |
NR | NR | Antiretroviral therapy* |
| Wong, 2021, NY, United States | Pfizer/ BioNTech and Moderna |
Retrospective cohort 22 |
2 months [Dec 14, 2020 –Feb 12, 2021] | 48 patients with IBD receiving biologic therapies Vs. 14 HCWs and 29 healthy volunteers |
NR | Immunocompromised:26 IBD patients (100%) who received the 2nd vaccine dose had positive anti-RBD tests Vs. 100% in healthy controls |
NR | NR | NR | NR | TNF antagonist monotherapy, vedolizumab monotherapy, ustekinumab |
AIIRD=Autoimmune inflammatory rheumatic diseases; Anti-RBD=Anti receptor-binding domain; AU=Arbitrary units; BAU=Binding antibody units; BCL2 inhibitors= B-cell lymphoma 2; BCR-ABL TKI; BTK inhibitors= Bruton tyrosine kinase; CA=cancer; 95% CI=95% Confidence Interval; DMARDs=Disease modifying anti-rheumatic drugs; HD=Hemodialysis; IBD=Inflammatory Bowel Disease; IMIDs= Immune modulatory drugs; IQR=Interquartile range; JAK2= Janus kinase 2; KTR= Kidney transplant recipient; LTR=Lung transplant recipient; MDS=Myelodysplastic syndrome; MMF=Mycophenolate mofetil; MS=Multiple Sclerosis; mTOR= mammalian target of rapamycin; N=number reported; NR=Not reported; RA=Rheumatoid Arthritis; RTX=Rituximab; S=Spike; SCT=Stem Cell Transplantation; SD=Standard Deviation; SLE=Systemic Lupus Erythematosus; SOT=Solid organ transplant; TKI= Tyrosine kinase inhibitor; TNF=tumor necrosis factor; UI= Units; VE=Vaccine Effectiveness.
*All HIV patients were on antiretroviral therapy and had a median CD4+ T cell count on 913 cells/uL (range of 649 to 1678 cells/uL).