Table 2.
Pooled adjusted and unadjusted effects of prior ICI exposure on COVID-19 outcomes
| Outcome | Studies | Events/N | OR (95% CI) | Heterogeneity | ||
|---|---|---|---|---|---|---|
| ICI | No ICI | I2 | P-value | |||
| Adjusted effects | ||||||
| Mortalitya,b | 5 [26, 28, 30, 32, 33] | 30/122c | 237/963c | 0.70 (0.40–1.23) | 0% | 0.606 |
| Subgroup analysis | ||||||
| Sample size | ||||||
| < 100 patients | 3 [28, 30, 32] | 18/72c | 12/108c | 0.71 (0.29–1.73) | 0% | 0.595 |
| ≥ 100 patients | 2 [26, 33] | 12/50 | 223/855 | 0.90 (0.22–3.69) | 40% | 0.195 |
| Risk of bias | ||||||
| Low | 2 [26, 30] | 21/83 | 221/784 | 0.68 (0.34–1.35) | 0% | 0.451 |
| Moderate/High | 3 [28, 32, 33] | 9/39c | 16/179c | 0.75 (0.27–2.15) | 6% | 0.346 |
| Location | ||||||
| Asia | 1 [33] | 2/6 | 7/99 | 3.03 (0.29–31.98) | NA | NA |
| Europe | 2 [26, 28] | 10/52c | 216/811c | 0.63 (0.31–1.25) | 0% | 0.749 |
| America | 2 [30, 32] | 18/64 | 14/53 | 0.67 (0.22–2.05) | 2% | 0.314 |
| Adjuvant therapy | ||||||
| ICI monotherapy | 1 [28] | NR | NR | 0.15 (0.01–1.65) | NA | NA |
| ICI + chemotherapy | 1 [28] | NR | NR | 1.96 (0.29–13.18) | NA | NA |
| Severityd,e | 3 [30, 33] | 19/45 | 132/546 | 1.62 (0.48–5.43) | 57% | 0.095 |
| Subgroup analysis | ||||||
| Adjuvant therapy | ||||||
| ICI monotherapy | 1 [28] | NR | NR | 0.26 (0.03–1.88) | NA | NA |
| ICI + chemotherapy | 1 [28] | NR | NR | 0.97 (0.14–6.45) | NA | NA |
| Hospitalizationd,e | 1 [31] | 18/29 | 150/382 | 2.84 (1.22–6.72) | NA | NA |
| Unadjusted effects | ||||||
| Mortalityb | 8 [24–26, 29, 30, 32–34] | 51/198 | 317/1241 | 0.91 (0.60–1.38) | 2% | 0.411 |
| Subgroup analysis | ||||||
| Sample size | ||||||
| < 100 patients | 4 [24, 25, 30, 32] | 21/89 | 28/133 | 0.95 (0.46–1.94) | 0% | 0.609 |
| ≥ 100 patients | 4 [26, 29, 33, 34] | 30/109 | 289/1108 | 1.05 (0.51–2.18) | 44% | 0.150 |
| Risk of bias | ||||||
| Low | 5 [24, 26, 29, 30, 34] | 39/145 | 295/1089 | 0.89 (0.56–1.41) | 0% | 0.450 |
| Moderate/High | 3 [25, 32, 33] | 12/53 | 22/152 | 1.06 (0.34–3.25) | 42% | 0.178 |
| Location | ||||||
| Asia | 1 [33] | 2/6 | 7/99 | 4.45 (0.72–27.44) | NA | NA |
| Europe | 3 [24–26] | 13/69 | 13/836 | 0.60 (0.30–1.22) | 0% | 0.989 |
| America | 3 [29, 30, 32] | 20/71 | 30/167 | 1.30 (0.61–2.78) | 0% | 0.389 |
| International | 1 [34] | 16/52 | 50/139 | 0.79 (0.40–1.57) | NA | NA |
| Cancer type | ||||||
| Lung cancer | 3 [30, 33, 34] | 28/96 | 58/184 | 0.98 (0.55–1.74) | 0% | 0.495 |
| Non-lung solid cancer | 3 [25, 29, 33] | 6/30 | 26/215 | 4.00 (0.30–52.88) | 87% | < 0.001 |
| Adjuvant therapy | ||||||
| ICI monotherapy | 4 [25, 29, 33, 34] | 16/60 | 128/380 | 0.88 (0.43–1.81) | 6% | 0.364 |
| ICI + chemotherapy | 3 [29, 33, 34] | 7/23 | 76/352 | 1.12 (0.34–3.70) | 46% | 0.159 |
| Comparator groupf | ||||||
| No treatment | 5 [24–26, 33, 34] | 32/127 | 120/421 | 0.86 (0.42–1.77) | 34% | 0.193 |
| Chemotherapyg | 5 [25, 26, 29, 33, 34] | 33/131 | 106/334 | 0.83 (0.46–1.51) | 16% | 0.310 |
| Targeted therapy | 5 [24, 26, 29, 33, 34] | 30/112 | 26/120 | 1.19 (0.63–2.22) | 0% | 0.753 |
| Surgery | 3 [26, 29, 33] | 14/57 | 11/48 | 1.11 (0.45–2.77) | 0% | 0.840 |
| Radiotherapy | 3 [26, 29, 33] | 15/57 | 20/98 | 2.03 (0.48–8.66) | 36% | 0.212 |
| Hormone therapy | 2 [26, 29] | 13/51 | 22/73 | 1.43 (0.12–16.47) | 59% | 0.117 |
| Severityb,d,h,i | 6 [25, 27–29, 31, 33] | 72/130 | 699/1522 | 1.47 (0.95–2.27) | 5% | 0.384 |
| Subgroup analysis | ||||||
| Sample size | ||||||
| < 100 patients | 2 [25, 28] | 18/30 | 54/100 | 1.99 (0.50–7.86) | 2% | 0.313 |
| ≥ 100 patients | 4 [27, 29, 31, 33] | 41/83 | 658/1439 | 1.40 (0.82–2.40) | 26% | 0.258 |
| Location | ||||||
| Asia | 1 [33] | 4/6 | 36/99 | 3.50 (0.61–20.06) | NA | NA |
| Europe | 3 [25, 27, 28] | 55/86 | 569/917 | 1.05 (0.61–1.78) | 0% | 0.925 |
| America | 2 [29, 31] | 13/38 | 94/506 | 2.35 (1.14–4.83) | 0% | 0.322 |
| Cancer type | ||||||
| Lung cancerj | 2 [30, 33] | 18/44 | 17/43 | 1.27 (0.51–3.19) | 0% | 0.758 |
| Non-lung solid cancer | 4 [25, 29, 31, 33] | 22/49 | 97/445 | 1.49 (0.72–3.07) | 0% | 0.407 |
| Adjuvant therapy | ||||||
| ICI monotherapy | 4 [25, 29, 31, 33] | 22/44 | 175/633 | 1.25 (0.56–2.79) | 0% | 0.579 |
| ICI + chemotherapy | 3 [29, 31, 33] | 10/15 | 112/605 | 8.72 (3.03–25.11) | 0% | 0.703 |
| Comparator groupf | ||||||
| No treatment | 3 [25, 31, 33] | 31/59 | 68/285 | 2.39 (1.24–4.62) | 0% | 0.490 |
| Chemotherapy | 5 [25, 28, 29, 31, 33] | 35/74 | 60/230 | 1.75 (0.84–3.67) | 0% | 0.592 |
| Targeted therapy | 3 [28, 31, 33] | 19/45 | 19/77 | 2.17 (0.95–4.93) | 0% | 0.499 |
| Surgery | 2 [29, 33] | 5/13 | 7/19 | 0.99 (0.18–5.35) | 0% | 0.788 |
| Radiotherapy | 2 [29, 33] | 6/13 | 4/22 | 5.91 (0.98–35.71) | 0% | 0.836 |
| Hormone therapy | 2 [28, 29] | 5/15 | 5/19 | 1.33 (0.25–6.98) | 0% | 0.421 |
| Hospitalizationb,d,i | 5 [25, 29, 31, 32, 34] | 99/137 | 368/694 | 1.04 (0.49–2.22) | 53% | 0.076 |
| Subgroup analysis | ||||||
| Sample size | ||||||
| < 100 patients | 2 [25, 32] | 35/47 | 47/53 | 0.36 (0.09–1.40) | 21% | 0.261 |
| ≥ 100 patients | 3 [29, 31, 34] | 64/90 | 321/641 | 1.60 (0.92–2.79) | 12% | 0.321 |
| Risk of bias | ||||||
| Low | 2 [29, 34] | 46/61 | 171/259 | 1.15 (0.59–2.25) | 0% | 0.970 |
| Moderate/High | 3 [25, 31, 32] | 53/76 | 197/435 | 0.74 (0.15–3.65) | 76% | 0.016 |
| Cancer type | ||||||
| Lung cancerj | 2 [30, 34] | 69/94 | 172/193 | 1.32 (0.72–2.39) | 0% | 0.570 |
| Non-lung solid cancer | 3 [25, 29, 31] | 28/46 | 167/358 | 1.07 (0.52–2.17) | 0% | 0.559 |
| Adjuvant therapy | ||||||
| ICI monotherapy | 4 [25, 29, 31, 34] | 51/74 | 344/669 | 1.06 (0.59–1.89) | 0% | 0.772 |
| ICI + chemotherapy | 3 [29, 31, 34] | 26/31 | 321/641 | 2.10 (0.37–12.03) | 62% | 0.073 |
| Comparator groupf | ||||||
| No treatment | 3 [25, 31, 34] | 76/105 | 135/269 | 1.25 (0.46–3.40) | 61% | 0.075 |
| Chemotherapy | 4 [25, 29, 31, 34] | 80/112 | 112/223 | 1.49 (0.66–3.33) | 42% | 0.159 |
| Targeted therapy | 3 [29, 31, 34] | 64/90 | 52/124 | 2.54 (1.37–4.72) | 0% | 0.919 |
| Surgery | 1 [29] | 5/7 | 5/11 | 3.00 (0.40–22.71) | NA | NA |
| Radiotherapy | 1 [29] | 5/7 | 4/9 | 3.13 (0.38–25.57) | NA | NA |
| Hormone therapy | 1 [29] | 5/7 | 4/9 | 3.13 (0.38–25.57) | NA | NA |
| ICU admissione | 2 [25, 32] | 6/47 | 13/53 | 0.38 (0.12–1.16) | 0% | 0.967 |
| Prolonged hospitalization (> 8 days)e | 1 [34] | 10/17 | 21/41 | 1.36 (0.43–4.27) | NA | NA |
| Subgroup analysis | ||||||
| Adjuvant therapy | ||||||
| ICI + chemotherapy | 1 [34] | 3/7 | 21/41 | 0.71 (0.14–3.60) | NA | NA |
aOverlapping populations were observed between Pinato et al. [27] with Garassino et al. [34] and Lee et al.[26], of which Pinato et al.[27] was excluded due to smaller cumulative sample size
bSubgroup analysis based on study design was not performed due to paucity of studies (< 2 subsets with ≥ 2 studies)
cThe event rate may be underestimated as Yarza et al.[28] did not provide the number of deaths among patients receiving and not receiving ICI
dOverlapping populations were observed between Luo et al.[30] and Robilotti et al.[31], of which Robilotti[31] et al. was prioritized due to larger sample size
eA priori-determined subgroup and sensitivity analysis was not performed due to paucity of studies
fFor study-specific estimates, see Supplementary Table S5
gAssaad et al. was excluded as both arms had no events[24]
hSubgroup analysis based on risk of bias was not performed due to paucity of studies (< 2 subsets with ≥ 2 studies)
iSubgroup analysis based on study location was not performed due to paucity of studies (< 2 subsets with ≥ 2 studies)
jOverlapping lung cancer patients were observed between Luo et al.[30] and Robilotti et al.[31], of which Luo et al.[30] was prioritized due to larger sample size. CI, confidence interval; ICI, immune checkpoint inhibitor; ICU, intensive care unit; OR, odds ratio