Table 4.
Accuracy of COVID-19 serology tests stratified by potential sources of heterogeneity.
| Subgroup | IgM | IgG | IgM or IgG | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of arms (studies) | TP | FN | Pooled sensitivity (95% CI) | No. of arms | TP | FN | Pooled sensitivity (95% CI) | No. of arms | TP | FN | Pooled sensitivity (95% CI) | |
| Time post-onset | ||||||||||||
| ELISA | ||||||||||||
| First week | 3 | 80 | 86 | 48.0 (40.0–56.0) | 7 | 704 | 131 | 84.0 (82.0–87.0) | 4 | 445 | 77 | 85.0 (82.0–88.0) |
| Second week | 4 | 212 | 107 | 66.0 (61.0–72.0) | 8 | 491 | 147 | 77.0 (73.0–80.0) | 5 | 482 | 78 | 86.0 (83.0–89.0) |
| Third week | 6 | 925 | 184 | 83.0 (81.0–86.0) | 20 | 2,502 | 245 | 91.0 (90.0–92.0) | 2 | 123 | 2 | 98.0 (94.0–100.0) |
| Third week later | 1 | 62 | 5 | 93.0 (83.0–98.0) | 6 | 844 | 171 | 83.0 (81.0–85.0) | 2 | 194 | 21 | 90.0 (85.0–94.0) |
| CLIA | ||||||||||||
| First week | 6 | 666 | 405 | 62.0 (59.0–65.0) | 11 | 1,086 | 729 | 60.0 (58.0–62.0) | 2 | 334 | 298 | 53.0 (49.0–57.0) |
| Second week | 5 | 462 | 433 | 52.0 (48.0–55.0) | 9 | 772 | 452 | 63.0 (60.0–66.0) | 4 | 654 | 258 | 72.0 (69.0–75.0) |
| Third week | 6 | 686 | 2,249 | 23.0 (22.0–25.0) | 13 | 1,790 | 3,727 | 32.0 (31.0–34.0) | 6 | 1,152 | 759 | 60.0 (58.0–62.0) |
| Third week later | 5 | 495 | 238 | 68.0 (64.0–71.0) | 6 | 1,159 | 255 | 82.0 (80.0–84.0) | 2 | 467 | 58 | 89.0 (86.0–92.0) |
| LFIA | ||||||||||||
| First week | 5 | 109 | 300 | 27.0 (22.0–31.0) | 5 | 119 | 291 | 29.0 (25.0–34.0) | 16 | 1,725 | 1,080 | 61.0 (60.0–63.0) |
| Second week | 3 | 169 | 2,723 | 6.0 (5.0–7.0) | 3 | 204 | 2,711 | 7.0 (6.0–8.0) | 6 | 501 | 3,027 | 14.0 (13.0–15.0) |
| Third week | 12 | 547 | 474 | 54.0 (50.0–57.0) | 12 | 672 | 698 | 49.0 (46.0–52.0) | 9 | 1,192 | 1,329 | 47.0 (45.0–49.0) |
| Third week later | 3 | 68 | 85 | 44.0 (36.0–53.0) | 3 | 129 | 24 | 84.0 (78.0–90.0) | 7 | 646 | 624 | 51.0 (48.0–54.0) |
| Antigen target | ||||||||||||
| ELISA | ||||||||||||
| Surface protein | 6 | 449 | 280 | 62.0 (58.0–65.0) | 24 | 2,513 | 592 | 81.0 (80.0–82.0) | 8 | 835 | 148 | 85.0 (83.0–87.0) |
| Nucleocapsid protein | 7 | 537 | 96 | 85.0 (82.0–88.0) | 21 | 1,513 | 292 | 84.0 (82.0–85.0) | 2 | 284 | 8 | 97.0 (95.0–99.0) |
| Surface and nucleocapsid proteins | 5 | 480 | 336 | 59.0 (55.0–62.0) | 13 | 2,490 | 782 | 76.0 (75.0–78.0) | 6 | 629 | 94 | 87.0 (84.0–89.0) |
| CLIA | ||||||||||||
| Surface protein | 3 | 254 | 371 | 41.0 (37.0–45.0) | 8 | 956 | 390 | 71.0 (69.0–73.0) | 3 | 487 | 181 | 73.0 (69.0–76.0) |
| Nucleocapsid protein | 0 | 5 | 464 | 144 | 76.0 (73.0–80.0) | 3 | 421 | 29 | 94.0 (91.0–96.0) | |||
| Surface and nucleocapsid proteins | 4 | 770 | 324 | 70.0 (68.0–73.0) | 9 | 1,668 | 793 | 68.0 (66.0–70.0) | 5 | 879 | 638 | 58.0 (55.0–60.0) |
| LFIA | ||||||||||||
| Surface protein | NA | |||||||||||
| Nucleocapsid protein | 1 | 101 | 26 | 80.0 (71.0–86.0) | 3 | 206 | 325 | 39.0 (35.0–43.0) | 1 | 80 | 63 | 56.0 (47.0–64.0) |
| Surface and nucleocapsid proteins | 4 | 211 | 148 | 59.0 (53.0–64.0) | 4 | 218 | 141 | 61.0 (55.0–66.0) | 3 | 231 | 77 | 75.0 (70.0–80.0) |
| Clinical setting | ||||||||||||
| ELISA | ||||||||||||
| Inpatient only | 11 | 792 | 282 | 74.0 (71.0–76.0) | 15 | 1,730 | 355 | 83.0 (81.0–85.0) | 6 | 905 | 165 | 85.0 (82.0–87.0) |
| Outpatient | 0 | 7 | 584 | 61 | 91.0 (88.0–93.0) | 0 | ||||||
| Inpatient and outpatient | 6 | 560 | 104 | 84.0 (81.0–87.0) | 14 | 1,769 | 148 | 92.0 (91.0–93.0) | 6 | 1,266 | 139 | 90.0 (88.0–92.0) |
| No reported | 10 | 1,083 | 463 | 70.0 (68.0–72.0) | 39 | 5,073 | 1,153 | 81.0 (80.0–82.0) | 11 | 1,227 | 288 | 81.0 (79.0–83.0) |
| CLIA | ||||||||||||
| Inpatient only | 10 | 1,282 | 519 | 71.2 (69.0,73.3) | 15 | 2,006 | 548 | 78.5 (76.8,80.1) | 7 | 1,757 | 472 | 78.8 (77.1,80.5) |
| Outpatient | 0 | 1 | 123 | 29 | 0 | |||||||
| Inpatient and outpatient | 4 | 712 | 219 | 76.3 (73.4,79.0) | 14 | 2,199 | 625 | 74.0 (72.0,75.9) | 8 | 2,332 | 471 | 83.2 (81.8,84.6) |
| No reported | 8 | 841 | 919 | 33.6 (31.0,36.3) | 19 | 2,269 | 2,120 | 44.2 (42.6,45.8) | 8 | 697 | 842 | 45.0 (43.0,48.0) |
| LFIA | ||||||||||||
| Inpatient only | 4 | 216 | 216 | 50.0 (45.0–55.0) | 3 | 201 | 179 | 53.0 (48.0–58.0) | 6 | 1,554 | 1,170 | 57.0 (55.0–59.0) |
| Outpatient | 4 | 654 | 4,636 | 12.0 (11.0–13.0) | ||||||||
| Inpatient and outpatient | 5 | 212 | 107 | 66.0 (61.0–72.0) | 8 | 579 | 613 | 49.0 (46.0–51.0) | 7 | 785 | 797 | 50.0 (47.0–52.0) |
| No reported | 21 | 2,031 | 5,411 | 27.0 (26.0–28.0) | 20 | 1,946 | 5,187 | 27.0 (26.0–28.0) | 17 | 1,472 | 4,952 | 23.0 (22.0–24.0) |
| Serological kit as index test (whether testing was by commercial kit or an in-house assay) | ||||||||||||
| ELISA | ||||||||||||
| Commercial serological kit | 23 | 2,022 | 703 | 74.0 (73.0–76.0) | 66 | 8,167 | 1,731 | 83.0 (82.0–83.0) | 21 | 2,632 | 617 | 81.0 (80.0–82.0) |
| In-house assay | 6 | 640 | 238 | 73.0 (70.0–76.0) | 13 | 1,220 | 102 | 92.0 (91.0–94.0) | 5 | 965 | 125 | 89.0 (86.0–90.0) |
| Unclear | 0 | 0 | 0 | |||||||||
| CLIA | ||||||||||||
| Commercial serological kit | 20 | 1,697 | 3,510 | 33.0 (31.0–34.0) | 43 | 4,790 | 5,427 | 47.0 (46.0–48.0) | 18 | 3,153 | 1,565 | 67.0 (65.0–68.0) |
| In-house assay | 2 | 1,069 | 212 | 83.0 (81.0–85.0) | 4 | 1,493 | 151 | 91.0 (89.0–92.0) | 2 | 949 | 131 | 88.0 (86.0–90.0) |
| Unclear | 0 | 2 | 116 | 68 | 63.0 (56.0–70.0) | 0 | ||||||
| LFIA | ||||||||||||
| Commercial serological kit | 28 | 2,397 | 5,148 | 32.0 (31.0–33.0) | 25 | 2,489 | 5,100 | 33.0 (32.0–34.0) | 30 | 4,263 | 11,073 | 28.0 (27.0–29.0) |
| In-house assay | 2 | 696 | 963 | 42.0 (40.0–44.0) | ||||||||
| Unclear | 4 | 199 | 700 | 22.0 (19.0–25.0) | 4 | 186 | 830 | 18.0 (16.0–21.0) | 4 | 202 | 414 | 33.0 (29.0–37.0) |
| Type of specimen for RT–PCR reference test | ||||||||||||
| ELISA | ||||||||||||
| Nasopharyngeal | 11 | 575 | 296 | 66.0 (63.0–69.0) | 27 | 3,796 | 934 | 80.0 (79.0–81.0) | 10 | 1,322 | 418 | 76.0 (74.0–78.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 7 | 484 | 132 | 79.0 (75.0–82.0) | 17 | 1,426 | 291 | 83.0 (81.0–85.0) | 6 | 837 | 273 | 75.0 (73.0–78.0) |
| Not reported | 11 | 1,435 | 458 | 76.0 (74.0–79.0) | 38 | 4,566 | 682 | 87.0 (86.0–88.0) | 12 | 1,958 | 129 | 94.0 (93.0–95.0) |
| CLIA | ||||||||||||
| Nasopharyngeal | 7 | 578 | 2,328 | 20.0 (18.0–21.0) | 16 | 1,364 | 2,791 | 33.0 (31.0–34.0) | 6 | 1,075 | 397 | 73.0 (71.0–75.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 6 | 656 | 246 | 73.0 (70.0–76.0) | 8 | 788 | 283 | 74.0 (71.0–76.0) | 6 | 1,253 | 181 | 87.0 (86.0–89.0) |
| Not reported | 13 | 1,688 | 1,325 | 56.0 (54.0–58.0) | 30 | 4,872 | 3,711 | 57.0 (56.0–58.0) | 11 | 2,436 | 1,218 | 67.0 (65.0–68.0) |
| LFIA | ||||||||||||
| Nasopharyngeal | 8 | 992 | 1,366 | 42.0 (40.0–44.0) | 8 | 1,004 | 1,272 | 44.0 (42.0–46.0) | 13 | 2,180 | 6,808 | 24.0 (23.0–25.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 9 | 1,020 | 1,301 | 44.0 (42.0–46.0) | 9 | 1,124 | 1,305 | 46.0 (44.0–48.0) | 8 | 719 | 5,477 | 12.0 (11.0–12.0) |
| Not reported | 17 | 1,339 | 4,106 | 25.0 (23.0–26.0) | 16 | 1,331 | 4,436 | 23.0 (22.0–24.0) | 18 | 1,880 | 4,612 | 29.0 (28.0–30.0) |
| Subgroup | IgM | IgG | IgM or IgG | |||||||||
| No. of arms (studies) | TN | FP | Pooled specificity (95% CI) | No. of arms | TN | FP | Pooled specificity (95% CI) | No. of arms | TN | FP | Pooled specificity (95% CI) | |
| Time post-onset | ||||||||||||
| ELISA | ||||||||||||
| First week | 3 | 440 | 34 | 93.0 (90.0–95.0) | 7 | 27,47 | 129 | 96.0 (95.0–96.0) | 4 | 726 | 64 | 92.0 (90.0–94.0) |
| Second week | 4 | 432 | 13 | 97.0 (95.0–98.0) | 8 | 1,064 | 35 | 97.0 (96.0–98.0) | 5 | 9,861 | 14 | 100.0 (100.0–100.0) |
| Third week | 6 | 3,535 | 18 | 99.0 (99.0–100.0) | 20 | 8,177 | 597 | 93.0 (93.0–94.0) | 2 | 306 | 0 | 100.0 (99.0–100.0) |
| Third week later (22–28 day) | 1 | 109 | 3 | 97.0 (92.0–99.0) | 6 | 2,749 | 81 | 97.0 (96.0–98.0) | 2 | 224 | 3 | 99.0 (96.0–100.0) |
| CLIA | ||||||||||||
| First week | 6 | 1,392 | 38 | 97.0 (96.0–98.0) | 11 | 9,424 | 159 | 98.0 (98.0–99.0) | 2 | 238 | 22 | 92.0 (87.0–95.0) |
| Second week | 5 | 982 | 29 | 97.0 (96.0–98.0) | 9 | 1,376 | 50 | 96.0 (95.0–97.0) | 4 | 427 | 102 | 81.0 (77.0–84.0) |
| Third week | 6 | 1,084 | 290 | 79.0 (77.0–81.0) | 13 | 1,838 | 84 | 96.0 (95.0–96.0) | 6 | 939 | 15 | 98.0 (97.0–99.0) |
| Third week later (22–28 day) | 5 | 910 | 20 | 98.0 (97.0–99.0) | 6 | 1,826 | 30 | 98.0 (98.0–99.0) | 2 | 508 | 15 | 97.0 (95.0–98.0) |
| LFIA | ||||||||||||
| First week | 5 | 58 | 42 | 58.0 (48.0–68.0) | 5 | 88 | 9 | 91.0 (83.0–96.0) | 16 | 994 | 52 | 95.0 (94.0–96.0) |
| Second week | 3 | 72 | 12 | 86.0 (76.0–92.0) | 3 | 31 | 24 | 56.0 (42.0–70.0) | 6 | 164 | 30 | 85.0 (79.0–89.0) |
| Third week | 12 | 341 | 58 | 85.0 (82.0–89.0) | 12 | 347 | 135 | 72.0 (68.0–76.0) | 9 | 175 | 52 | 77.0 (71.0–82.0) |
| Third week later (22–28 day) | 2 | 273 | 2 | 99.0 (97.0–100.0) | 2 | 274 | 1 | 100.0 (98.0–100.0) | 7 | 512 | 20 | 96.0 (94.0–98.0) |
| Antigen target | ||||||||||||
| ELISA | ||||||||||||
| Surface protein | 6 | 2,396 | 4 | 100.0 (100.0–100.0) | 24 | 7,008 | 143 | 98.0 (98.0–98.0) | 8 | 1,737 | 17 | 99.0 (98.0–99.0) |
| Nucleocapsid protein | 7 | 1,075 | 32 | 97.0 (96.0–98.0) | 21 | 4,889 | 125 | 98.0 (97.0–98.0) | 2 | 9,651 | 14 | 100.0 (100.0–100.0) |
| Surface and nucleocapsid proteins | 5 | 1,365 | 32 | 98.0 (97.0–98.0) | 13 | 4,806 | 251 | 95.0 (94.0–96.0) | 6 | 764 | 10 | 99.0 (98.0–99.0) |
| CLIA | ||||||||||||
| Surface protein | 3 | 508 | 6 | 99.0 (97.0–100.0) | 8 | 1,056 | 87 | 92.0 (91.0–94.0) | 3 | 1,516 | 3 | 100.0 (99.0–100.0) |
| Nucleocapsid protein | 0 | 5 | 1,319 | 14 | 99.0 (98.0–99.0) | 3 | 1,557 | 2 | 100.0 (100.0–100.0) | |||
| Surface and nucleocapsid proteins | 4 | 774 | 27 | 97.0 (95.0–98.0) | 9 | 6,268 | 144 | 98.0 (97.0–98.0) | 2 | 380 | 34 | 92.0 (89.0–94.0) |
| LFIA | ||||||||||||
| Surface protein | NA | |||||||||||
| Nucleocapsid protein | 1 | 37 | 3 | 93.0 (80.0–98.0) | 3 | 52 | 20 | 72.0 (60.0–82.0) | 1 | 75 | 4 | 95.0 (88.0–99.0) |
| Surface and nucleocapsid proteins | 4 | 415 | 20 | 95.0 (93.0–97.0) | 4 | 425 | 100 | 81.0 (77.0–84.0) | 3 | 286 | 25 | 92.0 (88.0–95.0) |
| Clinical setting | ||||||||||||
| ELISA | ||||||||||||
| Inpatient only | 11 | 2,057 | 70 | 97.0 (96.0–97.0) | 15 | 3,964 | 627 | 86.0 (85.0–87.0) | 6 | 1,275 | 3 | 100.0 (99.0–100.0) |
| Outpatient | 0 | 7 | 5,641 | 75 | 99.0 (98.0–99.0) | 0 | ||||||
| Inpatient and outpatient | 6 | 2,083 | 17 | 99.0 (99.0–100.0) | 14 | 5,397 | 234 | 96.0 (95.0–96.0) | 6 | 1,470 | 63 | 96.0 (95.0–97.0) |
| No reported | 10 | 3,517 | 44 | 99.0 (98.0–99.0) | 39 | 11,119 | 266 | 98.0 (97.0–98.0) | 11 | 12,251 | 88 | 99.0 (99.0–99.0) |
| CLIA | ||||||||||||
| Inpatient only | 10 | 1,798 | 35 | 98.0 (97.0–99.0) | 15 | 3,435 | 68 | 98.0 (98.0–98.0) | 7 | 2,251 | 67 | 97.0 (96.0–98.0) |
| Outpatient | 0 | 1 | 149 | 1 | 99.0 (96.0–100.0) | 0 | ||||||
| Inpatient and outpatient | 4 | 949 | 19 | 98.0 (97.0–99.0) | 14 | 8,680 | 170 | 98.0 (98.0–98.0) | 8 | 3,065 | 30 | 99.0 (99.0–99.0) |
| No reported | 8 | 967 | 39 | 96.0 (95.0–97.0) | 19 | 4,679 | 172 | 96.0 (96.0–97.0) | 8 | 218 | 108 | 67.0 (61.0–72.0) |
| LFIA | ||||||||||||
| Inpatient only | 4 | 75 | 47 | 61.0 (52.0–70.0) | 3 | 43 | 14 | 75.0 (62.0–86.0) | 6 | 623 | 53 | 92.0 (90.0–94.0) |
| Outpatient | 4 | 247 | 178 | 58.0 (53.0–63.0) | ||||||||
| Inpatient and outpatient | 5 | 413 | 14 | 97.0 (95.0–98.0) | 8 | 455 | 13 | 97.0 (95.0–99.0) | 7 | 552 | 6 | 99.0 (98.0–100.0) |
| No reported | 21 | 1,372 | 194 | 88.0 (86.0–89.0) | 20 | 1,137 | 198 | 85.0 (83.0–87.0) | 17 | 1,147 | 78 | 94.0 (92.0–95.0) |
| Serological kit as index test (whether testing was by commercial kit or an in-house assay) | ||||||||||||
| ELISA | ||||||||||||
| Commercial serological kit | 23 | 6,288 | 127 | 98.0 (98.0–98.0) | 66 | 23,800 | 1,176 | 95.0 (95.0–96.0) | 21 | 12,676 | 144 | 99.0 (99.0–99.0) |
| In-house assay | 6 | 1,510 | 20 | 99.0 (98.0–99.0) | 13 | 2,360 | 51 | 98.0 (97.0–98.0) | 5 | 1,566 | 10 | 99.0 (99.0–100.0) |
| Unclear | 0 | 0 | 0 | |||||||||
| CLIA | ||||||||||||
| Commercial serological kit | 20 | 2,370 | 359 | 87.0 (86.0–88.0) | 43 | 12,762 | 393 | 97.0 (97.0–97.0) | 18 | 4,452 | 174 | 96.0 (96.0–97.0) |
| In-house assay | 2 | 1,285 | 6 | 100.0 (99.0–100.0) | 4 | 2,705 | 39 | 99.0 (98.0–99.0) | 2 | 751 | 15 | 98.0 (97.0–99.0) |
| Unclear | 0 | 2 | 248 | 2 | 99.0 (97.0–100.0) | 0 | ||||||
| LFIA | ||||||||||||
| Commercial serological kit | 28 | 1,841 | 200 | 90.0 (89.0–91.0) | 25 | 1,567 | 194 | 89.0 (87.0–90.0) | 30 | 2,529 | 309 | 89.0 (88.0–90.0) |
| In-house assay | 2 | 478 | 23 | 95.0 (93.0–97.0) | ||||||||
| Unclear | 4 | 27 | 61 | 31.0 (21.0–41.0) | 4 | 47 | 31 | 60.0 (49.0–71.0) | 4 | 40 | 6 | 87.0 (74.0–95.0) |
| Type of specimen for RT–PCR reference test | ||||||||||||
| ELISA | ||||||||||||
| Nasopharyngeal | 11 | 1,073 | 37 | 97.0 (95.0–98.0) | 27 | 10,648 | 346 | 97.0 (97.0–97.0) | 10 | 1,412 | 97 | 94.0 (92.0–95.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 7 | 875 | 26 | 97.0 (96.0–98.0) | 17 | 7467 | 616 | 92.0 (92.0–93.0) | 6 | 510 | 60 | 89.0 (87.0–92.0) |
| Not reported | 11 | 5,866 | 71 | 99.0 (98.0–99.0) | 38 | 13,488 | 339 | 98.0 (97.0–98.0) | 12 | 13,642 | 57 | 100.0 (99.0–100.0) |
| CLIA | ||||||||||||
| Nasopharyngeal | 7 | 830 | 294 | 74.0 (71.0–76.0) | 16 | 5,900 | 122 | 98.0 (98.0–98.0) | 6 | 699 | 28 | 96.0 (94.0–97.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 6 | 1,135 | 22 | 98.0 (97.0–99.0) | 8 | 2,671 | 23 | 99.0 (99.0–99.0) | 6 | 2,042 | 124 | 94.0 (93.0–95.0) |
| Not reported | 13 | 1,954 | 55 | 97.0 (96.0–98.0) | 30 | 10,332 | 322 | 97.0 (97.0–97.0) | 11 | 2,779 | 47 | 98.0 (98.0–99.0) |
| LFIA | ||||||||||||
| Nasopharyngeal | 8 | 785 | 79 | 91.0 (89.0–93.0) | 8 | 743 | 39 | 95.0 (93.0–96.0) | 13 | 1,514 | 215 | 88.0 (86.0–89.0) |
| Sputum, saliva, or oral, throat, or pharyngeal | 9 | 885 | 103 | 90.0 (87.0–91.0) | 9 | 844 | 49 | 95.0 (93.0–96.0) | 8 | 950 | 196 | 83.0 (81.0–85.0) |
| Not reported | 17 | 645 | 130 | 83.0 (80.0–86.0) | 16 | 513 | 160 | 76.0 (73.0–79.0) | 18 | 643 | 65 | 91.0 (88.0–93.0) |