1 Direct observation of repeated infections with endemic 1 coronaviruses 2 3 Marta Galanti, Jeffrey Shaman 4 5 6 Department of Environmental Health Sciences, Mailman School of Public Health, 7 Columbia University, 722 West 168 th Street, New York, NY 10032 8 9 10 11 Corresponding author - contact information 12 Dr. Marta Galanti 13 Post-Doctoral Research Scientist, 14 Department of Environmental Health Sciences 15 Mailman School of Public Health 16 722 West 168 th St. NY, NY 10032 17 Columbia University 18 [email protected]19 20 21 22
32
Embed
Direct observation of repeated infections with endemic … › ~jls106 › galanti_shaman_ms_supp.pdf · 2020-04-16 · 1 1 Direct observation of repeated infections with endemic
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Direct observation of repeated infections with endemic 1
coronaviruses 2
3
Marta Galanti, Jeffrey Shaman 4
5
6
Department of Environmental Health Sciences, Mailman School of Public Health, 7
Columbia University, 722 West 168th Street, New York, NY 10032 8
Figure 3: Total symptom score associated with infections by any coronavirus type. Each point 373
represents an infection event, and each cluster represents a family group. Each family group F1 374
to F9 is composed of a parent and 1 to 4 children. 375
376
377
378
F1 F2 F3 F4 F5 F6 F7 F8 F9FAMILY CLUSTERS
-5
0
5
10
15
20
25
30
35
40
45
SYM
PTO
MS
SCO
RE
OVE
R -3
/+7
DAY
S FR
OM
PO
SITI
VE
23
Supplementary Material 379 380 381 382
Table S1: Table with timepoint Kaplan-Meier data for the probability of at least one infection with OC43, HKU1, 383 229E and NL63. 384 Table S2: Characteristics of repeated infections. 385 Table S3: Table with timepoint Kaplan-Meier data for the probability of re-infection with OC43 and HKU1 386 Text S1: Sensitivity to PCR threshold. 387 Figure S1: Probability of having tested positive within x weeks from enrollment, PCR threshold 50nA 388 Figure S2: Probability of a re-infection with the same beta-coronavirus within x weeks from previous infection, 389 PCR threshold 50nA 390 Figure S3: Probability of having tested positive within x weeks from enrollment, PCR threshold 100nA 391 Figure S4: Probability of a re-infection with the same beta-coronavirus within x weeks from previous infection, 392 PCR threshold 100nA 393 394 395 396 397
24
398 Table S1: Kaplan-Meier data for the probability of at least one infection with each coronavirus OC43, HKU1,229E, 399 NL63, as shown in Figure 1. Columns show: the week from enrollment (WEEK), the number of individuals that 400 after i weeks from enrollment have not tested positive yet for each coronavirus (OC43 -, HKU1 -,229-, NL63-), the 401 number of individuals testing positive during week i (OC43 +, HKU1 +,229+, NL63+) and the number of 402 individuals censored after week i (OC43 -CEN, HKU1 -CEN,229-CEN, NL63-CEN). 403 404
WEEK OC43 - OC43+ OC43- CEN
HKU1 - HKU1 + HKU1-CEN
229- 229+ 229-CEN
NL63- NL63+ NL63-CEN
1 191 2 0 191 0 0 191 3 0 191 0 0
2 189 1 0 191 1 0 188 4 0 191 0 0
3 188 4 0 190 0 0 184 1 0 191 2 0
4 184 1 0 190 0 0 183 1 0 189 0 0
5 183 1 0 190 1 0 182 2 0 189 1 0
6 182 4 0 189 2 0 180 1 0 188 1 0
7 178 6 2 187 0 2 179 1 2 187 0 2
8 170 1 2 185 1 2 176 0 2 185 0 2
9 167 2 6 182 0 6 174 2 6 183 1 6
10 159 2 6 176 0 5 166 1 6 176 0 6
11 151 1 1 171 0 2 159 0 2 170 0 2
12 149 3 4 169 2 4 157 0 3 168 0 4
13 142 2 2 163 2 3 154 0 3 164 1 3
14 138 0 2 158 2 2 151 3 2 160 0 2
15 136 0 1 154 0 3 146 4 2 158 2 3
16 135 0 6 151 1 5 140 0 5 153 2 6
17 129 1 5 145 1 4 135 1 4 145 0 5
18 123 2 4 140 0 3 130 0 4 140 0 4
19 117 1 8 137 0 10 126 3 10 136 0 9
20 108 1 14 127 0 14 113 1 13 127 0 14
21 93 1 2 113 0 4 99 1 3 113 0 4
22 90 1 1 109 2 1 95 0 1 109 0 1
23 88 0 2 106 0 4 94 0 2 108 1 2
24 86 0 11 102 0 10 92 0 11 105 0 11
25 75 1 10 92 1 10 81 0 12 94 0 12
26 64 0 8 81 0 11 69 0 10 82 0 11
27 56 0 2 70 0 2 59 0 2 71 0 2
28 54 0 3 68 1 2 57 0 3 69 0 3
29 51 0 13 65 0 13 54 0 14 66 0 13
30 38 0 0 52 0 0 40 0 0 53 0 0
31 38 0 0 52 0 0 40 0 0 53 0 0
32 38 0 0 52 0 0 40 0 0 53 0 0
25
33 38 0 0 52 0 0 40 0 0 53 0 0
34 38 0 0 52 0 0 40 0 0 53 0 0
35 38 1 0 52 0 0 40 0 0 53 0 0
36 37 0 0 52 0 0 40 0 0 53 0 0
37 37 0 0 52 0 0 40 0 0 53 0 0
38 37 0 0 52 0 1 40 0 1 53 0 1
39 37 0 0 51 0 0 39 0 0 52 0 0
40 37 1 0 51 0 0 39 0 0 52 0 0
41 36 0 0 51 0 0 39 0 0 52 0 0
42 36 0 0 51 0 0 39 0 0 52 0 0
43 36 0 0 51 0 0 39 0 0 52 0 0
44 36 0 0 51 1 0 39 0 0 52 0 0
45 36 0 1 50 0 1 39 0 1 52 0 1
46 35 1 1 49 0 1 38 0 1 51 0 1
47 33 0 0 48 0 2 37 0 1 50 0 2
48 33 0 0 46 0 0 36 0 0 48 0 0
49 33 0 0 46 0 0 36 0 0 48 1 0
50 33 0 1 46 0 1 36 0 0 47 1 1
51 32 0 0 45 0 0 36 0 0 45 0 0
52 32 0 1 45 0 4 36 0 1 45 0 4
53 31 0 0 41 0 0 35 1 0 41 0 0
54 31 1 0 41 1 1 34 0 0 41 0 1
55 30 0 0 39 0 0 34 0 0 40 0 0
56 30 2 0 39 1 0 34 1 0 40 0 0
57 28 0 0 38 0 0 33 0 0 40 0 0
58 28 0 1 38 2 2 33 0 3 40 0 2
59 27 1 0 34 0 0 30 0 0 38 0 0
60 26 1 1 34 2 1 30 0 1 38 0 1
61 24 0 4 31 2 4 29 0 2 37 0 4
62 20 0 2 25 1 4 27 0 3 33 0 4
63 18 0 0 20 1 1 24 0 1 29 2 0
64 18 0 0 18 0 0 23 0 0 27 0 0
65 18 0 0 18 0 0 23 0 0 27 0 0
66 18 1 1 18 0 1 23 0 1 27 0 1
67 16 0 0 17 0 1 22 0 0 26 0 1
68 16 0 0 16 0 1 22 0 1 25 0 1
69 16 0 0 15 0 0 21 0 0 24 0 0
70 16 1 2 15 0 1 21 0 4 24 0 5
71 13 0 1 14 0 1 17 0 4 19 0 3
26
72 12 0 6 13 0 4 13 0 6 16 0 8
73 6 0 1 9 0 1 7 0 1 8 0 1
74 5 0 1 8 0 1 6 0 1 7 0 1
75 4 0 1 7 0 1 5 0 1 6 0 1
76 3 0 0 6 0 0 4 0 0 5 0 0
77 3 0 1 6 0 2 4 0 3 5 0 1
78 2 0 0 4 0 1 1 0 1 4 0 1
79 2 0 0 3 0 0 0 0 0 3 0 0
80 2 0 2 3 0 3 0 0 0 3 0 3
81 0 0 0 0 0 0 0 0 0 0 0 0
405
27
Table S2: Characteristics of repeat infections. Participants are identified by the numbers 1 to 12. Each row describes 406 an infection episode, for episodes lasting multiple weeks we report the first and last positive sample. For each 407 episode, the score is measured as a sum of daily scores across the window -3/+7 days around first positive result. 408 Age is measured at enrollment. Asterisks identify coinfections with other respiratory viruses. 409 410
Table S3: Kaplan-Meier data for the probability of re-infection with coronaviruses OC43 and HKU1, as shown in 413 Figure 2. Columns show: the weeks from a previous infection (WEEK), the number of participants that after i weeks 414 from previous infection with OC43 (OC43+) and HKU1 (HKU1+) have not yet being re-infected; the number of 415 participants that after i weeks from previous infection test positive for the same virus (RE-OC43, RE-HKU1) and 416 the number of participants censored after i weeks from previous infection (OC43 -CENSORED, HKU1 -417 CENSORED). Participants testing positive n times during the study are counted n times in this analysis. 418 419 420
WEEK OC43+ RE-OC43 OC43-CENSORED
HKU1+ RE-HKU1 HKU1- CENSORED
1 60 0 2 30 0 2
2 58 0 1 28 0 0
3 57 0 0 28 0 1
4 57 0 2 27 0 1
5 55 2 4 26 0 2
6 49 0 1 24 0 0
7 48 1 5 24 1 0
8 42 0 3 23 0 0
9 39 0 0 23 0 0
10 39 0 1 23 0 0
11 38 1 1 23 0 3
12 36 0 1 20 0 3
13 35 0 0 17 0 1
14 35 0 0 16 0 3
15 35 0 1 13 0 2
16 34 0 2 11 0 1
17 32 0 3 10 0 1
18 29 0 3 9 0 1
19 26 0 2 8 0 1
20 24 0 1 7 0 1
21 23 0 1 6 0 1
22 22 0 0 5 0 0
23 22 0 1 5 0 0
24 21 0 1 5 0 0
25 20 0 0 5 0 0
26 20 0 0 5 0 0
27 20 0 0 5 0 0
28 20 0 0 5 0 0
29 20 0 1 5 0 0
30 19 0 0 5 0 0
31 19 0 0 5 0 0
32 19 0 0 5 0 0
29
33 19 0 0 5 0 0
34 19 1 0 5 0 0
35 18 0 0 5 0 0
36 18 0 1 5 0 0
37 17 0 0 5 0 0
38 17 1 1 5 0 0
39 15 1 0 5 1 0
40 14 0 0 4 0 0
41 14 0 0 4 0 0
42 14 0 0 4 0 0
43 14 1 0 4 0 0
44 13 1 0 4 0 1
45 12 0 1 3 0 0
46 11 0 1 3 0 0
47 10 1 0 3 0 0
48 9 1 0 3 0 0
49 8 1 0 3 0 0
50 7 0 0 3 0 0
51 7 0 0 3 0 0
52 7 0 0 3 0 0
53 7 0 0 3 0 0
54 7 0 2 3 0 0
55 5 0 1 3 0 0
56 4 0 0 3 0 1
57 4 0 0 2 0 0
58 4 0 0 2 0 1
59 4 0 0 1 0 1
60 4 0 0 0 0 0
61 4 0 0 0 0 0
62 4 0 0 0 0 0
63 4 0 0 0 0 0
64 4 0 0 0 0 0
65 4 0 1 0 0 0
66 3 0 0 0 0 0
67 3 0 1 0 0 0
68 2 0 0 0 0 0
69 2 0 2 0 0 0
70 0 0 0 0 0 0
421
30
422 Supplementary Text S1: Sensitivity to PCR threshold. 423
424 In the main text samples positiveforaparticularviruswereidentifiedbyanelectricalsignalintensityof425 ≥2nA/mm2(withtheexceptionofCoronavirusOC43forwhichpositiveresultswereidentifiedbyan426 intensityof≥25nA/mm2,permanufacturerspecifications).Here we test the sensitivity of our finding to 427 different choices of the threshold for PCR positivity for all viruses (25nA/mm2and100nA/mm2). 428 429 Positivity threshold 50nA/mm2 for all infections 430 431 Among all participants enrolled and using a 50nA/mm2threshold, 73 individuals tested positive at least once 432 during the study for any coronavirus infection. 44 individuals tested positive at least once for OC43, 28 tested 433 positive for 229E, 8 tested positive for NL63, and 24 tested positive for HKU1. In addition, 10 individuals tested 434 positive multiple times during the study for the same coronavirus: 8 tested positive twice for OC43, 2 tested positive 435 twice for HKU1 and nobody tested positive multiple times for 229E and NL63. Among the 8 participants that 436 experienced multiple OC43 infections, 1 individual tested positive 3 separate times, and 7 tested positive twice. The 437 median time between reinfection events was 43 weeks. The shortest time for a reoccurrence of infection was 4 438 weeks (OC43), the longest was 48 weeks (OC43). 439 Figure S1and Figure S2 show, respectively, the probability of testing positive within x weeks after enrollment and 440 the probability of a re-infection with the same beta-coronavirus within x week of a previous documented infection. 441 442 443 Positivity threshold 100nA for all infections 444
445 Among all participants enrolled and using a 100nA/mm2threshold, 67 individuals tested positives at least once 446 during the study for any coronavirus infection. 40 individuals tested positive at least once for OC43, 21 tested 447 positive for 229E, 6 tested positive for NL63, and 23 tested positive for UKU1. In addition, 8 individuals tested 448 positive multiple times during the study for the same coronavirus: 7 tested positive twice for OC43, 1 tested positive 449 twice for HKU1 and nobody tested positive multiple times for 229E and NL63. The median time between 450 reinfection events was 44.5 weeks. The shortest time for a second infection was 37 weeks (OC43), the longest was 451 48 weeks (OC43). Figure S3 and Figure S4 show, respectively, the probability of testing positive within x weeks 452 after enrollment and the probability of a re-infection with the same beta-coronavirus within x week of a previous 453 documented infection. 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473
31
Figure S1: Kaplan- Meier plots for the probability of testing positive within x weeks after enrollment for each of the 474 4 types of seasonal coronaviruses. The shaded area is the 95% CI. PCR positivity threshold is 50nA/mm2. 475 476
477 478 Figure S2: Probability of re-infection with the same beta-coronavirus type (OC43 in red and HKU1 in black) within 479 x weeks after a first documented infection. Dashed lines show the 95% CI. PCR positivity threshold is 50nA/mm2. 480
Figure S3: Kaplan- Meier plots for the probability of testing positive within x weeks after enrollment for each of the 485 4 types of seasonal coronaviruses. The shaded area is the 95% CI. PCR positivity threshold is 100nA/mm2. 486
487 488 Figure S4: Probability of re-infection with the same beta-coronavirus type (OC43 in red and HKU1 in black) within 489 x weeks after a first documented infection. Dashed lines show the 95% CI. PCR positivity threshold is 100nA/mm2. 490