Science - USA (2020-09-04)

Arunachalamet al.,Science 369 , 1210–1220 (2020) 4 September 2020 6of11

Top BTMs enriched in DEGs COVID-19 (n=7)

vs healthy (n=5) for each cluster

A

C

D

FGH

E

B

1

10

100

1000

10000

0204060

Days post symptom onset

Concentration (fg/ml)

Severity

Healthy

Moderate

Severe

ICU

Proportion variance explained

0.0

0.2

0.4

0.6

0.8

1.0

Age

Severity

Time

Gender

resid

Days symptomsSeverityTAP1IFITM1IFIT2S TAT 1IFIT1IFIT3DDX60IFIH1DDX58OASLPMLRSAD2SP100HESX1HERC5USP18EIF2AK2PLSCR1AS1OIRF7SERPING1PARP9MX2IFI27APOBEC3AOAS3SIGLEC1ATF3C1QBBCL2A1IFNGR2MGST1HLX

Days post

symptom onset

20

5

Severity

Moderate

Severe

ICU

−3

−2

−1

0

1

2

3

z-score

antigen processing and presentation (M200)

enriched in antigen presentation (I) (M71)

reg. of antigen presentation and immune response (M5.0)

Monocyte surface signature (S4)

TLR and inflammatory signaling (M16)

immune activ ric cluster (M37.0)

enriched in antigen presentation (II) (M95.0)

enriched in T cells (I) (M7.0)

cell cycle and transcription (M4.0)

antiviral IFN signature (M75)

enriched in activated dendritic cells (II) (M165)

type I interferon response (M127)

innate antiviral response (M150)

0

10

20

Log of

1/P val

% Path

is DEG

0.3

0.6

0.9

A

IFN signaling

Antigen presentation

Cor: 0.85

5

10

15

20

0.0 2.5 5.0 7.5 10.0

Log of Concentration, fg/ml

33 gene ISG Score

new_id

cov 1

cov 2

cov 3

cov 4

cov 5

cov 6

cov 7

hd2

hd3

hd4

hd5

IFN-α ELISA of plasma

CITE-seq vs IFN-α ELISA Bulk RNA-seq of total PBMCs Bulk RNA-seq of total PBMCs

ATF3IFITM1PARP9PLSCR1PMLMX2IFIH1DDX58HLXOAS3SIGLEC1OASLC1QBIFIT1IFIT3RSAD2SP100DDX60IFI27STAT1APOBEC3AMGST1IFNGR2BCL2A1SERPING1IFIT2HERC5EIF2AK2OAS1HESX1USP18IRF7TAP1 celltypegroup

0.51.0

subjectexp peraverage

Exp r. z−score

−2

−1

0

1

2

group

COVID−19

Healt hy

celltype

C10−PDC

C11−C MONO

C16−C MONO

C3−C MONO

C5−CDC2

CITE-seq of COVID-19 (n=7) and healthy (n=5) subjects

CITE-seq of COVID-19 (n=7) and healthy (n=5) subjects

Experiment layout CITE-seq of COVID-19 (n=7) and healthy (n=5) subjects

Mixing ~1:2 and

CITE-seq

Total PBMCs

Frozen

PBMCs

Magnetic enrichment

Subjects of dendritic cells

7 COVID-19 infected

5 healthy control

RESEARCH | RESEARCH ARTICLE