The n e w e ng l a n d j o u r na l of m e dic i n e

C or r e sp ondence

Multiorgan and Renal Tropism of SARS-CoV-2

To the Editor: Severe acute respiratory syn- mains poorly defined. Here, we present data from
drome coronavirus 2 (SARS-CoV-2) preferentially an autopsy series of 27 patients (see the clinical
infects cells in the respiratory tract,1,2 but its di- data in Table S1 in the Supplementary Appendix,
rect affinity for organs other than the lungs re- available with the full text of this letter at NEJM

A B
103 103
o.

RNA Copies per Cell

Log10 SARS-CoV-2
N

<Cutoff
ea x

ve s

101 101
nt

H ryn

Li ney
Ph gs

d
Ki rt

Bl in
tie

Br r

value
oo
n
a

a
d
Lu
Pa

1 (Male; 52 yr) 10–1 10–1

2 (Male; 70 yr) 10–3 10–3
3 (Male; 71 yr)
10–5 10–5
4 (Male; 63 yr)
5 (Male; 66 yr)

H r
rt

n
d
Ph gs

ve
ey
yn

oo
ai
ea
n

Li

Br
dn
6 (Female; 54 yr)

ar
Lu

Bl
Ki
7 (Female; 75 yr)
8 (Male; 82 yr) C
9 (Female; 87 yr) NA
10 (Male; 84 yr)
11 (Male; 85 yr)
12 (Male; 76 yr) NA
13 (Male; 90 yr) NA
14 (Male; 90 yr)
15 (Female; 75 yr)
16 (Female; 77 yr)
17 (Male; 86 yr) Lung, PCR (+) Kidney, PCR (+)
18 (Male; 93 yr) In Situ Hybridization
19 (Male; 77 yr)
DNA SARS-CoV-2 DNA SARS-CoV-2
20 (Male; 58 yr) NA DNA Nephrin Nephrin
21 (Female; 85 yr) NA NA
Tubule
22 (Male; 75 yr)

SARS-CoV-2 RNA No. of Glomerulus

Copies per Cell Coexisting DNA SARS-CoV-2 Glomerulus
Conditions Nephrin
1 600 Lung, PCR (+) Kidney, PCR (+)
1 5 Immunofluorescence

Figure 1. Multiorgan SARS-CoV-2 Tropism and Spatially Resolved Affinity for Kidney Cells.
Panel A shows detection of SARS-CoV-2 in the organs in association with the number of coexisting conditions in each patient. The red ar-
row highlights the viral load in the kidneys (one of the most common targets of SARS-CoV-2). Viremia as such did not correlate with the de-
tected multiorgan tropism. NA denotes not available. Panel B shows the SARS-CoV-2 viral load in key organs, with a broad organotropism
of the virus. The red arrow highlights the viral load in the kidneys, and the red rectangles indicate the median values in all organs. Each gray
dot represents data from one patient. Panel C shows renal tropism detected with the use of in situ hybridization (spatially resolved viral
RNA detection) and indirect immunofluorescence (spatially resolved viral protein detection) with confocal microscopy. In situ hybridization
showed SARS-CoV-2 RNA detected in the lung and renal parenchyma (boxed areas show examples in each organ). Immunofluorescence of
the lung specimen showed cells with SARS-CoV-2 protein (boxed areas), and immunofluorescence of the kidney specimen showed SARS-CoV-2
protein in areas of the glomerular epithelial (orange arrow), endothelial (white arrows), and tubular (white outline) cells. Scale bars represent
50 μm in the in situ hybridization images and 10 μm in the immunofluorescence images. PCR denotes polymerase chain reaction.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

.org) that show that SARS-CoV-2 can be detected beyond the respiratory tract, including the kid-
in multiple organs, including the lungs, pharynx, neys, liver, heart, and brain, and we speculate that
heart, liver, brain, and kidneys. organotropism influences the course of Covid-19
We first quantified the SARS-CoV-2 viral load disease and, possibly, aggravates preexisting con-
in autopsy tissue samples obtained from 22 pa- ditions.
tients who had died from Covid-19. Seventeen
patients (77%) had more than two coexisting Victor G. Puelles, M.D., Ph.D.
conditions (Fig. 1A), and a greater number of Marc Lütgehetmann, M.D.
coexisting conditions was associated with SARS- Maja T. Lindenmeyer, Ph.D.
CoV-2 tropism for the kidneys (Table S2), even in Jan P. Sperhake, M.D.
patients without a history of chronic kidney Milagros N. Wong, M.D.
disease (Table S3). The highest levels of SARS- Lena Allweiss, Ph.D.
CoV-2 copies per cell were detected in the respi- Silvia Chilla
ratory tract, and lower levels were detected the Axel Heinemann, M.D.
kidneys, liver, heart, brain, and blood (Fig. 1B). Nicola Wanner, Ph.D.
These findings indicate a broad organotropism Shuya Liu, Ph.D.
of SARS-CoV-2. Fabian Braun, M.D.
Since the kidneys are among the most com- Shun Lu, Ph.D.
mon targets of SARS-CoV-2, we performed in Susanne Pfefferle, M.D.
silico analysis of publicly available data sets of Ann S. Schröder, M.D.
single-cell RNA sequencing. This analysis re- Carolin Edler, M.D.
vealed that RNA for angiotensin-converting University Medical Center Hamburg–Eppendorf
Hamburg, Germany
enzyme 2 (ACE2), transmembrane serine prote-
ase 2 (TMPRSS2), and cathepsin L (CTSL) — RNA Oliver Gross, M.D.
of genes that are considered to facilitate SARS- University Medical Center Göttingen
Göttingen, Germany
CoV-2 infection3 — is enriched in multiple kid-
ney-cell types from fetal development through Markus Glatzel, M.D.
adulthood (Fig. S1). This enrichment may facili- Dominic Wichmann, M.D.
tate SARS-CoV-2–associated kidney injury, as Thorsten Wiech, M.D.
previously suggested.4 Stefan Kluge, M.D.
We also quantified the SARS-CoV-2 viral load Klaus Pueschel, M.D.
in precisely defined kidney compartments ob- Martin Aepfelbacher, M.D.
tained with the use of tissue microdissection Tobias B. Huber, M.D.
from 6 patients who underwent autopsy (1 patient University Medical Center Hamburg–Eppendorf
Hamburg, Germany
who was included in the previously mentioned t​.­huber@​­uke​.­de
22 patients as an internal negative control, plus
5 additional patients). Three of these 6 patients Drs. Puelles, Lütgehetmann, Lindenmeyer, and Sperhake
contributed equally to this letter.
had a detectable SARS-CoV-2 viral load in all kid- Supported by grants (CRC/1192, to Dr. Puelles; CRC/841, to
ney compartments examined, with preferential Dr. Lütgehetmann; and CRC/1192, HU 1016/8-2, HU 1016/11-1,
targeting of glomerular cells (Fig. S2). We also and HU 1016/12-1, to Dr. Huber) from the German Research
Foundation and grants (eMed Consortia Fibromap, to Dr.
detected viral RNA and protein with high spatial Puelles; and STOP-FSGS-01GM1518C, to Dr. Huber) from the
resolution using in situ hybridization and indi- Federal Ministry of Education and Research.
rect immunofluorescence with confocal micros- Disclosure forms provided by the authors are available with
the full text of this letter at NEJM.org.
copy (Fig. 1C). Data on additional controls are
provided in Figures S3 and S4. This letter was published on May 13, 2020, at NEJM.org.
On the basis of these findings, renal tropism
1. Coronavirus disease 2019 (COVID-2019): situation report —
is a potential explanation of commonly reported 51. Geneva:​World Health Organization, 2020 (https://www​.who​
new clinical signs of kidney injury in patients .int/​docs/​default​-­source/​coronaviruse/​situation​-­reports/​
with Covid-19,5 even in patients with SARS-CoV-2 20200311​-­sitrep​-­51​-­covid​-­19​.pdf).
2. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in up-
infection who are not critically ill. Our results per respiratory specimens of infected patients. N Engl J Med
indicate that SARS-CoV-2 has an organotropism 2020;​382:​1177-9.

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 Correspondence

3. Sungnak W, Huang N, Bécavin C, et al. SARS-CoV-2 entry
factors are highly expressed in nasal epithelial cells together
with innate immune genes. Nat Med 2020 April 23 (Epub ahead
of print).
4. Su H, Yang M, Wan C, et al. Renal histopathological analysis
of 26 postmortem findings of patients with COVID-19 in China.
Kidney Int 2020 April 9 (Epub ahead of print).
5. Pei G, Zhang Z, Peng J, et al. Renal involvement and early
prognosis in patients with COVID-19 pneumonia. J Am Soc
Nephrol 2020 April 28 (Epub ahead of print).
DOI: 10.1056/NEJMc2011400
Correspondence Copyright © 2020 Massachusetts Medical Society.

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