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Pulmonary long-term consequences of COVID-19 infections after hospital discharge

Abstract

Objectives: COVID-19 survivors are reporting residual abnormalities after discharge from the hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. The aim of this study was to describe lung function and to identify biomarkers in serum and induced sputum samples from patients recovering from COVID-19 hospitalisation. Methods: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalisation. Patients’ epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardised 6-minute walk test (6 MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. Results: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% (47/100) of patients. CT was normal in 48% (48/100) of patients. Lung function was normal (FEV1 ≥80%, FVC ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide [DLCO] ≥80%) in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p <0.0001) and a lower serum LDH level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 during hospital stay. Conclusions: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases. Blanco, J.R.; Cobos-Ceballos, M.J.; Navarro, F.; Sanjoaquin, I.; Arnaiz de las Revillas, F.; Bernal, E.; Buzon-Martin, L.; Viribay, M.; Romero, L.; Espejo-Pérez, S.; Valencia, B.; Ibañez, D.; Ferrer-Pargada, D.; Malia, D.; Gutierrez-Herrero, F.G.; Olalla, J.; Jurado-Gamez, B.; Ugedo, J.

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Pulmonary long-term consequences of COVID-19 infections after hospital discharge

Author: Blanco, J.R.; Navarro, F.; Ugedo, J.; Espejo-Pérez, S.; Bernal, E.; Jurado-Gamez, B.; Cobos-Ceballos, M.J.; Ibañez, D.; Romero, L.; Valencia, B.; Buzon-Martin, L.; Olalla, J.; Malia, D.; Gutierrez-Herrero, F.G.; Ferrer-Pargada, D.; Arnaiz de las Revillas
Year: 2021
DOI: 10.1016/j.cmi.2021.02.019
Source: https://zaguan.unizar.es/record/100742/files/texto_completo.pdf
Jou nal P e-p oo
Pulmona y long- e m consequences o COVID-19 in ec ions a e hospi al discha ge
J.R. Blanco, M.J. Cobos-Ceballos, F. Na a o, I. Sanjoaquin, F. A naiz de las
Re illas, E. Be nal, L. Buzon-Ma in, M. Vi ibay, L. Rome o, S. Espejo-Pé ez, B.
Valencia, D. Ibañez, D. Fe e -Pa gada, D. Malia, F.G. Gu ie ez-He e o, J. Olalla, B.
Ju ado-Gamez, J. Ugedo
PII: S1198-743X(21)00101-4
DOI: h ps://doi.o g/10.1016/j.cmi.2021.02.019
Re e ence: CMI 2434
To appea in: Clinical Mic obiology and In ec ion
Recei ed Da e: 11 No embe 2020
Re ised Da e: 9 Feb ua y 2021
Accep ed Da e: 18 Feb ua y 2021
Please ci e his a icle as: Blanco J, Cobos-Ceballos M, Na a o F, Sanjoaquin I, A naiz de las Re illas
F, Be nal E, Buzon-Ma in L, Vi ibay M, Rome o L, Espejo-Pé ez S, Valencia B, Ibañez D, Fe e -
Pa gada D, Malia D, Gu ie ez-He e o F, Olalla J, Ju ado-Gamez B, Ugedo J, Pulmona y long- e m
consequences o COVID-19 in ec ions a e hospi al discha ge, Clinical Mic obiology and In ec ion,
h ps://doi.o g/10.1016/j.cmi.2021.02.019.
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© 2021 Eu opean Socie y o Clinical Mic obiology and In ec ious Diseases. Published by Else ie L d. All
igh s ese ed.
Ti le: Pulmona y long- e m consequences o COVID-19 in ec ions a e hospi al
discha ge
AUTHORS:
JR. Blanco
1,2
MJ. Cobos-Ceballos
3,4
F. Na a o
5
I. Sanjoaquin
6
F. A naiz de las Re illas
7
E. Be nal
8
L. Buzon-Ma in
9
M. Vi ibay
10
L. Rome o
2
S. Espejo-Pé ez
3,11
B. Valencia
12
D. Ibañez
13
D. Fe e -Pa gada
14
D. Malia
15
FG. Gu ie ez-He e o
16
J. Olalla
5
B. Ju ado-Gamez
3,4
J. Ugedo
17
Jou nal P e-p oo
1. Se icio de En e medades In ecciosas. Hospi al Uni e si a io San Ped o,
Log oño, La Rioja, SPAIN.
2. Cen o de In es igación Biomédica de La Rioja, Log oño, La Rioja, SPAIN
3. Ins i u o Maimónides de In es igación Biomédica de Có doba. Uni e sidad
de Có doba. SPAIN
4. Se icio de Neumología. Hospi al Uni e si a io Reina So ía, Có doba.
SPAIN
5. Se icio de Medicina In e na. Hospi al Cos al de Sol, Ma bella. Málaga.
SPAIN
6. Se icio de En e medades In ecciosas. HCU Lozano Blesa, Za agoza.
SPAIN
7. Se icio de En e medades In ecciosas. H Uni e si a io Ma qués de
Valdecilla, San ande . SPAIN
8. Sección de En e medades In ecciosas. Hospi al Gene al Uni e si a io
Reina So ía de Mu cia. Uni e sidad de Mu cia. SPAIN
9. Se icio de Medicina In e na. Hospi al Uni e si a io de Bu gos. SPAIN
10. Vi o, Labo a
11. Se icio de Radiología. Hospi al Uni e si a io Reina So ía, Có doba. SPAIN
12. Se icio de Neumología. Hospi al Cos al de Sol, Ma bella. Málaga. SPAIN
13. Se icio de Radiología. HCU Lozano Blesa, Za agoza. SPAIN
14. Se icio de Neumología. H Uni e si a io Ma qués de Valdecilla, San ande .
SPAIN
15. Se icio de Neumología. Hospi al Gene al Uni e si a io Reina So ía de
Mu cia. SPAIN
16. Se icio de Neumología. Hospi al Uni e si a io de Bu gos. SPAIN
17. Se icio de Neumología. Hospi al Uni e si a io San Ped o, Log oño, La
Rioja. SPAIN
Keywo ds: COVID-19, In acellula adhesion molecule, Lung di usion capaci y,
Os eop o ege in, Plasminogen ac i a o inhibi o , Tissue inhibi o o ma ix
me allop o einases, Tomog aphy
Co esponding au ho :
D . José-Ramón Blanco
Hospi al San Ped o – Cen o de In es igación Biomédica de La Rioja (CIBIR)
Depa amen o de En e medades In ecciosas
Pique as 98, 26006 Log oño, La Rioja, Spain
Telephone: +34 941298993
Email: [email p o ec ed] ; j blanco [email protected]
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ABSTRACT
Objec i es: COVID-19 su i o s a e epo ing esidual abno mali ies a e
discha ge om he hospi al. Limi ed in o ma ion is a ailable abou his s age o
eco e y o he linge ing e ec s o he i us on pulmona y unc ion and
in lamma ion. The aim o his s udy was o desc ibe lung unc ion and o iden i y
bioma ke s in se um and induced spu um samples om pa ien s eco e ing
om COVID-19 hospi alisa ion.
Me hods: Pa ien s admi ed o Spanish hospi als wi h labo a o y-con i med
COVID-19 in ec ion by a eal- ime PCR (RT-PCR) assay o se e e acu e
espi a o y synd ome co ona i us 2 (SARS-CoV-2) we e ec ui ed o his s udy.
Each hospi al sc eened hei lis s o discha ged pa ien s a leas 45 days a e
symp om onse . SARS-CoV-2-in ec ed pa ien s we e di ided in o mild/mode a e
and se e e disease g oups acco ding o he se e i y o hei symp oms du ing
hospi alisa ion. Pa ien s’ epidemiological and medical his o ies, como bidi ies,
ch onic ea men s, and labo a o y pa ame e s we e e alua ed. Pulmona y
unc ion es s, he s anda dised 6-minu e walk es (6 MWT) and ches
compu ed omog aphy (CT) we e also pe o med. The le els o p o eases, hei
inhibi o s, and shed ecep o s we e measu ed in se um and induced spu um
samples.
Resul s: A o al o 100 pa ien s wi h espi a o y unc ion es s we e included in
his s udy. The median numbe o days a e he onse o symp oms was 104
(IQR 89.25, 126.75). COVID-19 was se e e in 47% (47/100) o pa ien s. CT
was no mal in 48% (48/100) o pa ien s. Lung unc ion was no mal (FEV1
≥80%, FVC ≥80%, FEV1/FVC ≥0.7, and di using capaci y o ca bon monoxide
[DLCO] ≥80%) in 92% (92/100), 94% (94/100), 100% (100/100) and 48%
(48/100) o pa ien s, espec i ely. Mul i a ia e analysis showed ha a DLCO
<80% (OR 5.92; 95%CI 2.28-15.37; p <0.0001) and a lowe se um LDH le el
(OR 0.98; 95%CI 0.97-0.99) we e associa ed wi h he se e e disease g oup o
SARS-CoV-2 du ing hospi al s ay.
Conclusions: A di usion de ici (DLCO <80%) was s ill p esen a e hospi al
discha ge and was associa ed wi h he mos se e e SARS-CoV-2 cases.
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INTRODUCTION
App oxima ely 104 million indi iduals wo ldwide ha e eco e ed om COVID-19
(h ps://co ona i us.jhu.edu/map.h ml). Howe e , some su i o s epo
pe sis en se e e symp oms and o gan dys unc ion [1]. These symp oms migh
be, in pa , a consequence o he cy okine s o m su e ed in he acu e phase o
he in ec ion [2]. P e ious s udies ha e shown ha highe le els o
p oin lamma o y cy okine esponses du ing he acu e phase o o he
co ona i us in ec ions such as se e e acu e espi a o y synd ome (SARS) [3]
and he Middle Eas Respi a o y Synd ome Co ona i us (MERS-CoV) [4], we e
associa ed wi h se e e lung disease. Unlike p e ious co ona i uses, COVID-19
does no seem o be jus a espi a o y a lic ion; a he , i is a i al in ec ious
p ocess in ol ing mul iple sys ems [5].
Residual lung abno mali ies ha e been ound in pa ien s wi h SARS-CoV-2 1-3
mon hs a e discha ge om he hospi al [6-9]. Howe e , limi ed in o ma ion is
a ailable abou he se um in lamma o y s a e du ing eco e y om SARS-CoV-
2. The impac o esidual in lamma ion on he lungs is e en a e . Because he
pe sis ence o his in lamma o y s a e in blood and spu um could ha e impo an
p ognos ic implica ions, we pe o med his s udy.
METHODS
Pa icipan s
This was a p ospec i e s udy o pa ien s olde han 18 yea s o age who we e
admi ed o di e en Spanish hospi als wi h labo a o y-con i med COVID-19
in ec ion by eal- ime PCR (RT-PCR) assay o SARS-CoV-2. Each hospi al
sc eened hei lis s o discha ged pa ien s. These pa ien s we e in e iewed by
phone a leas 45 days a e symp om onse and asked o collabo a e i hey
me inclusion c i e ia. Exclusion c i e ia included pa ien s wi h a need o p io
in asi e mechanical en ila ion, ch onic in ec ious diseases, ch onic lung
diseases, concu en au oimmune o cance diseases, ch onic use o
co icos e oids o immunosupp essi e he apy, p egnancy, alcohol/d ug abuse,
o pa ien s whose condi ions did no allow pa icipa ion in his s udy. The s udy
was app o ed by he Ins i u ional Resea ch E hics Commi ees. All pa icipan s
p o ided w i en in o med consen .
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Pa ien s we e di ided in o mild (mild and mode a e) and se e e g oups
acco ding o he se e i y o hei symp oms du ing hei hospi al s ays. The mild
g oup did no ha e pneumonia imaging; he mode a e g oup showed
pneumonia; and he se e e g oup had dyspnoea, espi a o y equency
≥ 30/minu e, blood oxygen sa u a ion ≤93%, PaO
2
/FiO
2
a io <300, and/o lung
in il a es >50% o he lung ield wi hin 24-48 hou s [10]. Pa ien s equi ing
in asi e mechanical en ila ion we e excluded because o i s impac on
sys emic in lamma ion [11].
Epidemiological, medical his o y, como bidi ies, ch onic ea men s, and
labo a o y pa ame e s we e e alua ed. Smoking s a us was de e mined om
sel -adminis e ed su ey esponses. An h opome ic measu emen s included
body mass index (BMI). A leas 45 days a e symp om onse , pulmona y
unc ion es ing, s anda dised 6-minu e walk es s (6 MWT) [12], and ches
compu ed omog aphy (CT) we e pe o med. Lung unc ion included o ced i al
capaci y (FVC), o ced expi a o y olume in he i s second (FEV1), FEV1/FVC
a io and di usion capaci y o he lung o ca bon monoxide (DLCO). Di usion
de ici was conside ed a DLCO <80% o he p edic ed alue [13]. The 6 MWT, a
p ac ical and simple es ha p o ides a global measu e o unc ional capaci y,
was pe o med in acco dance wi h in e na ional ecommenda ions [12].
Pe iphe al oxygen sa u a ion (SpO
2
) was moni o ed using a handheld oxime e .
∆SpO
2
-6 MWT was de ined as he di e ence be ween he es ing and nadi
SpO
2
. The 6 MWT dis ance was also e alua ed [14]. CT was conside ed no mal
in he absence o g ound-glass opaci ica ion, c azy-pa ing pa e ns,
consolida ion, o linea opaci ies [15].
The le els o bioma ke s we e measu ed in se um and induced spu um
samples. Se um samples we e ob ained om blood d awn a a da e close o he
es s al eady desc ibed and s o ed a -80ºC. Spu um was induced as p e iously
desc ibed [16] and s o ed a -80°C. I was ob ained, whene e possible, on he
same day as he espi a o y unc ion es s. The concen a ions o mul iple
p o eases and hei inhibi o s (plasminogen ac i a o inhibi o [PAI]-1, PAI-2,
and issue inhibi o o ma ix me allop o einases [TIMP]-1). Shed ecep o
(in acellula adhesion molecule [ICAM]-1, ICAM-3, os eop o ege in [OPG])
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we e e alua ed in se um and spu um samples. These pa ame e s we e
analysed in duplica e employing comme cially a ailable ELISA ki s. The lowe
de ec ion limi s a e shown (Supplemen a y Table 1). All samples we e es ed
indi idually (one sample pe well), bu samples om all g oups we e measu ed
on he same pla e. The hook e ec , a s a e o an igen excess ela i e o he
an ibody p obes, esul ing in alsely lowe ed alues, was uled ou a e
analysing undilu ed and dilu ed samples.
Da a analysis
Ca ego ical a iables we e epo ed as equencies and p opo ions. Con inuous
a iables wi h a no mal dis ibu ion a e p esen ed as he mean (s anda d
de ia ion [SD]), and hose wi h a non-no mal dis ibu ion a e p esen ed as he
median (in e qua ile ange alues [IQR] p25, p75). To compa e he
demog aphic and clinical a iables be ween g oups, he chi-squa e es o
Fishe 's exac es was used o each ca ego ical a iable, as app op ia e. Fo
quan i a i e a iables, he nonpa ame ic Mann-Whi ney U es was used.
Mul i a ia e analysis was ca ied ou using bina y logis ic eg ession wi h he
o wa d condi ional me hod, in oducing DLCO (<80 s. ≥80%) as he
dependen a iable. Independen a iables we e all a iables ha we e
s a is ically signi ican in he bi a ia e analysis, o clinical implica ions. The
esul s o he mul i a ia e model we e adjus ed, and we p esen he odds a io
and i s 95% con idence in e al (CI). S a is ical signi icance was se a p <0.05.
Analyses we e pe o med using SPSS 24.0 so wa e (SPSS Inc., Chicago, IL,
USA).
RESULTS
A o al o 108 pa ien s we e included in his s udy. O he sample, 100 had
adequa e espi a o y unc ion es s. Mos (69%9 we e >50 yea s (69/100), 64%
we e male (64/100), and 90% we e Caucasian (90/100). The median numbe o
days a e he onse o symp oms was 104 (IQR 89.25, 126.75). Common
como bidi ies included hype ension (25%; 25/100), diabe es melli us (10%;
10/100), ca dio ascula disease (4%; 4/100), and ch onic kidney disease (2%;
2/100). Obesi y (BMI ≥30%) was p esen in 37% (37/100), and 59% ne e had
smoked (59/100). Ch onic he apy included angio ensin-con e ing enzyme
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inhibi o s/angio ensin II ecep o blocke s use (17%, 17/100), s a in use (12%,
12/100), and aspi in use (3%, 3/100). COVID-19 was se e e in 47% o pa ien s
(47/100). Lung unc ion was no mal (FVC ≥80%, FEV1 ≥80%, FVC/FEV1 ≥0.7,
and DLCO ≥80%) in 92% (92/100), 94% (94/100), 100% (100/100), and 48%
(48/100), espec i ely. Con ol CT was no mal in 48% (48/100).
Gi en he high pe cen age o subjec s wi h DLCO <80% and i s in ol emen in
lung damage, his lung pa ame e was e alua ed. Table 1 shows he pa ien
cha ac e is ics acco ding o DLCO se e i y. Wi h he excep ion o signi ican
da a e e ing o he se e i y o COVID-19 disease du ing hospi alisa ion and
he leng h o hospi al, no o he signi ican di e ences we e obse ed.
Table 2 shows he analy ical pa ame e s acco ding o DLCO se e i y. Finally,
Table 3 p o ides in o ma ion abou he es s ca ied ou and he minimum ime
elapsed un il es s we e pe o med. No di e ences we e obse ed a e
analysing ∆SpO
2
-6 MWT (da a no shown).
Mul i a ia e analysis showed ha a DLCO <80% was associa ed wi h se e e
disease in he SARS-CoV-2 g oup du ing hei hospi al s ays (OR 5.92; 95% CI
2.28-15.37; p <0.0001) as we e lowe se um LDH le els (OR 0.98; 95% CI
0.97-0.99; p 0.002).
DISCUSSION
Since he SARS-CoV-2 ou b eak, he e has been inc easing conce n abou he
po en ial isk o pa enchymal ib osis and lung unc ion impai men . The mos
impo an ac o is lung di usion capaci y [17]. Zhao e al. [6] epo ed ha h ee
mon hs a e COVID-19 discha ge, a high pe cen age o CT abno mali ies
(70.9%) and DLCO anomalies (16.4%) we e s ill p esen in eco e ing pa ien s.
O he au ho s, such as Mo e al. [7], epo ed ha nea ly a mon h a e hospi al
discha ge ha , ega dless o he deg ee o SARS-CoV-2 se e i y, no signi ican
di e ences in FEV1, FVC, o i s a io we e obse ed. Howe e , he DLCO alue
was signi ican ly lowe as he se e i y o he clinical pic u e inc eased (47.2% in
o al; 30.4% in mild illness and 84.2% in se e e pneumoniae). In his s udy, he
au ho s included a small numbe o pa ien s wi h p e ious pulmona y pa hology,
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one o he exclusion c i e ia o ou s udy. Likewise, F ija-Masson e al. [9] also
obse ed ha mo e han hal o pa ien s wi h COVID-19 pneumonia, some o
whom had espi a o y como bidi ies, exhibi ed abno mal lung unc ion one
mon h a e symp om onse , wi hou a clea ela ionship wi h pneumonia ex en
on ches CT. Huang e al. [18] obse ed ha 30 days a e discha ge om he
hospi al, pa ien s exhibi ed nea ly signi ican di e ences in DLCO alues
(<80%), 42.5% in non-se e e cases, and 75.6% in se e e cases (p < 0.053). In
ha s udy, pa ien s wi h a p e ious his o y o pulmona y esec ion, neu ological
disease, o men al illness we e excluded. In ou s udy, DLCO indings we e
close o hose obse ed by Mo e al. [7] and Huang e al. [18], while he CT
indings we e clea ly be e han hose epo ed by Zhao e al. [6].
A e he 2003 ou b eak o SARS, su i o s e alua ed wi hin h ee mon hs o
discha ge showed ha lung ib o ic changes occu ed mos ly in se e ely sick
pa ien s [19]. These same au ho s also obse ed ha when assessing lung
ib o ic changes, DLCO sco es we e mo e sensi i e han ches adiog aphy
and/o high- esolu ion CT. These esul s a e simila o hose obse ed by ou
g oup. Du ing he ollow-up o SARS pa ien s, abno mal CT (30%) and impai ed
DLCO unc ion (15.5%) [20] we e s ill p esen six mon hs la e . These au ho s
also obse ed signi ican impai men in DLCO unc ion (23.7%) one yea a e
illness onse [21]. All hese da a sugges ha some o he eco e ed COVID-19
pa ien s will ha e signi ican ly impai ed lung unc ion mon hs a e discha ge.
Con a y o ou expec a ions, LDH le els we e signi ican ly lowe in pa ien s wi h
DLCO abno mali ies (<80%). Howe e , se um LDH is a sensi i e, bu densome
ma ke o cell inju y [22]. One o he easons could be ha i s le els a y in
mul iple ci cums ances (cell damage ela ed o ischaemia, exposu e o bac e ial
oxins, chemical poisoning, e c.), which is why se um LDH is di icul o use as a
alid bioma ke o lung damage o in lamma ion [22]. Howe e , some au ho s
ha e obse ed ha LDH (cu -o alue o 344.5 U/L) could be a p edic i e ac o
o ea ly ecogni ion o lung inju y and se e e COVID-19 cases [23]. These
le els a e clea ly highe han hose p esen ed by ou pa ien s.
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and se e e cases o COVID-19. Lance In ec Dis. 2020;20(6):656-657.
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Table 1. Pa ien cha ac e is ics among SARS-CoV-2 su i o s acco ding
o DLCO se e i y.
DLCO <80
(n = 52)
DLCO
≥80
(n = 48)
P
alue
Age in yea s, mean (± SD)
Age >50 yea s, n (%)
54.98 ±10.72
34 (65.4)
54.75 ± 9.83
35 (72.9)
0.911
0.416
Male sex, n (%) 33 (63.5) 31 (64.6) 0.907
Caucasian, n (%) 47 (90.4) 43 (89.6) 0.894
Ne e smoke his o y, n (%) 32 (61.5) 27 (56.3) 0.591
Como bidi ies
Ca dio ascula disease, n (%) 4 (7.7) 0 (0) 0.119
Hype ension, n (%) 15 (28.8) 10 (20.8) 0.355
Diabe es melli us, n (%) 7 (13.5) 3 (6.4) 0.324
Ch onic enal ailu e, n (%) 2 (3.8) 0 (0) 0.496
Ch onic aspi in use, n (%) 2 (3.8) 1 (2.1) 1.000
Ch onic s a in use, n (%) 8 (15.4) 4 (8.3) 0.362
Ch onic ACE/ARA-II use, n (%) 9 (17.3) 8 (16.7) 0.932
SARS
-
CoV
-
2
da a du ing
hospi al
iza ion admission
Se e i y
disease du ing hospi al
admission, n (%)
34 (65.4)
13 (27.1)
<0.0001
Days o hospi aliza ion
,
median
(p25, p75)
7.0 (5.0; 9.75)
8.0 (6.0; 11.0)
0.038
No e: ACE = angio ensin con e ing enzyme inhibi o s; ARA-II = angio ensin II ecep o
blocke s; BMI = Body mass index; DLCO = di usion capaci y o he lung o ca bon
monoxide; SD = S anda d de ia ion
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Table 2. Analy ical cha ac e is ics among SARS-CoV-2 su i o s
acco ding o DLCO se e i y.
DLCO <80
(n = 52)
DLCO
≥80
(n = 48)
P
alue
Se um pa ame e s
, median (p25, p75)
WBC coun , cells/μL 6.10 (5.30; 6.59) 5.70 (5.0; 6.6) 0.383
Glucose, mg/dL
97.0 (93.25; 112.7)
32.4 (27.7; 39.9)
0.016
C ea inine, mg/dL 0.87 (0.74; 1.01) 0.87 (0.76; 0.98) 0.970
ALT, UI/L 21.0 (16-0; 32.0) 24.0 (18.0; 33.0) 0.224
AST, UI/L
22.0 (17.0; 25.0)
24.0 (20.0; 27.0)
0.034
LDH
, UI/L
187.0 (164.0; 201.0)
196.0 (174.2; 256.7)
0.006
CRP g/dL 3.0 (1.0; 4.0) 4.0 (1.0; 4.0) 0.751
OPG
pg/ml
62.6 (48.0; 81.0) 58.0 (48.4; 72.5) 0.410
TIMP-1
ng/ml
278.1 (249.8; 306.8) 281.3 (242.6; 312.3) 0.598
ICAM-1
ng/ml
169.9 (131.5; 245.9) 173.5 (122.5; 243.6) 0.738
ICAM-3
ng/ml
141.8 (115.8; 187.9) 136.6 (106-2; 163.0) 0.143
PAI-1
ng/ml
125.6 (98.2; 146.5) 119.2 (107.3; 142.4) 0.945
PAI-2
ng/ml
4.3 ±(2.8; 6.7) 3.7 (2.1; 5.2) 0.492
Induced spu um samples
, median (p25, p75)
OPG
pg/ml
1.0 (1.0; 9.71) 1.0 (1.0; 11.1) 0.912
TIMP-1
ng/ml
68.9 (35.0; 120.4) 48.5 (35.0; 75.1) 0.112
ICAM-1
ng/ml
2.2 (0.9; 3.5) 2.21 (0.1; 2.38) 0.083
ICAM-3
ng/ml
34.2 (12.6; 86.1) 38.27 (16.2; 92.4) 0.812
No e: ALT = Alanine amino ans e ase; AST = Aspa a e amino ans e ase; CRP = C- eac i e
p o ein; DLCO = di usion capaci y o he lung o ca bon monoxide; ICAM = In acellula
adhesion molecule; LDH = Lac a e dehyd ogenase; OPG = Os eop o ege in; PAI =
Plasminogen ac i a o inhibi o ; TIMP = Tissue inhibi o o ma ix me allop o einase;
WBC =
Whi e blood cell coun
.
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Table 3. Pulmona y unc ion es and compu ed omog aphy among
SARS-CoV-2 su i o s acco ding o DLCO se e i y.
DLCO <80
(n = 52)
DLCO
≥80
(n = 48)
P
alue
Days
a e symp oms onse
*
Days a e symp oms onse >90,
n (%)
100.0 (87.5; 108.7)
36 (69.2)
11
4
.
5 (94.2; 133.7)
38 (79.2)
0.012
0.258
Func iona
l lung pa ame e and imaging CT
FVC (%)*
FVC >80%, n(%)
106.9 (91.0; 113.7)
48 (92.3%)
104.5 (94.7; 114.7)
46 (95.8%)
0.904
0.906
FEV1 (%)*
FEV1 >80%, n (%)
102.5 (94.1; 113.0)
48 (91.7)
107.2 (98.0; 118.0)
44 (91.7)
0.214
0.458
FEV1/FVC a io* 1.0 (0.9; 1.0) 0.97 (0.92; 1.01) 0.066
6MWT dis ance, mean (± SD)
6MWT dis ance >550,n (%)
5
13
.
0 (450.0; 594.6)
20 (39.2)
577.0 (540.0; 645.0)
31 (66)
0.001
0.008
Pa hologic CT, n (%) 31 (59.6) 20 (42.6) 0.900
No e: Da a p esen ed as median (P25; P75)*;
6MWT = 6-minu e walk es ; CT = ches -
compu ed omog aphy;
DLCO = di usion capaci y o he lung o ca bon monoxide;
FEV1 =
o ced expi a o y olume in he i s second; FVC = o ced i al capaci y;
SD = S anda d
de ia ion
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