Mize ae al. Pneumonia (2024) 16:2
h ps://doi.o g/10.1186/s41479-023-00123-7
RESEARCH
The e ec i eness o glucoco icoid
ea men inpos -COVID-19 pulmona y
in ol emen
Jan Mize a1† , Samuel Genzo 1,2*† , Milan So a1,3 , Ladisla S anke2 , Radim Bu ge 4 , Pe Jakubec1 ,
Ma in Vykopal1 , Pa ol Pobeha5 and Jana Zaple alo á6
Abs ac
Ra ionale Pe sis en espi a o y symp oms ollowing Co ona i us Disease 2019 (COVID-19) a e associa ed wi h esid-
ual adiological changes in lung pa enchyma, wi h a isk o de elopmen in o lung ib osis, and wi h impai ed pul-
mona y unc ion. P e ious s udies hin ed a he possible e icacy o co icos e oids (CS) in acili a ing he esolu ion
o pos -COVID esidual changes in he lungs, bu he a ailable da a is limi ed.
Aim To e alua e he e ec s o CS ea men in pos -COVID espi a o y synd ome pa ien s.
Pa ien s andme hods Pos -COVID pa ien s we e ec ui ed in o a p ospec i e single-cen e obse a ional s udy
and scheduled o an ini ial (V1) and ollow-up isi (V2) a he Depa men o Respi a o y Medicine and Tube culosis,
Uni e si y Hospi al Olomouc, comp ising o pulmona y unc ion es ing, ches x- ay, and complex clinical examina-
ion. The decision o adminis e CS o main ain wa ch ul wai ing (WW) was in line wi h Czech na ional guidelines.
Resul s The s udy in ol ed 2729 COVID-19 su i o s (45.7% male; mean age: 54.6). F om 2026 pa ien s wi h com-
ple e V1 da a, 131 pa ien s we e indica ed o CS he apy. These pa ien s showed signi ican ly wo se adiological
and unc ional impai men a V1. Mean ini ial dose was 27.6 mg (SD ± 10,64), and he mean du a ion o CS he apy
was 13.3 weeks (SD ± 10,06). Following he apy, signi ican ly be e imp o emen o s a ic lung olumes and ans e
ac o o ca bon monoxide (DLCO), and signi ican ly be e a es o good o comple e adiological and subjec i e
imp o emen we e obse ed in he CS g oup compa ed o con ols wi h a ailable ollow-up da a (n = 894).
Conclusion Be e imp o emen o pulmona y unc ion, adiological indings and subjec i e symp oms we e
obse ed in pa ien s CS compa ed o wa ch ul wai ing. Ou indings sugges ha glucoco icoid he apy could ben-
e i selec ed pa ien s wi h pe sis en dyspnea, signi ican adiological changes, and dec eased DLCO.
Keywo ds Pos -co id synd ome, Pulmona y ib osis, Co icos e oids, Wa ch ul wai ing, Pulmona y unc ion
Open Access
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Pneumonia
†Jan Mize a and Samuel Genzo con ibu ed equally o his wo k.
*Co espondence:
Samuel Genzo
samuel.genzo @ nol.cz
Full lis o au ho in o ma ion is a ailable a he end o he a icle
Page 2 o 10
Mize ae al. Pneumonia (2024) 16:2
In oduc ion
Pos -COVID-19 (Co ona i us Disease 2019) synd ome
is a se o espi a o y and non- espi a o y symp oms
ha pe sis o mo e han 3 mon hs a e he in ec ion
wi h he Se e e acu e espi a o y synd ome co ona i us
2 (SARS-CoV-2). These symp oms should ha e a pa ho-
physiological connec ion wi h he COVID-19 and should
no be explicable by ano he cause [1, 2]. The e m meas-
u able pos -COVID disabili y can be used o pa ien s
p esen ing wi h abno mal indings on CXR, high- esolu-
ion compu ed omog aphy (HRCT), o pulmona y unc-
ion es ing, in he absence o subjec i e symp oms [3].
The epo ed p e alence o pos -COVID lung ib o-
sis a ies g ea ly ac oss s udies, anging om 6% [3] o
44%, [4] likely due o me hodological and e minologi-
cal disc epancies, such as he lack o dis inc ion be ween
in e s i ial in lamma ion ( e e sible changes) and ib o-
sis (pe manen changes). The mos equen ly desc ibed
adiological and his ological indings in pa ien s wi h
espi a o y o m o pos -COVID-19 synd ome a e con-
sis en wi h o ganizing pneumonia (OP), ollowed by
non-speci ic in e s i ial pneumonia (NSIP) [5]. O he
adiological indings should aise suspicion o a di e en
cause, o a p e-exis ing espi a o y disease.
Mul iple pa hophysiological pa hways and mecha-
nisms a e in ol ed in he ib o ic emodeling o lung
issue, especially he down egula ion o ACE-2 ecep-
o s a e he binding o SARS-CoV-2 i ions, esul ing
in inc eased p o-in lamma o y and p o- ib o ic ac i i y.
This leads o he up egula ion o a ious e ec o mol-
ecules (ma ix me allop o einases 1 and 7, in e leukins:
IL-1, 6 and 8, galec in-3 media ed pa hways, ans o m-
ing g ow h ac o -β, TNF-α, ICAM, VCAM e c [6, 7].
Mo eo e , pulmona y asculopa hy and he esul an
hypoxic emodeling may also be in ol ed [8, 9]. In he
majo i y o pa ien s, he po en ially ib ogenic in lam-
ma o y p ocess seems o be sel -limi ed and migh
esol e wi hou any he apy in he pos -acu e s age o he
COVID-19 [10, 11].
In he case o pe sis en lung in e s i ial in ol emen
a e COVID-19 pneumonia, sys emic glucoco icoids
(CS) a e equen ly used [5, 12]. The ea men wi h CS
leads o down egula ion o a b oad spec um o p o-
in lamma o y and p o- ib o ic molecules (IL-1, 2, 4, 5, 8,
13; ICAM, VCAM, e c.) and can hus help he esolu ion
o in lamma o y and ib ogenic changes h ough mul i-
ple pa hways [13–19]. Howe e , he CS seem o be mos
e ec i e p io o he de elopmen o de ini i e ib o ic
changes, he e o e app op ia e iming o he ea men is
likely essen ial [5]. The exis ing li e a u e sugges s possi-
ble bene i s o CS o selec ed indi iduals wi h espi a o y
o m o pos -COVID-19 synd ome, especially in cases o
pe sis en o ganizing pneumonia, bu hei gene al use
is cu en ly no ecommended [20–26]. The nume ous
and po en ially se ious sys emic and o gan speci ic side
e ec s o CS a e well desc ibed in he li e a u e [27–29].
Se e al s udies o he use o CS in pos -COVID pa ien s
ha e been published o da e, [5, 30, 31] hin ing a he
possible e icacy o CS in he espi a o y pos -COVID-19
synd ome. These s udies ha e b ough impo an insigh s
o he e icacy o CS, howe e , he coho size in hese
s udies was usually small, [5, 30] and mos o he s ud-
ies did no con ain a con ol g oup [5, 31]. Addi ionally,
some s udies in ol ed only limi ed [31] o no [30] pul-
mona y unc ion es s (PFT). The p esen s udy aims o
expand on he cu en knowledge by p o iding a la ge ,
obus da ase , and mo e impo an ly, a con ol g oup
wi h pa ien s managed by wa ch ul wai ing (WW).
This s udy aims o answe wo ques ions: Fi s ly, how
do he pa ien s ea ed by CS compa e o he pa ien s
managed by WW wi h espec o he a e o imp o e-
men o pa ame e s o pulmona y unc ion, adiological
indings and subjec i e symp oms? And secondly, wha
a e he cha ac e is ics o he pa ien s who a e ea ed
wi h CS in eal-li e clinical p ac ice?
Ma e ials andme hods
Rec ui men
F om May 13, 2020, o Janua y 11, 2022, mo e han h ee
housand pa ien s we e e alua ed in he newly es ab-
lished pos -COVID ambula o y cen e a he Depa men
o Pulmona y Diseases and Tube culosis, Uni e si y Hos-
pi al Olomouc, Czech Republic. The a ailabili y o he
pos -COVID ambula o y was publicly announced on he
websi e o he Uni e si y Hospi al Olomouc. The pa ien s
we e in i ed o pa icipa e in a longi udinal obse a ional
s udy o COVID-19 su i o s. Those who ag eed o pa -
icipa e in he s udy signed an in o med consen o m.
Fo he 12 adolescen pa ien s he consen o m was
signed by a pa en . Non-pa icipan s ecei ed he same
le el o medical ca e as s udy pa icipan s, bu hei clini-
cal da a we e no included in he da ase .
The inclusion c i e ia o he s udy we e: a minimum
age o 15, and a p e ious COVID-19 in ec ion, de ined
as: a his o y o a posi i e SARS-CoV-2 PCR es , a his-
o y o a posi i e SARS-CoV-2 an igen es coupled wi h
ypical symp oms, o posi i e le els o SARS-CoV-2 IgM
an ibodies in non- accina ed indi iduals who expe i-
enced ypical symp oms. No p ima y exclusion c i e ia
we e de ined, howe e he pa ien s wi h a p obable e u-
a ion o SARS-CoV-2 in ec ion we e excluded pos hoc
(pa ien s ha had no e idence o ha ing had co id i.e., an
absence o a posi i e PCR o an igen es o SARS-CoV-2
and unde ec able SARS-CoV-2 an ibody le els in se um).
Addi ionally, he pa ien s wi h insu icien da a (such as
missing baseline pulmona y unc ion es ing), and he
Page 3 o 10
Mize ae al. Pneumonia (2024) 16:2
pa ien s on ch onic CS medica ion ( heuma oid a h i is,
solid o gan ansplan ecipien s, e c.), o pa ien s wi h
newly ini ia ed CS he apy o easons o he han pos -
COVID espi a o y sequelae (b onchial as hma exace -
ba ion, newly diagnosed sa coidosis, e c.) we e excluded
pos -hoc om he s a is ical analysis o a oid bias.
Cou se o  hes udy
The s udy p o ocol manda ed wo p ima y isi s. The
ini ial isi (V1) was scheduled o a mean o 12 weeks
(1–68, SD ± 7.55) ollowing in ec ion. The second ollow-
up isi (V2) was scheduled based on clinical necessi y,
wi hin a mean in e al o 21 weeks (3–50, SD ± 7.96)
be ween he wo isi s. In a limi ed numbe o subjec s,
addi ional check-ups we e necessa y; howe e , he scope
o hese addi ional examina ions was limi ed based on
clinical equi emen s. Bo h V1 and V2 consis ed o an
ex ensi e pa ien in e iew, documen ed in ee- o m
by one o he in es iga ing pneumologis s (N = 14). The
ocus o hese in e iews was on he symp oms o acu e
COVID-19, pe sis ing o newly eme ging symp oms,
como bidi ies, medica ions, occupa ional his o y, and
o he de ails cus oma y o a comp ehensi e pneumo-
logical examina ion. The esul s o a ca dio- espi a o y
ocused physical examina ion we e eco ded in ee- o m
acco ding o he s anda ds o he depa men . The ches
X- ay (CXR) in pos e oan e io p ojec ion was ob ained
and in e p e ed by a ained adiologis (N = 25). Ches
HRCT was pe o med in selec ed indi iduals based on
clinical necessi y. Pulmona y unc ion es ing (PFT) -
including spi ome y, body-ple hysmog aphy, and lung
di usion capaci y o ca bon monoxide (DLCO) - was
conduc ed by expe ienced spi ome y echnicians using
he Mas e Sc een by Jaege ®, wi h acco dance o he
ecen Ame ican Tho acic Socie y (ATS) and Eu opean
Respi a o y Socie y (ERS) guidelines [32]. Da a e ie al
was accomplished h ough he Sen ySui eTM Ve sion
2.19 by Ca eFusion. Addi ionally, a se o blood es s was
aken a V1 and V2, including ou ine biochemis y, di -
e en ial blood coun and SARS-CoV-2 an ibodies. How-
e e , om Oc obe 2021 onwa ds, he aking o blood
es s was limi ed o cases wi h clinical necessi y due o
limi ed inancial esou ces. The blood es s we e he e-
o e no included in s a is ical analysis o a oid selec ion
bias.
The ea men wi h glucoco icoids (CS) was consid-
e ed in pa ien s wi h pe sis en pa hological indings on
CXR and/o HRCT and/o impai ed pulmona y unc ion
pa ame e s, namely dec eased DLCO. The p esence o
symp oms alone was no conside ed o be an indica ion
o glucoco icoid he apy. In pa ien s conside ed o glu-
coco icoid he apy, addi ional c i e ia such as age, ail y,
como bidi ies, and o he indi idual isk ac o s we e
e alua ed by he examining physician. Finally, selec ed
pa ien s we e p esc ibed o al glucoco icoids (p edniso-
lone o an equi alen dose o me hylp ednisolone).
The ini ial dose and he ape ing egimen we e indi-
idualized, wi h doses lowe han 0.5mg/kg o p edni-
solone being u ilized in pa ien s wi h highe es ima ed
isk o ad e se e ec s. The maximum ini ial dose o
p ednisolone was 40 mg aken in a single daily dose.
The mean p esc ibed ini ial dose o p ednisolone was
27.6mg (SD ± 10,64), and he mean du a ion o glucoco -
icoid he apy was 13.3 weeks (SD ± 10,06). The dose was
educed o 20mg a e 14 days. The dose o 20mg was
aken o up o 14 days and was hen ape ed g adually
by 5mg pe week. The dose ape ing egimen could be
modi ied by he in es iga ing physician. This app oach
was in line wi h he na ional posi ional documen on he
ea men o pulmona y impai men in pa ien s eco e -
ing om COVID-19 [12].
Cons uc ion andanalysis o  heda ase
Fou main da a sou ces we e u ilized: he medical docu-
men a ion, he da abase o labo a o y es esul s, he
da abase o adiological s udies and he Czech na ional
egis y o SARS-CoV-2 accina ion and es s. The da a
we e ex ac ed, encoded, and s o ed in a Mic oso Excel
sp eadshee and alida ed by he main au ho p io o
s a is ical analysis.
The medical documen a ion was sea ched manually,
including he epo s om he wo main isi s (V1 and
V2) and all in e im check-ups. Biome ic da a we e ga h-
e ed (sex, age, weigh , heigh , BMI). The da e o he i s
posi i e SARS-CoV-2 es (o onse o symp oms) was
ex ac ed om he medical documen a ion and alida ed
agains he Czech na ional egis y o SARS-CoV-2 acci-
na ion and es s. The easons o missing ollow-up we e
eco ded. Selec ed como bidi ies in he pa ien ’s medical
his o y we e eco ded, including a e ial hype ension
(AHT), diabe es melli us (DM), ischemic hea disease
(IHD), pulmona y embolism (PE), dyslipidemia (DLD),
hypo hy oidism (HT), b onchial as hma (BA), ch onic
obs uc i e pulmona y disease (COPD), sa coidosis,
in e s i ial lung disease (ILD). The como bidi y sco e
(ComS) was es ablished by adding one poin o each o
he en selec ed como bidi ies.
The se e i y o acu e COVID-19 was classi ied in o
one o h ee ca ego ies: mild, de ined as a mild ambu-
la o y cou se wi hou pneumonia; mode a e, in ol -
ing pneumonia bu no equi ing oxygen he apy; and
se e e, in ol ing pneumonia ha equi ed oxygen
he apy, en ila o y suppo , in ensi e ca e, o c i ical
ca e. The da a ega ding espi a o y and ex apulmo-
na y symp oms du ing acu e COVID-19 and du -
ing pos -COVID phase we e eco ded. The a e o
Page 4 o 10
Mize ae al. Pneumonia (2024) 16:2
subjec i e imp o emen was es ima ed based on he
e bal desc ip ions in he medical documen a ion and
eco ded on a scale anging om 0 o 10 (0 o 100%
imp o emen wi h 10% s ep size). SIS sco es 9–10 we e
conside ed comple e imp o emen , SIS sco es 5–8
we e conside ed good imp o emen , while SIS sco e o
0 was conside ed as no imp o emen . Pos -co id adio-
logical sco e (PRS) was es ablished based on he ex en
o pos -COVID changes as desc ibed by he adiolo-
gis . The sco e anged om 0 (no changes), h ough
1 (changes on HRCT only), 2 (minimum e icula o
linea opaci ies), 3 (se e al g ound glass opaci ies,
pa chy o e icula opaci ies), 4 (ex ensi e opaci ies o
di use e icula opaci ies in less han 3/6 lung ields)
o 5 (changes desc ibed in 4 bu in ol ing mo e han
3/6 lung ields). The a e o adiological imp o emen
be ween he wo main isi s was e alua ed by side- o-
side compa ison o he adiological s udies by a sin-
gle pneumologis expe ienced in eading adiological
s udies and eco ded as a scale anging om 0 o 10 (0
o 100% imp o emen wi h 10% s ep size). RIS sco es
9–10 we e conside ed comple e imp o emen , RIS
sco es 5–8 we e conside ed good imp o emen , while
RIS sco e o 0 was conside ed as no imp o emen . The
PFT da a encompassed p edic ed alues, ac ual meas-
u ed alues, and ela i e alues (exp essed as a pe cen -
age o p edic ed) whe e applicable. The da a ega ding
he use o CS we e ex ac ed by a pneumologis blinded
o he subjec i e and adiological imp o emen sco es,
PFT and labo a o y es esul s. The da a included he
delay om in ec ion o ini ia ion o he apy, he gluco-
co icoid molecule used, ini ial dosage exp essed as an
equi alen dose o p ednisolone, and he du a ion o
he adminis a ion in weeks.
The da a ega ding biome ic pa ame e s, subjec i e
symp oms and hei imp o emen , adiological indings,
and hei imp o emen , selec ed PFT pa ame e s and
hei dynamics, he se e i y o COVID-19, and he da a
desc ibing he indica ion, ini ial dosage and du a ion o
CS he apy we e s a is ically desc ibed and hypo heses
we e es ed by means o uni a ia e analysis. Pa ame ic
and non-pa ame ic es s we e used as applicable (S u-
den ’s - es , Mann-Whi ney U es , Chi-squa e es ). All
es s we e conduc ed a he alpha le el o 0.05. Logis ic
eg ession was employed o in es iga e po en ial p edic-
o s o a lack o subjec i e and adiological imp o emen ,
de ined as a SIS o 0 and a RIS o 0, espec i ely. The
p edic o s e alua ed in he logis ic eg ession included
age, sex, COVID-19 se e i y, he use o glucoco icoids,
como bidi y sco e, and obesi y (de ined as BMI > = 30).
All s a is ical es s we e pe o med by an expe ienced
s a is ician using he IBM SPSS S a is ics e sion 29 (IBM
Co p., A monk, NY, USA).
Resul s
F om May 13, 2020, o Janua y 11, 2022, a o al o 2729
su i o s o COVID-19 we e ec ui ed o he p ospec i e
obse a ional s udy (1247 male, 45.7%). A e applying
he pos -hoc exclusion c i e ia, 2026 pa ien s (919 male,
45,36%) we e included in he s a is ical analysis, wi h
131 pa ien s (6.47%) in he CS g oup and 1895 pa ien s
in he WW g oup. The mean age in he coho was 54.37
yea s (SD ± 14.67), wi h he pa ien s in he CS g oup
being signi ican ly olde (mean age 63.44 ± 11.42) han
he pa ien s in he WW g oup (mean age 53.74 ± 14.66;
p < 0.0001). The BMI was compa able be ween he s udy
g oups (mean 29.52, SD ± 5.87 in he o al sample). The
pa ien s in he CS g oup had signi ican ly highe num-
be o como bidi ies han he pa ien s in he WW g oup
wi h he mean como bidi y sco es o 1.63 (SD ± 1.25) and
1.02 (SD ± 1.13), espec i ely (p = 0.0004). The pa ien s
in he CS g oup we e signi ican ly mo e likely o be he
su i o s o se e e COVID-19 han he pa ien s in he
WW g oup (70.99% s. 22.16%, espec i ely; p < 0.0001).
The pa ien s in he CS g oup we e signi ican ly mo e
likely o epo dyspnea han he pa ien s in he WW
g oup (80.15% s. 50.18%, espec i ely; p < 0.0001),
while he incidence o pe sis en cough was compa able
be ween he s udy g oups (36.64% s. 29.97%, espec-
i ely; p = 0.1384). The alues o s a ic lung olumes and
pa ame e s o pulmona y di usion capaci y obse ed a
he baseline (V1) we e s a is ically signi ican ly lowe in
he CS g oup compa ed o he WW g oup (p < 0.0001).
The pos -COVID adiological sco e was signi ican ly
highe in he CS g oup compa ed o he WW g oup wi h
a PRS o 3.75 (SD ± 1.43) and 0.82 ± 1.37, espec i ely
(p < 0.0001). See Table1 o he epidemiological and base-
line cha ac e is ics o he sample and he subg oups.
The ollow-up da a we e a ailable in 131 pa ien s in he
CS g oup and 894 pa ien s in he WW g oup. The pul-
mona y unc ion es (PFT) esul s a baseline (V1) and
ollow-up (V2) isi s a e p esen ed in he Table2. Vi al
capaci y (VC) has imp o ed signi ican ly in bo h he CS
g oup (mean inc ease by 403.7ml, SD ± 510.05, o 10.29%
o p edic ed alue, SD ± 13.33, p = 0.0003 and < 0.0001,
espec i ely) and he WW g oup (mean inc ease by
95.1 ml, SD ± 353.23, o 2.68% o p edic ed alue,
SD ± 9.94, p = 0.0336 and 0.0006, espec i ely). FEV1/
VC ( he Ti eneau index) has signi ican ly dec eased in
he WW g oup (-0.73%, SD ± 4.71; p = 0.0212), bu no
signi ican change was obse ed in he CS g oup. To al
lung capaci y (TLC) has imp o ed signi ican ly in he CS
g oup (mean inc ease by 649.84ml, SD ± 756.45, o 9.95%
o p edic ed alue, SD ± 12.16, p = 0.0001 and < 0.0001,
espec i ely), bu no in he WW g oup (mean inc ease
by 92.72 ml, SD ± 758.67, o 1.27% o p edic ed alue,
SD ± 12.84, p = 0.2036 and 0.1159, espec i ely). Residual
Page 5 o 10
Mize ae al. Pneumonia (2024) 16:2
Table 1 Epidemiological and baseline cha ac e is ics o he sample
a S uden ’s - es o wo samples; bComo bidi y sco e: calcula ed by adding 1 poin o each o he ollowing selec ed como bidi ies: a e ial hype ension, diabe es
melli us, ischemic hea disease, pulmona y embolism, dyslipidemia, hypo hy oidism, b onchial as hma, ch onic obs uc i e pulmona y disease, sa coidosis,
in e s i ial lung disease. The sco e was a ailable in 652 subjec s (46 in he CS g oup and 606 in he WW g oup); cMann-Whi ney U es ; eChi-squa e es ; mild: no
pneumonia, no oxygen he apy, mode a e: pneumonia no equi ing oxygen he apy, se e e: pneumonia equi ing oxygen he apy
o al sample (N = 2026) CS g oup (N = 131) WW g oup (N=1895) p- alue
(mean ± SD) (mean ± SD) (mean ± SD)
Age 54.37 ± 14.67 63.44 ± 11.42 53.74 ± 14.66 <0.0001a
BMI 29.52 ± 5.87 29.82 ± 5.37 29.49 ± 5.90 0.5407a
ComSb1.06 ± 1.15 1.63 ± 1.25 1.02 ± 1.13 0.0004c
PRSd1.01 ± 1.55 3.75 ± 1.43 0.82 ± 1.37 <0.0001c
VC [%p edic ed] 100.52 ± 16.30 86.93 ± 17.25 101.48 ± 15.80 <0.0001c
FEV1/VC [%] 79.61 ± 6.80 79.96 ± 7.75 79.58 ± 6.73 0.2795c
TLC [%p edic ed] 105.37 ± 15.70 90.78 ± 16.36 106.40 ± 15.14 <0.0001c
RV [%p edic ed] 126.04 ± 30.42 108.24 ± 28.88 127.29 ± 30.14 <0.0001c
DLCOc [%p edic ed] 79.62 ± 16.53 57.69 ± 15.94 81.13 ± 15.46 <0.0001c
KCOc [%p edic ed] 89.00 ± 14.78 79.31 ± 16.00 89.67 ± 14.46 <0.0001c
n (%) n (%) n (%) p- aluee
Male sex 919 (45.36%) 85 (64.89%) 834 (44.01%) <0.0001
Acu e COVID-19 se e i y
mild 1046 (51.63%) 7 (5.34%) 1039 (54.83%) <0.0001
mode a e 433 (21.37%) 27 (20.61%) 406 (21.42%) 0.9812
se e e 513 (25.32%) 93 (70.99%) 420 (22.16%) <0.0001
Pe sis en espi a o y symp oms
dyspnea 1056 (52.12%) 105 (80.15%) 951 (50.18%) <0.0001
cough 616 (30.40%) 48 (36.64%) 568 (29.97%) 0.1384
Table 2 Compa ison o pulmona y unc ion es esul s be ween he wo main isi s
a Mann-Whi ney U es ; bPa ien s wi h a ailable ollow-up da a
Baseline isi (V1) Follow-up isi (V2) Mean di e ence p- aluea
(mean ± SD) (mean ± SD) MD ± SD
CS g oup (N = 131) VC [L, ml] 3.25 ± 0.86 3.65 ± 0.89 403.7 ± 510.05 0,0003
VC [%p edic ed] 86.93 ± 17.25 97.22 ± 14.96 10.29 ± 13.33 <0.0001
FEV1/VC [%] 79.96 ± 7.75 79.04 ± 7.69 -0.92 ± 5.23 0,3299
TLC [L, ml] 5.68 ± 1.21 6.30 ± 1.25 649.84 ± 756.45 0,0001
TLC [%p edic ed] 90.78 ± 16.36 100.09 ± 14.86 9.95 ± 12.16 <0.0001
RV [L, ml] 2.48 ± 0.72 2.67 ± 0.71 204.69 ± 700.12 0,0366
RV [%p edic ed] 108.24 ± 28.88 115.32 ± 27.35 8.37 ± 29.19 0,0299
DLCOc [%p edic ed] 57.69 ± 15.94 66.90 ± 14.93 10.18 ± 12.55 <0.0001
KCOc [%p edic ed] 79.31 ± 16.00 83.13 ± 16.51 4.43 ± 11.85 0,0969
WW g oup (N = 894b)VC [L, ml] 3.56 ± 0.98 3.65 ± 0.99 95.1 ± 353.23 0,0336
VC [%p edic ed] 99.23 ± 16.18 101.91 ± 15.65 2.68 ± 9.94 0,0006
FEV1/VC [%] 79.29 ± 7.00 78.56 ± 6.84 -0.73 ± 4.71 0,0212
TLC [L, ml] 6.11 ± 1.30 6.20 ± 1.34 92.72 ± 758.67 0,2036
TLC [%p edic ed] 105.16 ± 15.72 106.31 ± 14.65 1.27 ± 12.84 0,1159
RV [L, ml] 2.61 ± 0.71 2.63 ± 0.71 22.18 ± 611.47 0,6972
RV [%p edic ed] 126.57 ± 30.38 126.59 ± 28.51 0.18 ± 29.61 0,8244
DLCOc [%p edic ed] 77.79 ± 15.96 80.11 ± 14.71 2.79 ± 12.82 0,0101
KCOc [%p edic ed] 88.48 ± 15.43 89.10 ± 15.14 1.51 ± 10.01 0,5088

Page 6 o 10
Mize ae al. Pneumonia (2024) 16:2
olume (RV) has inc eased signi ican ly in he CS g oup
(a mean inc ease by 204.69 ml, SD ± 700.12, o 8.37%
o p edic ed alue, SD ± 29.19, p = 0.0366 and 0.0299,
espec i ely). No signi ican change o RV was obse ed
in he WW g oup. Signi ican inc ease o he ans e
ac o o ca bon monoxide co ec ed o hemoglobin
le el (DLCOc) was obse ed in bo h he CS g oup (a
mean inc ease by 10.18% o p edic ed alue, SD ± 12.55,
p < 0.0001) and he WW g oup (a mean inc ease by 2.79%
o p edic ed alue, SD ± 12.82, p < 0.0101). Nei he g oup
has shown a s a is ically signi ican inc ease o he ans-
e coe icien o ca bon monoxide co ec ed o hemo-
globin le el (KCOc), wi h a mean inc ease by 4.43% o
p edic ed alue (SD ± 11.85; p = 0.0969) in he CS g oup,
and 1.51% o p edic ed alue (SD ± 10.01; p = 0.5088) in
he WW g oup. Table3 compa es bo h s udy g oups wi h
espec o he a e o change o he PFT esul s be ween
he wo main isi s. The inc ease o s a ic lung olumes
(VC, TLC, RV) was signi ican ly highe in he CS g oup
compa ed o he WW g oup (p < 0.0001 o VC and TLC,
p = 0.0013 and 0.003 o absolu e and %p edic ed alues
o RV, espec i ely). Simila ly, he inc ease o DLCOc was
signi ican ly highe in he CS g oup (p < 0.0001). The di -
e ences be ween he a es o change o FEV1/VC and
KCOc we e no s a is ically signi ican (p = 0.1594 and
0.0564, espec i ely).
A he ollow-up isi (V2), he mean Radiologi-
cal Imp o emen Sco e (RIS) was 5.9 (SD ± 3.11) and
5.7 (SD ± 3.67) o he CS and WW g oup, espec-
i ely (p = 0.7966). Comple e adiological imp o emen
(de ined as RIS 9 o 10) was obse ed mo e equen ly in
he CS g oup han he WW g oup wi h 21 (16.03%) s. 94
(10.51%), espec i ely, bu he di e ence was bo de line
non-signi ican (OR 1.62, 95%CI 0.97–2.71). Good adio-
logical imp o emen (de ined as RIS 5 o 8) was obse ed
signi ican ly mo e equen ly in he CS g oup han he
WW g oup wi h 64 (48.85%) s. 98 (10.96%), espec i ely
(OR 7.76, 95%CI 5.19–11.59). The equency o no adio-
logical imp o emen (de ined as RIS o 0) was compa a-
ble be ween he s udy g oups wi h 12 (9.16%) cases in he
CS g oup and 55 (6.15%) cases in he WW g oup, espec-
i ely (OR 1.54, 95%CI 0.80–2.96).
Finally, he mean Subjec i e Imp o emen Sco e
(SIS) a he ollow-up isi (V2) was 7.1 (SD ± 2.71) and
6.7 (SD ± 3.27) o he CS and WW g oup, espec i ely
(p = 0.7). Comple e subjec i e imp o emen (de ined as
SIS 9 o 10) was obse ed signi ican ly mo e equen ly
in he CS g oup han he WW g oup wi h 45 (34.35%) s.
189 (21.14%), espec i ely (OR 1.95, 95%CI 1.32–2.90).
Good subjec i e imp o emen (de ined as SIS 5 o 8) was
seen signi ican ly mo e equen ly in he CS g oup han
he WW g oup wi h 66 (50.38%) s. 196 (21.92%), espec-
i ely (OR 3.62, 95%CI 2.48–5.27). The equency o he
subjec s epo ing no subjec i e imp o emen (de ined as
SIS o 0) was compa able be ween he s udy g oups wi h
8 (6.11%) cases in he CS g oup and 57 (6.38%) cases in
he WW g oup, espec i ely (OR 0.96, 95%CI 0.44–2.05)
(Table4).
Logis ic eg ession analysis was conduc ed o e alua e
he likely p edic o s o lack o subjec i e and adiological
imp o emen , de ined as SIS = 0 and RIS = 0, espec i ely.
Age, sex, COVID-19 se e i y, he use o CS, Como -
bidi y sco e (ComS), and obesi y we e selec ed as inde-
penden a iables. The only independen a iable ha
signi ican ly p edic ed he lack o subjec i e imp o e-
men was he Como bidi y sco e, whe e a uni inc ease
in he sco e inc eased he odds o he pa ien epo ing
no subjec i e imp o emen 1.307 imes (95% CI 1.031–
1.658; p = 0.027). The only independen a iable ha sig-
ni ican ly p edic ed he lack o adiological imp o emen
was he inc easing se e i y o acu e COVID-19, wi h OR
0.271 (95% CI 0.119–0.618) and 0.323 (95% CI 0.156–
0.671) o a mode a e and se e e cou se o COVID-19,
espec i ely (p = 0.002).
Table 3 Compa ison o CS and WW g oups wi h espec o he changes o pulmona y unc ion
a Pa ien s wi h a ailable ollow-up da a; bMann-Whi ney U es
CS g oup (N = 131) WW g oup (N=894a) Mean di e ence p- alueb
(mean ± SD) (mean ± SD) (MD ± SD)
ΔVC [ml] 403.7 ± 510.05 95.1 ± 353.23 308.59 ± 46.10 <0.0001
ΔVC [%p edic ed] 10.3 ± 13.33 2.7 ± 9.94 7.62 ± 1.21 <0.0001
ΔFEV1/VC [%] -0.9 ± 5.23 -0.7 ± 4.71 -0.19 ± 0.48 0,1594
ΔTLC [ml] 649.8 ± 756.45 92.7 ± 758.67 557.13 ± 70.79 <0.0001
ΔTLC [%p edic ed] 9.9 ± 12.16 1.3 ± 12.84 8.68 ± 1.15 <0.0001
ΔRV [ml] 204.7 ± 700.12 22.2 ± 611.47 182.51 ± 64.50 0,0013
ΔRV [%p edic ed] 8.4 ± 29.19 0.2 ± 29.61 8.19 ± 2.74 0,003
ΔDLCOc [%p edic ed) 10.2 ± 12.55 2.8 ± 12.82 7.39 ± 1.18 <0.0001
ΔKCOc [%p edic ed] 4.4 ± 11.85 1.5 ± 10.01 2.92 ± 1.09 0,0564
Page 7 o 10
Mize ae al. Pneumonia (2024) 16:2
Discussion
Bo h he pa ien s ecei ing o al CS and he pa ien s in
he wa ch ul wai ing g oup ha e seen s a is ically signi i-
can inc eases in s a ic lung olumes and DLCO. Mos
o he baseline cha ac e is ics (Age, BMI, VC, FEV1/VC,
DLCO, KCO) in ou s udy we e e y close o he cha ac-
e is ics o he smalle coho (n = 35) desc ibed by Myall
e al. [5] o e ing a good oppo uni y o compa ison. The
a e o imp o emen o i al capaci y (9.6% o p edic ed
alue, SD ± 13.6) epo ed in he a o emen ioned s udy
was compa able o ou esul s, howe e , he epo ed
imp o emen o DLCO (31.49% o p edic ed alue,
SD ± 27.7) was much highe han in ou s udy, albei wi h
highe a iance p obably due o smalle sample size.
In e es ingly, he s udy epo ed a signi ican imp o e-
men in KCO by a mean o 19.9% o p edic ed (95%
CI 9.72–30.1), wi h no signi ican imp o emen being
obse ed in ou coho . The au ho s b ie ly s a e ha he
unc ional imp o emen in hei coho was mi o ed
by good esolu ion o adiological changes and clinical
imp o emen , which seems o be in line wi h ou coho ,
whe e comple e and good adiological and subjec i e
imp o emen was equen ly obse ed in he CS g oup.
Myall e  al. sugges CS he apy only o symp oma ic
pa ien s wi h in ol emen o mo e han 15% o lung
pa enchyma on ches CT, wi h he lack o spon aneous
imp o emen . The ini ial dosage was simila o ou s udy
(a mean dose o 26.6 s. 27.6mg o p ednisolone, espec-
i ely). We specula e ha one o he easons o be e
imp o emen o DLCO and KCO epo ed by Myal e al.
may be he ea lie ini ia ion o he apy (6 weeks s. a
mean o 12 weeks, SD 7.55), and pe haps e en he leng h
o he apy (3 weeks s. a mean o 21 weeks, SD ± 7.96).
Fu he mo e, he mo e es ic i e indica ion o VC he -
apy based on 6-minu e walk es (6MWT), o he p es-
ence o desa u a ion > = 4% may ha e been a mo e p ecise
selec ion ool o he conside a ion o CS he apy, indi-
ca ing possible o e p esc ip ion in ou coho , whe e
he c i e ia we e less s ic (dec eased DLCOc, pe sis-
en adiological abno mali ies and pe sis en espi a o y
symp oms). We acknowledge he lack o 6MWT as one
o he weaknesses o ou s udy. Impo an ly, ou s udy
shows ha pa ien s in he CS medica ing g oup displayed
signi ican ly be e a es o imp o emen o s a ic lung
olumes and DLCO compa ed o he wa ch ul wai ing
g oup, and ha he di e ence seems o be la ge enough
o be clinically ele an .
Dhoo ia e  al. [31] conduc ed an in es iga o -ini-
ia ed, single-cen e , open-label, pa allel-g oup, an-
domized, supe io i y ial ( he COLDSTER ial)
compa ing wo p ednisolone dosage egimens in 130
pa ien s wi h pos -COVID di use lung abno mali-
ies (PC-DPLAS). The CS he apy was ini ia ed 3–8
weeks pos -COVID - ea lie han in ou s udy. The sub-
jec s we e andomized in o wo equally sized g oups
o ecei e ei he he high-dose egimen (ini ial dose
o 40 mg o p ednisolone ape ed o e 6 weeks) o
he low-dose egimen (10mg o p ednisolone o e 6
weeks). The inclusion c i e ia we e di use lung abno -
mali ies a ec ing a leas 20% o he lung pa enchyma
on semiquan i a i e assessmen on hin sec ion CT,
and a leas one o he ollowing: mMRC sco e o 2 o
highe , es ing SpO2 94% o below, o desa u a ion by
a leas 4% du ing 6MWT. No signi ican di e ence was
obse ed be ween he wo CS egimens wi h ega ds o
he a e o comple e adiological esponse (de ined as
90% o g ea e imp o emen on he ollow-up ches CT
scan), which was seen in 24.6% and 18.5% in high and
low-dose CS g oups, espec i ely. Simila ly, no signi i-
can di e ence be ween he s udy g oups was obse ed
wi h espec o he a e o “good o comple e adiologi-
cal esponse” (de ined as 50% o g ea e imp o emen ),
Table 4 Compa ison o CS and WW g oups wi h espec o he adiological and subjec i e imp o emen
a Pa ien s wi h a ailable ollow-up da a; bRadiological imp o emen sco e (0–10); cMann-Whi ney U es ; dSubjec i e imp o emen sco e (0–10); eRIS 9–10; RIS 5–8;
gRIS = 0; hSIS 9–10; iSIS 5–8; iSIS = 0
CS g oup (N = 131) WW g oup (N = 894a) Mean di e ence p- aluec
(mean ± SD) (mean ± SD) (MD ± SD)
RISb5.9 ± 3.11 5.7 ± 3.67 0.17 ± 0.30 0.7966
SISd7.1 ± 2.71 6.7 ± 3.27 0.40 ± 0.26 0.7
n (%N) n (%N) OR (95% CI)
Comple e adiological imp o emen :e21 (16.03%) 94 (10.51%) 1.62 (0.97 - 2.71)
Good adiological imp o emen : 64 (48.85%) 98 (10.96%) 7.76 (5.19 - 11.59)
No adiological imp o emen :g12 (9.16%) 55 (6.15%) 1.54 (0.80 - 2.96)
Comple e subjec i e imp o emen :h45 (34.35%) 189 (21.14%) 1.95 (1.32 - 2.90)
Good subjec i e imp o emen :i66 (50.38%) 196 (21.92%) 3.62 (2.48 - 5.27)
No subjec i e imp o emen :j8 (6.11%) 57 (6.38%) 0.96 (0.44 - 2.05)
Page 8 o 10
Mize ae al. Pneumonia (2024) 16:2
which was seen in 84.6% and 80.0% in he high and low
dose egimen, espec i ely. The epo ed a es o adio-
logical esponse we e highe han in ou coho , whe e
he comple e esponse in he CS g oup was obse ed
in 16.03% and “comple e o good” esponse in 48.85%.
Howe e , he compa ison is no di ec as he adio-
logical imp o emen in ou coho was sco ed semi-
quan i a i ely using pai ed ches X- ays a he han he
quan i a i e assessmen o he CT scans used in he
COLDSTER ial. Despi e his majo me hodological
di e ence, he esul s consis en ly show ha he majo -
i y o pa ien s p esc ibed CS ha e expe ienced signi i-
can adiological imp o emen . Impo an ly, ou da a
show ha he a es o “good o comple e” adiological
imp o emen we e signi ican ly highe in he CS e sus
wa ch ul wai ing g oup. Un o una ely, he PFT in he
COLDSTER ial only encompassed s anda d spi om-
e y and only he alue o FVC a week 6 was epo ed,
wi hou p o iding he baseline alue. The epo ed
mean FVC a week 6 is signi ican ly lowe e en in com-
pa ison wi h he mean baseline alue obse ed in ou
coho , e en mo e so when compa ed o he alue a
V2. Addi ionally, he e we e signi ican di e ences
be ween he s udy popula ion and ou coho wi h
espec o sex, age and COVID-19 se e i y.
Goel e  al. [30] epo ed on 49 pa ien s wi h long
COVID, abno mal indings on ches CT, and es ing o
exe ion hypoxemia. 24 o he pa ien s we e ea ed wi h
de lazaco o 8 o 10 weeks, ini ia ed 4 weeks a e he
in ec ion - ea lie han in ou coho . A he ini ia ion o
he apy, 58% o he pa ien s epo ed Modi ied Medical
Resea ch Council (mMRC) sco e o 4, which dec eased
o a sco e 2 o less in 86% o he pa ien s ollowing CS
ea men . The occu ence o b ea hlessness has hal ed,
he incidence o cough has dec eased by almos 70%.
The majo i y o he pa ien s (71%) epo ed subjec-
i e imp o emen , which is in line wi h pa ien s in ou
coho , whe e 50.38% and 34.35% o pa ien s ea ed
wi h CS ha e epo ed good and comple e subjec i e
imp o emen , espec i ely. Comple e adiological eso-
lu ion o pos -COVID esidual changes was seen in 25%
o he pa ien s, which is close o he 16.03% o pa ien s
wi h comple e adiological esponse in he CS g oup o
ou coho . Addi ionally, Goel e al. epo he 6-min-
u e walk es dis ance (6MWD) inc ease by an a e age
o 75m. Indica ion c i e ia o CS he apy we e abno -
mali ies on HRCT o he lungs ( e icula ions, g ound
glass opaci ies o pa enchymal bands) and oxygen sa u a-
ion (SpO2) below 90%, o desa u a ion by mo e han 4%
du ing 6MWT. De lazaco was adminis e ed in a dose
equi alen o 0,25–0,5mg/kg o p ednisolone, which is
compa able o ou s udy, and ape ed o e 6 o 10 weeks
(usually 8 weeks) based on adiological eco e y. The
weakness o he s udy was he lack o pulmona y unc-
ion es ing and he small coho size.
Acco ding o Bieksiene e al. [20] imely glucoco icoid
he apy can be bene icial in p e en ing he de elopmen
o de ini i e ib o ic changes in pa ien s wi h pos -
COVID pulmona y impai men , ypically wi hin he i s
12 weeks om he acu e s age o he disease. In he case
o mo e d ama ic la e-s age disease p esen a ions, such
as acu e ib inous o ganizing pneumonia, se e al cases o
good esponse o co icos e oid pulses (up o 1g me hyl-
p ednisolone o 3 consecu i e days) ollowed by ape ing
o lowe doses o CS ha e been epo ed in he li e a u e
[23, 24, 33].
Limi a ions o  hes udy
One o he majo limi a ions o he p esen s udy is he
ac ha he da a ex ac ion p ocess is s ill ongoing. The
esul s o he s udy should he e o e be iewed as in e im.
This is pa ially ou weighed by he ela i ely la ge size
and obus ness o he a ailable da a. Ano he weakness
o his s udy is he lack o andomiza ion as his was a
eal-li e s udy and he decision o CS he apy was d i en
by pe cei ed clinical necessi y wi h a p ima y in en ion
no o ha m. The dosage o CS used in he s udy was
no s anda dized and was subjec o he decision o he
in es iga ing physician. Finally, he cu en ly incomple e
da a ega ding he cou se o acu e COVID-19 only pe -
mi ed a ough di ision in o mild, mode a e and se e e
ca ego ies, bu did no p o ide enough da a o accu a ely
label he su i o s o c i ical COVID-19. This will likely
change in he u u e as mo e da a a e being ex ac ed
om he sou ce in o ma ion.
Conclusion
Despi e he ma ked di e ences be ween s udy popula-
ions and me hodological di e ences, mos o he pub-
lished s udies epo a o able adiological, subjec i e,
and unc ional ou comes in mos pa ien s ea ed wi h
glucoco icoids o pos -COVID pulmona y in ol e-
men . Ou s udy con i ms hese p e ious obse a ions
by p o iding a compa a i ely la ge da ase and a com-
pa ison o an unma ched con ol g oup, showing be e
unc ional, adiological, and subjec i e imp o emen in
selec ed pa ien s ea ed wi h o al co icos e oids.
Conside ing ou da a alongside p e iously published
s udies, he sugges ed indica ion c i e ia should include
signi ican pa enchymal in ol emen , dec eased alue
o DLCO and pe sis en subjec i e symp oms. Res ing
desa u a ion, o desa u a ion du ing he 6-minu e walk
es may u he suppo he decision and lead o mo e
p ecise indica ion o CS he apy.
One possible app oach o imp o e clinical decision
making may be he use o a i icial in elligence d i en
Page 9 o 10
Mize ae al. Pneumonia (2024) 16:2
algo i hms, as demons a ed by an a ilia ed collec i e o
Myska e al. [34], who ha e used he da a om Olomouc
pos -COVID da ase o es he pe o mance o 9 di e -
en machine lea ning algo i hms in p edic ing imp o e-
men in he pa ien s indica ed o CS he apy. The bes
esul s we e achie ed by he Decision T ee app oach,
eaching 73.52% balanced accu acy on a alida ion po -
ion o he da ase .
The au ho s con inue wi h he wo ks on he Olomouc
pos -COVID da ase , aiming a p o iding mo e de ailed
da a on como bidi ies and o he clinical pa ame e s. The
au ho s aim o make he da ase publicly a ailable and o
p o ide da a om u he ollow-up o hope ully b ing
new insigh s abou he mo e long- e m ou comes o
hese pa ien s, as he e a e s ill ques ions o be answe ed.
The opics o u u e esea ch include, among o he s, he
op imum leng h o he apy, he c i e ia o cessa ion o
he apy, he possible bene i s o an i ib o ics in combi-
na ion wi h CS, o he incidence and cha ac e is ics o
elapses ollowing CS cessa ion.
Au ho s’ con ibu ions
J.M. w o e manusc ip ex , collec ed and analyzed da a; S.G. coope a ed on
w i ing he manusc ip ex , collec ed and analyzed da a; M.S. collec ed and
analyzed da a; R.B. collec ed and analyzed da a; J.Z. analyzed da a and helped
wi h manusc ip p epa a ion; P.J. helped wi h p epa a ion o manusc ip ex ,
collec ed and analyzed da a; M.V. helped wi h manusc ip p epa a ion; P.P.
helped wi h manusc ip p epa a ion and da a analyzis; L.S. helped wi h manu-
sc ip p epa a ion and da a analyzis.
Funding
The s udy was suppo ed by Czech Heal h Resea ch Council g an numbe
NU22-A-105.
A ailabili y o da a and ma e ials
The da a ha suppo he indings o his s udy a e no openly a ailable due
o easons o sensi i i y and a e a ailable om he co esponding au ho
upon easonable eques . Da a a e loca ed in con olled access da a s o age a
Palacky Uni e si y Olomouc, Czech epublic.
Decla a ions
E hics app o al and consen o pa icipa e
All subjec s ag eed o join he s udy and signed in o med consen . The con-
sen o mino s had o be signed by hei legal ep esen a i e (a pa en ). The
local e hical commi ee app o ed he s udy (E hical Commi ee o Uni e si y
Hospi al Olomouc and Facul y o Medicine and Den is y o Palacky Uni e si y
Olomouc, Czech Republic), wi h decision numbe 98/21 (da e 7/JUN/2021).
Compe ing in e es s
The au ho s decla e no compe ing in e es s.
Au ho de ails
1 Depa men o Respi a o y Medicine and Tube culosis, Facul y o Medicine
and Den is y Palacky Uni e si y Olomouc, Uni e si y Hospi al Olomouc,
Olomouc, Czech Republic. 2 Cen e o Digi al Heal h, Facul y o Medicine
and Den is y, Palacky Uni e si y Olomouc, Hne o inska 976/3, Olomouc 779
00, Czech Republic. 3 Depa men o Respi a o y Medicine and Tube culosis,
Facul y o Medicine and Den is y Masa yk, Uni e si y Hospi al B no, Uni e si y
B no, B no, Czech Republic. 4 Dep . o Telecommunica ions, Facul y o Elec ical
Enginee ing and Communica ion, B no Uni e si y o Technology, B no, Czech
Republic. 5 Depa men o Respi a o y Medicine and Tube culosis, L.Pas eu
Uni e si y Hospi al and Facul y o Medicine P.J. Sa a ik Uni e si y Kosice,
Kosice, Slo akia. 6 Depa men o Medical Biophysics, Facul y o Medicine
and Den is y Palacky Uni e si y Olomouc, Olomouc, Czech Republic.
Recei ed: 3 Oc obe 2023 Accep ed: 2 Decembe 2023
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