B idging he e idence gap: expe consensus on managemen o SARS-
CoV-2 acu e in ec ion and pos eCOVID-19 condi ion in
immunocomp omised pa ien s
Lo enzo M. Canziani
1
,
*
, An onella d'A minio Mon o e
2
, Maddalena Giannella
3
,
4
,
Jesús Rod íguez-Ba~
no
5
,
6
, E elina Tacconelli
1
1)
Di ision o In ec ious Diseases, Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona, Ve ona, I aly
2)
Icona Founda ion, Milan, I aly
3)
In ec ious Diseases Uni , Depa men o In eg a ed In ec ious Risk Managemen , IRCCS Azienda Ospedalie o-Uni e si a ia di Bologna, Bologna, I aly
4)
Depa men o Medical and Su gical Sciences, Alma Ma e S udio um Uni e si y o Bologna, Bologna, I aly
5)
Unidad Clínica de En e medades In ecciosas y Mic obiología, Hospi al Uni e si a io Vi gen Maca ena; Depa amen o de Medicina, Uni e sidad de Se illa;
Ins i u o de Biomedicina de Se illa (IBiS)/CSIC, Se ille, Spain
6)
CIBERINFEC, Ins i u o de Salud Ca los III, Mad id, Spain
a icle in o
A icle his o y:
Recei ed 2 May 2025
Accep ed 4 May 2025
A ailable online 13 May 2025
Edi o : L. Leibo ici
Keywo ds:
COVID-19
Delphi su ey
Expe opinion
Immunocomp omized pa ien
Long COVID
The COVID-19 pandemic highligh ed he inhe en empo al
dispa i y be ween he gene a ion o eliable scien ific e idence and
he u gen clinical needs o pa ien s, pa icula ly hose exhibi ing
significan , albei less p e alen , como bidi ies. This empo al lag
equen ly esul ed in he apeu ic decision-making unde condi-
ions o e iden ia y sca ci y. Immunocomp omised indi iduals
exhibi an ele a ed suscep ibili y o SARS-CoV-2 in ec ion. How-
e e , he in e sec ion o specific immunosupp essi e como bidi ies
and COVID-19 is a ely cha ac e ized wi hin COVID-19 esea ch.
This unde ep esen a ion s ems no only om he ela i ely low
p e alence o hese combined condi ions bu also om he
inhe en me hodological complexi ies associa ed wi h conduc ing
obus clinical in es iga ions, pa icula ly andomized con olled
ials, wi hin pa ien popula ions o en cha ac e ized by high
mo ali y a es and clinical he e ogenei y.
In May 2023, WHO o ficially decla ed he end o he COVID-19
pandemic as a global heal h eme gency, la gely due o he wide-
sp ead implemen a ion o mass accina ion campaigns and he
a ailabili y o e ec i e medical he apies. Since hen, he incidence
o new COVID-19 cases has significan ly declined wo ldwide, and
guidelines de eloped du ing he pandemic ha e quickly become
o e ly es ic i e o ou da ed. Meanwhile, he dynamic e olu ion o
clinical needs, pa icula ly o immunocomp omised indi iduals,
has ou paced he gene a ion o imely and high-quali y e idence o
in o m op imal managemen s a egies.
In his pos -pandemic se ing, clinicians equen ly encoun e
complex decision-making scena ios in which cu en e idence o e s
limi ed di ec guidance. Wi hin ORCHESTRA (“Connec ing Eu opean
coho s o inc ease common and e ec i e esponse o SARS-CoV-2
pandemic”), a Ho izon2020- unded p ojec (h ps://o ches a-coho .
eu/)[1], a se ies o ou Delphi su ey we e conduc ed o add ess c i -
ical knowledge gaps conce ning COVID-19 managemen in key immu-
nocomp omised popula ions: solid o gan ansplan s [2], hema ologic
malignancies [3], heuma ological diseases [4], and people wi h HIV [5].
The Delphi me hod is a well-es ablished echnique ha employs i e a-
i e ques ionnai es wi h agg ega ed eedback om expe panellis s o
elici in o med opinion, pa icula ly in a eas cha ac e ized by e idence
gaps. The main opics explo ed in hese su eys included he iden ifi-
ca ion o high isk o de eloping se e e COVID-19, he diagnos ic al-
go i hms employed, he u iliza ion o ea ly an i i al he apy (including
an i-spike monoclonal an ibodies, emdesi i , ni ma el i / i ona i ,
and molnupi a i ), he in e ac ion be ween COVID-19 and he ele an
como bidi y, and pos eCOVID-19 condi ion (PCC). No ably, he
This a icle was published as pa o a supplemen suppo ed by he ORCHESTRA
p ojec . The ORCHESTRA p ojec has ecei ed unding om he Eu opean Union’s
Ho izon 2020 esea ch and inno a ion p og amme unde g an ag eemen No
101016167. The iews exp essed in his a icle a e he sole esponsibili y o he
au ho and he Commission is no esponsible o any use ha may be made o he
in o ma ion i con ains.
*Co esponding au ho : Lo enzo M. Canziani, Di ision o In ec ious Diseases,
Depa men o Diagnos ics and Public Heal h, Uni e si y o Ve ona, Piazzale L. A.
Scu o 10, 37134, Ve ona, I aly.
E-mail add ess: lo enzoma ia.canziani@uni .i (L.M. Canziani).
Con en s lis s a ailable a ScienceDi ec
Clinical Mic obiology and In ec ion
jou nal homepage: www.clinicalmic obiologyandin ec ion.com
h ps://doi.o g/10.1016/j.cmi.2025.05.008
1198-743X/©2025 The Au ho s. Published by Else ie L d on behal o Eu opean Socie y o Clinical Mic obiology and In ec ious Diseases. This is an open access a icle unde
he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
Clinical Mic obiology and In ec ion 31 (2025) S1eS2
ques ions pe aining o PCC we e s anda dized ac oss all ou Delphi
su eys, and he findings ha e been published sepa a ely [6].
D awn om in e na ional expe ise, consensus was eached on
64 s a emen s. They ep esen a collabo a i e syn hesis o expe
opinion suppo ed by he a ailable li e a u e, o e ing p ac ical
guidance on key pa ien ca e a eas in he selec ed immunocom-
p omised popula ions.
A key insigh de i ed om his expe ience was he ea fi med
impo ance o pa ien -cen ed ca e as he o e a ching guiding
amewo k. Assessing he immedia e isks o an indi idual
pa ien dpa icula ly when balancing he ypically mild ajec o y
o SARS-CoV-2 in ec ion agains a p e-exis ing, clinically significan
como bidi yd equi es nuanced clinical judgmen . This decision-
making p ocess in ol es he in eg a ion o nume ous pa ien -
specific a iables ha a e bes syn hesized by he ea ing physi-
cian. In such complex scena ios, expe opiniondin o med by
li e a u e and eal-wo ld clinical expe iencedplays a c ucial ole in
ou lining a ange o easonable, con ex -specific app oaches a he
han a single p esc ip i e pa hway.
The second heme eme ging om he su ey is he ecogni ion
o inc eased isk o SARS-CoV-2 in ec ion and se e e COVID-19 ha
is s ill p esen in hese immunocomp omised pa ien s. This
inc eased ulne abili y unde sco es he need o p io i ize hese
popula ions in public heal h s a egies, including esou ce alloca-
ion o accina ion campaigns, ea ly an i i al ea men access,
and a ge ed p e en i e in e en ions. A he indi idual pa ien
le el, i ein o ces he impo ance o main aining igilan clinical
ollow-up, pe sonalized isk assessmen , and imely he apeu ic
decision-making o mi iga e complica ions and imp o e ou comes.
Reflec ing he su ey's emphasis on pa ien -cen ed ca e and he
need o a ge ed app oaches in immunocomp omised indi iduals,
ega ding he diagnos ic p ocess, i has been emphasized ha bo h
an igen and PCR-based es s main ain adequa e posi i e p edic i e
alue in he cu en epidemiological scena io. Because o he lowe
incidence o COVID-19, es ing should be limi ed o only symp oma ic
pa ien s a he han uni e sal sc eening a hospi al admission.
The use o ea ly an i i al he apy in clinical p ac ice con inues o
be conside ed aluable by he panel, al hough i s implemen a ion
emains cons ained by se e al ac o s. Molnupina i is no a ail-
able in many coun ies igh now, whe eas he e ec i eness o an i-
spike monoclonal an ibodies o p e en ion and ea men de-
pends on he suscep ibili y o ci cula ing a ian s. Remdesi i e-
qui es in a enous adminis a ion, posing logis ical challenges, and
he use o ni ma el i / i ona i is equen ly limi ed by d uged ug
in e ac ions. Ne e heless, specific p esc ibing pa e ns o ea ly
an i i al he apy appea o be eme ging om expe expe ience:
combina ion he apy has gene ally been a oided, and in se e ely
immunocomp omised pa ien sdpa icula ly hose wi h B-cell
deple iond he eme ging clinical scena io o pe sis en COVID-19
symp oms has led o he p ac ice o adminis e ing addi ional
an i i al dosing. This end highligh s an impo an gap in he
cu en e idence base and unde sco es he need o ailo ed he -
apeu ic s a egies in his high- isk popula ion.
Tempo a y discon inua ion o immunosupp essi e agen sdsuch
as an i-CD20 monoclonal an ibodies and an ime aboli esdis gene -
ally ecommended. Glucoco icoids, howe e , a e ypically excluded
om his app oach, as hey emain he co ne s one o ea men in
mode a e o se e e COVID-19. The iming o medical p ocedu es in
pa ien s wi h COVID-19 has become mo e flexible, eflec ing he
inc eased manageabili y o he disease; sho pos ponemen s a e
o en su ficien , and ex ended delays a e no longe ou inely neces-
sa y in mos clinical se ings. In ansplan se ings, wi h he excep-
ion o lung g a s, SARS-CoV-2 posi i i yin dono s is no conside ed a
con aindica ion, and nei he p e-emp i e an i i al he apy no al-
e a ions o induc ion immunosupp ession a e equi ed.
Recommenda ions on PCC in immunocomp omised pa ien s
emain limi ed. The ORCHESTRA panel expe s iden ified ch onic a-
igue as he mos equen p esen a ion o PCC in he a ge pop-
ula ions. Key isk ac o s o he de elopmen o PCC include se e e
acu eCOVID-19, olde age, and emalesex. In case o ch onic a igue o
a h algia o new onse , a diagnos ic wo kup o ule ou au oimmune
diso de s has been sugges ed. P e en i e s a egiesdincluding ull-
cou se accina ion and imely an i i al he apydshould be s ongly
encou aged o educe he isk o PCC in his ulne able popula ion.
Mo ing beyond he limi a ions o cu en e idence, his comp e-
hensi e e o , encompassing ou dis inc Delphi su eys, p oac i ely
add essed he u gen clinical needs o immunocomp omised pa ien s
acingSARS-CoV-2 in ec ion and i s sequelae. The esul ing consensus
o e s a aluable esou ce, empowe ing clinicians wi h expe -
in o med guidance o na iga e he complexi ies o diagnosis, ea -
men , and long- e m managemen in solid o gan ansplan s, he-
ma ologic malignancies, heuma ological diseases, and people wi h
HIV. The su ey exe cise no only p o ided p ac ical ecommenda-
ions bu also helped o highligh c i ical gaps in he cu en e idence
base. No ably, his app oach no only add esses he immedia e chal-
lenges o he ecen pandemic bu alsop o ides a aluable amewo k
o u u e pandemic p epa edness plans, ensu ing ha he unique
needs o immunocomp omised indi iduals a e p oac i ely consid-
e ed and add essed in e ol ing heal h c ises. Howe e , eliance on
expe consensus alone is no su ficien in he long e m. The e e-
mains a p essing need o mo e ad anced, agile me hod-
ologiesdcapable o in eg a ing eal-wo ld da a, adap i e ial
designs, and mul idisciplina y inpu d o ensu e ha e idence keeps
pace wi h eme ging challenges and mee s he nuanced needs o
ulne able pa ien popula ions.
Funding
This a icle was published as pa o a supplemen suppo ed by
he ORCHESTRA p ojec . The ORCHESTRA p ojec has ecei ed
unding om he Eu opean Union's Ho izon 2020 esea ch and
inno a ion p og amme unde g an ag eemen no. 101016167. The
iews exp essed in his a icle a e he sole esponsibili y o he
au ho and he Eu opean Commission is no esponsible o any use
ha may be made o he in o ma ion i con ains.
Conflic o in e es
The au ho s decla e ha hey ha e no conflic s o in e es .
Re e ences
[1] Azzini AM, Canziani LM, Da is RJ, Mi andola M, Hoelsche M, Meye L, e al.
How Eu opean esea ch p ojec s can suppo accina ion s a egies: he case o
he ORCHESTRA p ojec o SARS-CoV-2. Vaccines 2023;11:1361. h ps://
doi.o g/10.3390/ accines11081361.
[2] Tazza B, Ca occia N, Toschi A, Pascale R, Gk ania-Klo sas E, Na a o PO, e al.
ORCHESTRA Delphi consensus: diagnos ic and he apeu ic managemen o
SARS-CoV-2 in ec ion in solid o gan ansplan ecipien s. Clin Mic obiol In ec
2025;31:S21e31. h ps://doi.o g/10.1016/j.cmi.2025.02.010.
[3] Canziani LM, Azzini AM, Salman on-Ga cía J, Sa oldi A, Caponcello MG,
Pasquini Z, e al. ORCHESTRA Delphi consensus: diagnos ic and he apeu ic
managemen o SARS-CoV-2 in ec ion in haema ological pa ien s. Clin Mic o-
biol In ec 2025;31:S32e42. h ps://doi.o g/10.1016/j.cmi.2025.03.004.
[4] Caponcello MG, Na a o PO, Bonazze i C, Campoli C, Sa oldi A, Gen ilo i E,
e al. ORCHESTRA Delphi consensus: diagnos ic and he apeu ic managemen
o SARS-CoV-2 in ec ion in pa ien s wi h heuma ological diseases. Clin
Mic obiol In ec 2025;31:S14e20. h ps://doi.o g/10.1016/j.cmi.2025.02.030.
[5] Ta elli A, Ve go i A, Cingolani A, Bai F, AzziniAM, Ha a GL, e al. ORCHESTRA Delphi
consensus: clinical managemen o SARS-CoV-2 in ec ion in people wi h HIV. Clin
Mic obiol In ec 2025;31:S43e54. h ps://doi.o g/10.1016/j.cmi.2025.03.006.
[6] Gen ilo i E, Canziani LM, Caponcello MG, Azzini AM, Sa oldi A, De Na do P,
e al. ORCHESTRA Delphi consensus: diagnos ic and he apeu ic managemen
o pos -COVID-19 condi ion in ulne able popula ions. Clin Mic obiol In ec
2025;31:S3e13. h ps://doi.o g/10.1016/j.cmi.2025.04.009.
L.M. Canziani e al. / Clinical Mic obiology and In ec ion 31 (2025) S1eS2S2
