ORIGINAL RESEARCH
published: 25 Sep embe 2020
doi: 10.3389/ med.2020.576162
F on ie s in Medicine | www. on ie sin.o g 1Sep embe 2020 | Volume 7 | A icle 576162
Edi ed by:
Geo ge Be sias,
Uni e si y o C e e, G eece
Re iewed by:
Ma ia Del Pila Es e ez Diz,
Uni e sidad de São Paulo, B azil
Gecilma a Sal ia o Pileggi,
Facul y o Heal h Sciences o Ba e os
D . Paulo P a a (FACISB), B azil
*Co espondence:
João Eu ico Fonseca
[email p o ec ed]
†ORCID:
João Eu ico Fonseca
o cid.o g/0000-0003-1432-3671
‡As lis ed in Collabo a i e G oup
Au ho ship Sec ion
Special y sec ion:
This a icle was submi ed o
Rheuma ology,
a sec ion o he jou nal
F on ie s in Medicine
Recei ed: 25 June 2020
Accep ed: 14 Augus 2020
Published: 25 Sep embe 2020
Ci a ion:
Romão VC, Oli ei a-Ramos F,
C uz-Machado AR, Ma ins P,
Ba ei a S, Sil a-Dinis J,
Mendonça-Galaio L, P oença H, Melo
C is ino J, Sacadu a-Lei e E,
Khmelinskii N, Romeu JC, Fonseca JE
and he CHULN Rheuma ology
Depa men (2020) A COVID-19
Ou b eak in a Rheuma ology
Depa men Upon he Ea ly Days o
he Pandemic. F on . Med. 7:576162.
doi: 10.3389/ med.2020.576162
A COVID-19 Ou b eak in a
Rheuma ology Depa men Upon he
Ea ly Days o he Pandemic
Vasco C. Romão1,2, Filipa Oli ei a-Ramos1,2, Ana Ri a C uz-Machado1,2,
Pa ícia Ma ins1,2, So ia Ba ei a1,2, Joana Sil a-Dinis1,2, Luís Mendonça-Galaio3,
Helena P oença4, José Melo C is ino4, Ema Sacadu a-Lei e3, Niki a Khmelinskii1,2,
José Ca los Romeu1, João Eu ico Fonseca1,2*†and
he CHULN Rheuma ology Depa men 1‡
1Rheuma ology Depa men , Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e , Lisbon, Po ugal, 2Rheuma ology Resea ch Uni , Ins i u o de Medicina Molecula João Lobo An unes,
Faculdade de Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal, 3Occupa ional Heal h Depa men , Hospi al de San a
Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic Medical Cen e , Lisbon, Po ugal, 4Clinical Pa hology
Depa men , Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic Medical Cen e ,
Lisbon, Po ugal
Objec i es: To desc ibe ou expe ience wi h a co ona i us disease 2019 (COVID-19)
ou b eak wi hin a la ge heuma ology depa men ea ly in he pandemic.
Me hods: Symp oma ic and asymp oma ic heal hca e wo ke s (HCWs) had a
naso-o opha yngeal swab o de ec ion o se e e acu e espi a o y synd ome
co ona i us 2 (SARS-CoV-2) and we e ollowed clinically. Re e se ansc ip ion
polyme ase-chain eac ion (RT-PCR) was epea ed o documen cu e, and se ological
esponse was assessed. Pa ien s wi h isk con ac s wi hin he depa men in he 14
days p eceding he ou b eak we e sc eened o COVID-19 symp oms.
Resul s: 14/34 HCWs (41%; 40 ±14 yea s, 71% emale) es ed posi i e o
SARS-CoV-2, and 11/34 (32%) de eloped symp oms bu we e RT-PCR-nega i e. Hal
o RT-PCR-posi i e HCWs did no epo e e , cough, o dyspnea be o e es ing, which
we e absen in 3/14 cases (21%). Mild disease p e ailed (79%), bu 3 HCWs had
mode a e disease equi ing u he assessmen , which excluded se e e complica ions.
Ne e heless, symp om du a ion (28 ±18 days), i al shedding (31 ±10 days
pos -symp om onse , ange 15–51), and wo k absence (29 ±28 days) we e p olonged.
13/14 (93%) o RT-PCR-posi i e and none o he RT-PCR-nega i e HCWs had a posi i e
humo al esponse Highe IgG indexes we e obse ed in indi iduals o e 50 yea s o
age (14.5 ±7.7 s. 5.0 ±4.4, p=0.012). O 617 heuma ic pa ien s, 8 (1.3%)
de eloped COVID-19 symp oms (1/8 hospi aliza ion, 8/8 comple e eco e y), ollowing
a consul a ion/p ocedu e wi h an asymp oma ic (7/8) o mildly symp oma ic (1/8) HCW.
Conclusions: A COVID-19 ou b eak can occu among HCWs and heuma ic pa ien s,
swi ly sp eading o e he p esymp oma ic s age. Mild disease wi hou ypical symp oms
should be ecognized and may e ol e wi h delayed i al shedding, p olonged eco e y,
and adequa e immune esponse in mos indi iduals.
Keywo ds: COVID-19, heuma ology p ac ice, heuma ic pa ien s, heal hca e wo ke s (HCW), p esymp oma ic
ansmission
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
INTRODUCTION
Following he ini ial desc ip ions in ea ly Janua y 2020 o a no el
o m o se e e pneumonia in pa ien s om Wuhan, China (1–
4), he co ona i us disease 2019 (COVID-19) quickly sp ead a
a global le el. On Janua y 30, he Wo ld Heal h O ganiza ion
decla ed i a public heal h eme gency o in e na ional conce n
(5), and i was subsequen ly upda ed o a pandemic on Ma ch
11 (6). A e he i s epo ed case in Po ugal (Ma ch 2),
exponen ial g ow h led o he ins i u ion o majo es ic i e
measu es (7).
Consis en ly high in ec ion a es among heal hca e wo ke s
(HCWs) ha e been epo ed in se e al ha d-hi coun ies, such
as China (8,9), I aly (10), Spain (11), and he Uni ed S a es
(12), despi e adequa e sa e y measu es (13). One possibili y is
ha in-hospi al ansmission among pa ien s and HCWs migh
be a key o m o con agion (9,14,15). This is pa icula ly
ele an gi en he ansmission dynamics o se e e acu e
espi a o y synd ome co ona i us 2 (SARS-CoV-2), whe eby
p esymp oma ic/asymp oma ic con amina ion is likely o play a
majo ole in disease sp eading (14–19).
In he ea ly days o he pandemic, mos ocus was gi en
o se e e clinical pic u es (2,8,9,20), and epo s on mild
o asymp oma ic disease we e sca ce (21,22). This may
ha e con ibu ed o an ini ial o e sigh o mo e gene al, less
se e e mani es a ions, such as uppe espi a o y and diges i e
symp oms (23). These milde disease o ms migh be easily
unde alued, including by HCWs esponding o he pandemic.
In heal hca e acili ies, his may acili a e he gene alized
sp ead among HCWs, who can se e as disease- ansmission
agen s (9,14–16). This ac may be pa icula ly ele an
in ou pa ien -o ien ed depa men s wi h a high olume o
clinical ac i i y (e.g., heuma ology). In addi ion, heuma ology
p ac ice equi es daily close physical con ac wi h pa ien s wi h
heuma ic and musculoskele al diseases (RMDs), who a e o en
immunosupp essed and ha e an inc eased o e all in ec ious isk.
In he p esen epo , we aim o desc ibe ou expe ience wi h
a COVID-19 ou b eak wi hin ou depa men , upon he ini ial
weeks o he pandemic, highligh ing clinical, i ological, and
immunological ou comes o HCWs and RMD pa ien s.
MATERIALS AND METHODS
Ou b eak Cha ac e iza ion
O e he week o Ma ch 9–15, 2020, se e al HCWs o he
heuma ology depa men o Cen o Hospi ala Uni e si á io
Lisboa No e (CHULN) de eloped mild symp oms compa ible
wi h COVID-19. All s a (symp oma ic/asymp oma ic)
unde wen sc eening o SARS-CoV-2 on Ma ch 15–16. Double
naso-o opha yngeal swabs we e ob ained, and samples we e
es ed o SARS-CoV-2 by e e se ansc ip ion-polyme ase
chain eac ion (RT-PCR; cobas R
SARS-CoV-2 ki , cobas R
6800
Sys em, Roche Diagnos ics, USA). All he con i med and
suspec ed cases we e qua an ined and e e ed o public heal h
au ho i ies. Daily emo e clinical moni o ing o HCWs was
conduc ed by 2 asymp oma ic heuma ologis s in conjunc ion
wi h public heal h and occupa ional medicine specialis s.
Tes ing o HCWs was epea ed (i) 7–14 days a e he i s
nega i e es in subjec s wi h pe sis ing symp oms and (ii) 5–7
days ollowing he esolu ion o e e and imp o emen in
espi a o y symp oms in con i med cases (24). Two consecu i e
nega i e es s we e equi ed o con i m i al shedding cessa ion
and allow e u n o wo k (25). Immunological esponse o
SARS-CoV-2 was e alua ed by chemiluminescen immunoassay
(MAGLUMI R
800 CLIA Sys em, MAGLUMI R
2019-nCoV
(SARS-CoV-2) IgM/IgG-ki s, Snibe Co., L d., China) in all
HCWs, ollowing symp om esolu ion and double-nega i e
RT-PCR in con i med cases.
We con ac ed pa ien s obse ed du ing he p e ious 2 weeks
in he day-ca e uni , ou pa ien clinic, and p ocedu es oom
who had possible con ac s wi h con i med RT-PCR-posi i e
HCWs. Each pa ien was sc eened o sugges i e symp oms
and eques ed o emain in isola ion o 14 days pos -con ac
wi h he depa men . Pa ien s wi h symp oms compa ible wi h
COVID-19 we e e e ed o he na ional heal h sys em ho line
and signaled o heal h au ho i ies, who had also ecei ed he lis
o sc eened pa ien s.
S udy P ocedu es
All HCWs o he heuma ology depa men who we e
wo king du ing Ma ch 2–13, 2020, including isi ing ellows,
we e in i ed o pa icipa e in his s udy. A s anda dized
ques ionnai e was adminis e ed o collec demog aphic da a,
symp om cha ac e iza ion, disease cou se and ou come,
ea men , como bidi ies, and concomi an he apy. Resul s
o labo a o y and imaging s udies pe o med, including RT-
PCR and IgG/IgM o SARS-CoV-2 we e e iewed. Disease
cou se was classi ied as mild, mode a e ( equi ing physical
examina ion and labo a o y/imaging s udies), o se e e
( equi ing hospi aliza ion). Mo eo e , pa ien s obse ed in he
depa men be ween Ma ch 2–13 who de eloped symp oms
sugges i e o COVID-19 had an appoin men scheduled, upon
de ini e esolu ion, o clinical obse a ion. The same da a
we e collec ed as o HCWs, in addi ion o a iables ela ed o
he RMD and associa ed ea men . Pa ien s obse ed in he
pe iod o in e es who did no de elop COVID-19 symp oms
o did so ou side he 14-day window a e he las con ac wi h
he depa men , we e excluded. All s udy pa icipan s signed
a s udy-speci ic in o med consen . This s udy was app o ed
by he Lisbon Academic Medical Cen e E hics Commi ee
( e e ence 171/20).
S a is ical Analysis
Demog aphic and clinical cha ac e is ics we e p esen ed as
equency, mean ±s anda d de ia ion, o median [in e qua ile
ange (IQR)] as applicable. Compa ison o con inuous a iables
be ween HCW g oups was pe o med using K uskal–Wallis
(3 g oups) o Mann–Whi ney U- es (2 g oups). Ca ego ical
a iables we e compa ed using Chi-squa e o Fishe ’s exac es .
Ag eemen be ween RT-PCR and se ological es s was done
using Kappa s a is ic. Pea son co ela ion was applied o s udy
he ela ion o IgG humo al esponse and clinical a iables.
S a is ical analyses we e pe o med using S a a-12.1 o Mac
(S a aCo p, College S a ion, USA) and G aphPad-P ism-7 o
MacOS (G aphPad So wa e, USA). P- alue was conside ed
signi ican a p<0.05.
F on ie s in Medicine | www. on ie sin.o g 2Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
RESULTS
Clinical and Vi ological Cou se o HCWs
A o al o 25/34 HCWs (17 heuma ologis s, 8 esiden s, 4 isi ing
ellows, 1 nu se, 1 heal h aid, 2 sec e a ies, and 1 cleaning aid)
de eloped symp oms sugges i e o a i al in ec ion, 14 o whom
had a posi i e RT-PCR o SARS-CoV-2 (Table 1,Figu e 1,
Supplemen a y Figu e 1). Ten ou o 14 (71%) posi i e cases
we e emale o younge han 50 yea s old. Only 4/14 (29%)
subjec s had a p e ious his o y o ca dio ascula disease and/o
me abolic synd ome, whe eas 3/14 (21%) had a diagnosis o
immune-media ed in lamma o y disease (one o whom ea ed
wi h me ho exa e 15 mg/week). Impo an ly, 5/14 (36%) HCWs
did no de elop e e , which las ed ≤3 days in 4/9 (44%)
emaining cases. Cough was also absen in he same p opo ion
(36%). O no e, 7/14 (50%) subjec s did no de elop any o he
mani es a ions o he ypical COVID-19 iad p io o he posi i e
RT-PCR es , which we e comple ely missing in 3 cases (21%)
h oughou he disease. In u n, milde symp oms we e al eady
p esen du ing he week p io o he ou b eak iden i ica ion in
se e al ins ances. Anosmia and dysgeusia we e p esen in o e
hal he cases, including 1 subjec (HCW6) who did no de elop
e e , cough, o dyspnea.
The majo i y o cases (11/14, 79%) had a benign cou se.
The e we e no hospi aliza ions, bu 3/14 HCWs (aged 45–61
wi h ele an como bidi ies) unde wen clinical, labo a o y,
and adiog aphic e alua ion 7–12 days a e symp om onse
due o pe sis en e e , cough, ches pain, and/o sho ness
o b ea h (Supplemen a y Table 1). Lymphopenia (1/3),
h ombocy openia (1/3), aised lac a e dehyd ogenase (1/3),
D-dime s (2/3), ib inogen (2/3), and C- eac i e p o ein (CRP;
2/3) we e iden i ied, bu hypoxemia and adiog aphic signs o
COVID-19 pneumonia we e absen . Se en subjec s (50%) we e
ea ed wi h hyd oxychlo oquine (400 mg/day, median 9 days,
ange 7–14 days), and 4 ecei ed concomi an azi h omycin (500
mg/day, 5 days). One HCW de eloped a bac e ial sinus in ec ion,
ea ed wi h amoxicillin/cla ulana e. Seconda y ansmission o
household membe s was con i med in 7/14 (50%) cases, one o 2
close ela i es, all wi h mild disease.
Despi e he a o able cou se o mos cases, symp om du a ion
was p olonged (median 24.5 days, IQR 15–39, ange 2–
58; Table 1,Figu e 1,Supplemen a y Figu e 1). A he end
o ollow-up, 2 subjec s had pe sis en symp oms (Figu e 1,
Supplemen a y Figu e 1). Likewise, naso-o opha yngeal RT-
PCR emained posi i e on a e age o 31 ±10 days om
symp om onse (median 29.5 days, IQR 25–35, ange 15–51;
Figu e 1). This esul ed in he need o epea RT-PCR es s
equen ly, wi h a median numbe o es s pe posi i e subjec o
5 (IQR 4–6, ange 4–9). O no e, 8/34 (24%) o epe i ion es s
in comple ely asymp oma ic subjec s we e posi i e. Ye , his was
less han in indi iduals who epea ed es ing while s ill showing
some symp oms (13/25, 52%, p=0.024; Figu e 1). On a e age,
HCWs we e away om wo k o 29.2 ±9.8 days (median 24.5,
IQR 23–36, ange 16–51).
Ele en subjec s de eloped a ious symp oms bu es ed
nega i e e en upon e es ing (Table 1,Figu e 1). These HCWs
epo ed complain s o cough (55%), hino hea (45%), so e
h oa (82%), and o he symp oms in simila equency and
du a ion o con i med cases o e he same ime ame. Howe e ,
e e , a igue, malaise, headache, myalgia, anosmia, and dysgeusia
we e signi ican ly less common. No ably, hese HCWs had a
compa able demog aphic and como bidi y p o ile o hose wi h
posi i e RT-PCR and he 9 asymp oma ic subjec s wi h nega i e
RT-PCR (Table 1).
No HCWs epo ed a el om a eas wi h ac i e communi y
ansmission. A esiden (HCW6) wea ing a su gical mask
obse ed a sugges i e case in he eme gency depa men 3 days
be o e symp om onse (Ma ch 8), who did no ul ill es ing
c i e ia a he ime ( a el om endemic a ea). A consul an
(HCW4) had a sho , unp o ec ed con ac in he week p eceding
he ou b eak wi h an inpa ien om ano he depa men who
was la e ound o ha e COVID-19. O no e, 7/14 o in ec ed
HCWs had a common link o ou heuma ological p ocedu es
uni , ha ing spen he mos hou s he e o e he p e ious
2 weeks. None heless, he emaining RT-PCR-posi i e HCWs
had minimal exposu e o his acili y, and 2 heuma ologis s
(HCW18/21), who spen mo e han 10 h/week in he uni ,
es ed nega i e. Finally, all bu 10 HCWs (5 RT-PCR-posi i e,
5 RT-PCR-nega i e) we e p esen , unp o ec ed, in a 2.5-h
depa men al mee ing (Ma ch 10) add essing he local esponse
o he pandemic. A he ime, only 1 HCW (HCW7) had
symp oms (mild hino hea).
Immunological Response
A e a median (IQR) o 45 (40.5–48.5) days ollowing
symp om onse (o he i s RT-PCR es o asymp oma ic
subjec s), 32 HCWs had an assessmen o he se ological
esponse (Figu e 2). A posi i e IgM and IgG index (>1.0
AU/mL) was seen in, espec i ely, 2/14 (14.3%) and 13/14
(92.9%) o he con i med RT-PCR-posi i e cases and none
o he symp oma ic/asymp oma ic RT-PCR-nega i e subjec s
(Figu es 2A,B). Bo h es s had a 96.9% ag eemen in case
classi ica ion (Kappa coe icien 0.936). Assessmen iming was
simila o he HCWs wi h bo de line posi i e IgM (HCW 11/12,
1.10–1.18 AU/mL) o IgG (HCW 12/14, 1.10 AU/mL) compa ed
o o he RT-PCR-posi i e subjec s. In addi ion, HCW10 had an
IgG index below he posi i e h eshold, despi e 2 posi i e RT-
PCR es s, no immunosupp ession, and compa able e alua ion
iming and clinical cou se.
Wi hin he RT-PCR-posi i e g oup, conside able a ia ion
was seen in he an ibody esponse (Figu e 2B). No ably, subjec s
o e 50 yea s old had a highe mean IgG index (14.5 ±7.7
AU/mL) han younge indi iduals (5.0 ±4.4 AU/mL, p=
0.012; Figu e 2C). Al hough he numbe s a e small, he 3 olde
HCWs (HCW 8/11/13) who had an IgG index abo e 10 AU/mL
expe ienced a mo e se e e disease cou se wi h high e e and
cough, and 2 o hem had aised D-dime s, ib inogen, and CRP.
In con as , he emaining olde HCW (HCW 7) had a mild
cou se wi h limi ed hino hea and gas oin es inal symp oms
and de eloped a lowe IgG index (4.99 AU/mL). Ne e heless,
a posi i e end was obse ed in he co ela ion be ween age and
IgG index (Pea son =0.53, p=0.051; Figu e 2D). No o he
F on ie s in Medicine | www. on ie sin.o g 3Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
TABLE 1 | Demog aphic and clinical cha ac e is ics o s udy pa icipan s.
O e all (n=34) SARS-CoV-2 RT-PCR es esul s and symp oms p- alue
Posi i e (n=14) Nega i e, symp oms Nega i e, no symp oms
(n=11) (n=9)
Age, yea s ( ange) 41 ±12 (26–66) 40 ±14 (26–62) 40 ±8 (28–52) 44 ±15 (27–66) 0.759
Age ≥60 yea s, n(%) 4 (11.8) 2 (14.3) 0 2 (22.2) 0.286
Female, n(%) 23 (67.7) 10 (71.4) 8 (72.7) 5 (55.6) 0.723
Como bidi ies, n(%) 20 (58.8) 8 (57.1) 6 (54.6) 6 (66.7) 0.849
A e ial hype ension 5 (14.7) 3 (21.4) 0 2 (22.2) 0.279
Ca diac disease 3 (8.8) 2 (14.3) 0 1 (11.1) 0.601
Diabe es melli us 2 (5.9) 2 (14.3) 0 0 0.324
Obesi y 3 (8.8) 2 (14.3) 1 (9.1) 0 0.768
COPD/as hma 3 (8.8) 1 (7.1) 2 (18.2) 0 0.464
Ch onic hinosinusi is 4 (11.8) 1 (7.1) 2 (18.2) 1 (11.1) 0.806
IMID 6 (17.7) 3 (21.4) 1 (9.1) 2 (22.2) 0.732
Cance his o y 2 (5.9) 0 1 (9.1) 1 (11.1) 0.241
Smoking his o y (e e ) 9 (26.5) 4 (28.6) 2 (18.2) 3 (33.3) 0.790
Concomi an he apy, n(%) 5 (14.7) 3 (21.4) 0 2 (22.2) 0.279
ACEi/ARB 5 (14.7) 3 (21.4) 0 2 (22.2) 0.279
NSAIDs 1 (2.9) 0 1 (9.1) 0 0.588
DMARDs 3 (8.8) 1 (7.1) 1 (9.1) 1 (12.5) 1.000
COVID-19 symp oms, n(%)/du a ion, days 25 (73.5)/24 ±19 14 (100)/28 ±18 11 (100)/20 ±20 0 –
Fe e 11 (32.4)/6 ±8 9 (64.3)/7 ±9 2 (18.2)/2 ±1 – 0.042
Cough 15 (44.1)/25 ±19 9 (64.3)/25 ±14 6 (54.6)/26 ±26 – 0.622
Dyspnea 3 (8.8)/3 ±31 2 (14.3)/14 ±10 1 (9.1)/66 1.000
Ches igh ness 4 (11.8)/17 ±16 3 (21.4)/22 ±16 1 (9.1)/4 – 0.603
Malaise 10 (29.4)/15 ±14 9 (64.3)/16 ±15 1 (9.1)/6 – 0.012
Fa igue 12 (35.3)/25 ±21 10 (71.4)/24 ±21 2 (18.2)/27 ±25 – 0.015
Headache 11 (32.4)/16 ±18 10 (71.4)/17 ±19 1 (9.1)/5 – 0.004
Rhino hea 14 (41.2)/18 ±16 9 (64.3)/24 ±17 5 (45.5)/7 ±3 – 0.435
So e h oa 16 (47.1)/7 ±7 7 (50.0)/9 ±9 9 (81.8) 5 ±3 – 0.208
Anosmia 9 (26.5)/15 ±13 8 (57.1)/16 ±13 1 (9.1)/6 – 0.033
Dysgeusia 8 (23.5)/12 ±7 8 (57.1)/12 ±7 0 – 0.003
A h algia 1 (2.9)/25 1 (7.4)/25 0 – 1.000
Myalgia 11 (32.4)/14 ±17 8 (57.1)/16 ±20 3 (27.3)/8 ±9 – 0.004
Abdominal pain 2 (5.9)/3 ±1 0 2 (18.2)/3 ±1 – 0.183
Nausea/ omi ing/dia hea 7 (20.6)/11 ±11 5 (35.7)/13 ±12 2 (18.2)/5 ±0 – 0.407
Dizziness 3 (8.8)/9 ±6 2 (14.3)/10 ±8 1 (9.1)/8 – 1.000
Disease se e i y, n(%)
Mild 22 (64.7) 11 (78.6) 11 (100) – 0.230
Mode a e 3 (8.8) 3 (21.4) 0
Se e e 0 0 0
Hospi aliza ion 0 0 0 – –
T ea men , n(%)/du a ion, days
None/suppo i e 27 (79.4) 7 (50) 11 (100) 9 (100) –
Hyd oxychlo oquine 7 (20.6)/9 ±3 7 (50)/9 ±3 0 0
Azi h omycin 4 (11.8)/5 ±0 4 (28.6)/5 ±0 0 0
Complica ions, n(%) 1 (2.9) 1 (7.4) 0 0 –
Symp om esolu ion, n(%) 23 (92) 12 (85.7) 11 (100) – –
Seconda y ansmission, n(%) 7 (20.6) 7 (50) – – –
Days o 2 nega i e es s ( ange) 31 ±10 (15–51) 31 ±10 (15–51) – – –
ACEi, angio ensin-con e ing enzyme inhibi o s; ARB, angio ensin-II ecep o blocke s; ch onic obs uc i e pulmona y disease; DMARDs, disease-modi ying an i- heuma ic d ugs; IMID,
immune-media ed in lamma o y disease; NSAIDs, non-s e oidal an i-in lamma o y d ugs. Con inuous alues ep esen ed as mean ±SD.
F on ie s in Medicine | www. on ie sin.o g 4Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
FIGURE 1 | E olu ion o symp oms and RT-PCR es esul s o heal hca e wo ke s wi h con i med o suspec ed COVID-19. Each ow ep esen s a heal hca e wo ke
(HCW) ollowed o e ime (columns). Resul s o e e se ansc ip ion polyme ase-chain eac ion (RT-PCR) a e indica ed as posi i e (L), nega i e (—) o inde e mina e
(±). Mild symp oms include symp oms o he han e e , cough, and dyspnea as e e ed o in he ex and Table 1.
clinical ac o was associa ed wi h an ibody esponse, including
sex; ea men ; o p esence/du a ion o e e , cough, o dyspnea.
Seconda y T ansmission o Pa ien s Wi h
RMDs
A o al o 617 pa ien s we e iden i ied as ha ing had a po en ial
isky con ac , 561 (91%) o whom we e con ac ed by elephone
and sc eened o COVID-19 symp oms s a ing wi hin he
14-day window (Figu e 3). We iden i ied 8 (1.3% o o al)
emale pa ien s (mean age 66.8 ±14.9 yea s) who de eloped
symp oms compa ible wi h COVID-19 (Table 2). Six pa ien s
had a diagnosis o an in lamma o y RMD; 3 we e ea ed wi h
con en ional syn he ic disease-modi ying an i heuma ic d ugs
(csDMARDs) and glucoco icoids and 2 wi h biologic DMARDs
(bDMARDs). All con ac s ook place wi hin he same 2 days
(Ma ch 9 and 11), all bu one we e wi h a con i med in ec ed
HCW, and pa ien s denied addi ional suspicious con ac s.
Con ac acing o Pa ien 1 wi hin he depa men con i med
i o be limi ed o a symp oma ic physician wi h nega i e
RT-PCR and se ology (HCW24). Impo an ly, in 7/8 cases,
he HCW was asymp oma ic a he ime o con ac , and 1
pa ien (Pa ien 6) had a consul a ion wi h a physician (HCW7)
p esen ing only mild se ous hino hea. O no e, 5/8 con ac s
we e in he con ex o diagnos ic (ul asound) o he apeu ic
p ocedu es (meso he apy), which in ol ed p olonged close
physician–pa ien con ac .
Pa ien s de eloped symp oms on a e age 4.3 ±2.1 days
( ange 2–9) a e he con ac . Hal epo ed e e , 88% had
cough, and only 1 pa ien epo ed dyspnea. Gene al and uppe
ai way symp oms we e common, including anosmia (50%)
and dysgeusia (63%). Nasopha yngeal swabs we e pe o med
in 6/8 cases (8.8 ±3.1 days pos -symp om onse ), 2 o
which we e posi i e o SARS-CoV-2, and 1 was inconclusi e.
Two pa ien s we e no es ed due o di icul y in eaching
heal h au ho i ies o pe sonal choice (sel -isola ion). Pa ien s
wi h nega i e/una ailable es s s ill had sugges i e COVID-
19 symp oms.
All bu one pa ien had a mild- o-mode a e cou se and we e
clinically eco e ed a e an a e age o 24.8 ±5.9 days. A 90-yea -
old woman wi h gian cell a e i is and ele an ca dio ascula
como bidi ies, exposed o long- e m me ho exa e and low-
dose glucoco icoids, was hospi alized a e 6 days o e e and
3 days o wo sening ches pain and dyspnea. She equi ed
oxygen he apy, ecei ed a combina ion o hyd oxychlo oquine
(400 mg/day) and lopina i / i ona i (800/200 mg/day), and
was discha ged a e 10 days. Impo an ly, none o he pa ien s
expe ienced a la e o he baseline RMD.
DISCUSSION
Ou s udy p o ides impo an lessons on he ulne abili y and
impac o a COVID-19 ou b eak wi hin a la ge heuma ology
depa men a a ime when uni e sal su gical mask use was
no ecommended. O e a single week, 41% o HCWs we e
con i med o be in ec ed by SARS-CoV-2, and an addi ional 32%
de eloped mos ly o e lapping symp oms. Al hough we could no
de ec he index case, he sp ead o he con agion was as and
occu ed when almos all HCWs we e asymp oma ic o exhibi ed
only mino symp oms, easily dismissed o a ibu ed o ano he
concu en i al disease. These indings a e in acco dance wi h
F on ie s in Medicine | www. on ie sin.o g 5Sep embe 2020 | Volume 7 | A icle 576162

Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
FIGURE 2 | Immunological esponse o SARS-CoV-2 in ec ion among heal hca e wo ke s. (A) Pe cen age o heal hca e wo ke s (HCWs) wi h a posi i e
immunological esponse o se e e acu e espi a o y synd ome co ona i us 2 (SARS-CoV-2) in ec ion, de ined as an IgM o IgG index equal o abo e 1.0 AU/mL.
Analysis di e en ia ed by HCW g oup, depending on he p esence o COVID-19 symp oms and he esul o e e se ansc ip ion-polyme ase chain eac ion
(RT-PCR). N=32 (RT-PCR+,N=14; RT-PCR– symp oms, n=10; RT-PCR– no symp oms, n=8). *None o he HCWs in his g oup de eloped an i-SARS-CoV-2
an ibodies (i.e., equency =0%) (B) Index o an i-SARS-CoV-2 an ibodies (IgG and IgM) acco ding o RT-PCR esul and COVID-19 symp oms. Dashed line
ep esen s posi i e h eshold (1.0 AU/mL). E o ba s ep esen mean wi h s anda d de ia ion. (C) Dis ibu ion o an i-SARS-CoV-2 IgG an ibodies in RT-PCR+HCWs,
acco ding o age g oup (below o abo e 50 yea s old). E o ba s ep esen mean wi h s anda d de ia ion. *p=0.012. (D) Co ela ion be ween age and
an i-SARS-CoV-2 IgG an ibodies in RT-PCR+HCWs. , Pea son co ela ion coe icien .
cu en conce ns a ound he p esymp oma ic o asymp oma ic
ansmission o SARS-CoV-2 among HCWs and pa ien s (9,14–
16). As i al shedding and in ec iousness a e highe in he 2–
3 days p io o symp om onse and apidly dec ease he ea e
(26,27), a high p opo ion o con agion occu s du ing he
p esymp oma ic s age (18,26). In addi ion, asymp oma ic (17,
22,28,29) and mild disease o ms wi h limi ed uppe espi a o y
symp oms a e now widely ecognized (23,27) and may escape
igilance p o ocols, mo e ocused on he p esence o e e , cough,
and dyspnea. This was ce ainly he case in ou clus e , in which
es ing o all HCWs o he depa men , whe he symp oma ic
o no , was i al o iden i y cases and con ain he ou b eak.
The e o e, in heal hca e se ings, con inuous mask use, social
dis ancing, and mild-symp om moni o ing should be adop ed
among HCWs, oge he wi h p oac i e es ing s a egies, o
accoun o po en ial p e/asymp oma ic ca ie s (15).
The ou b eak had a p o ound epe cussion in he clinical
ac i i y o he depa men . In ec ed subjec s had p o ac ed
symp oms and we e away om wo k o a ound 1 mon h.
In addi ion, p olonged i al shedding (up o 51 days) led
o equen RT-PCR epe i ion (median 5 es s) un il cu e
was con i med, consuming subs an ial esou ces. Ou indings
ega ding i al RNA swab posi i i y a e longe han p e iously
epo ed (20,30–32), which may be ela ed o di e ences in
specimen collec ion (double naso- and o opha yngeal swab in
ou s udy), s udy popula ion, o disease se e i y. In e es ingly,
simila nasopha yngeal i al loads in pa ien s wi h mild and
se e e disease ha e been epo ed (30) al hough a sepa a e s udy
concluded o he wise (33). Mo eo e , some da a sugges ha a
posi i e RT-PCR does no deno e he ac ual p esence o iable
i us, especially a e he i s week (27,34). Howe e , his is
no ye ully es ablished, and we would, he e o e, ad oca e o 2
consecu i e nega i e es s be o e HCWs e u n o wo k. In e ec ,
21/59 (36%) o epea es s we e posi i e, and in 5 ins ances,
a posi i e o inde e mina e es ollowed a i s nega i e esul ,
highligh ing he di icul ies o in e p e a ion (34).
F on ie s in Medicine | www. on ie sin.o g 6Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
FIGURE 3 | Flow cha o RMD pa ien sc eening o symp oms sugges i e o COVID-19. Pa ien s wi h possible con ac s wi h heal hca e wo ke s wi h posi i e e e se
ansc ip ion-polyme ase chain eac ion (RT-PCR) o se e e acu e espi a o y co ona i us 2 (SARS-CoV-2) in he pe iod o Ma ch 2–13, 2020, we e con ac ed by
elephone and sc eened o COVID-19 symp oms s a ing wi hin he subsequen 14 days. See Me hods o de ails.
All HCWs had a mild- o-mode a e disease cou se, and he e
we e no majo complica ions. We belie e he posi i e ou come
o he coho is mainly ela ed o he young mean age wi h only
2 HCWs olde han 60 yea s. Al e na i ely, a lowe ini ial i al
exposu e load could also explain an o e all milde pheno ype
(33). Ne e heless, mos o he in ec ed HCWs (93%) de eloped
an immune esponse, which ended o be mo e obus in olde
indi iduals. This, in u n, may be seconda y o a mo e se e e
clinical cou se, known o be s ongly associa ed wi h age (20,35).
A possible explana ion o his inding could be a highe peak
i al load, also p e iously shown o be posi i ely co ela ed wi h
age (30). Indeed, we highligh ha 2/13 (15.4%) IgG-posi i e
HCWs, bo h unde 30 yea s old and wi h a e y mild disease
cou se, had bo de line IgG indexes. Ne e heless, o he ac o s,
such as T-cell–media ed immuni y (36–38), may be in ol ed,
as 1 HCW in he 40- o 50-yea -old ange who had cough
and 2 posi i e RT-PCR es s did no de elop IgG an ibodies 47
days pos -symp om onse . Conco dance be ween se ology and
RT-PCR was o he wise excellen , con i ming p e ious epo s
(20,30,31). Al hough i canno be comple ely excluded, his
sugges s he e we e no alse-nega i e RT-PCR esul s, including
in symp oma ic HCWs.
Finally, seconda y ansmission o a mino i y o pa ien s did
occu om 4 HCWs who we e asymp oma ic (75%) o had mild
uppe ai way symp oms (25%), mos ly in close p oximi y con ac .
As one o he con i med cases only con ac ed wi h HCW 24
(nega i e RT-PCR and se ology), we canno exclude undisclosed
communi y con agion o nosocomial ansmission h ough
omi es (39). Also, we admi ha pa ien s wi h nega i e/missing
RT-PCR could be alse nega i e o undiagnosed cases, possibly
due o a la ge in e al be ween symp om onse and es ing.
O no e, all con ac s occu ed when p e en i e measu es had
al eady been adop ed, and 80% o ace- o- ace clinical ac i i y
had been de e ed, which migh explain he low numbe o
in ec ed pa ien s. We admi he possibili y ha con agion
could ha e ollowed he opposi e ou e (p e/asymp oma ic
pa ien s o HCWs) al hough symp om iming does sugges
o he wise. No wi hs anding he ad anced age and long- e m use
o cs/bDMARDs and low-dose glucoco icoids in hal he cases,
all pa ien s had a a o able ou come. This is in acco dance wi h
ecen da a ha did no demons a e an inc eased incidence o
se e e disease in RMD pa ien s (40,41).
Ou s udy has some limi a ions. Due o i s eal-li e na u e,
clinical assessmen and RT-PCR iming we e clinically based
F on ie s in Medicine | www. on ie sin.o g 7Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
TABLE 2 | Clinical ea u es o RMD pa ien s wi h con i med o suspec ed COVID-19.
Pa ien ID 1 2 3 4 5 6 7 8
Age/Sex 52/F 90/F 68/F 55/F 83/F 70/F 46/F 68/F
Rheuma ic disease RA/SLE
o e lap
GCA Vi al eac i e
a h i is ( esol ed)
APS Sa coidosis RA PsA Ro a o cu
endinopa hy
Disease du a ion 11.1 y 10.1 y 7.7 mo 2.2 y 13.7 y 4.7 mo 15.7 y 11.2 mo
Disease ac i i y Low Remission Remission No e en s Remission Low Mode a e Low/mild
Como bidi ies HT, hea dx,
COPD
HT, CV dx,
OP
HT, COPD HT, CV dx,
COPD
HT, hea dx,
ILD, CKD
Dyspepsia,
sphe ocy osis
N/A HT, u e ine
cance (pas )
Smoking s a us Pas Pas Pas Ac i e Ne e Ne e Ne e Ne e
DMARDs (dose, mg) AZT (150),
LEF (20)
MTX (12.5/w),
denosumab
(60/6 mo)
No No No MTX (15/w),
HCQ (400)
IFX (3/kg) No
Glucoco icoids
(dose, mg)
DFZ (9) PDN (5) No No No PDN (7.5) No No
NSAIDs No No Nimesulide No Aceme acin No Aceme acin No
ACEi/ARB Ramip il No No Pe indop il Ramip il No No Lisinop il
HCW con ac (#) RT-PCR– (24) RT-PCR+(1) RT-PCR+(1) RT-PCR+(14) RT-PCR+(1) RT-PCR+(7) RT-PCR+(1) RT-PCR+(1)
Con ac da e 9/3/2020 11/3/2020 9/3/2020 9/3/2020 9/3/2020 11/3/2020 11/3/2020 11/3/2020
Con ac ype US (shoulde ) Meso he apy
(shoulde )
Consul a ion Consul a ion Meso he apy
(lumba spine)
Consul a ion Meso he apy
(heel)
Meso he apy
(shoulde )
Con ac du a ion 15min 10 min 30 min 30 min 10 min 30 min 10 min 10 min
Days om con ac o
symp om onse
9 2 4 4 4 3 4 4
COVID-19 symp oms
(o de o appea ance)
(1) F , Mal,
F g, Hdx,
Rhin, Cgh; (2)
Ansm, Dysg
(1) Mal, F g.
Myalg, A h,
Cgh; (2) F ,
Hdx, Rhin; (3)
Chx, Dysp,
Ansm, Dysg
(1) Mal, F g, Hdx,
Th , Cgh, A h; (2)
Ansm, Dysg; (3)
GI, Dizz
(1) Mal, Hdx,
Rhin, Myalg.
GI; (2) Cgh,
F g; (3) Ansm,
Dysg
(1) F , Mal,
Fa , Hdx,
Rhin, A h,
Myalg, Dizz
(1) Abd, GI;
(2) Rhin, Cgh;
(3) Chx, Hdx
(1) F g, Cgh;
(2) Dysg (3)
Hdx, Abd
(1) Mal, F g,
Hdx, Th ,
Cgh; (2) Abd,
GI; (3) F ,
Myalg, Dizz
Diagnos ic RT-PCR
es (symp om day)
Posi i e (13) Posi i e (4) Inconclusi e (11)
Nega i e (21)
Nega i e (9) N/A Nega i e (8) N/A Nega i e (8)
Symp om du a ion 14 20 30 21 31 25 29 28
Hospi aliza ion (days) No Yes (10) No No No No No No
ICU admission N/A No N/A N/A N/A N/A N/A N/A
Complica ions No No No No No No No No
Ta ge ed ea men No HCQ,
LOP+RIT
No No No No No No
T ea men changes ↓DFZ 6 mg Suspended
MTX
No No ↑NSAID eq No No No
Ou come Cu e Cu e Cu e Cu e Cu e Cu e Cu e Cu e
Days o 2 nega i e
es s
34 20 N/A N/A N/A N/A N/A N/A
Abd, abdominal pain; ACEi, angio ensin-con e ing enzyme inhibi o s; Ansm, anosmia; APS, an iphospholipid synd ome; ARB, angio ensin-II ecep o blocke s; A h, a h algia;
AZT, aza hiop ine; Chx, ches pain/ igh ness; Cgh, cough; CKD, ch onic kidney disease; COPD, ch onic obs uc i e pulmona y disease; COVID-19, co ona i us disease 2019; CV,
ce eb o ascula ; dx, disease; DFZ, de lazaco ; Dizz, dizziness/ e igo; DMARDs, disease-modi ying an i- heuma ic d ugs; Dysg, dysgeusia; Dysp, dyspnoea; F eq, equency; F g,
a igue; F , e e ; GCA, gian cell a e i is; GI, gas oin es inal, including nausea, omi ing, dia hea; HCQ, hyd oxychlo oquine; HCW, heal hca e wo ke ; Hdx, headache; HT, hype ension;
ICU, in ensi e ca e uni ; IFX, in liximab; ILD, in e s i ial lung disease; LEF, le lunomide; LOP, lopina i ; Mal, malaise; mo, mon hs; MTX, me ho exa e; N/A, no applicable; NSAIDs,
non-s e oidal an i-in lamma o y d ugs; OP, os eopo osis; PDN, p ednisolone; PsA, pso ia ic a h i is; RA, heuma oid a h i is; RIT, i ona i ; Rhin, hino hea; RMD, heuma ic and
musculoskele al diseases; RT-PCR, e e se ansc ip ion-polyme ase chain eac ion; SLE, sys emic lupus e y hema osus; Th , so e h oa ; US, ul asound; w, weeks; y, yea s.
and di e ed sligh ly be ween subjec s. As compu ed omog aphy
was no pe o med, we canno comple ely exclude COVID-19
pneumonia. Two ellows could no be es ed o se ology upon
inishing hei cle kship. Also, 9% o he iden i ied RMD pa ien s
could no be eached.
In conclusion, we demons a e ha a COVID-19
ou b eak can occu among HCWs and heuma ic pa ien s,
sp eading o e he p esymp oma ic s age and e ol ing wi h
mild- o-mode a e symp oms, delayed i al shedding, and
p olonged eco e y.
F on ie s in Medicine | www. on ie sin.o g 8Sep embe 2020 | Volume 7 | A icle 576162
Romão e al. COVID-19 Ou b eak in Rheuma ology Depa men
DATA AVAILABILITY STATEMENT
All da ase s p esen ed in his s udy a e included in he
a icle/Supplemen a y Ma e ial.
ETHICS STATEMENT
This s udy was e iewed and app o ed by Comissão de É ica do
Cen o Académico de Medicina de Lisboa ( e e ence 171/20).
The pa ien s/pa icipan s p o ided hei w i en in o med
consen o pa icipa e in his s udy. W i en in o med consen
was ob ained om he indi idual(s) o he publica ion o any
po en ially iden i iable images o da a included in his a icle.
AUTHOR CONTRIBUTIONS
VR, FO-R, and JF designed he p ojec , collec ed and analyzed
he da a, and d a ed he manusc ip . AC-M, PM, SB, and JS-D
con ac ed pa ien s and ob ained he ele an clinical da a. LM-G
and ES-L coo dina ed he occupa ional heal h esponse. HP and
JC conduc ed labo a o y es ing, including RT-PCR and se ology.
NK and JR o e iewed clinical moni o ing and da a collec ion o
heal hca e wo ke s. All membe s o he CHULN Rheuma ology
Depa men (collabo a i e g oup) ac i ely pa icipa ed in da a
acquisi ion. All au ho s ha e con ibu ed o s udy concep ion and
design and au ho s ha e c i ically e iewed he manusc ip o
impo an in ellec ual con en and ha e ead and app o ed i s
inal e sion.
ACKNOWLEDGMENTS
We acknowledge Ms. Sand a Guima ães, Ms. Vene anda
Ba oca, and Ms. Inalda San os om he CHULN Rheuma ology
Depa men o hei assis ance o s udy p ocedu es. We hank
D . Ál a o Ay es Pe ei a and D . Tiago Ma ques om he
CHULN In ec ious Diseases Depa men o he clinical suppo
in e alua ing con i med and suspicious cases. We hank D . Cla a
Almeida om he CHULN Occupa ional Heal h Depa men
o he con ibu ion ega ding se ological assay esul s. This
manusc ip has been eleased as a p e-p in a medRxi (42).
COLLABORATIVE GROUP AUTHORSHIP
The CHULN Rheuma ology Depa men : Manuel An ónio
(Rheuma ology Depa men , Hospi al de San a Ma ia, Cen o
Hospi ala Uni e si á io Lisboa No e, Lisbon Academic Medical
Cen e , Lisbon, Po ugal; Rheuma ology Resea ch Uni , Ins i u o
de Medicina Molecula João Lobo An unes, Faculdade de
Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal); Ped o
Á ila-Ribei o (Rheuma ology Depa men , Hospi al de San a
Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon
Academic Medical Cen e , Lisbon, Po ugal; Rheuma ology
Resea ch Uni , Ins i u o de Medicina Molecula João Lobo
An unes, Faculdade de Medicina, Uni e sidade de Lisboa,
Lisbon, Po ugal); Ri a Ba os (Rheuma ology Depa men ,
Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa
No e, Lisbon Academic Medical Cen e , Lisbon, Po ugal;
Rheuma ology Resea ch Uni , Ins i u o de Medicina Molecula
João Lobo An unes, Faculdade de Medicina, Uni e sidade
de Lisboa, Lisbon, Po ugal); Raquel Campanilho-Ma ques
(Rheuma ology Depa men , Hospi al de San a Ma ia, Cen o
Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e , Lisbon, Po uga; Rheuma ology Resea ch Uni ,
Ins i u o de Medicina Molecula João Lobo An unes, Faculdade
de Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal);
Susana Capela (Rheuma ology Depa men , Hospi al de San a
Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon
Academic Medical Cen e , Lisbon, Po ugal; Rheuma ology
Resea ch Uni , Ins i u o de Medicina Molecula João Lobo
An unes, Faculdade de Medicina, Uni e sidade de Lisboa,
Lisbon, Po ugal); Inês Co dei o (Rheuma ology Depa men ,
Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa
No e, Lisbon Academic Medical Cen e , Lisbon, Po ugal;
Rheuma ology Resea ch Uni , Ins i u o de Medicina Molecula
João Lobo An unes, Faculdade de Medicina, Uni e sidade
de Lisboa, Lisbon, Po ugal); Bianca C is ea (Rheuma ology
Depa men , Hospi al de San a Ma ia, Cen o Hospi ala
Uni e si á io Lisboa No e, Lisbon Academic Medical Cen e ,
Lisbon, Po ugal; In e nal Medicine 1 Depa men , Hospi al
de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e,
Lisbon Academic Medical Cen e , Lisbon, Po ugal); Edua do
Dou ado (Rheuma ology Depa men , Hospi al de San a
Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon
Academic Medical Cen e , Lisbon, Po ugal; Rheuma ology
Resea ch Uni , Ins i u o de Medicina Molecula João Lobo
An unes, Faculdade de Medicina, Uni e sidade de Lisboa,
Lisbon, Po ugal); Luís Gaião (Rheuma ology Depa men ,
Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa
No e, Lisbon Academic Medical Cen e , Lisbon, Po ugal);
Raquel F ei as (Rheuma ology Depa men , Hospi al de San a
Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon
Academic Medical Cen e , Lisbon, Po ugal; Rheuma ology
Depa men , Hospi al Ga cia de O a, Almada, Po ugal); Ca la
Maciei a (Rheuma ology Depa men , Hospi al de San a Ma ia,
Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e , Lisbon, Po ugal); Joana Ma ins-Ma inho
(Rheuma ology Depa men , Hospi al de San a Ma ia, Cen o
Hospi ala Uni e si á io Lisboa No e, Lisbon Academic Medical
Cen e , Lisbon, Po ugal; Rheuma ology Resea ch Uni , Ins i u o
de Medicina Molecula João Lobo An unes, Faculdade de
Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal); Ana Te esa
Melo (Rheuma ology Depa men , Hospi al de San a Ma ia,
Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e , Lisbon, Po ugal; Rheuma ology Resea ch Uni ,
Ins i u o de Medicina Molecula João Lobo An unes, Faculdade
de Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal);
Ca los Mi anda Rosa (Rheuma ology Depa men , Hospi al
de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e,
Lisbon Academic Medical Cen e , Lisbon, Po ugal); Ma ga ida
Mon ei o (Rheuma ology Depa men , Hospi al de San a Ma ia,
Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e , Lisbon, Po ugal; Rheuma ology Resea ch Uni ,
Ins i u o de Medicina Molecula João Lobo An unes, Faculdade
de Medicina, Uni e sidade de Lisboa, Lisbon, Po ugal); Lila
F on ie s in Medicine | www. on ie sin.o g 9Sep embe 2020 | Volume 7 | A icle 576162