P o ocol
E alua ion o Lac obacillus Co yni o mis K8 Consump ion by
Heal h Ca e Wo ke s Exposed o COVID-19 (Lac oCo 2 P ojec ):
P o ocol o a Randomized Con olled T ial
Raquel Rod íguez-Blanque1,2, PhD; Juan Ca los Sánchez-Ga cía1, PhD; Angel Cobos Va gas3, RN; M Soco o Ley a
Ma ínez3, RN; Sil ia Ma ínez Diz3, PhD; Jona han Co és-Ma ín1, PhD; Ma ía Isabel To a -Gál ez1, PhD
1G upo de In es igación CTS-1068, Depa amen o de En e me ía, Facul ad de Ciencias de la Salud, Uni e sidad de G anada, G anada, Spain
2Hospi al Uni e si a io Clínico San Cecilio, G anada, Spain
3G upo de In es igación CTS-1068, Hospi al Uni e si a io Clínico San Cecilio, G anada, Spain
Co esponding Au ho :
Juan Ca los Sánchez-Ga cía, PhD
G upo de In es igación CTS-1068
Depa amen o de En e me ía, Facul ad de Ciencias de la Salud, Uni e sidad de G anada
A da. Ilus acion, 60
G anada, 18071
Spain
Phone: 34 644322567
Email: jsanga @ug .es
Abs ac
Backg ound: Lac obacillus co yni o mis K8 CECT5711 has immune-modula ing p ope ies, enhances he immune esponse
o i al an igens leading o he p oduc ion o speci ic an ibodies, and has an i-in lamma o y ac i i y, which may help o p e en
uncon olled in lamma o y p ocesses leading o espi a o y and o he o gan ailu es.
Objec i e: The pu pose o his s udy is o e alua e he e ec o he consump ion o a p obio ic s ain on he incidence and
se e i y o COVID-19 in heal h pe sonnel who ca y ou hei p o essional wo k among pa ien s wi h in ec ion o suspec ed
in ec ion by SARS-CoV-2.
Me hods: This is a double-blind andomized clinical ial in which he expe imen al g oup will ecei e a capsule o L co yni o mis
K8 pe day (3×109colony o me uni s/day), and he con ol g oup will ecei e a daily placebo capsule consis ing o mal odex in.
A sample size o 314 olun ee s was calcula ed. Volun ee s mus mee he ollowing inclusion c i e ia: olde han 20 yea s and
ac i e heal h pe sonnel ca ing o pa ien s wi h COVID-19, including all p o essionals such as medical doc o s, nu ses, and
ca e ake s a he 2 e e al hospi als ha ea pa ien s wi h COVID-19. The main ou come o he clinical ial will be he incidence
o symp oma ic in ec ion by SARS-CoV-2 in pe sonnel who ca e o pa ien s wi h suspec ed o con i med COVID-19.
Resul s: The s udy had o be ex ended o he 2 e e al hospi als ha ea pa ien s wi h COVID-19 in he p o ince o G anada
(Andalusia, Spain); Hospi al San Cecilio and Hospi al Vi gen de las Nie es. A o al o 255 indi iduals me he inclusion c i e ia
and we e andomly assigned o one o he 2 g oups.
Conclusions: The esul s o his andomized con olled ial will p o ide aluable in o ma ion ega ding he adminis a ion o
L co yni o mis K8 agains COVID-19, including whe he he e a e ewe in ec ious p ocesses due o his i us o , in case o
occu ence, whe he he disease is milde in pa icipan s aking he p obio ic s ain.
T ial Regis a ion: ClinicalT ials.go NCT04366180; h p://www.clinical ials.go /c 2/show/NCT04366180
In e na ional Regis e ed Repo Iden i ie (IRRID): RR1-10.2196/37857
(JMIR Res P o oc 2023;12:e37857) doi: 10.2196/37857
KEYWORDS
COVID-19; co ona i us; Lac obacillus; heal h ca e wo ke s; Lac obacilo; abajado es de la salud; SARS-CoV-2; p obió ico
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In oduc ion
Humans ha e consumed lac ic bac e ia h oughou his o y, bu
i was a he beginning o he 20 h cen u y when his
consump ion was i s ela ed o bene icial p ope ies o heal h
[1]. F om ha momen on, mul iple s udies bo h in i o and in
i o ha e shown he bene icial e ec s ha he consump ion o
his ype o bac e ia, called p obio ics, has on heal h. E ec s
such as he imp o emen o in es inal unc ion [2,3], p e en ion
o in es inal in ec ions [4], and immunomodula ion ha e been
widely demons a ed [5]. In addi ion o hese bene icial e ec s,
he consump ion o p obio ics has been ela ed o a educ ion
in he incidence and se e i y o espi a o y in ec ions [4,6].
O al adminis a ion o lac ic acid bac e ia has been associa ed
wi h an inc ease in inna e and acqui ed immune esponses [7,8].
The consump ion o ce ain s ains has been shown o induce
an inc ease in IgA ela ed o he an i-in ec i e p ope ies o
p obio ic bac e ia in dia hea [9,10]. Inna e immuni y is
inc eased h ough an inc ease in he p opo ion and ac i i y o
phagocy ic cells o he immune sys em, such as monocy es and
neu ophils. The unc ion o na u al kille cells is also enhanced
by he consump ion o p obio ic bac e ia [11]. Ac i a ion o he
inna e immune sys em is essen ial, as i p oduces cy okines ha
will lead o mo e specialized ac i a ion o he speci ic immune
esponse. I has been sugges ed ha i is h ough his mechanism
ha p obio ic bac e ia ac i a e he immune esponse, hus being
able o unc ion as adju an s in accina ion p ocesses [12].
The Eu opean Food Sa e y Agency (EFSA) has published
guidelines on how s udies should be conduc ed o demons a e
he e ec o a p obio ic o na u al ing edien on he immune
sys em. Among i s ecommenda ions is he use o accina ion
p o ocols ha demons a e how he adminis a ion o he
p obio ic ansla es in o an imp o emen in he esponse o an
an igen [13]. Recen ly, a s udy ca ied ou a he Cen e Ins i u e
o Food Science and Technology and Nu i ion o he Spanish
Na ional Resea ch Council demons a ed ha he adminis a ion
o Lac obacillus co yni o mis K8 CECT5711 inc eases he
esponse o speci ic an ibodies agains hepa i is A in a
accina ion p o ocol agains his i us [14]. In addi ion, a ce ain
e ec on memo y T-helpe lymphocy es was obse ed, which
inc eased in he p obio ic g oup wi h espec o baseline alues
(mean 660, SD 223 cells/µL s mean 551, SD 213 cells/µL).
These esul s highligh he po en ial o his p obio ic s ain o
imp o e he immune esponse agains i al an igens.
To e alua e his ac i i y ha boos s he immune esponse,
ano he s udy was ca ied ou in an olde popula ion. This
popula ion is mo e suscep ible o in ec ions due o he
cha ac e is ic immunosenescence o age. A o al o 98 olde
people esiding in nu sing homes pa icipa ed in his s udy. The
olun ee s ecei ed a daily capsule o L co yni o mis K8
CECT5711 (3×109colony o me uni s/day) o 2 weeks p io
o being accina ed agains he lu o a placebo. The pe cen age
o se ocon e sion was highe in he g oup ecei ing he p obio ic
han in he con ol g oup (93.1% s 72.7%; P=.04). Du ing he
mon hs o Oc obe o Ap il, he olun ee s we e moni o ed, and
he incidence o local symp oms associa ed wi h espi a o y
in ec ions (so e h oa , cough, and nasal conges ion) was 48%
lowe in he g oup ha ecei ed he p obio ic s ain han in he
con ol g oup (P=.007). Fu he mo e, he consump ion o
analgesics was signi ican ly educed in his g oup by 86%
(P=.008) [15]. This la es s udy co obo a es he s ain’s abili y
o imp o e he immune esponse agains i al an igens e en in
he olde popula ion.
We a e cu en ly expe iencing a pandemic due o COVID-19
( he English ac onym o COVID-19), which s a ed in he
Chinese ci y o Wuhan in Decembe 2019. Ha ing eached mo e
han 100 e i o ies, he disease was decla ed a pandemic by he
Wo ld Heal h O ganiza ion on Ma ch 11, 2020 [16]. The numbe
o con i med cases con inued o g ow un il eaching 5,371,660
cases wo ldwide on May 22, 2020. In Spain, a he end o May
2020, despi e he con ainmen measu es ini ia ed in ea ly Ma ch,
mo e han 235,772 cases we e egis e ed, and o hese pa ien s,
mo e han 27,940 died [17].
The COVID-19 in ec ion p oduces lu-like symp oms, including
e e , d y cough, dyspnea, myalgia, and a igue. In se e e cases,
i is cha ac e ized by pneumonia, acu e espi a o y dis ess
synd ome, and sep ic shock, which lead o dea h in
app oxima ely 3% o hose in ec ed. T ansmission occu s
h ough small d ople s ha a e emi ed when speaking, sneezing,
o coughing by a ca ie and pass di ec ly o ano he pe son
h ough inhala ion o by con ac wi h con amina ed objec s in
he ecipien ’s nasal and ocula mucous memb anes. Symp oms
s a a e app oxima ely 7-20 days o exposu e, and p e en ion
a he popula ion le el consis s o equen hand washing,
disin ec ing su aces wi h alcohol, and a oiding close con ac
wi h o he people [15].
Some d ugs ha e been p oposed as an i i al ea men s, such
as hyd oxychlo oquine, lopina i , i ona i , and o he s; se e e
pneumonia is ea ed wi h b oad-spec um an ibio ics. The e is
no up- o-da e, e ec i e ea men o he COVID-19 in ec ion.
An a icle published in Ma ch 2020 shows how he immune
esponse o he COVID-19 i us is simila o he esponse
gene a ed by he in luenza i us [18]. Some au ho s p opose
he use o p obio ics as a s a egy o mi iga e he e ec s o
i uses [19].
Heal h ca e wo ke s (HCWs) a e a inc eased isk o COVID-19
in ec ion due o close con ac wi h highly in ec ious pa ien s as
well as exposu e o undiagnosed o subclinical in ec ed cases.
The s ess and physical exhaus ion associa ed wi h he pandemic
may also impac he immune esponse o HCWs [20]. A ecen
s udy examined 97 s udies and ound ha app oxima ely 11%
o pa ien s wi h COVID-19 we e people wi h unde lying disease
[21]. This ep esen ed a conside able pe cen age o all
COVID-19 cases [22]. Al hough he numbe o se e e cases
and mo ali y among HCWs was lowe han in o he popula ions
[21], he numbe o COVID-19 cases has led o a sho age o
HCWs, hus adding an ex a bu den o he igh agains his
pandemic.
I has been sugges ed by se e al au ho s ha p obio ics could
play a ole in p e en ing and alle ia ing he se e i y o
COVID-19 due o hei immune-modula ing, an i-in lamma o y,
an ioxidan , and an i i al p ope ies [23-25]. The
Loigolac obacillus co yni o misK8 CECT 5711 s ain has been
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shown o ha e he immune-modula ing capaci y in adul s [26]
and child en [27,28]. Resea ch has shown ha his s ain causes
an inc ease in hepa i is A i us an ibody le els a e o al
adminis a ion in heal hy adul s as pa o hepa i is A accina ion
[14]. A s udy in olde people ound ha he adminis a ion o
L co yni o mis K8 s eng hened he immune esponse o
in luenza accina ion and educed symp oms associa ed wi h
espi a o y in ec ions [15]. A ecen andomized con olled ial
conduc ed wi h nu sing home esiden s showed he bene i s o
L co yni o mis K8 in he COVID-19 pandemic. This is because
i may enhance he speci ic immune esponse ollowing
COVID-19 in ec ion and also aid accine-speci ic esponses
among he olde popula ion [29].
In his con ex , i is p oposed ha he immunomodula o y
p ope ies o L co yni o mis K8 CECT5711 migh be use ul o
COVID-19 managemen .
Me hods
Aim o he S udy
The objec i e o his s udy is o e alua e he e ec s o he
consump ion o L co yni o mis K8 on he incidence and se e i y
o symp oma ic in ec ion by SARS-CoV-2 and he se e i y o
COVID-19 in HCWs who ca y ou hei p o essional wo k
among pa ien s wi h in ec ion o suspec ed in ec ion by
SARS-CoV-2 a 2 e e al hospi als ha ea indi iduals wi h
COVID-19 in he p o ince o G anada (Andalusia, Spain).
Desc ip ion o T ea men s
The adminis a ion o he expe imen al p oduc and he placebo
will be ca ied ou in he o m o a gela in capsule ha will ha e
he same weigh , consis ency, and colo .
The Expe imen al G oup will ecei e ha d gela in capsules ha
will con ain 3×109colony o ming uni s o Lco yni o mis K8
(120 mg), 10 mg magnesium s ea a e, and 120 mg mal odex in.
The con ol g oup will ecei e ha d gela in capsules ha will
con ain magnesium s ea a e (10 mg) and mal odex in (220 mg).
Indi iduals om bo h g oups will ake 1 capsule a day
(p e e ably wi h dinne ).
Capsules o he p obio ic and placebo will be p o ided by
Biosea ch Li e (G anada, Spain).
S udy Design
The s udy is a nu i ional, andomized, double-blind, con olled,
and pa allel-g oup obse a ional p ospec i e coho s udy.
Volun ee s will be dis ibu ed in o 2 g oups: a con ol g oup
and an expe imen al g oup. The s udy will be pe o med as
shown in Figu e 1.
The ial has been egis e ed on ClinicalT ials.go
(NCT04366180).
Figu e 1. S udy lowcha .
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E hics App o al
This clinical esea ch p o ocol has been p epa ed wi h ull
unde s anding and in acco dance wi h he s anda ds o Good
Clinical P ac ice in acco dance wi h CPMP/ICH/135/95, he
Decla a ion o Helsinki (64 h Gene al Assembly, Fo aleza,
B azil, Oc obe 2013), ISO 14155, and all ele an na ional
guidelines. All in es iga o s pa icipa ing in he s udy a e
app op ia ely quali ied. The p o ocol was app o ed by he
Resea ch E hics Commi ee o he p o ince o G anada
(3/2020_P_054; CEIM/CEI P o ince o G anada). Volun ee s
will be included in he s udy a e in o med w i en consen is
ob ained.
Pa icipan s, In e en ion, and Ou comes
Inclusion C i e ia
The inclusion c i e ia included indi iduals olde han 18 yea s
and ac i e HCWs, including all p o essional ca ego ies such as
medicine, nu sing, and ca e aking, who a end cases classi ied
as posi i e o suspicious o COVID-19 in he eme gency
depa men , in ensi e ca e uni (ICU), o in he wa ds designa ed
o ca e o such pa ien s; and he abili y o comple e he su eys
and ha ing signed he in o med consen .
Exclusion C i e ia
The exclusion c i e ia excludes indi iduals wi h a posi i e es
o COVID-19 con i med by polyme ase chain eac ion o
se ology, indi iduals wi h concomi an pa hology such as HIV,
ansplan a ion, ac i e cance , o o he ac i e
immunosupp ession, and women who a e p egnan o in end o
become p egnan in he subsequen mon hs.
Rec ui men
The ec ui men o pa icipan s will ake place a he San Cecilio
Uni e si y Clinical Hospi al and a he Vi gen de las Nie es
Uni e si y Hospi al in G anada among HCWs wi h high
exposu e o pa ien s wi h COVID-19.
Randomiza ion, Alloca ion, and Blinding
Pa ien s will be andomly alloca ed o a con ol g oup o
expe imen al g oup in a 1:1 a io by he block andomiza ion
me hod wi h a block size o 4. Pa icipan s and in es iga o s
will be blinded o he ea men alloca ion du ing he cou se o
he in e en ion. The blind will be b oken a e s a is ical
analysis is comple ed.
Capsules o he con ol and expe imen al g oups will be
p o ided in whi e con aine s labeled wi h a andom numbe .
In e en ion
Pa icipan s mee ing he inclusion c i e ia will be andomly
assigned o he con ol o expe imen al g oup. Du ing he
in e en ion, pa icipan s will be asked o inges a capsule pe
day wi h some ood (p e e ably wi h dinne ). Follow-up isi s
will be scheduled a he beginning, midpoin (1 mon h), and
end o he in e en ion pe iod (2 mon hs). A he i s isi ,
baseline da a (age, sex, li es yle, medica ion, concomi an
diseases, and cu en symp oms) will be collec ed. A ollow-up
isi s, da a abou symp oms, medica ion, and ad e se e ec s
will be eco ded (Table 1).
Table 1. De ailed s udy p ocedu es.
V4 (12 mon hs)V3 (W8)V2 (W4)V1 (W0)Visi s (V) pe week (W)
✓In o med consen o m
✓Inclusion o exclusion c i e ia
✓Randomiza ion o alloca ion
✓T ea men dis ibu ion
✓Basal da a
✓
✓a
✓COVID-19 es
✓✓Symp oms ques ionnai e
✓✓✓Medica ion ques ionnai e
✓✓Ad e se e ec s ques ionnai e
✓Re u n o unconsumed capsules
✓E alua ion o he immune esponse o he
accine
aCOVID-19 es da a would be collec ed only i pe o med.
Ou comes Measu es
P ima y Ou comes
The main ou come will be he incidence o symp oma ic
SARS-CoV-2 in ec ion con i med by polyme ase chain eac ion
o se ology in HCW ca ing o pa ien s wi h suspec ed o
con i med COVID-19 a he San Cecilio Clinical Uni e si y
Hospi al and a he Vi gen de las Nie es Uni e si y Hospi al.
Seconda y Ou comes
Incidence o hospi al admissions caused by SARS-CoV-2
in ec ion, he incidence o ICU admissions caused by
SARS-CoV-2 in ec ion, he incidence o pneumonia caused by
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SARS-CoV-2 in ec ion, he incidence o he need o oxygen
suppo , he incidence o gas oin es inal symp oms, days wi h
a body empe a u e o >37.5 °C, days o pe sis en cough, days
o pe sis en eeling o a igue, and use o pha macological
ea men s. Da a o mild symp oms will be eco ded daily in
he no ebook o he olun ee , and, in he case o hospi aliza ion,
da a will be collec ed by in es iga o s om medical his o ies.
In addi ion, he immune esponse and side e ec s o he
COVID-19 accine in hese HCWs will be assessed. Da a will
be collec ed on he accines ecei ed by he HCWs, including
he name and ype o accine, doses ecei ed, da e o
accina ion, and immune esponse o he HCWs.
Wi hd awal, D opou , Discon inua ion, and
Compliance
Wi hd awal will be allowed a any ime du ing he ial.
In es iga o s may ecommend discon inuing he ial i , in hei
opinion, s aying in he s udy would be de imen al o he
pa icipan ’s well-being. This decision mus be based on he
appea ance o an ad e se e ec ha will be duly included in
he case epo o m.
Volun ee s will e u n he unconsumed capsules. Compliance
≤80% o he o al will be conside ed a iola ion o he p o ocol
and will be conside ed d opou s.
Ad e se E ec s
L co yni o misspecies a e included in he Quali ied P esump ion
o Sa e y lis published by he EFSA, which gua an ees sa e y
o consump ion [30]. On each isi , i will be moni o ed o
ad e se e ec s, which will be eco ded in he pa ien ’s medical
his o y and e alua ed by he p incipal in es iga o . In he e en
o se ious ad e se e en s conside ed ela ed o he expe imen al
p oduc , he esea che will in o m he heal h au ho i ies and
he Clinical Resea ch E hics Commi ee in ol ed in he clinical
ial.
Sample Size
Gi en ha he cu en a es o in ec ion among heal h
p o essionals wo ldwide a e e y di e en , he sample size has
been based on he compa ison o 2 independen p opo ions o
he use o he chi-squa e es . Fo an α o 5% and a powe o
80%, aking a pe cen age o a ec ed indi iduals in he con ol
g oup o 15% and 10% as he minimum meaning ul di e ence
o be de ec ed, a sample o 157 pe b anch would be necessa y,
aking in o accoun a loss o 10% o pa icipan s.
S a is ical Analysis
Due o he u gency o he ci cums ances o he pandemic, he
s a is ical me hods ha e no been ully planned. A s a is ical
analysis plan will be p epa ed du ing he execu ion o he s udy
and be o e he closu e o he da abase. The s a is ical me hods
o be used, he s a egy o be ollowed in he case o missing
alues, and he ables and igu es o include in he s a is ical
epo will be desc ibed in de ail.
The sample size has been calcula ed assuming 10% d opou s.
I is no planned o eplace wi hd awal pa icipan s.
In en ion- o- ea analysis will be ca ied ou , aking in o accoun
all he da a o he ec ui ed olun ee s, e en i hey ha e no
comple ed he in e en ion.
In gene al, he da a will be p esen ed as absolu e equencies
and pe cen ages in he case o quali a i e a iables. Fo he
quan i a i e a iables, cen al endency s a is ics, such as he
mean and median, and dispe sion s a is ics, such as he SD,
IQR, minimum and maximum alues, and o indica e he shape
o he dis ibu ion, shape measu es such as coe icien s o
skewness and ku osis, will be used. In he case o o dinal
a iables, depending on he numbe o ca ego ies, one o m o
ano he o desc ip ion will be used. In all cases, a column ha
includes he numbe o olun ee s wi h a ailable da a mus be
added o he da a p esen a ion able. The analyses will be di ided
by andomiza ion g oup.
To analyze he compa isons be ween g oups, pa ame ic es s
(S uden es o ANOVA) and nonpa ame ic es s
(Mann-Whi ney Uo K uskal-Wallis) will be used o
con inuous a iables acco ding o he cha ac e is ics o he s udy
a iables (assump ion no mali y), while o ca ego ical a iables,
chi-squa e es s o Fishe exac es s will be used.
In he case o be ween- isi compa isons o con inuous a iables,
pa ame ic es s (S uden es o pai ed da a o epea ed
measu es ANOVA) and nonpa ame ic es s (Wilcoxon o
F iedman) will be used, as app op ia e, acco ding o he
cha ac e is ics o he s udy a iables (assump ion o no mali y)
and he numbe o isi s o be compa ed, while he ca ego ical
a iables will be compa ed using he McNema es . The e ec
size will be es ima ed using CIs.
The signi icance le el o he s a is ical es s used will be .05.
All calcula ions will be pe o med wi h he SPSS s a is ical
so wa e package ( e sion 26; IBM Co p).
Fo he analysis o ad e se e en s, a desc ip i e analysis
( equencies and pe cen ages) will be ca ied ou h oughou
he s udy, p esen ing a lis o he ad e se e en s g ouped
acco ding o se e i y. These e en s will be lis ed by olun ee
and andomiza ion g oups.
Ad e se e en s and concomi an medica ion will be coded using
a s anda diza ion sys em. In he case o ad e se e en s, he mos
cu en e sion o he MedDRA sys em will be used, and o
concomi an medica ion, he ATC code will be used.
Da a Managemen
To u he ensu e he accu acy and eliabili y o he collec ed
da a, a ho ough p ocess o da a cleansing will be implemen ed
be o e compu e iza ion a he coo dina ing cen e in G anada,
Spain. Any e o s o inconsis encies iden i ied du ing his
p ocess will be ec i ied o cla i ied wi h he ele an sou ce
documen s o da abase manage s. The sou ce documen s and
da abases will also be subjec ed o egula da a cleansing
p ocedu es o main ain hei in eg i y h oughou he minimum
5-yea e en ion pe iod a e he s udy’s conclusion.
Addi ionally, any pe sonal in o ma ion will be ca e ully
sc eened and emo ed as pa o he da a cleansing p ocess o
gua an ee anonymi y and con iden iali y.
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Dissemina ion
Communica ions and scien i ic epo s ha eme ge om his
s udy will be ca ied ou unde he esponsibili y o he p incipal
in es iga o in ag eemen wi h he associa ed in es iga o s.
Publica ion ules will ollow in e na ional ecommenda ions.
The indings will also be sha ed wi h na ional heal h au ho i ies.
Au ho ship will ollow he guidelines es ablished by he
In e na ional Commi ee o Medical Jou nal Edi o s [31], which
equi e subs an i e con ibu ions o he design, conduc ,
in e p e a ion, and epo ing o a ial.
Resul s
The s udy had o be ex ended o he 2 e e al hospi als ha ea
COVID-19 cases in he p o ince o G anada (Andalusia, Spain),
Hospi al San Cecilio and Hospi al Vi gen de las Nie es because
he p ojec ed ec ui men was no su icien o he objec i e o
he s udy and i was necessa y o expand he sample ob ained
in o de o each as close as possible o he calcula ed sample.
Finally, 255 olun ee s we e ec ui ed and andomly dis ibu ed
in o 2 g oups: he con ol g oup (n=128) and he p obio ic g oup
(n=127). In o de o measu e addi ional seconda y ou comes,
he p ojec was kep open by collec ing da a ela ed o accines
and immune esponses. The s udy s a ed in July 2020, wi h he
i s pa o he s udy ending in Sep embe 2020. In o de o
measu e addi ional seconda y ou comes, he p ojec was kep
open by collec ing da a ela ed o accines and immune
esponses un il Sep embe 2021. We will s a analyzing
esponses in July 2023, wi h publica ion o esul s expec ed in
he second hal o 2023.
Discussion
P incipal Findings
This s udy is conduc ed o e alua e he e icacy o he e ec s
o L co yni o misK8 consump ion on he incidence and se e i y
o COVID-19 in HCWs wo king wi h SARS-CoV-2–in ec ed
o suspec ed pa ien s in e e al hospi als o pa ien s wi h
COVID-19 in he p o ince o G anada. This andomized
con olled ial aims o s udy whe he he consump ion o L
co yni o mis K8 will educe he incidence o SARS-CoV-2
in ec ion in he s a ca ing o pa ien s wi h suspec ed o
con i med COVID-19 disease a he San Cecilio Uni e si y
Hospi al and Vi gen de las Nie es Uni e si y Hospi al. Fo his
pu pose, he incidence o hospi al admissions caused by
SARS-CoV-2 in ec ion, bo h in he gene al hospi aliza ion a ea
and in he ICU a ea, will be s udied in HCWs ca ing o
SARS-CoV-2–in ec ed pa ien s.
I is impo an o de e mine he p e alence o pneumonia caused
by SARS-CoV-2 in ec ion and he need o oxygen supply o
hese pa ien s. The p esence o e e will be s udied, and he
numbe o days will be quan i ied, as well as he pe sis ence o
cough and eeling o a igue. On he o he hand, i will also be
assessed whe he hese wo ke s ha e needed pha macological
ea men .
This in e en ion aims o shed ligh on he use o p obio ics o
enhance he immune e ec agains SARS-CoV-2. In addi ion,
his in e en ion s udy aims o con ibu e o he unde s anding
o he e ec o aking p obio ics o imp o e he immune
esponse o accines agains SARS-CoV-2. An a icle published
in Ma ch 2020 shows how he immune esponse o he
COVID-19 i us is simila o he esponse gene a ed by he
in luenza i us [18]. When he immune sys em wo ks p ope ly,
he i s ba ie o SARS-CoV-2 is he inna e esponse. This
inna e esponse, cha ac e ized by in e e on and cy okines,
which a e small p o eins esponsible o symp oms such as
e e , headaches, and muscle pain, has 2 unc ions: o slow
down he eplica ion and sp ead o he i us un il he speci ic
immune esponse (which, when i is a i us ha has no been
p e iously con ac ed, akes app oxima ely 2 o 3 weeks) is
ac i a ed. The speci ic immune esponse is wha will s op and
ul ima ely elimina e he in ec ion. This speci ic esponse also
con ols he inna e esponse in o de o p e en excessi e ac i i y
om damaging he issues. When his esponse wo ks in a
co ec and coo dina ed manne , he in ec ion is o e come,
showing symp oms mo e o less simila o hose o he lu.
Howe e , in an olde popula ion expe iencing dys unc ion o
he age- ela ed immune esponse, called immunosenescence,
o in a popula ion in which he esponse appea s o be poo ly
coo dina ed, he inna e esponse occu s la e o is ine ec i e,
gi ing he i us ime o eplica e and sp ead and delaying he
ac i a ion o he speci ic esponse. Be o e he massi e in asion
o issues, he inna e esponse exagge a edly damages issues,
causing espi a o y ailu e and ailu e in o he o gans, such as
he kidney. Gi en his si ua ion, some au ho s speak o 3 disease
s a es ha equi e di e en app oaches: an asymp oma ic s a e,
a second s a e wi h nonse e e symp oms, and a hi d s a e wi h
se e e espi a o y symp oms and a high i al load. Du ing he
i s 2 s a es, a speci ic immune esponse is equi ed o elimina e
he i us and p e en he disease om p og essing o s a e 3.
In his phase, s a egies o enhance he immune esponse a e
impo an . Howe e , in s a e 3, when he immune sys em has
ailed and he i us has sp ead, he damage o he issues causes
a massi e in lamma o y esponse; he s a egy should be aimed
a con olling ha in lamma ion [27]. Se e al clinical ials ha e
e idenced he posi i e e ec s o ce ain p obio ic s ains on he
p e en ion o espi a o y ac in ec ions. In ac , some au ho s
p opose he use o p obio ics as a s a egy o mi iga e he e ec s
o SARS-CoV-2 [19]. Mechanisms ha would be in ol ed in
a posi i e e ec o p obio ic ea men s on espi a o y i uses
include enhancemen o he in es inal epi helial ba ie ,
compe i ion wi h pa hogens o nu ien s and adhesion o he
in es inal epi helium, p oduc ion o an imic obial subs ances,
and modula ion o he hos immune sys em [19]. L co yni o mis
K8 CECT5711 has immunomodula o y p ope ies ha could
be use ul o COVID-19 managemen . On he one hand, we
ha e p e iously discussed i s abili y o imp o e he immune
esponse agains i al an igens, leading o he p oduc ion o
speci ic an ibodies [14,15]. On he o he hand, he s ain has
been shown in animal expe imen s o ha e an i-in lamma o y
capaci y in models o in lamma ion [3,27]. This
an i-in lamma o y ac i i y would also be o in e es in he case
o COVID-19, as i could help p e en uncon olled
in lamma o y p ocesses om leading o espi a o y and o he
o gan ailu e.
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The wo king hypo hesis is ha he adminis a ion o L
co yni o mis K8 will s imula e he immune esponse o people
exposed o COVID-19, ac ing as an adju an ha con ibu es
o de eloping an e ec i e esponse agains he i us, and
he e o e ewe in ec ious cases a e p esen ed due o his i us
o , in he e en o an occu ence, he disease is milde among
he pa icipan s aking he p obio ic s ain.
The high deg ee o exposu e among HCWs pu s hem a high
isk o con ac ing he i us. I we add o his si ua ion he ac
ha he s ess and physical o e exe ion caused by he pandemic
can a ec he immune esponse, he isk inc eases e en mo e.
The s udy has been designed o demons a e i he consump ion
o hese p obio ic bac e ia migh con ibu e o educing he le el
o incidence, o a leas he se e i y o in ec ion, in his
popula ion.
Conclusions
Fu he knowledge in his a ea could lead o an imp o emen
in he immune esponse o HCWs o nonin ec ion wi h
SARS-CoV-2 o o a educ ion o symp oms in cases o
in ec ion. This would ensu e ha HCW wo k o ces a e no
impai ed in hei abili y o cope wi h SARS-CoV-2 and ha
hose in ec ed wi h SARS-CoV-2 a e able o e u n o wo k
mo e quickly han hose who do no ake p obio ic supplemen s.
Acknowledgmen s
We hank all pa icipan s o hei aluable con ibu ions. We would especially like o hank he managing di ec o s o he San
Cecilio and Vi gen de las Nie es Uni e si y Hospi als.
Da a A ailabili y
The da a se s gene a ed du ing his s udy a e a ailable om he co esponding au ho upon easonable eques .
Au ho s' Con ibu ions
All au ho s pa icipa ed in he w i ing and eading o he manusc ip and app o ed he inal e sion.
Con lic s o In e es
None decla ed.
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Abb e ia ions
EFSA: Eu opean Food Sa e y Agency
HCW: heal h ca e wo ke
ICU: in ensi e ca e uni
Edi ed by T Leung; submi ed 09.03.22; pee - e iewed by D Pucia o, YL Leung; commen s o au ho 05.03.23; e ised e sion ecei ed
07.03.23; accep ed 12.04.23; published 28.06.23
Please ci e as:
Rod íguez-Blanque R, Sánchez-Ga cía JC, Cobos Va gas A, Ley a Ma ínez MS, Ma ínez Diz S, Co és-Ma ín J, To a -Gál ez MI
E alua ion o Lac obacillus Co yni o mis K8 Consump ion by Heal h Ca e Wo ke s Exposed o COVID-19 (Lac oCo 2 P ojec ):
P o ocol o a Randomized Con olled T ial
JMIR Res P o oc 2023;12:e37857
URL: h ps://www. esea chp o ocols.o g/2023/1/e37857
doi: 10.2196/37857
PMID: 37285326
©Raquel Rod íguez-Blanque, Juan Ca los Sánchez-Ga cía, Angel Cobos Va gas, M Soco o Ley a Ma ínez, Sil ia Ma ínez
Diz, Jona han Co és-Ma ín, Ma ía Isabel To a -Gál ez. O iginally published in JMIR Resea ch P o ocols
(h ps://www. esea chp o ocols.o g), 28.06.2023. This is an open-access a icle dis ibu ed unde he e ms o he C ea i e
Commons A ibu ion License (h ps://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and
ep oduc ion in any medium, p o ided he o iginal wo k, i s published in JMIR Resea ch P o ocols, is p ope ly ci ed. The
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copy igh and license in o ma ion mus be included.
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