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Machine Learning First Response to COVID-19: A Systematic Literature Review of Clinical Decision Assistance Approaches during Pandemic Years from 2020 to 2022

Abstract

The first author received research funds from the Basque Government as the head of the Grupo de Inteligencia Computacional, Universidad del Pais Vasco, UPV/EHU, from 2007 until 2025. The current code for the grant is IT1689-22. Additionally, the author participates in Elkartek project KK-2022/00051. The Spanish MCIN has also granted the authors a research project under code PID2020-116346GB-I00.

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Machine Learning First Response to COVID-19: A Systematic Literature Review of Clinical Decision Assistance Approaches during Pandemic Years from 2020 to 2022

Author: Badiola Zabala, Goizalde,López Guede, José Manuel,Estévez Sanz, Julián,Graña Romay, Manuel María
Publisher: MDPI
Year: 2024
DOI: 10.3390/electronics13061005
Source: https://addi.ehu.eus/bitstream/10810/66551/1/electronics-13-01005.pdf
Ci a ion: Badiola-Zabala, G.;
Lopez-Guede, J.M.; Es e ez, J.; G aña,
M. Machine Lea ning Fi s Response
o COVID-19: A Sys ema ic Li e a u e
Re iew o Clinical Decision
Assis ance App oaches du ing
Pandemic Yea s om 2020 o 2022.
Elec onics 2024,13, 1005. h ps://
doi.o g/10.3390/elec onics13061005
Academic Edi o : Gab iella Olmo
Recei ed: 15 Janua y 2024
Re ised: 27 Feb ua y 2024
Accep ed: 3 Ma ch 2024
Published: 7 Ma ch 2024
Copy igh : © 2024 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
elec onics
Sys ema ic Re iew
Machine Lea ning Fi s Response o COVID-19: A Sys ema ic
Li e a u e Re iew o Clinical Decision Assis ance App oaches
du ing Pandemic Yea s om 2020 o 2022
Goizalde Badiola-Zabala 1,*, Jose Manuel Lopez-Guede 1,2 , Julian Es e ez 1,3 and Manuel G aña 1,3
1Compu a ional In elligence G oup, Basque Coun y Uni e si y (UPV/EHU), 01006 Vi o ia-Gas eiz, Spain;
[email p o ec ed] (J.M.L.-G.); [email p o ec ed] (M.G.)
2
Depa men o Sys ems and Au oma ic Con ol, Facul y o Enginee ing o Vi o ia, Basque Coun y Uni e si y
(UPV/EHU), Nie es Cano 12, 01006 Vi o ia-Gas eiz, Spain
3Depa men o Compu e Science and A i icial In elligence, Facul y o In o ma ics, Basque Coun y
Uni e si y (UPV/EHU), Paseo Manuel de La dizabal 1, 20018 Donos ia-San Sebas ian, Spain
*Co espondence: [email p o ec ed]
Abs ac : Backg ound: The decla a ion o he COVID-19 pandemic igge ed global e o s o con ol
and manage he i us impac . Scien is s and esea che s ha e been s ongly in ol ed in de eloping
e ec i e s a egies ha can help policy make s and heal hca e sys ems bo h o moni o he sp ead and
o mi iga e he impac o he COVID-19 pandemic. Machine Lea ning (ML) and A i icial In elligence
(AI) ha e been applied in se e al on s o he igh . Fo emos is diagnos ic assis ance, encompassing
pa ien iage, p edic ion o ICU admission and mo ali y, iden i ica ion o mo ali y isk ac o s,
and disco e ing ea men d ugs and accines. Objec i e: This sys ema ic e iew aims o iden i y
o iginal esea ch s udies in ol ing ac ual pa ien da a o cons uc ML- and AI-based models o
clinical decision suppo o ea ly esponse du ing he pandemic yea s. Me hods: Following he
PRISMA me hodology, wo la ge academic esea ch publica ion indexing da abases we e sea ched
o in es iga e he use o ML-based echnologies and hei applica ions in heal hca e o comba he
COVID-19 pandemic. Resul s: The li e a u e sea ch e u ned mo e han
1000 pape s;
220 we e
selec ed acco ding o speci ic c i e ia. The selec ed s udies illus a e he use ulness o ML wi h
espec o suppo ing heal hca e p o essionals o (1) iage o pa ien s depending on disease se e i y,
(2) p edic ing admission o hospi al o In ensi e Ca e Uni s (ICUs), (3) sea ch o new o epu posed
ea men s and (4) he iden i ica ion o mo ali y isk ac o s. Conclusion: The ML/AI esea ch
communi y was able o p opose and de elop a wide a ie y o solu ions o p edic ing mo ali y,
hospi aliza ions and ea men ecommenda ions o pa ien s wi h COVID-19 diagnos ic, opening
he doo o u he in eg a ion o ML in clinical p ac ices igh ing his and o ecoming pandemics.
Howe e , he ansla ion o he clinical p ac ice is impeded by he he e ogenei y o bo h he da ase s
and he me hodological and compu a ional app oaches. The li e a u e lacks obus model alida ions
suppo ing his desi ed ansla ion.
Keywo ds: COVID-19; machine lea ning; a i icial in elligence; mo ali y; p edic ion; isk ac o s;
d ug epu posing; d ug
1. In oduc ion
The se e e acu e espi a o y synd ome co ona i us 2 (SARS-CoV-2) was i s epo ed
in Wuhan in Decembe 2019 wi h common clinical symp oms, such as e e , cough, muscle
o body aches, a igue, conges ion o unny nose. The i us was decla ed a po en ial
heal h haza d o people wi h backg ound diseases as i a ec s he uppe -lowe espi a o y
sys em and can cause lung in ec ions and ch onic lung obs uc ion. The Wo ld Heal h
O ganiza ion (WHO) decla ed a pandemic c isis on 11 Ma ch 2020. An ea ly es ima ion
Elec onics 2024,13, 1005. h ps://doi.o g/10.3390/elec onics13061005 h ps://www.mdpi.com/jou nal/elec onics
Elec onics 2024,13, 1005 2 o 38
o he
SARS-CoV-2
a e age ep oduc ion a e (i.e., he a e age numbe o cases o in ec-
ion caused by an iden i ied in ec ed indi idual) was 3.28 [
1
], explaining he pe cei ed
exponen ial g ow h o cases a he e y beginning o he pandemic. The po en ial o
heal h complica ions and he apid sp ead o he i us induced go e nmen s a ound he
wo ld o dic a e s ic popula ion con ol measu es o p e en he sp ead o he i us.
As a esul o he panicked global esponse, demand o inno a i e heal hca e esou ces
inc eased d ama ically. O e he cou se o his pandemic, in ense esea ch has add essed
designing A i icial In elligence (AI), Machine Lea ning (ML) and obo ic solu ions o
imp o e diagnos ic se ices, isk assessmen , moni o ing, and ele-assis ance, aiming o
educe signi ican ly he wo kload o on -line heal hca e wo ke s. Such p essu e on he
scien i ic communi y has gene a ed a eal sunami o publica ions. A sea ch unde he e m
COVID-19 e u ns o e ou -hund ed- housand e e ences in PubMed; his igu e gi es
a good imp ession o he magni ude o he ask o any e iew e o . In his se ing, i is
p oposed ha ML and AI can supplemen da a analysis, o ins ance colla ing candida e
d ug ela ionships, looking o pha maceu ical a ge s in he mids o massi e amoun s
o da a, inding bioma ke s and simula ing he eac ion o main compounds, g ea ly ac-
cele a ing he speed o esea ch and imp o ing quali y and e icacy [
2
]. Hence, ML and
AI p omised g ea po en ial wi h espec o da a-d i en solu ions o help humankind deal
wi h COVID-19 [3].
E en a e he decla a ion o he end o he pandemic by he WHO on 6 May 2023,
COVID-19
is no a ully unde s ood disease, wi h mul iple biological and clinical mani-
es a ions. New symp oms o he disease con inue o be epo ed [
4
], and he guidelines
conce ning which pa ien s should be conside ed Pe sons Unde In es iga ion (PUIs) o
COVID-19 o es ed o SARS-CoV-2 in ec ion ha e been con inually e ol ing du ing he
pandemic yea s. Indeed, clinical needs a e e ised equen ly [
5
]. One o he salien ea u es
o COVID-19 ha has un olded a e se e al yea s in o he pandemic is he e olu ion o he
symp oms o he disease [
6
], o en a ibu ed o he e olu ion o he unde lying i us [
7
],
accompanied by he changes and unce ain ies associa ed wi h he de ec ion and es ing
me hods [
8
]. This unce ain y in he case labeling se iously comp omises he ex apola-
ion o he esul s o Machine Lea ning (ML) algo i hms (i.e., gene aliza ion o ex e nal
alida ion) o di e en pe iods and si es o he pandemic. On he o he hand, some isks
ac o s we e iden i ied ea ly on and emain as such h ough he e olu ion o he pandemic.
Pa amoun isks a e obesi y [9–11] and age [12,13].
P e ious e iews o he use o ML o AI ools in he con ex o COVID-19 a e ei he
e y b oad o deal wi h na ow issues. B oad e iews [
14
–
16
] ackle a wide a ie y o
echniques and issues ha a e some imes un ela ed o clinical decision issues in COVID-19
pa ien s, such as he epidemiological model o disease ansmission [
16
]. O he s deal wi h
he p oblem o disease diagnosis in gene al [
17
]. Na ow e iews deal wi h speci ic aspec s,
such as he e ec s o age [
12
,
13
], obesi y [
10
,
18
], d ug epu posing [
19
], ca dio- ascula
isks [20], analysis o medical images [21,22], and es ing de ices [8].
This s a e o he a has been e iewed ollowing esea ch ques ions ha had been
aised p e iously in o de o c ea e a pa hway o he ealiza ion o a speci ic s udy and
no only o c ea e a e iew o a speci ic opic [
17
,
21
,
22
]. This pape p esen s a sys ema ic
e iew o ML app oaches ha ha e been p oposed in he ea ly pandemic esponse o deal
wi h ele an clinical decision issues: pa ien iage a admi ance, p edic ion o in ensi e
ca e uni (ICU) admi ance, p edic ion o dea h ou come, and iden i ica ion o mo ali y
isks. Addi ionally, we e iew AI-based app oaches o ea men design, speci ically a
sea ch ia AI ools o d ugs a ge ing he COVID-19 pa hogen, SARS-CoV-2.
2. Resea ch Ques ions
The main aim o his pape is o e iew he di e se ML app oaches ha we e p oposed
as a i s esponse o he COVID-19 pandemic in o de o alle ia e he cogni i e and
adminis a i e bu den o heal hca e p o ide s. Mos pa ien s en e a hospi al h ough he
Eme gency Depa men (ED); hence, ML ools may ha e a g ea impac he e wi h espec
Elec onics 2024,13, 1005 3 o 38
o managing he expec ed o e load. Howe e , i is impe a i e o assess he quali y o he
s udies om an ML me hodological poin o iew in o de o asce ain i hese s udies may
be (ha e been) ans e ed e ec i ely and in a imely manne o he clinical p ac ice as
ac ual suppo o he clinician.
This scien i ic objec i e is made conc e e in he ollowing Resea ch Ques ions:
RQ1
Did s udies ollow open science s anda ds? Speci ically, ha e he da a used been
published in open access?
RQ2 Which ML models ha e been mos equen ly p oposed and alida ed?
RQ3
Which a iables/ ea u es a e aken in o accoun and which a e he mos signi i-
can isks ound?
RQ4 Which alida ion p o ocols o ML models ha e been mos equen ly applied?
RQ5
Which pe o mance measu es a e epo ed? Which a e he pe o mances achie ed
acco ding o hese measu es?
3. Me hods
Sea ch S a egy
A sys ema ic li e a u e sea ch was conduc ed in acco dance wi h he P e e ed Re-
po ing I ems o Sys ema ic Re iews and Me a-Analysis (PRISMA) guidelines. Li e a u e
sea ches we e conduc ed in he Web o Science and IEEExplo e si es. The sea ch s ing
con ained he ollowing e ms: “(COVID-19 OR SARS-CoV-2 OR co ona i us) AND (ma-
chine lea ning OR deep lea ning OR a i icial in elligence)”. The JabRe e e ence da abase
manage was used o pe o m he li e a u e sea ch om Janua y 2020 o June 2022. The se-
lec ion p ocess is as ollows: i les and abs ac s o he pape s e ie ed ia he sea ch a e
sc eened, emo ing hose ha do no mee he inclusion c i e ia (no duplica ed, epo ing
ac ual p edic i e pe o mance esul s o e a da ase collec ed in a clinical se ing, no
being epidemiological s udies based on agg ega ed da a, gi ing a de ailed speci ica ion o
eco ded a iables, gi ing de ailed desc ip ions o ML and s a is ical me hods). Selec ed
pape s we e analyzed acco ding o he esea ch ques ions enume a ed abo e.
4. Resul s
4.1. Sea ch Resul s
The bibliog aphic sea ch yielded 2119 esea ch pape s. A e sc eening i les and
abs ac s, 1759 did no mee he inclusion c i e ia. A u he 140 s udies we e excluded in he
nex s age when he ull ex s o his se o a icles we e assessed, lea ing 220 pape s eligible
o analysis. Figu e 1illus a es he pipeline o he pape -selec ion p ocess.
Tables 1–3
summa ize he salien de ails o he selec ed pape s dis ibu ed in o he ollowing clinical
heal hca e opics whe e ML has been p oposed o decision assis ance: (1) iage o pa ien s
a admission, (2) isk o COVID-19- ela ed ICU admission and (3) isk ac o s o COVID-19-
ela ed dea h.
Elec onics 2024,13, 1005 4 o 38
Figu e 1. Flowcha o he pape -selec ion p ocess.
Elec onics 2024,13, 1005 5 o 38
Table 1. S udies epo ing a pa ien iage sys em. Da a segmen a ion (DS), Da a Augmen a ion (DA), Da ase Sou ce access (DSS), T aining Da ase (T ), Tes ing
Da ase (Te), Accu acy (AC), F1-sco e (F1), Sensi i i y (Se), Speci ici y (Sp), Recall (R), C oss-Valida ion (CV), Ex e nal Valida ion (EV), In e nal Valida ion (IV).
Re . Region Model Fea u es DS DA DSS T Te AC F1 Se AUC Sp R Valida ion
[23]Wuhan,
China RF
age, hype ension, ca dio ascula
disease, gende and diabe es o he
clinical ea u es modali y
and dime ized plasmin agmen D,
N/A N/A P i a e 290 72 0.97 0.97 0.99 0.97 0.94 N/A N/A
[24] Beijing Lasso eg ession
Age, Tempe a u e, HR, e e
classi ica ion; headache,
in e leukin-6; sys olic blood p essu e;
monocy e a io; pla ele coun ;
dias olic blood p essu e
N/A Random
o e sampling P i a e 105 27 N/A 0.57 N/A 0.84 0.727 1.00 10- old CV
[25] N/A XGBoos Top 60 impo an ea u es consis ing
o 19 p o eins, 11 me aboli es,
7 lipids, and 23 mRNAs N/A N/A P i a e 108 27 N/A N/A N/A 0.93 N/A N/A 5- old CV
[26] China RF and SVM
28 ea u es (age, gende , whi e blood
cell, neu ophil pe cen age,
lymphocy e pe cen age, monocy e
pe cen age, ...)
N/A Boo s ap
esampling N/A 40 11 0.9 N/A 0.88 N/A 0.9 N/A 10- old CV
[27] N/A BN, NB, MLP,
LWL and RF
age and gende , blood o issue
sample esul s, he pe iod o he
illness, symp oms and lab esul s,
and isk ac o s
N/A N/A N/A 880 587 0.99
(MLP) N/A N/A N/A N/A 0.99
(MLP) N/A
[28]Salamanca,
Spain RF, xgboos
and LR
demog aphic a iables,
como bidi ies, clinical cha ac e is ics,
physical examina ion pa ame e s
and biochemical pa ame e s
a ailable a hospi al admission
N/A N/A N/A 734 184 N/A N/A 0.9 0.83 0.52 N/A
10-s a i ied
old CV
scheme wi h
10 epe i ions
[29] China DL
clinicians o es ima e an indi idual
COVID-19 pa ien isk and make
decisions based on a ailabili y o
esou ces o c i ical pa ien s and
pa ien o e load
N/A N/A N/A 752 188 N/A N/A 0.95 0.894 0.95 0.44 N/A
[30] Ox o d LR, RF and
XGBoos
p esen a ion blood es s, blood gas
es ing, i al signs, and esul s o
PCR es ing o espi a o y i uses N/A N/A N/A 303 77 N/A N/A 0.774 0.939 0.948 N/A 10- old CV
[31]Mad id,
Spain x-means
clus e ing
10 Vi al signs, 29 labo a o y es s and
168 ICD-10 codes N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
[32] China
RF, GB, SVM, NB,
KNN, LR
Demog aphic da a, como bidi ies,
ou pa ien medica ions, i al signs
and labo a o y alues N/A N/A N/A 80% 20% 0.9 N/A N/A N/A N/A N/A N/A
[33] N/A XGBoos 24 ea u es (a e PCA) N/A N/A P i a e 102 25 0.97 0.96 N/A 1 N/A 0.95 EV
[33,34] B azil N/A ea u es o ou ine blood analysis N/A smo e N/A N/A N/A 0.91 0.87 0.83 0.74 0.91 0.83 EV

Elec onics 2024,13, 1005 6 o 38
Table 1. Con .
Re . Region Model Fea u es DS DA DSS T Te AC F1 Se AUC Sp R Valida ion
[35] Pa ia ResNe 50
age, SBP, DBP, RT, SPO2, empe a u e,
hemogoblin, whi e blood cell,
lymphocy es, Pla ele s, C- eac i e
p o ein and Lac a e dehyd ogenase
N/A
Image noise,
Colou
ji e ing, lip,
cen e c opping
N/A 337 45 0.9872 0.9922 N/A 0.9997 N/A 98.62 15% da ase
[36] N/A Ada Boos , RF,
XGBoos , Ca Boos
age, sex, espi a o y pa ame e s
(SPO2, RR), ca dio ascula
pa ame e s, body empe a u e,
symp oms, associa ed como bidi ies,
ull blood coun ,
biochemical pa ame e s
N/A
b igh ness
changes,
con as
adjus men
and pa allel
shi ing
P i a e 380 95 0.9859 N/A 0.9793 N/A 0.9897 N/A 5- old CV
[37] Mexico NN, LR, SVM,
KNN
APACHE II sco e, whi e blood cell
coun , ime om symp oms o
admission, SPO2 and blood
lymphocy es coun
N/A N/A Public 301,421 64,590 0.81–
0.931 N/A 0.83–
0.961 N/A 0.8–0.92 N/A 15% o da ase
[38]
Cheikh
Zaid
Hospi al,
Mo occo
X_GBoos ,
AdaBoos , RF
and Ex aT ees
Sex. Age. Pla ele , Lymphocy e, PLR,
ALT, AST, LDH, D-dime s,
C_ eac i e p o ein, Weigh ,
Como bidi ies
N/A N/A P i a e 225 97 1 N/A 1 1 1 N/A N/A
[39]JinYinTan
Hospi al,
China RF, SVM, LR
ches compu ed omog aphy, e e ,
malignan umo , HR, SBP,
hemoglobin concen a ion,
neu ophil- o-lymphocy e a io
N/A N/A P i a e N/A N/A 0.845–
0.885 N/A 0.923–
0.967 0.928–
0.970 0.695–
0.79 N/A 10- old CV
[40] N/A RF, XGBoos ,
KNN, MLP, LR,
J48, NB
Gende , age, leng h o
hospi aliza ion, Smoking, ICU
admission, hype ension, pneumonia,
diabe es, ca diac disease, symp oms,
BUN, WBC, C- eac i e p o ein,
hype sensi i e oponin, glucose,
e y h ocy e sedimen a ion a e,
c ea inine, alkaline phospha ase
N/A SMOTE N/A 1350 150 0.9503 N/A 0.907 0.9902 0.951 N/A 10- old CV
[41] N/A DL X- ays, adiology epo s and
RT-PCR da a N/A N/A p i a e 11,599 800 0.77 N/A 0.683 0.925 0.966 N/A
in e nally
(B own-Ap il)
and ex e nally
(Ex e nal and
Xiangya-
Feb ua y)
Elec onics 2024,13, 1005 7 o 38
Table 1. Con .
Re . Region Model Fea u es DS DA DSS T Te AC F1 Se AUC Sp R Valida ion
[42] Tu key
LR, SVM, Vo ed
Pe cep on, KNN,
K s a , LWL, NB,
SGD, DT,
Hoe ding DT, RF
age, da a, lymphocy es coun (LYM),
neu ophils coun (NEU), whi e
blood cells (WBC), mean co puscula
olume (MCV), mean pla ele
olume (MPV) and e y h ocy e
dis ibu ion wid h (RDW),
eosinophils coun (EOS), monocy es
coun (MONO), ed blood cells coun
(RBC), hema oc i , hemoglobin and
(mean co puscola hemoglobin con-
cen a ion (MCVC)
N/A N/A p i a e 3362 840 0.8762–
0.9786 0.9271–
0.988 0.9107–
0.9920 0.8810–
0.9786 0.8762–
0.9786 N/A 10- old CV
[43] N/A E icien Ne CXR images N/A N/A public/
p i a e 455 150 0.8667 0.7865–
0.9174 N/A 0.95 N/A 0.7–1 IV
[44] China LR Age, Sex, Como bidi y, p ima y
symp ons, ou comes,
labo a o y indica o s
lung
images seg-
men a ion N/A N/A 628 158 N/A N/A 0.833 0.732 0.781 N/A 5- old CV
[45] China LR
CK-MB, neu ophils, PCT, α-HBDH,
D-dime , LDH, glucose, PT, APTT,
RDW (SD and CV), ib inogen
and AST
N/A N/A p i a e N/A N/A N/A N/A N/A 0.83 N/A N/A EV
[46]Sou h
Ko ea XGB body empe a u e, pulse a e, RR,
blood p essu e, any symp oms, and
pas medical his o y N/A N/A p i a e 119,576 29,895 0.923 0.861 N/A 0.95 0.933 0.807 N/A
[47] UK RF
Age, Gende , BMI, Smoking S a us,
SPO2, Tempe a u e, como bidi ies,
Albumin, Whi e Blood Coun , Blood
U ea Ni ogen, Lymphocy e Coun
N/A N/A p i a e 1196 299 0.76 0.67 0.78 0.83 0.75 N/A 5- old CV
[48] Ko ea LGBM, ORL
AGE and SEX and BMI, HR,
empe a u e, SBP, DBP, ch onic
ca diac disease, as hma, ch onic
obs uc i e pulmona y disease,
hemoglobin, pla ele s, WBC
N/A N/A p i a e 3,940 1688 0.85–0.88 0.49–0.57 N/A N/A N/A 0.44–
0.56 10- old CV
[49] Is ael Mul is a e Cox
eg ession Age, sex, pa ien being in
1 o 3 clinical s a es N/A N/A N/A 297 33 N/A N/A N/A 0.88 N/A N/A 8- old CV
epea ed
8 imes
[50]
Philippines
DT Sex, Age, Region, N/A Random un-
de sampling N/A 197,164 N/A 0.8142 0.1674 0.8165 0.876 0.8141 N/A 5- old CV
Elec onics 2024,13, 1005 8 o 38
Table 2. S udies p edic ing he ans e o ICU and Leng h o S ay (LoS) in o COVID-19 pa ien s. Da a segmen a ion (DS), Da a Augmen a ion (DA), Da ase Sou ce
access (DSS), T aining Da ase (T ), Tes ing Da ase (Te), Accu acy (AC), F1-sco e (F1), Sensi i i y (Se), Speci ici y (Sp), Recall (R), C oss-Valida ion (CV), Ex e nal
Valida ion (EV), In e nal Valida ion (IV).
Re . Region Model Fea u es DS DA DSS T Te AC F1 Se AUC Sp R Valida ion
[51] Ge many Explainable
Boos ing
Machine 49 a iables N/A N/A N/A 949 237 0.73 N/A N/A 0.69 N/A N/A 5- old CV
[52]Galicia,
Spain
MLP.
DeepNe wo k,
RF, AB,SVM,
KNN, LR
Age, gende , diabe es, hype ophy,
hyd ocele, pneumonia, equen
u ina ion, he apeu ic ad ice, whi e
blood cells, hea ailu e
N/A Smo e, adasyn N/A 110,454 N/A N/A N/A N/A 0.761 N/A N/A 10- old CV
[53] B azil RF, XGB, LR 67 a ibu es N/A N/A N/A 5644 N/A 0.94 0.91 N/A 0.9 0.95 0.92 10- old CV
[54]Wuhan,
China N/A 194 a iables N/A N/A N/A 586 147 N/A N/A >0.571 >0.622 >0.353 N/A 3- old CV
[55] Sou h Asia RF, KNN, SVM Alcoholic be e ages, animal
p oduc s, ce eals excluding bee ,
mea , ege al p oduc s N/A N/A N/A N/A N/A >0.77 N/A N/A N/A N/A N/A N/A
[56]Dubai,
UAE DT Age, gende , na ionali y,
blood g oup, BMI N/A N/A N/A 1513 504 0.96 N/A 0.965 N/A 0.878 N/A 10- old CV
[57] USA XGBoos Age, gende , acu e diagnoses N/A N/A N/A 2313 N/A N/A N/A 0.9 N/A 0.58 N/A N/A
[58]Wuhan,
China XGBoos
lymphocy e pe cen age, p o h ombin
ime, lac a e dehyd ogenase, o al
bili ubin, eosinophil pe cen age N/A N/A N/A 98 25 N/A N/A 0.8 0.92 0.9 N/A 5- old CV
[59] NY, USA RF 31 a iables N/A N/A N/A 1375 612 N/A 0.762 0.728 0.79 0.763 N/A 10- old CV
[60] Denma k RF Age, sex, BMI, como bidi ies,
smoking, lab es s and empo al
ea u es N/A N/A N/A 42,526 N/A N/A N/A N/A 0.995 N/A N/A N/A
[61] NY, USA LR, DT, RF,
GBDT
RT-PCR esul s, ou ine labo a o y
es ing esul s and pa ien
demog aphic in o ma ion N/A N/A N/A N/A N/A N/A N/A 0.761 0.854 0.808 N/A 5- old CV
[62] I an LR, NN, C5.0, RF,
XGBoos
demog aphic cha ac e is ics,
pa ien ’s backg ound, disease
symp oms and a a ge a iable N/A N/A N/A 318 80 0.7901–
0.852 N/A 0.9091–
0.9273 N/A 0.5385–
0.7308 N/A 10- old CV
[63]
Philadelphia,
PA
and P o i-
dence, RI,
USA
RF
demog aphic, clinical and labo a o y
a iables aken on admission o he
ICU including age, sex, empe a u e,
SpO2, WBC, absolu e lymphocy e
coun , se um c ea inine
concen a ion, CRP
and como bidi ies
ches X- ays
we e
segmen ed N/A P i a e 546 108 0.727 0.707 0.714 0.732 0.746 N/A 5- old CV
Elec onics 2024,13, 1005 9 o 38
Table 2. Con .
Re . Region Model Fea u es DS DA DSS T Te AC F1 Se AUC Sp R Valida ion
[64]Kingdom
o Saudi
A abia DL
The da ase con ains demog aphic
ea u es, labo a o y esul s om
comple e blood coun CBC
and adiological indings
and como bidi y
Ches X- ay
segmen a-
ion SMOTE P i a e 1210 303 0.904 N/A 0.86 0.875 0.84 N/A 10- old CV
[65] N/A XGBoos Sex, Ma i al s a us, Age, numbe o
admissions, ype o admissions,
hospi aliza ion da a, como bidi ies N/A N/A N/A 5212 579 0.917 0.918 0.916 0.91 0.913 N/A 10- old CV
[66] N/A
Gaussian mix u e
mode b ea hing equency (BF) and (SpO2) N/A N/A N/A N/A N/A 0.878 N/A N/A 0.94 N/A N/A N/A
[67]
Tel-A i
Sou asky
Medical
Cen e ,
Is ael
Ca Boos demog aphics, backg ound disease,
i al signs and lab measu emen s N/A N/A P i a e 20,029 5007 0.8 N/A N/A 0.76 N/A 0.7
20- old CV and
EV on da a
om a
di e en
hospi al
[68] USA DL
condi ion, p ocedu e, measu emen ,
obse a ion, d ug, de ices, paye ,
isi , heal h p o ide s, medical si es
and pe sonal in o ma ion
N/A N/A Public 9545 200 N/A N/A N/A 0.9 N/A N/A
10 imes by
andomly
spli ing
aining and
alida ion da a
[69]Saudi
A abia J48
demog aphics, como bidi ies, signs
and symp oms o COVID-19 illness,
labo a o y alues,
mechanical en ila ion
N/A N/A P i a e 1101 367 0.731 N/A N/A 0.7542 N/A N/A 10- old CV
[70]Saudi
A abia RF
Age, gende , Weigh , ca ee , Hea
disease, Hype ension, Diabe es
melli us, S oke, Vascula disease,
lymphocy e absolu e alue
N/A N/A p i a e 115 - 0.9416 0.9414 N/A N/A N/A 0.9416 29 samples o
alida ion
[71]Tokyo,
Japan LR Age, gende , como bidi ies, smoing
s a us, empe a u e, RR, SBP, DBP,
HR, SpO2 N/A N/A P i a e N/A N/A 0.9 0.695 N/A 0.875 0.976 0.513 No alida ion
[65] N/A XGBoos Sex, Ma i al s a us, Age, numbe o
admissions, ype o admissions,
hospi aliza ion da a, como bidi ies N/A N/A N/A 5212 579 0.917 0.918 0.916 0.91 0.913 N/A 10- old CV
[72]London,
UK LR, RF and
XGBoos 64 clinical ea u es N/A N/A p i a e 299 145 N/A 0.42–0.60 N/A 0.76–0.87 N/A 0.48 3- old CV
[73]Basque
Coun y,
Spain Ca Boos
p essu e o oxygen, pla ele s,
lymphocy es, monocy es and
eosinophils and he highes alues
o CRP, age, p ocalci onin,
u ea, LDH
N/A N/A P i a e N/A N/A N/A N/A 0.99 N/A 0.95 N/A EV
[74]Lomba dy;
I aly LR age, gende , home medica ions,
como bidi ies and en ila ion
pa ame e s om he i s 24 h in ICU N/A SMOTE P i a e N/A N/A 0.7–0.76 0.71–0.75 N/A 0.77–0.8 N/A 0.72–
0.75 10- old CV
Elec onics 2024,13, 1005 16 o 38
applied andom o e sampling (3%), and 1% o pape s applied o he echniques such as
boo s ap esampling. The emaining 83% o s udies did epo balanced da ase s.
4.3. RQ 2: Machine Lea ning Algo i hms
A majo i y o he selec ed s udies ha e benchma ked models in o de o achie e he
highes accu acy and bes pe o mance acco ding o he p oposed casuis y. The mos
equen ly used algo i hms we e Random Fo es (RF), Logis ic Reg ession (LR), G adien
Boos e (XGB) and Suppo Vec o Machines (SVM) wi h 18.88%, 13.29%, 9.84% and 7.71%
equency, espec i ely. These models a e also he ones ha ha e achie ed he highes
o e all p ecision in compa ison o he emaining ones. The equency o appea ance o ML
algo i hms o e he selec ed pape s is ep esen ed in Figu e 3. Many pape s did y se e al
algo i hms, so ha hese numbe s include o e lapping s udies.
Figu e 3. Numbe o selec ed pape s epo ing esul s o speci ic ML algo i hms. Ac onyms:
RF Random Fo es , LR Logis ic eg ession, GBM, LGBM, GBDT, XGB, XGBoos and Ca Boos a e
compe ing implemen a ions o g adien boos ing, Adaboos Adap i e Boos ing, DT and J48 a e
implemen a ions o decision ees in R and Weka, espec i ely, SVM suppo ec o machines, KNN k-
nea es neighboo , DL and DeepNN a e deep lea ning implemen a ions, MLP mul i-laye pe cep on,
NB nai e Bayes and NN neu al ne wo k.
Among he epo ed models, he LR app oach is he mos deeply oo ed in classical
s a is ics. I is a linea eg ession o a logis ic unc ion ha can be in e p e ed as a pos e io
p obabili y o he posi i e class; he e o e, i allows one o assess he impo ance o each
inpu a iable as an odd a io and he di ec ion o he in luence o he a iables, i.e., i ising
alues inc ease o dec ease he isk. Fo his eason, many s udies applied only LR, also
i he aim o he s udy was o assess he isks o speci ic ac o s like age, gende o o he s.
The emaining app oaches a e ML app oaches, which can p o ide some in o ma ion on
he in luence o impo ance o inpu a iables, bu o en hey canno p o ide he di ec ion
o he o he in luence. The mos popula ML algo i hm is he well known RF which
o en p o ides he bes accu acy esul s and a iable impo ance based on he Gini index
o da a spli s in he ee lea es. Ano he classical app oach is he SVM ha has been
ex ensi ely used in medical s udies o p edic i e model cons uc ion. Howe e , i is no
easy o assess a iable impo ance om SVM, so his aspec is o en omi ed in s udies
exploi ing SVMs. Boos ing app oaches such as Adaboos and di e se la o s o G adien
Boos ing ha e also been popula in COVID-19 s udies abou clinical decision assis ance,
epo ing some imes op imal pe o mances bu lacking he explana o y abili y o a iable
impo ance assessmen . I is impo an o no ice ha di e se ML pla o ms, such as R

Elec onics 2024,13, 1005 17 o 38
packages, Py hon, Weka o Ma lab oolboxes, p o ide sligh ly di e en implemen a ions
o he same models ha may e en appea wi h di e en names. In his e iew, we ha e
no del ed in o his le el o de ail, bu an exhaus i e wo k o compa ison should assess
he di e ences o epo ed esul s o di e se implemen a ions o e he same da ase s.
A i icial Neu al Ne wo ks (ANN), such as he popula Mul i Laye Pe cep on (MLP) o e
a wide spec um o po en ial models wi h many po en ial di e ences in hype pa ame e s
and aining algo i hms. In his s udy, we ound ew Deep Lea ning (DL) app oaches
because da ase s a e o en small ela i e o he la ge da ase s equi ed by DL aining.
Ano he incon enience o ANNs is hei educed explainabili y. Va iable impo ance in
ANNs is a he di icul o es ima e. In his e iew, i is no possible o conclude ha any o
he ML app oaches ound in he e iewed pape s is supe io and should be ecommended
o e he emaining app oaches.
4.4. RQ 3: Fea u es
In some s udies, he numbe o p edic o s is e y high, while o he s gi e only he
numbe o p edic o s wi hou mo e speci ics. Some s udies, which ha e ga he ed many
a iables, decided o conside ML app oaches o es ima e he impo ance o he a i-
ables and hus educe he dimensionali y by some ea u e-ex ac ion o -selec ion p ocess.
None heless, o he a icles ha speci y he a iables employed, hei majo i y did use
a common co e se o a iables. O he a iables we e usually con ex -dependen . Age,
gende , whi e blood cell coun ing, como bidi ies and blood oxygen sa u a ion a e he mos
equen ly conside ed p edic i e a iables. The mos commonly used ea u es and hei
espec i e equencies o appea ance in he s udies a e p esen ed in Figu e 4.
Figu e 4. Dis ibu ion o disc iminan ea u es o e he selec ed pape s.
Elec onics 2024,13, 1005 18 o 38
4.5. RQ 4: In e nal and Ex e nal Valida ion
Da a a e o en spli in o wo o h ee da ase s ( ain, alida ion and es ) when i comes
o alida ion o an ML p edic i e model. In mos o he su eyed s udies, 70–90% o he
da a we e used o ain he models including hype pa ame e selec ion, while he es
se ed o ex e nal es ing. Un o una ely, 16% o he s udies did no gi e any in o ma ion
abou he alida ion p ocedu e ollowed. Al hough using a hi d pa i ion o he da ase
o in e nal alida ion and model hype pa ame e selec ion was p edominan , ex e nal
alida ion was explici ly men ioned only in en s udies. The mos commonly used me hod
o in e nal alida ion was k- old c oss alida ion. Rega ding he numbe o olds, o e 60%
o he s udies epo ed k = 10, almos 26% o he o he s epo ed k = 5, se ing k = 20, k = 8
and k = 3 was epo ed by 2% each and he emaining 9% o s udies epo ed he use o
c oss alida ion bu did no speci y he numbe o olds used.
4.6. RQ 5: E alua ion Me ics
The me ics used o e alua e he pe o mance o he model we e collec ed and a e
compa ed in Tables 1–3. Accu acy, F1-sco e, sensi i i y, AUC, speci ici y and ecall we e he
me ics epo ed in he s udies. Mos s udies epo ed accu acy sco e and AUC, while he
leas used me ic was ecall. The e is s ong a iabili y in he epo ed esul s. Fo ins ance,
he minimum and maximum AUC alues epo ed o models p edic ing mo ali y was
0.997 and 0.57, espec i ely, while accu acy alues anged in he in e al [0.56, 0.99].
5. Re iew o Su eyed App oaches
In his sec ion, we p o ide a discou se e iew o he main app oaches dealing wi h he
iden i ied c i ical clinical issues. Tables 1–3p o ide summa y de ails o he main cha ac e is-
ics o he pape s o iage a hospi al admission, admission o ICU and
dea h, espec i ely.
5.1. Pa ien T iage Me hods
The iden i ica ion o ell ale COVID-19 symp oms [
132
–
134
] and he ea ly wa ning
o COVID-19-posi i e cases [
61
,
135
–
137
] we e he i s s eps owa ds he managemen o
he disease [
138
–
140
]; classi ying pa ien s acco ding o hei se e i y is he nex c i ical
s ep. Nume ous s udies ha e p esen ed models using ML echniques o p edic pa ien
ou comes [
141
] and se e i y assessmen [
142
,
143
] in SARS-CoV-2-in ec ed pa ien s in
di e en egions o he wo ld [
46
,
47
], p e en ing se e e disease p og ession while aiming o
minimize cos s o he pa ien , he heal hca e sys em and socie y a la ge. I was shown ha
i is possible o disc imina e be ween h ee s a es o he pa ien s’ disease e olu ion and ha
i is possible o make accu a e p edic ions o a pa ien ’s hospi al wo kload based on s a is ics
conce ning age, gende and daily clinical s a us (c i ical, se e e o mode a e) [32,49].
Thus, one o he p ima y esea ch goals is guiding hospi al s a wi h alida ed e -
idence gi ing ad ice on he op imal assignmen o limi ed esou ces while imp o ing
pa ien ou comes [28,50]. The e o e, ML and AI ools ha e been p oposed o he c ea ion
o iage assis an sys ems helping o speed up he decision o he admi ance o pa ien s
in o COVID-19 es ic ed a eas and o de e mine which pa ien s will equi e ei he s anda d
o in ensi e ca e [
25
,
37
,
144
,
145
]. In his spi i , online calcula ion ools o ea ly pa ien
iage we e p oposed [
29
]. Some applica ions o an ML-based classi ie aided in excluding
pa ien s ega ding hei se e i y wi hin 1 h o hospi al admission [
30
] on he basis o ou ine
in o ma ion. Some pape s [
38
] epo ed he ex ensi e compa ison o se e al ML models,
such as XGBoos , AdaBoos , RF and Ex aT ees. Some au ho s educed he iage p oblem
o a classi ica ion o pa ien s in o c i ically ill and non-c i ically ill in o de o p io i ize
hose in immedia e need o u gen ca e [
146
], some p oposing RF models [
23
] be ed wi h
mul imodal da a o a a ie y o algo i hms be es ed ( ee-based, unc ion algo i hms and
lazy lea ning algo i hms) o his ask [42].
Classi ica ion o COVID-19 se e i y in o iage ca ego ies has was also ca ied ou
on clinical da a and labo a o y es s ob ained du ing pa ien examina ion in ED [
31
] and
26 blood ou ine indica o s and se e al demog aphic ea u es [
26
] using a speci ically
Elec onics 2024,13, 1005 19 o 38
de eloped RF-SMA-SVM model. A no el SV-LAR model was exhibi ed o iage based on
blood sample ou ine da a [
34
], in line wi h o he app oaches exploi ing blood sample es
da a o ea ly iage [48]
Some o he s udies also ocused on he di e en ial diagnosis o COVID-19 om o he
simila diseases o o de ec pa ien s wi h high isk o u u e lung diseases, such as a
diagnos ic model o aid in he ea ly iden i ica ion o suspec ed COVID-19 pneumonia
pa ien s [
24
] on admission in e e clinics. O he s classi ied he diagnosis o he pa ien s
in o h ee ca ego ies: COVID-19 pneumonia, non-COVID-19 pneumonia and he heal hy
ones [
43
]. S ill, ano he app oach [
35
] p oposed a DL-based sys em o he classi ica ion o
he se e i y o pneumonia conside ing wo se e i y scales. Addi ional wo ks disc imina ed
be ween in luenza H1N1 and COVID-19 pa ien s [27] using an MLP algo i hm.
Many au ho s wo k wi h models p edic ing se e e COVID-19 based on p o eomics
da a [
39
,
40
]; in his line o wo k, C- eac i e p o ein [
147
,
148
], LDH [
149
–
151
],
pla ele s [152,153]
and D-dime [
45
,
154
,
155
] we e ound o be mos associa ed wi h p edic ing he se e i y
o COVID-19.
Ano he line o esea ch ied o de ec di e en le els o se e i y isk o COVID-19
pa ien s based on X- ay imaging [
33
,
36
,
156
]. Some au ho s concluded ha using adiologi-
cal ea u es in conjunc ion wi h blood es s, ea ly iden i ica ion o pa ien s wi h COVID-19,
who a e a isk o disease p og ession, can be achie ed on admission o hospi al [
44
]. Fu -
he mo e, a p ognos ic model using imaging da a [
41
] no only p edic s he se e i y o a
pa ien ’s illness, bu also he ime un il he pa ien encoun e s his o he i s c i ical e en .
5.2. P edic ion o ICU Admission, P og ession and Leng h o S ay
The co ona i us disease ook i s oll on heal hca e sys ems a ound he wo ld, wi h some
pa ien s equi ing leng hy gene al and in ensi e ca e. Unde he p essu e o an unp ece-
den ed bu den on heal hca e sys ems, he e is a need o ools helping decision make s
o plan esou ce alloca ion a he uni , hospi al and na ional le els, which can be ackled
wi h ML me hods [
157
]. In essence, clinicians will be in e es ed in ML app oaches ha
a e able o p edic whe he pa ien s diagnosed wi h COVID-19 will equi e di e en le els
o hospi al ca e ( ans e om he basic hospi al o ICU) [
52
,
53
,
158
]. Fo ins ance, i is
desi able o eliably p io i ize pa ien s wi h COVID-19 who a e a isk o needing ans e
o he ICU wi hin he nex 24 h, which has b oad implica ions and u ili y o clinical p ac ice
and hospi al ope a ions, on he basis o isks o espi a o y ailu e, shock, in lamma ion
and enal ailu e in he p og ession o COVID-19 [59]. Dealing wi h child en [159] is e en
mo e di icul , because he e y low p e alence o se e e COVID-19 means e y sca ce
da a. Despi e hese d awbacks, some esea che s demons a ed a DL app oach using a
la ge ea u e se o p edic bo h he isk o hospi aliza ion o in ec ed child en and he isk
o se ious complica ions in hospi alized pedia ic pa ien s [
68
]. Ano he line o esea ch
deals wi h he p edic ion o ICU wo kload o e a sho - e m ime ho izon [60] in o de o
a ain op imal esou ce managemen .
Ex ensi e e alua ions o ML algo i hms belonging o nine ca ego ies ha e been e-
po ed o p edic ion o clinical ou comes such as ICU admission o mo ali y, using da a
a ailable om he ini ial COVID-19 de ec ion [
160
]. Speci ically, ICU admission has been
p edic ed on he basis o demog aphic da a [
161
] and como bidi ies [
162
] and some ea ly
symp oms [
163
]. Accu a e assessmen o ICU admission, ICU leng h o s ay and mo ali y
o COVID-19 pa ien s o op imal alloca ion o ICU esou ces has also been epo ed [
54
].
The Explainable Boos ing Machine analysis [
51
] enables one o pe o m p edic i e modeling
o COVID-19 in he ICU as well as he iden i ica ion o isk ac o s. La ge and exhaus i e
clinical da abases ex ac ed om he Elec onic Heal h Reco ds (EHR) allow he applica ion
o DL app oaches o p edic he p obabili y o ICU admission and mo ali y [
164
]. In a
qui e di e en se ing, beha io al AI echniques ha e been also applied o assis in ensi is s
in dealing wi h he decisions conce ning ICU eligibili y [77] in Denma k.
ML me hods can be used o gain knowledge abou complex clinical si ua ions an icipa -
ing u u e complica ions [
74
]. In his ega d, op imally p edic ing mo ali y o COVID-19
Elec onics 2024,13, 1005 20 o 38
pa ien s in he ICU has been epo ed wi h DL echniques [
63
] and ML [
58
], while decision
suppo ools applicable o c i ically ill pa ien s wi h COVID-19 a high isk o 28-day
mo ali y in he ICU allowed assis ance in c i ical decisions such as end-o -li e decisions
and bed alloca ion in cases o limi ed ICU capaci y [
69
]. Fu he mo e, supe ised bina y
p edic ion classi ica ion using a ime-sliding window-based app oach o p edic he isk o
in uba ion 72 h om he end o he 24 h sampling pe iod has been epo ed [
165
]. Mul iple
s udies sugges ed ha adop ing ea ly measu es o ea pa ien s a isk o de e io a ion
could p e en o dec ease s a us wo sening and he need o mechanical en ila ion; in his
way, e e ence [
67
] epo s a model ha p edic s he isk o de e io a ion o each hou ,
while he goal o he s udy in [
73
] was o moni o pa ien p og ession o a sco e o 5 o
mo e on he WHO Clinical P og ession Scale be o e hey equi e mechanical en ila ion.
COVID-19 hospi al eadmission has been ano he subjec o esea ch in e es , due o
i s impac on he op imal managemen o hospi al se ices. ML models can success ully
p edic COVID-19 eadmission [
65
,
75
,
166
]. Conside ing isk ac o s, hese wo ks also
ca ego ized cases wi h a high isk o ein ec ion in o de o classi y pa ien s, making he
u iliza ion o hospi al esou ces mo e e icien . Al e na i ely, o he wo ks [
55
] ocused he
eco e y o COVID-19 pa ien s on die a y adap a ion by pe o ming an analysis o he
ene gy in ake o di e en ood ca ego ies om di e en coun ies, compa ing se e al ML
algo i hms o p edic he eco e y a e.
Al e na i ely, he moni o ing o pa ien s in need o espi a o y suppo would p o ide
goal-o ien ed ools o pa ien isk s a i ica ion and an ale sys em o sel -ca e pa ien s, de-
ec ing highly dis essing s a es when esou ces a e possibly cons ained.
Bu dick e al. [57]
ocused on an ML algo i hm o help e icien iage o pa ien s and esou ce alloca ion by
assessing en ila ion needs among COVID-19 pa ien s, achie ing a p ecise p edic ion o
he mechanical en ila ion esou ce needs wi hin 24 h. Bolou ani e al. [
167
] p oposed an
ML model ha p edic s espi a o y ailu e wi hin 48 h o ED admission. Izadi e al. [
168
]
aimed o iden i y pa ien s who may be a inc eased isk o se e e COVID-19 ou comes due
o he onse o acu e espi a o y dis ess synd ome.
Based p ima ily on pa ien age and measu es o oxygena ion s a us du ing he ED s ay,
i was possible o iden i y pa ien s wi h high isk o poo ou comes, i.e., hose equi ing
in ensi e ca e, hose equi ing mechanical en ila ion and hose wi h high in-hospi al
mo ali y isk [
72
]. The s udy o Saada mand e al. [
62
] p edic ed he equi emen o
oxygen-based ea men o hospi alized COVID-19 pa ien s. Simila ly, Aslam [
64
] iden-
i ied he impac o pa icula a ibu es on he p edic ion o mo ali y and mechanical
en ila ion suppo [
66
] in COVID-19 pa ien s. Iga ashi e al. [
71
] in oduced a model ha
can be implemen ed as a iage ool o de ec he need o supplemen al oxygen.
Finally, unde s anding ha COVID-19 hospi aliza ion imes a e o en long and may
a y subs an ially om pa ien o pa ien , some wo ks [
56
,
70
,
76
] aimed o de elop a eliable
p edic ion model o ED leng h o s ay o COVID-19 pa ien s and o iden i y clinical ac o s,
such as age and como bidi ies, associa ed wi h ED leng h o s ay. AI echniques ha e been
shown also o p edic hospi al occupancy [169] and ICU admission [170].
5.3. Mo ali y P edic ion
In he hea o he pandemic yea s, heal hca e p o essionals o en complained o hei
limi a ions wi h espec o de e mining wi h some p ecision he p ognosis o pa ien s wi h
COVID-19 om he momen o admission h ough o subsequen phases. I has been
epo ed ha he cou se o COVID-19 su e e s unexpec ed changes so ha appa en ly
s able pa ien s suddenly wo sen. In hese si ua ions, e en he mos expe ienced clinicians
may be unable o adjus and espond in a imely manne o he new si ua ion. Thus, ML
and AI models we e p oposed o clinical decision-making, helping de ec complex pa e ns
in la ge da ase s [
20
,
92
,
171
,
172
]. Se e al s udies ha e shown he capabili y o ML-based
models o p edic mo ali y a he le el o indi idual pa ien s [
108
,
115
,
119
,
121
], and he
agg ega e le el o ci ies [
119
]. Rou ine clinical a iables ha e been shown o p o ide
enough p edic i e powe o pa ien
mo ali y [105,173],
while o he s udies ha e shown a
Elec onics 2024,13, 1005 21 o 38
capaci y o p edic he mo ali y o new i us a ian s [
174
] o he e ec o como bidi ies
in COVID-19 mo ali y [120].
Applica ion o AI ools, namely DL a chi ec u es, o medical imaging, speci ically
CT scans, which a e he ones mo e o en done on pa ien s wi h pneumonia complica-
ions, ha e been shown o be use ul o he diagnosis and p ognosis o di e se lung
a ec ions [
175
–
177
]. This app oach also has alue as a p elimina y sc eening ool aiming o
diminish he wo kload on hospi al s a and educe he a e o misdiagnosis o pa ien s wi h
COVID-19 [178–180].
The enhanced p edic ion o disease se e i y ia AI on CT images al-
lows imp o ed mo ali y p edic ion [
126
,
129
,
181
–
187
] and disc imina ion om o he o ms
o pneumonia no due o SARS-CoV-2 [
188
–
190
]. Some wo ks [
79
,
117
] c ea ed a adiomics-
and DL-based model showing he obus ness o he app oach on da a om se e al si es.
Mo eo e , AI allows one o e icien ly combine medical imaging in o ma ion wi h o he
sou ces o clinical and labo a o y in o ma ion [
100
,
106
,
191
]. Fo ins ance, Lu e al. [
192
]
demons a ed o e CT scan cha ac e is ics ob ained ia AI analysis ha he e is a posi i e
co ela ion be ween blood glucose le el on admission and lung lesions.
COVID-19 mo ali y has also been p edic ed on he basis o p o eomics da a. Yasa e al. [
87
]
epo ed an associa ion o a ia ions in blood p o eins wi h he se e i y o he pa ien ’s
condi ion. Addi ionally, Chen e al. [
127
] de eloped an ML p ocedu e o ind bioma ke s
ha de e mine disease se e i y in indi idual immune cells.
O he app oaches use he e ogeneous a iable selec ion om se e al clinical domains.
Azna -Gimeno e al. [
109
] c ea ed an easy- o-use web applica ion ha suppo s apid
decision-making in clinical p ac ice h ough he cons uc ion o a p edic ion model om
a la ge amoun o da a om se e al pandemic wa es ha p edic s ICU admi ance and
mo ali y. Ga a a e al. [
89
] ocused on an ea ly wa ning model based on demog aphic
and clinical a iables o p edic in-hospi al mo ali y o pa ien s wi h COVID-19 in he
ED. Laino e al. [
130
] applied ML echniques o guide he managemen o pa ien s wi h
COVID-19 by de eloping an accu a e in-hospi al mo ali y isk sco e o COVID-19 based
on en a iables. Vezzoli e al. [
124
] p esen ed a isk sco e o in-hospi al mo ali y whe e
mo e se e e pa ien s we e olde , had a lowe blood oxygena ion, lowe c ea inine clea ance
le els and highe p e alence o ele a ed oponin.
Domínguez-Olmedo e al. [
88
] de eloped a model able o p edic mo ali y in pa ien s
wi h COVID-19, which allows one o assess mo ali y om labo a o y alues wi h high
p ecision using he XGBoos model. Sanka ana ayanan e al. [
96
] p esen ed an app oach
using GRU-D ex e nal NN, p o iding an ale sys em o lag mo ali y o COVID-19-
posi i e pa ien s using clinical a iables and labo a o y esul s in a 72 h pe iod a e he
i s posi i e PCR es esul . Halasz e al. [
78
] de eloped an ML-based sco e o 30-day
mo ali y p edic ion in pa ien s wi h COVID-19 pneumonia. Ko e al. [
111
] de eloped an
AI model, EDRne , ha o ecas s he mo ali y a e o COVID-19 pa ien s based on 28 blood
bioma ke s and pa ien age and sex. Vepa e al. [
193
] ob ained da a including age, gende ,
e hnici y, SPO2, RR, empe a u e, obesi y [
18
], as hma, diabe es and hype ension, among
o he s, o a pe iod o almos wo mon hs. The esul s sugges ha low albumin, ele a ed
(CRP) and olde age all co ela e wi h mo ali y in hospi alized pa ien s.
Some esea che s ha e conside ed s udying he geog aphic and demog aphic di e -
ences in luencing bo h sp ead and mo ali y ac oss geog aphical loca ions.
Fidan e al. [84]
employed clus e ing echniques o de e mine ci ies wi h simila isk le els, analyzing he
incidence o cases and en i onmen al pa ame e s. Guzmán-To es e al. [
194
] poin ed
ou ha condi ions in each coun y may di e depending on di e en ac o s such as he
gene al heal h s a us o he people, epo ing ha he main causes o dea h in Mexico a e
ela ed o age, poo ea ing habi s, ch onic diseases and con ac wi h in ec ed people who
do no ha e adequa e ca e. Zawbaa e al. [
82
] p oposed a compa ison o he sp ead o
he disease among nine di e en coun ies, e ealing ha a e age young age, ho clima e,
p e alence o Bacillus Calme e–Gué in (BCG) accine and mala ia ea men a e c ucial
elemen s dec easing he mo ali y impac o he i us.

Elec onics 2024,13, 1005 22 o 38
5.4. Iden i ica ion o Mo ali y Risk Fac o s
Casi aghi e al. [
107
] epo ed a sys em p ima ily designed o ex ac he mos el-
e an adiological, clinical and labo a o y a iables o imp o e pa ien isk p edic ion
and subsequen ly p o ide decision c i e ia o clinicians o suppo pa ien isk assessmen .
Dabbah e al. [
110
] documen ed se e al new and signi ican p edic o s o mo ali y in
COVID-19; hese included de ailed an h opome y, acu e enal ailu e, u ina y ac in ec-
ion and pneumonia. In con as , Baqui e al. [
90
] conside ed demog aphic a iables as he
mos ele an ones, namely he s a e o esidence and i s de elopmen index, he dis ance
o he hospi al (especially o u al and less de eloped a eas), he le el o educa ion and
he inancing model o he hospi al, and s ain. The model p esen ed by Hu e al. [
104
]
could be aluable o clinicians who ha e o iden i y pa ien s a high isk o dea h, based
on age, high-sensi i i y C- eac i e p o ein le el, lymphocy e coun and dime le el, so ha
in e en ions can be aken a an ea lie s age o educe he isk o mo ali y in hese pa ien s.
Fo So oudeh e al. [
83
], he mos impo an ea u es in e ms o p edic ion capaci y,
ou o he many, we e SPO2 (LDH), age, BUN, base excess, c ea inine and WBC. Mah-
da i e al. [
80
] epo ed p omising esul s based on a educed numbe o ea u es such as
SPO2, age and ca dio ascula diso de s u ilizing SVM. The ele ance o LDH is also ound
in he wo k o K ysko e al. [
86
], whe e high le els o LDH, IL-6, IGM, D-dime , ib inogen
and glucose s ongly in luences he se e i y o cases.
Simila o Wang e al. [
93
] in hei inding ha lymphocy e and neu ophil le els in
pe iphe al blood could ep esen p ognos ic ma ke s indica ing ea ly wa ning implica ions,
Li e al. [
99
] epo ed GBDT was e ealed as he mos e ec i e model in e ms o pe o -
mance whe eby leukomonocy es, u ea, age and SPO2 u ned ou o be he mos signi ican
p edic o s. Lip ak e al. [
118
] iden i ied he ele a ed AST as he mos impo an p edic o
o COVID-19- ela ed hospi aliza ions.
Blagoje ic e al. [
81
] ocused on de ec ing he op 10 blood es cha ac e is ics ha a e
s ongly co ela ed wi h pa ien condi ion and based on hese cha ac e is ics p edic ing he
se e i y and clinical s a us. Addi ionally, ecen s udies ha e indica ed ha e i in le el
is conside ed a s ong bioma ke o he p ognosis o SARS-CoV-2 mo ali y [
101
], along
wi h o he se e e espi a o y diseases. Ano he equen ly employed a iable is he le el
o blood sa u a ion [112,113,116].
The s udy o Zhao e al. [
103
] showed ha , combined wi h he pe cen age o neu-
ophils, alanine amino ans e ase, gende and albumin would be associa ed wi h su i al
in pa ien s wi h COVID-19. Age [
122
,
128
] and gende [
123
] appea o be he mos signi -
ican p edic o s o mo ali y [
195
], bu in e ms o symp om–como bidi y combina ions,
Pneumonia–Hype ension, Pneumonia–Diabe es and Acu e Respi a o y Dis ess Synd ome
(ARDS)–Hype ension showed he mos signi ican associa ions wi h
COVID-19
mo al-
i y [
114
]. The s udy by Reina e al. [
125
] examined he hypo hesis ha p e-exis ing condi-
ions (como bidi ies) o pa ien s may inc ease he se e i y o pa ien s due
o SARS-CoV-2.
The C- eac i e p o ein has been consis en ly implica ed in nume ous s udies as a
signi ican indica o o pa ien ou come [
95
,
97
,
98
]. This pa ame e was also aken in o
conside a ion by Boo h e al. [
102
], in conjunc ion wi h blood u ea ni ogen, se um cal-
cium, se um albumin and lac ic acid o he p edic ion o mo ali y in pa ien s up o
48 h p io o dea h. Fang e al. [
94
] c ucially conside ed y oponin, b ain na iu e ic pep-
ide, whi e blood cell coun , aspa a e amino ans e ase and c ea inine, oge he wi h he
abo e-men ioned p o ein as indica o s con ibu ing o malignan p og ession. The com-
bina ion o C- eac i e p o ein and ad anced age, o example, we e he main ac o s o
Di Cas elnuo o e al. [91].
5.5. T ea men s and D ugs
Gi en he high cos in ime and esou ces o d ug disco e y, ML and AI
p oposed
[196–198]
o accele a e he d ug-disco e y p ocess by using in o ma ion abou
he biological, chemical and spa ial p ope ies o compounds and hei po en ial a ge s;
speci ically, COVID-19 DL has been s udied [
199
–
201
]. Thus, he COVID-19 pandemic is
Elec onics 2024,13, 1005 23 o 38
an oppo uni y o bio ech, pha maceu ical and AI companies o coope a e in accele a ing
hei esea ch and de elopmen o iden i y new and a e d ug molecules as well as pe son-
alized medicine [
202
]. Gaw iljuk e al. [
203
] p oposed a p ocess o mul iple i e a ions o ML
models as a p io i iza ion ool o disco e y p og ams o an i i al d ugs agains COVID-19.
P o eomics analysis o plasma om COVID-19 pa ien s e sus con ols led ia SVM ea u e
selec ion o he iden i ica ion o bioma ke s, which can be use ul o d ug a ge ing and
epu posing ia in silico p o ein docking [
204
]. Some wo ks use indi ec in o ma ion abou
he d ug’s e ec , such as ea u es o he images o cells ea ed wi h speci ic d ugs [
205
], so
clus e ing hese images may e eal simila i ies in he mode o ac ion o he d ugs. O he
indi ec in o ma ion used is he cons uc ion o a g aph ep esen a ion o he biological
ne wo k o COVID-19 ha ela es o he a ge s o he i us, making i easy o selec he
essen ial p o eins in he biological ne wo k. In his app oach, e . [
206
] ound i e g oups
o sui able d ugs ha con ain some candida es as po en ial ea men s o COVID-19.
DL app oaches ha e been deployed [
207
,
208
] o ain he molecula desc ip o da ase
o obus d ug disco e y and ea u e ex ac ion o comba COVID-19. Ea ly on in he
pandemic, some esea ch eams ocused on building he in as uc u e o a global e o in
his di ec ion [
209
,
210
]. The applica ion o DL app oaches o e chemical in o ma ion allows
one o ob ain high-le el ep esen a ions o ins ances om a public d ug bank da abase
as well as SARS-CoV-2 amino acid sequences p edic ing a ini y sco es ha ag ee wi h
he SARS-CoV-2 inhibi o s unde e alua ion a he ime o w i ing he pape [
211
]. O he
au ho s p opose o eso o a omic-le el simula ion in o de o ob ain he inpu o DL
app oaches [212].
Repu posing is he use o an exis ing d ug, usually a gene ic and low-cos one, o he
ea men o a new disease o a disease di e en om he one he d ug has been app o ed
o . Repu posing cu en d ugs o he ea men o COVID-19 p o ides a e y apid
pa hway o po en ially e ec i e ea men de elopmen [
19
,
213
–
215
], bo h because new
d ugs a e no equi ed o be de eloped and because, o many exis ing d ugs, sa e y and
e icacy has al eady been es ablished based on p e ious ials. Fo ins ance, some au ho s
claim ha Nai e Bayes achie ed ela i ely high accu acy (72%) p edic ing he e icacy o
epu posing d ugs o COVID-19 [
216
]. The analysis was conduc ed in silico, based on he
published sequences o some p o eins o he SARS-CoV-2 i us. Thus, hey do no ake in o
accoun he e olu ion o he i us and he po en ial o changes in he a ge p o eins. This
is a gene al issue o AI app oaches wi h espec o d ug epu posing o COVID-19.
Some au ho s ha e compa ed p edic ion models o D ug Ta ge In e ac ions (DTIs),
exploi ing he public D ugbank da abase and success ully iden i y in e ac ions be ween
d ugs and p o eins in he human cell [
217
,
218
]. Jin e al. [
219
] de eloped a DL app oach
using ComboNe o he p edic ion o chemical syne gy agains SARS-CoV-2, achie ing
a es ROC-AUC o 0.82, consis ing o an NN a chi ec u e ha join ly lea ns d ug– a ge
in e ac ions and d ug–d ug syne gy.
Bu dick e al. [
220
] ocused on p ecision medicines, as hey may be use ul in iden i ying
a sub-popula ion o COVID-19 pa ien s mos likely o bene i om hyd oxychlo oquine
ea men in a clinical ial. Zeng e al. [
221
] u ilized a ne wo k-based deep-lea ning
me hodology o d ug epu posing, connec ing d ugs, diseases, p o eins and pa hways.
The lack o eliable da a abou he e ec o a d ug on a new disease was esol ed in [
208
]
ia a no el da a-augmen a ion app oach ha exploi s esul s om ailed expe imen s
ha eed a g aph neu al ne wo k. Su e al. [
222
] applied mul iple nonnega i e ma ix
ac o iza ion app oaches o ea u e ex ac ion o i us–d ug associa ion, d ug chemical
s uc u es and i us genome sequences as a p ep ocessing s ep o g aph neu al ne wo k
p ocessing ha ob ains d ug– i us a ini ies. A simila ma ix- ac o iza ion p ocess o
ea u e ex ac ion coupled wi h g aph neu al ep esen a ions was p oposed by [
223
]. O he
esea che s applied a ans e lea ning app oach [
224
,
225
] using a p e- ained DL-based
d ug– a ge in e ac ion model o iden i y comme cially a ailable d ugs ha could ac
on
SARS-CoV-2
i al p o eins. Ke e al. [
226
] p oposed a compa ison o wo models o
de ec d ugs wi h po en ial an i i al e ec s, showing ha adequa e combina ion wi h
Elec onics 2024,13, 1005 24 o 38
o he d ugs a a lowe dose o gemci abine can o e come ad e se pulmona y e ec s while
simul aneously inhibi ing SARS-CoV-2. Yang e al. [
227
] epo ed ha Ca hepsin L (CTSL)
is a p o ease ha can ac i a e he p o ein ha leads o SARS-CoV-2; ne e heless, as he e
is s ill a lack o clinically a ailable CTSL inhibi o s, hey de eloped a DNN app oach o
iden i y small molecules and FDA-app o ed d ugs ha can block CTSL ac i i y o d ug
de elopmen and epu posing o COVID-19.
Mekni e al. [
228
] ocused on SVM me hodology o he p edic ion o inhibi o y ac i i y
o no el chemo- ypes agains SARS-CoV-2, showing an accu acy o 0.88 o la e u iliza ion
o p edic he inhibi o y ac i i y o compounds comme cially a ailable. Kowalewski e al. [
229
]
iden i ied nasal ca i y and espi a o y ac condi ions as a bo leneck o his in ec ion,
ained ML models o p edic inhibi o y ac i i y and sc eened o e 100,000 app o ed d ugs
and mo e han 14 million pu chasable chemicals o po en ial candida es o new inhaled
he apies. Al e na i ely, Pin o e al. [
230
] used mul i a ia e s a is ical me hods o selec he
mos sui able candida es o inhibi he disease.
Finally, u he clinical ials may depend on biomedical in o ma ion ob ained om
exis ing da a and ind pa e ns and signa u es in he unde lying molecula biology o he
COVID-19 mechanism and ML may ha e a p ominen ole in he design o new ials [
231
].
6. Discussion
DQ1. A e p edic i e models capable o suppo ing a COVID-19 ou b eak and how?
ML algo i hms can nei he be adequa ely ained no alida ed wi hou a la ge and
well cu a ed clinical da ase . In he ea ly s ages o an eme ging in ec ious disease, collec ed
da a will o en be noisy and incomple e. Al hough he e may no be a la ge his o ical
da ase o pa ien s su e ing om his disease, exis ing da abases, assuming hey ha e
been p ope ly mined, and pa e ns based on hese da a can con ibu e signi ican ly o he
choice o he mos app op ia e beha iou o adop in each si ua ion [
232
]. Many s udies
epo he po en ial o he applica ion o Big Da a and AI echnology o con ibu e o
p e en ion, diagnosis, ea men and decision making conce ning acu e in ec ious public
heal h e en s in he u u e. Acco ding o some au ho s, he COVID-19 pandemic has
p o ided an excellen oppo uni y o in eg a e AI ools in clinical ca e, al eady in oducing
changes in hospi al p ac ices [233] in some ad anced coun ies.
DQ2.
A e he e demog aphic and cul u al ac o s in luencing he de elopmen o p edic-
i e me hods o con on o add ess COVID-19?
Al hough mos o he a icles added o his s udy deal wi h da a om Asian pa ien s,
he e a e se e al a icles om Eu opean and Ame ican coun ies. In compa ing hese
s udies, while many u ilise simila a iables, cul u al o demog aphic ac o s ha e been e-
ealed o signi ican ly a ec he de ec ion o inc ease in disease con ac ion, demons a ing
he impo ance o hese ac o s in he COVID-19 ou b eak [
173
].In addi ion, key gene ic
ma ke s may se e as po en ial a ge s in he clinical p ognosis and ea men o COVID-19.
DQ3.
A e he e models wi h good pe o mance capable o ca ego izing pa ien s acco ding
o se e i y?
ML has p o en i s impo ance in nea ly all domains and i s echniques a e being
ac i ely used agains COVID-19 by esea che s wi h sa is ac o y esul s [
234
]. Among all
he a icles collec ed in his s udy, a ious s udies wi h e y p omising esul s ha e been
epo ed. Mos o he selec ed s udies employed p edic i e e e enced models o achie e
he highes accu acy and bes pe o mance acco ding o he p oposed casuis y. Among all
epo ed me ics wi h success ul esul s, he e a e se e al s udies ha ha e achie ed
accu acy and AUC abo e 0.99 [
27
,
35
,
60
], showing high sensi i i y alues so ha he mos
se e e cases may no easily go unno iced and can be de ec ed in ime. These a e s udies
ha use MLP, ResNe 50 o RF models and ob ain e y good esul s wi h demog aphic and
clinical a iables, wi hou he need o labo a o y es s o CT images, which a e a iable
and mo e di icul o ob ain and collec .
Elec onics 2024,13, 1005 25 o 38
DQ4.
Is ansla ion possible om scien i ic esea ch o clinical p ac ice wi h he cu en
da a on he disease ob ained du ing he pandemic?
Da ase s used o diagnosis, p edic ion and p e en ion o COVID-19 a e essen ially
classi ied in o medical imaging da ase s, speech-based da ase s and ex ual da ase s. On he
one hand, medical imaging da ase s, i.e., CT images, a e mainly analyzed o au oma ic
diagnosis, segmen a ion and augmen a ion o COVID-19. On he o he hand, ex ual da a
suppo p edic ion and analysis o COVID-19 cases, su eying pa ien s a us, in e en ions
and ea men s.
Based on he s udy, de eloped models add essing COVID-19 h ough in elligen
app oaches gene a e eliable pe o mance esul s i high ideli y and abundan da a a e
in ol ed. I is clea ha la ge da ase s a e no ypically used o he majo i y o he use
cases p e iously speci ied. Despi e he ac ha some public da ase s a e a ailable o
wo k wi h his ype o caseload, gi en he ecen eme gence o he disease and he lack o
many yea s o s udy, he size o hese da ase s is limi ed compa ed o he equi emen s o
ML app oaches.
Da a accessibili y and openness is conside ed a c i ical bo leneck in COVID-19 e-
sea ch as a esul o he apid sp ead. Being able o apply such applica ions in he eal wo ld
will only be possible wi h he a ailabili y o mo e open sou ce da a. This is conside ed one
o he limi a ions o be add essed in o de o u he imp o e COVID-19 esea ch.
This limi a ion p ima ily s ems om he seg ega ion o da a a na ional, egional,
hospi al and depa men al le els. Hence, he de elopmen o a cen al and uni o m
pla o m o in es iga o s o sha ing and accessing da a would be a p omising s a ing
poin . In addi ion o ha ing e oneous o uns uc u ed da a, he da ase s ha e a lo o noise
and null alues. The e o e, il e ing, cleaning and noise educ ion a e o he key challenges
o he success ul implemen a ion o models de eloped using in elligen app oaches.
A u he conside a ion ha mus be add essed is he es ablishmen o ce ain p o ocols
o s anda ds o da a collec ion in heal hca e acili ies. As well as ha ing e oneous o
uns uc u ed da a, he da ase s ha e a lo o noise and missing alues. The e o e, il e ing,
cleaning and noise educ ion a e o he impo an challenges o be conside ed o he
c ea ion o applica ions using in elligen app oaches.
7. Insigh s in o ML/AI Ad ances, Resea ch Di ec ions and Challenges
A he eques o e iewe s, we in oduce he e some hough s abou he u u e o
ML/AI applica ions in clinical decision suppo o COVID-19 and o he u u e pandemics.
Mode n ML and AI echniques a e da a d i en; hus, he main and o emos issue in he
use ulness o ML/AI echniques is he a ailabili y o la ge high-quali y da ase s. I is impos-
sible o o e -s ess he impo ance o good da a-ga he ing p ac ices o he de elopmen o
ML/AI suppo o he esponse o o hcoming pandemics. In con as , he p ice o be paid
by complacency and missing oppo uni ies o implemen a ion o s ong da a-ga he ing
p o ocols will be a g ea e economic dis up ion and poo e heal h ou comes, i.e., mo e
dea hs. Cu en Elec onic Heal h Reco d (EHR) sys ems a e dispe sed and do no in e op-
e a e ou side some small clus e s de eloped by he same company. Hence, in e na ional
s anda ds o EHR should be en o ced as well as da a-ga he ing p o ocols and open access
o da a in o de o allow o coope a i e analysis o da a in o de o aise ala ms and o
p oduce imely p edic i e models and isk assessmen s. Da a access should no be blocked
by comme cial in e es s in he name o da a p i acy when i is mos needed o democ a ic
public heal h managemen . Wi h he excep ion o some p ominen pe sonages, heal h da a
a e easily anonymized o a le el ha impedes spu ious uses.
Rega ding ML/AI models, we hink ha LR will emain one o he mos used models
in he u u e, because i s ounda ions a e well unde s ood and i has high explana o y
alue. Medical p ac i ione s a e well acquain ed wi h he echnique and hey accep i
wi h c i ical app aisal. O he s a is ical ML models, such as RF, SVM o g adien boos ing
app oaches, do no p o ide a simila deg ee o explana ions. They can be o alue in some
speci ic p oblems in o de o p o ide mo e accu a e p edic ions once he isk assessmen
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