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Joao Alexandre Lobo Marques
Simon James Fong Editors
Computerized
Systems
for Diagnosis
and Treatment
of COVID-19
Computerized Systems for Diagnosis
and Treatment of COVID-19
Joao Alexandre Lobo Marques · Simon James Fong
Editors
Computerized Systems
for Diagnosis and Treatment
of COVID-19
Editors
Joao Alexandre Lobo Marques Simon James Fong
Laboratory of Applied Neurosciences Faculty of Science and Technology
University of Saint Joseph University of Macau
Macao, Macao Macao, Macao
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
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The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Contents
v
vi Contents
Abstract The global pandemic triggered by the Corona Virus Disease firstly
detected in 2019 (COVID-19), entered the fourth year with many unknown aspects
that need to be continuously studied by the medical and academic communities.
According to the World Health Organization (WHO), until January 2023, more than
650 million cases were officially accounted (with probably much more non tested
cases) with 6,656,601 deaths officially linked to the COVID-19 as plausible root
cause. In this Chapter, an overview of some relevant technical aspects related to
the COVID-19 pandemic is presented, divided in three parts. First, the advances
are highlighted, including the development of new technologies in different areas
such as medical devices, vaccines, and computerized system for medical support.
Second, the focus is on relevant challenges, including the discussion on how com-
puterized diagnostic supporting systems based on Artificial Intelligence are in fact
ready to effectively help on clinical processes, from the perspective of the model pro-
posed by NASA, Technology Readiness Levels (TRL). Finally, two trends are pre-
sented with increased necessity of computerized systems to deal with the Long Covid
and the interest on Precision Medicine digital tools. Analyzing these three aspects
(advances, challenges, and trends) may provide a broader understanding of the impact
of the COVID-19 pandemic on the development of Computerized Diagnostic Support
Systems.
1 Introduction
During the last years, the global COVID-19 pandemic triggered by the Corona Virus
Disease, firstly detected in 2019, has created strong and significant impacts on man-
agement practices for public health systems, definition of health indicators, and the
development of new technologies. With an unprecedented speed in human history,
while the most devastating disease since the global alliance after the second World
War created the World Health Organization (WHO) was exponentially spreading, sci-
entific achievements and technology advances were obtained worldwide in crucial
areas to fight the pandemic, such as new vaccine development processes, low-cost
medical devices (from centrifuges to mechanical ventilators), computerized diag-
nostic systems using data from clinical laboratory analysis, medical imaging and
biosignals analysis systems.
The COVID-19 Pandemic entered through many different short-term cycles of
infections, and consequently number of deaths, in just a few years in different parts of
the world, which usually happened according to the restrictive public health measures
and the surges of new variants of the virus in different countries. Despite the better
understanding of the disease, it still presents many challenges and several unknown
aspects that need to be continuously studied by the medical/health and academic
communities. According to the World Health Organization (WHO), until January
2023, more than 650 million cases were officially accounted (with probably similar
number of even more non confirmed cases) with 6,656,601 deaths, with a current
average of 10,000 deaths per week officially linked to the COVID-19 as the most
plausible root cause.
In addition to the direct and obvious consequences to the patients’ health condi-
tions, the COVID-19 created a significant burden to the public health system in every
location, from developing countries to the most economically developed societies.
The number of necessary resources to support the exponential demand represented
a quite challenging condition, creating issues in several dimensions, such as hospital
beds, intensive care units devices, mechanical ventilators, antibiotics, or even gloves,
among many others. From the human side, the impact on the multidisciplinary staff
working on clinical premises was enormous. The professionals were under a dual
stress condition: first, the patients under extreme severe conditions and increasing
number of deaths from a disease with no treatment in many cases; and, second, the
personal risk of getting infected.
The harmful consequences of the COVID-19 in the whole world, created a global
effort to develop efficient processes and systems to cope with the new challenges
not only in the recurrent peaks, but also in a permanent way, since the disease is
recurrent and a large number of patients keep different symptoms and issues for a
long period of time, what is classified as Long COVID. It is important to notice that
during the first twelve to eighteen months, one of the main focus was to use different
computerized solutions based on epidemiological models. Since the beginning of
the pandemic, even With preliminary data, classic approaches, such as the SIR/SEIR
numerical models, were widely used [1]. With the pandemic global spread and more
Technology Developments to Face the COVID-19 Pandemic … 3
accurate data collected, including different variants of the virus, new approaches
were able to be tested [2], including nonlinear models [3] and probabilistic models
based on Monte Carlo simulation [4].
Today, despite all the efforts to automatize the diagnostic through computerized
systems, there is still a lack of practical applications working on clinical premises
and effectively improving physicians interpretation or providing diagnostic support.
The cause relies on many different aspects, such as poor integration between sci-
entific developments and industry, access to most recent technologies from many
different hospitals (especially the ones with lack of resources) and barrier to the
introduction of innovative processes, creating real constraints to the adoption of new
technologies. With that in mind, it becomes extremely necessary to comprehend the
positive impacts for the area of healthcare of adopting computerized systems for the
diagnostic and management of patients with COVID-19.
In this Chapter, a critical overview of some relevant technical aspects resulting
from the COVID-19 pandemic is presented, divided in three parts. First, the advances
are highlighted, including the development of new technologies in different areas
such as medical devices, vaccines, and computerized system for medical support.
Second, the focus is on relevant challenges, including the discussion on how com-
puterized diagnostic supporting systems based on Artificial Intelligence are in fact
ready to effectively help on clinical processes, from the perspective of the model
proposed by NASA, Technology Readiness Levels (TRL). Finally, two trends are
presented with increased necessity of computerized systems to deal with the Long
Covid and the interest on Precision Medicine digital tools.
As previously mentioned, the global effort created within technical and the academic
communities boosted new technology developments and scientific publications. In
this section, three areas are highlighted for discussion, as presented in Fig. 1.
One of the major technical advances during the COVID-19 pandemic was the fast
development of new technologies and the process acceleration for obtaining viable
types of vaccines against the SARS-Cov-2 virus and its variants. Regulatory agencies
such as the Food and Drug Administration (FDA) from the United States of America,
establish new processes to speed up the approvals with the maximum possible rigor
and evaluations of the clinical trials.
Many concerns were raised from different groups of health professionals and
members of organized societies, in order to make it possible to verify the credibility
and feasibility of the developed products. On this matter, it is important to highlight
4 J. A. Lobo Marques and S. J. Fong
Computerized
Development of New
System for Diagnosis
Vaccines Medical and Treatment
Devices
Fig. 1 Three areas of significant scientific and technological advances triggered during the COVID-
19 pandemic
that only vaccines developed by important and high level companies or joint institu-
tions were approved and released on the market, such as Pfizer, Johnson & Johnson,
among a few others were considered, given the significant technical challenge.
The Mayo Clinic provides a timeline updated with simplified and non technical
description, following the FDA approvals [5]. Firstly, in 2020, the FDA gave emer-
gency approval for use to two mRNA COVID-19 vaccines, the Pfizer-BioNTech and
the Moderna COVID-19 vaccines less trials, testing and retesting than is normally
required, but still proving that the products are safe for human use and effective
against the virus. Following, in 2021 emergency use authorization is provided to
the Janssen/Johnson & Johnson vaccine. In addition, the Pfizer-BioNTech vaccine is
approved for children aged between 5 to 15. More recently, in 2022, the Moderna vac-
cine, now called Spikevax, is authorized and the FDA authorizes the Pfizer-BioNTech
for children aged between 6 months to 11 years old. Finally, the Novavax vaccine
was approved for people aged more than 12 years old.
The scenario of technological development is completed with different vaccines
developed in China and India, and several plants in different countries. For exam-
ple, in India, currently with approximately 67% of the population fully vaccinated
with at least two doses, a local production of the formula developed by Oxford and
AstraZeneca is named Covishield. As another example, in Brazil, statistics indicate
that 81% of the population received at least two doses of any type of vaccine, the
local production of the brand Coronavac follows actually the formula of the giant
Chinese pharmaceutical company called Sinovac.
Another challenge is the high number of reinfections, which occurs when after
a first infection with the SARS-CoV-2 virus, the person recovers and later becomes
infected again. When someone is infected for the first time, some immune protection
against the virus, however, the reinfection is very common and the reasons are under
study. There are ongoing studies to better understand issues related to COVID-19
reinfection, for example, how often can it occur, who is at greater risk of reinfection,
Technology Developments to Face the COVID-19 Pandemic … 5
how long after the previous infection can a new infection occur, how severe/severity
and the risk of transmission to third parties after re-infection. Some reasons can
be stated, especially when associated, may be the cause of reinfection, such as the
long duration of the pandemic, since people change the capacity of response of
their immunity, making them again more vulnerable to reinfection. In addition, the
vaccine immune protection provided may lose effectiveness with time, creating the
challenge for public health systems to create permanent programs for administering
booster dose. From the epidemiology management perspective, after stressful periods
of lockdown, elevated number of deaths and economic constraints, there is a natu-
ral relaxation in some prevention measures, including protection and surveillance,
creating also weak processes for data collection and decreasing the data reliability.
Finally, the emergence of new variants of COVID-19, which can be more contagious,
even if not as deadly as before for vaccinated individuals. For example, the omicron
variant is twice as contagious as the previous ones, including delta. This variant is
associated with a greater likelihood of reinfection, however, although several new
variants of COVID-19 are discovered with some regularity, apparently this virus does
not mutate as much as the flu virus.
The area of medical devices is vast and this Section is to discuss some relevant tech-
nology advances as a result of the exponential spread of the COVID-19 worldwide,
creating significant constraints for public health systems. A key area is related to res-
piratory support technologies, since the use of Mechanical Ventilators with invasive
ventilation has been commonly adopted for severe cases of the disease when patients
are suffering from acute respiratory insufficiency (ARI). A position paper about the
topic is presented in [6].
A new technology development in the area is called “ELMO” and it is a helmet
for respiratory support designed and manufactured as a response to the COVID-19
pandemic. It is a non-invasive and safer respirator helmet for healthcare professionals
and patients created in April 2020 by a task force involving a public-private partner-
ship. The innovative equipment emerged as a new step for the treatment of patients
with hypoxemic acute respiratory failure by Covid-19 [7, 8]. The clinical trials related
to the new device are registered at the Clinical Trials portal [9]. According to the
ELMO Registry survey, a research developed by the Health Research Management
of the School of Public Health of Ceará (ESP/CE), an agency linked to the Health
Secretariat of the State of Ceará (Sesa), 66% of the patients who used the device did
not need to move to mechanical ventilator. So far, the study has evaluated about 1570
medical records of people who were hospitalized in the city of Fortaleza. Statistics
indicate the rates of the need of mechanical ventilators reach 60% of the total number
of patients in Intensive Care Units as a consequence of the COVID-19. With the new
developed technology, this number was reduced to 34%.
6 J. A. Lobo Marques and S. J. Fong
The data management becomes a critical aspect of this. Several aspects such as
data custody, handling, integrity, veracity, confidentiality, privacy, irrefutability and
guarantee of professional secrecy of information are necessary to be address. In
addition, the physician identity must be verified with digital signature, issued by
internationally accredited institutions and the data protection must be in compliance
with the requirements from the data protection law. This brings additional critical
responsibility for the Electronic Health Record Systems (EHRS) to keep reliable
and records with the proper security level to meet the standards of representation,
terminology and interoperability.
The high inter-patient variability of symptoms and severity of the Coronavirus dis-
ease influences multiple aspects, such as resources allocation, patient selection for
clinical trials, and individualized strategies for treatment, including vaccination. Vari-
ability aspects include a variety of demographics and clinical variables, including
geographic and social/economic characterization, biological aspects (age, sex, race),
previous diagnostic of comorbidities, and several studies are also identifying genetic
aspects, and immune system status and capacity to respond to the disease [?].
This scenario creates significant impact not only on the design and application
of clinical protocols and processes, but also on the development of computerized
systems for diagnostic support and treatment, which should obtain satisfactory and
acceptable performance during the modeling and testing phases, but mainly needs
to be validated and obtain the necessary maturity for effective implementation on
clinical premises for supporting the decision making process related to the patients.
There is a significant gap between academia and market. The results obtained
in the academic environment and published in scientific conferences and journals
sometimes are lost on the way to be launched as products in the market, with proper
testing, maturity, and problem-solving modeling. This gap should not be considered
as a negative aspect, in general. It is, actually, part or the process. The development
of specialized clinical support applications are a result of many technical advances
which first versions were published as academic works, until moving to the maturity
level to become a product.
Nevertheless, during the COVID-19 pandemic, the focus of helping the patients
in minimizing their risks or saving their lives, created the necessity to integrate with
the clinical practices to support medical decision solutions still in preliminary stages,
most of the times based on Artificial Intelligence (AI) and Machine Learning (ML)
advanced models and techniques. Some of them could perform a satisfactory role, but
on the other hand a significant number could not. One interesting path to provide a
classification of these systems could be adopting the classification scale Technology
Readiness Levels (TRL’s) to these systems, following specific strategies for efficient
definitions, given the specificity of this technical area [11]. An introduction with
comments regarding common challenges are presented in the following subsection.
8 J. A. Lobo Marques and S. J. Fong
4 Current Trends
As a relevant trend, the integration of two areas was selected to represent the contin-
uous impacts of the long term results of the pandemic: the challenge of a significant
number of patients living with persistent symptoms as a consequence of the disease,
which is classified as Long COVID; and the definition of personalized approaches
and multiple biometric data together with the use of Computerized Systems based
n Artificial Intelligence to establish a growing area of Precision Medicine, with a
focus on COVID-19 and Long Covid patients.
Technology Developments to Face the COVID-19 Pandemic … 9
Table 1 xxxx
Level Definition Contextualization in ML
TRL1 Basic principles Scientific publications and studies of a machine
observed learning technique and its applications. Not
considered a solution for real-life scenarios
TRL2 Technology concept Implementation of preliminary data analytic
formulated approaches. This is also a preliminary phase with no
possibility of clinical applications
TRL3 Experimental proof AI Components, such as different classifiers,
of concept implemented but not integrated as a system. Prior to
testing in lab environment. Limited solution for
practical application
TRL4 Technology Solution with AI algorithms validated in a laboratory
validated in the lab limited environment, normally using previously
available data. Still not possible to use in a real-life
environment and most of the times already demands a
significant amount of resources to create the testing
environment
TRL5 Technology Validation of the AI system in an environment closer
validated in a to the real application and integration of different
relevant environment modules. This is probably the most common phase of
AI systems with the intention to become a commercial
application
TRL6 Technology The AI solution is implemented in a simulated
demonstrated in a environment or advanced lab. The path between
relevant environment validation (TRL5) and demonstration is sometimes
interrupted with the lack of possible external
application of the system for demonstration
TRL7 System prototype The intelligent system is implemented as a prototype
demonstration in in one operational environment, such as a clinic or
operational hospital. Moving from relevant (TRL5 and TRL6) to
environment operational environment (TRL7) is a very difficult
step because of multiple requirements such as legal
aspects, regulatory frameworks and the significant
necessary investment
TRL8 System complete The AI system performance is tested and formally
and qualified approved in real life environment. In this level there is
still a long way to achieve a smooth user adoption of
the AI system in the operational environment
TRL9 Actual system System fully adopted and and AI support for decision
proven in operational making becomes part of the clinical processes and
environment protocols. The practical use of the system will
determine if it becomes a useful tool or just one
additional functionality not used in a daily basis
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isn’t she? Isn’t she? Oh, I’m so happy you’re here—do let’s all three
be pals—I hate everyone else in this beastly place ... little funny,
sorrowful, creamy kid, I like you—I like you——”
And all the while her eyes were on the soldier. And all this
boundless slippery exuberance was for the soldier—at the soldier—it
did not matter upon what pretext it vented itself. Warmth and
excitement to spare for Deb too ... Deb felt this, or she would have
torn herself away from the embrace ... but Jenny was wholly
unconscious that she was making love to a man with a girl as the
intermediary; she was no self-analyst. But the soldier and Deb, in
one look exchanged, established that mental kinship which exists
between those who see things alike introspectively and from the
outside view; with meaning duplicated and tripled; made grotesque
by circumstance or contrast; backwards from the future, and twisted
this way and that by imps of irony; kinship of those who can see
with the chill impersonality of gods on Olympus, and also with
pointed application to their own tiny scheme of things; restless
subtle kinship of those who dream and those who question.
And even as they silently hailed each other, he smiling a little
under his fair drawn eyebrows, and she very serious; hailed each
other through the froth and tumble of Jenny’s excited talk, the white
light which rayed the ceilings and walls of the room, was sucked into
soft inky chokiness....
“Little beast has gone out,” commented the soldier, in disrespectful
reference to Cora. “Light her again, and let’s sit round and be
comfortable.”
II
IV
Deb crossed straight to the long mirror, and made the discovery
that she had not been looking beautiful enough to say what she had
said. She began to dress for the evening with a sort of revengeful
deliberation. The deliberation was necessary to ensure good result.
No wise woman can fly, with spirit aflame, into her clothes, and then
hope to prove seductive. The dash was in her spirit, nevertheless.
She was angry with the big thing for not proving the mellow,
englamoured sanctuary she had every right to expect. This evolution
of a dream into fact was futile; worse than that—destructive—to
herself. A stupid, lop-sided business! Deb was not glad of love now it
had come. Only a troublesome but intelligent honesty kept her from
repudiating it altogether as the big thing; returning to her former
state of silver-misty anticipation.... “One can pretend, I suppose?”—
pretend that the soldier was a mere wayside incident. Only she knew
too much about wayside incidents, to commit that error.
—Well then, since she was so sure, were not the issues worth a
forced initiative on her part? Could she compete with Jenny’s
boldness—if she chose? For with Deb, as with Jenny, the soldier’s
steady, profiting self-control had become a nightmare which had to
be exchanged at all costs, even for his scorn, even for self-
destruction, even for evil....
Her temper resolved itself into action. There was mischief in her
selection of the pure ivory taffeta dress, the golden shoes, and
cobwebby gold stockings that the supple fancy could continue on
limbs straight and slender inside the blown white cup of her skirts.
Deb could wear white and pearl and dove-tints without fear of
looking miss-ish; by contrast with her deep colours, they enhanced
her vivid grace more than the traditional purple or flame. Sufficient
of purple in her sombre twilight eyes; flame enough in her lips. Her
hair she turned inwards, concealing its masses so skilfully, that, sleek
on top and bulging rhythmically into a smooth pear-shape round the
cheeks and the nape of the neck, it gave her somewhat the
appearance of the knave of clubs as pictured in a pack of cards.
Then she went back to the mirror, and scrutinized her looks long
and earnestly, and—like all heroines in every crisis of each love-affair
—reflected how queer it was that just these curves and colours
should have been the haphazard outward accessories to—her soul?
... no, souls were mawkish things!—to her essential Deb-ness.
CHAPTER V
I
II
III
... Had Jenny won that kiss in her absence?—Deb slid open the
door, in a bewilderment of dread and curiosity. Had Jenny——
Impossible to say. For La llorraine was sitting on the bed, eclipsing
by gesticulation and oratory, a helplessly recumbent invalid. The
soldier was calmly smoking and reading in the armchair at the
farther end of the room, his back to the bed, Cora among his feet.
His presence in the room seemed almost part of the general
acceptance. How funny, Deb thought, if they all suddenly started
questioning and sorting and clearing up....
It appeared that Nadya llorraine, at least, was doing something of
the sort.
“My dee-urr, now listen to me. I tell you how to win back that
husband of yours. I have said to me: it is enough now, it shall end!
Jenny, see how you lie here, wizout a manicure, your hair in a
puzzle, a blouse that has no seduction.... And he, that fool, that
booby,—shall I tell you vat vill happen? he falls into the hands of
adventuresses! My dee-urr, they snap him up from you....” Sincerity
of pity for the abandoned wife dominated any personal association
with the said adventuresses. “They snap him up—and spit him out!”
La llorraine dignified the process by accompanying pantomime,
grotesquely mimicked by the enormous shadow cast on the wall
behind her. “I will tell you that secret, Jenny, my dee-urr, which I
’ave learn: you must be woman to him as well as wife....” She
grasped Jenny’s wrist, swooped forward, and lowered her tones to a
key of thrilling confidence. She breathed in Jenny’s face. She took
possession of Jenny.
Deb and the soldier were cut off to a complete isolation.
“What have you got?” she bent over his shoulder to see the title of
the book he held. “Oh, that’s not fair!” indignantly. For the Chorus
had been half-reading half-acting Shaw’s “Pygmalion” for their
mutual amusement; and he had anticipated that portion of the play
to which Deb had been secretly straining forward.
“You wanted to make sure of being Eliza in that bit where she
throws the slippers, of course. You’re a shocking savage, Deb. And
anyway, the part isn’t fit for any gentlewoman, and naturally falls to
me. You can be Higgins.”
“I won’t be Higgins. I’ll be Eliza. You—you tempt slippers.”
“M’yes—I daresay I do. Slippers are mild. I’ll lend you my trench
boots.”
“Thanks.”
“Why do you hate me so, Deb?” lazily he threw back one hand to
where she was still leaning over his chair, and grasped some of her
hanging hair.
She was exultant at having at last urged him to a personal
reflection. “Because you don’t take enough notice of me,” she
replied, in a freakish impulse of candour.
“Dear Eliza, isn’t my step bent straight for this room, when I enter
the house?”
“That’s because of—Cora. Because we make you comfortable.”
“I suppose it is. Funny hair you’ve got, Eliza; like a strong, stormy
black sea. I thought women’s hair was always fluffy and soft.”
“As one woman’s was? ...” flitted through Deb’s mind. But she did
not say it.
He still examined with minute interest the thick tress which lay
across the palm of his hand. “To a man of ingenuity and resource, it
would be useful for all sorts of things if one were wrecked on an
island; Eliza, I wish I could be stranded on a desert island with your
hair.”
“With ... only my hair?” She was breaking through it now, that
nameless barrier which her nameless creed had set up; useless
barrier, Jenny had shown her.... Yes, but Jenny was different.
Because she was married?—well, because she was different.
Because she let her passions bubble over when and where and how
she chose ... unruly, undisciplined Jenny. But Deb had promised
herself to compete with Jenny this time.... A pulse ticked in each
wrist—two frantic little clocks. On the other side of the wall someone
—Antonia probably—was playing Debussy ... mournful, soul-
flattening discordances ... La llorraine’s rush of inaudible speech still
expounded man and the ways of man:
“And I say to ’im, that minute ago even, my dee-urr: ‘You should
kneel to your wife like a thief to a goddess, for you ’ave r-r-robbed
’er of all ’er gifts!’ Ha! ’e did not like that, Jenny, I tell you. He sulks
now in his room, the booby——”
“Well, it was rude, considering he was your guest,” from Jenny, in
shrill defence of her male property.
III