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Current practice and potential strategy in diagnosing COVID-19

Authors:

Abstract

Objective: To summarize the current practice and potential strategy in diagnosing coronavirus disease 2019 (COVID-19). Materials and methods: PubMed, Web of Science were systematically searched using terms including "COVID-19", "SARS-CoV-2" and "2019-nCoV". After removing duplicates, we then identified articles, letters and commentaries regarding diagnosing COVID-19. Results: Here we summarized relatively mature diagnostic methods like nuclear acid test and computed tomography. Besides, new aspects regarding these detection methods like suitable specimens for nuclear acid test, possible use of 18F-FDG PET/CT were also reported. Especially, we also presented several novel techniques for diagnosing COVID-19 like lung ultrasound. Conclusions: Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition) by National Health Commission is recommended to follow as it provides detailed diagnostic procedures using currently available tools. We suggest clinicians further explore the saliva's utility as a specimen for nuclear acid test and the use of lung ultrasound.
4548
Abstract. OBJECTIVE: To summarize the
current practice and potential strategy in diag-
nosing coronavirus disease 2019 (COVID-19).
MATERIALS AND M ETHODS: PubMed, Web
of Science were systematically searched us-
ing terms including “COVID-19”, “SARS-CoV-2”
and “2019-nCoV”. After removing duplicates, we
then identied articles, letters and commentar-
ies regarding diagnosing COVID-19.
RE SU LT S : Here we summarized relatively ma-
ture diagnostic methods like nuclear acid test
and computed tomography. Besides, new aspects
regarding these detection methods like suitable
specimens for nuclear acid test, possible use of
18F-FDG PET/CT were also reported. Especially,
we also presented several novel techniques for di-
agnosing COVID-19 like lung ultrasound.
CONCLUSIONS: Chinese Clinical Guidance for
COVID-19 Pneumonia Diagnosis and Treatment
(7th edition) by National Health Commission is
recommended to follow as it provides detailed
diagnostic procedures using currently available
tools. We suggest clinicians further explore the
saliva’s utility as a specimen for nuclear acid test
and the use of lung ultrasound.
Key Words:
COVID-19, Diagnosis, Nuclear acid test, CT image,
IgM-IgG test.
Introduction
In December 2019, a new type of coronavirus
broke out in Wuhan and spread rapidly in China.
Later, other regions around the world soon report-
ed conrmed cases. In February 2020, the coro-
navirus study group of the International Com-
mittee on Taxonomy of Virus named the virus
Severe Acute Respiratory Syndrome Coronavirus
2 (SARS-CoV-2). As of March 16, 2020, the virus
has infected more than 80,000 people in China
and more than 90,000 in other countries, posing a
signicant threat to global public health security1.
SARS-CoV-2 is a single-stranded RNA virus
that belongs to the coronavirus β genus, struc-
tural proteins of which include S proteins, N
proteins, M proteins, and E proteins2. Its infecting
procedure shares a great similarity with SARS-
CoV2,3. By binding to the angiotensin-converting
enzyme 2 receptor on the outside membrane, the
virus gradually fuses into the host cell, causing
great damage to its original function.
This novel coronavirus is mainly transmitted
by aerosol like respiratory droplets generated
during coughing and sneezing by symptomatic
patients4. Caution is due here since asymptom-
atic patients in incubation period can also help
its transmission. Besides, the median incubation
period is 6.4 days, ranging from 2.1 days to 11.1
days5. This long period can cause great trouble in
containing this widely-spread pandemic. Failing
in restraining international transportation result-
ed in a surge in the number of suspected and
conrmed infections globally. To slow down its
spread and eventually contain it, accurate, rapid
and convenient screening and diagnostic methods
are of great signicance. Here we summarized
current practice and potential strategies in diag-
nosing COVID-19. This brief review may be of
help to clinicians who work in fever clinics or
perform screening in public areas.
Diagnosis
Clinical Features
At the early onset of this pandemic disease, a
report from Hubei initially summarized clinical
characteristics of 138 patients6. The authors found
that the most common symptoms were fever
(98.6%), fatigue (69.6%) and dry cough (59.4%)
and that elderly patients were more likely to prog-
ress into a severe stage and later be transferred
to intensive care units. Recently, Spiteri et al7
European Review for Medical and Pharmacological Sciences 2020; 24: 4548-4553
D.-Y. WAN1, X.-Y. LUO1, W. DONG2, Z.-W. ZHANG2
1The West China College of Medicine, Sichuan University, Chengdu, China
2Department of Intensive Care Medicine, West China Hospital, Sichuan University, Chengdu, China
D.-Y. Wan, X.-Y. Luo, and W. Do ng contributed equally in writing this article
Corresponding Author: Zhong-Wei Zhang, MD; e-mail: 716461751@qq.com
Current practice and potential strategy in
diagnosing COVID-19
Current practice and potential strategy in diagnosing COVID-19
4549
reported 20 cases of COVID-2019 in European
region, clinical manifestations of which share
some similarity with those of patients reported
from Wuhan. Fever was also found to be the most
common syndrome (n=20; 52.63%), followed by
cough (n=14; 36.84%), weakness (n=8; 21.05%)
and headache (n=6; 15.79%).
Laboratory Examination
Blood samples of suspected patients were rou-
tinely collected when they entered the hospital.
Indexes like white blood cell count and concen-
trations of C-reactive protein were then detected.
Lippi et al8 summarized several abnormal labora-
tory manifestations in COVID-19 infected peo-
ple. They recommended some possible indexes
for identifying suspected patients like increase in
CRP concentration and decrease in both leuko-
cytes and lymphocytes.
Nuclear Acid Test
Real time reverse-transcription poly chain re-
action (RT-PCR), the usual detection method for
common respiratory virus is also the primary
diagnostic means for 2019-nCoV9,10. However,
current positive rates of this test can vary greatly,
depending on types of the specimens and gene
fragments used.
Liu et al11 collected laboratory results of 4,880
cases from Jan 22 to Feb 14 in Renmin Hospital
of Wuhan University and found that the positive
rate of tests based on nucleocapsid protein se-
quence was 40.81%. But in Wang et al12, positive
rate of test targeting at open reading form 1ab
was reported to be 32.27%. As for different spec-
imens, things were even more complicated. Re-
cently, several researches investigated the biodis-
tribution of COVID-19 in different tissues. It was
found that, apart from excretion from respiratory
tract, the virus can also be detected in blood12,
tears13, oral uids14 and feces12,15,16. However, tests
on feces, blood, tears only have positive rates
measuring 29% (n=44), 1% (n=3) and 5% (n=1)
respectively, which cannot satisfy the needs for
accurate diagnosis12,13. Fortunately, saliva had a
remarkable performance in serving as samples.
In a diagnostic study, self-collected saliva of
91.7% of patients generated positive outcomes14.
Despite the high positive rates, procedures for
sampling saliva also involve less exposure chanc-
es, further guaranteeing clinicians’ safety. How-
ever, the limited cases involved restrain its usage
in practical settings. Thus, more relevant studies
are urgently needed.
One of the limitations of RT-PCR is the
time-consuming procedures involved in prac-
tical settings. Besides, its accuracy also needs
great improvements. To satisfy the growing
needs for a rapid and accurate NAT method for
COVID-19, several researches were done and
some of them generated rather promising out-
comes. Pfefferle et al17 described a new method,
cobas 6800 in detail. This integrated technol-
ogy performed on a high-throughput platform
allows less hands-on time while maintaining
fast and reliable results. In another study, Chan
et al18 illustrated three novel real-time RT-
PCR methods targeting at the RNA-dependent
RNA polymerase, envelope and nucleocapsid
genes from SARS-CoV-2. Of notice, this newly
developed assay, entitled COVID-2019-RdRp/
Hel, had a relatively lower limit of detection.
Combined with the fact that saliva contained
higher concentration of viral load14, this tech-
nique may signicantly reduce the false nega-
tive numbers and therefore limit the spread of
SARS-CoV-2. Apart from real time RT-PCR,
uorescence quantitative PCR (FQ-PCR) was
also proposed19. The report declared their expe-
rience of applying high-throughput sequencing
to further the inconclusive result generated by
the FQ-PCR.
Imaging Features
Computed Tomography
Though NAT is considered as the gold stan-
dard for COVID-19, abundant false positive
cases indicate that another complimentary tool
is needed. Computed tomography (CT) then
acts as such tool20 ,21. This method was basically
available in all sorts of medical institutions and
can generate outcomes rapidly. Bilateral ground
glass opacity was discovered in 98% of the
suspected cases in one study22. A more detailed
article reporting imaging features of different
disease stages was available recently23. Patchy
ground glass opacities in the peripheral areas
with partial consolidation in the center were
found in most of the common patients. Larger
areas of opacities and consolidations can be
discovered in severe patients. Of note, while one
lesion can be absorbed under correct medical
care, another novel lesion may soon appear in
another area. This phenomenon may inform us
of the necessity of repeated CT scanning for
closely evaluating disease progression.
D.-Y. Wan, X.-Y. Luo, W. Dong, Z.-W. Zhang
4550
To evaluate its accuracy in identifying pa-
tients with COVID-19 from suspected groups,
a report of 1,014 cases analyzed the correlation
of chest CT and NAT24. Researchers discovered
that the positive rate of CT test was much higher
than that of RT-PCR. Attention is needed when
clinicians interpret the results. 52% of 308 pa-
tients with negative RT-PCR but positive CT
results were not considered as conrmed cases
at last. That is to say, CT test is more likely to
generate false positive outcomes, which may
result in waste of medical resources. Worse still,
the error can hardly be estimated as suspected
patients with positive CT images may eventually
be affected in hospitals full of genuine patients.
Li et al20 specially demonstrated its defect in
differentiating COVID-19 from other viruses,
partially explaining the high false positive rate.
Besides, the accuracy of CT test depends greatly
on the radiologist. In the research by Ai et al24,
we may notice that an expert with 12 years of
experience was involved in the interpretation.
Lung Ultrasound
Apart from CT, lung ultrasound (US) was also
recommended recently25. It was once reported
to be superior to standard CT for evaluation of
pneumonia or respiratory distress syndrome26.
Peng et al27 performed lung US on 20 patients and
summarized ve main clinical ndings, including
thickening of the irregular pleural line. Besides, a
strong connection between ultrasonography nd-
ings and the disease stages was also reported.
This indicates its great use in dynamically mon-
itoring COVID-19 progression. Chinese Critical
Ultrasound Study Group published Critical-Ul-
trasound-based Recommendations on Severe
COVID -19 recently, in which lung US ndings
and relevant managements were described in
detail28.
18F- FDG PET/CT
18F-FDG PET/CT is a technology that can re-
ect changes in metabolic and functional states in
patients while observing pathogenic structures of
lesion sites. Qin et al29 reported clinical ndings
gained by 18F-FDG PET/CT. Ground-glass opaci-
ties showed a high tracer uptake of 18F-FDG. Be-
sides, the image rstly suggested that COVID-19
may cause lymphadenitis. However, a letter
against its use for diagnosis was published30. One
reason is the complex procedure needed would be
unpractical in most clinical settings, and the other
reason is the risk of disease spreading due to the
long period it takes.
Immunological Examinations
When combined together, detection methods
mentioned above are of help in identifying in-
fected patients in clinical settings. Nevertheless,
containing COVID-19 demands detection meth-
ods with large scale screening and eld detection
ability, neither of which is satised by etiological
detection or medical imaging technology.
Fortunately, a qualied method was success-
fully developed31. This novel technique uses lat-
eral ow immunoassay to detect IgM and IgG
antibodies against COVID-19 in human blood
samples simultaneously. Apart from the short
period, both sensitivity and specicity are also
remarkably high. It may suggest its potential use
as a diagnostic tool for rapid screening in public
area like airport, station, etc. Of notice, this tech-
nique can only tell whether the subject is infected
recently instead of the current conditions.
Prospects
The paragraph above illustrated the results ob-
tained from different specimens. Current samples
used in clinical settings are mainly nasal or pha-
ryngeal swabs, which usually generate positive
rates only measuring 40% or so11. However, we
may notice a study discovering that saliva showed
a remarkable performance in RT-PCR tests14. We
therefore recommend researchers to focus on this
utility and further explore the accuracy of NAT
detecting this specimen.
Notably, though blood and tears did not seem
to be of interest during diagnostic procedures,
they were reported to have a strong relationship
with specic clinical manifestations. Chen et
al32 reported a group of 58 cases. Patients with
detectable viral RNA in blood all gradually de-
veloped to a severe stage. The only sample of
tear that yielded positive results was collected
from a patient with conjunctivitis13. Nevertheless,
inherent defects in both studies resulted in these
unconvincing statements. More researches are
still needed for further illustrations.
Besides, lung US also seemed to be a prom-
ising technology available in most clinical set-
tings with ability to provide rapid outcomes25.
Of notice, this technique was also reported to
Current practice and potential strategy in diagnosing COVID-19
4551
have several limits27. For example, it can not
detect pathological changes that are deep in the
lung and therefore CT would still be of neces-
si t y. 18F-FDG PET/CT proposed by Qin et al29
may not be available in clinical use due to its
inherent defects. However, as it can reveal ab-
normal metabolic and functional manifestations
of COVID-19, it may serve as an investigation
tool for the time being.
As for the immunological test described, we
believe that it can be of great help in countries
with urgent needs for rapid screening to contain
the spread of COVID-19. Of note again, IgM-IgG
test is not able to test the current health condition
of patients, it can only inform us whether the pa-
tient was infected recently31. Thus, it should only
be used in eld detection to identify suspected or
conrmed patients and may not serve as an indi-
cator in discharge criteria.
We here recommend the Chinese Clinical
Guidance for COVID-19 Pneumonia Diagno-
sis and Treatment (7th edition) published by
National Health Commission, in which diag-
nosis procedures were given in great detail21.
Briey, the procedures can be divided into two
separate parts. To determine whether one is a
suspected patient, epidemiological history or
clinical symptoms are needed. Exposure history
involves any form of body contact with con-
rmed cases within 14 days and clinical features
include symptoms like fever, CT images with
signs mentioned above and laboratory examina-
tion showing decrease in both leukocytes and
lymphocytes. One with exposure history can be
considered as a suspected patient if any two of
the clinical features show up, but only when an
exposure-free patient represents all three clini-
cal features can he be suspected. Later, samples
from a suspected patient will run NAT and
serology test. When any of NAT and IgM-IgG
test generates positive result, he or she will be
conrmed and receive further treatments.
Lately, America, Australia, Iran and Italy all
reported a tremendous increase in conrmed
cases recently, among which Italy is now the
most serious region attacked by SARS-CoV-21.
There was a growing concern that COVID-19
will rapidly spread the European continent
among the public, which caused great panic
and inuenced the economic hugely33. Timely
and rm measures shall be taken to contain
the COVID-19 before it causes more damaging
results. To achieve this goal, timely diagnosis is
of great signicance. We hope this review will
help those who are ghting at the frontline and
the containment of this pandemic.
Conflict of Interest
The Authors declare that they have no conict of interests.
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... A pandemic known as COVID-19 has broken out, resulting in a severe public health disaster worldwide [8][9][10]. COVID-19 immunization has been shown to reduce pneumonia on chest CT [11,12]. ...
... The novel coronavirus is transmitted through aerosols, such as airborne droplets scattered during the sneezing and coughing of symptomatic patients. The average incubation period is 6.4 days, which varies from 2.1 to 11.1 days (29). ...
Article
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The new viral pandemic of COVID-19 is caused by the new coronavirus (SARS-CoV-2), which has plunged the world into an economic and health crisis. The lack of specific treatment strategies is necessary to prevent the spread of infection caused by such a previously unknown viral agent. Evidence suggests that COVID-19 disease is associated with intestinal dysbiosis. Probiotics are living microbes that benefit human health by changing the composition of intestinal microbiota. The close relationship between the gastrointestinal tract and the respiratory tract indicates the influence of one on the function of the other. Emerging studies show the ability of probiotics to regulate immune responses in the respiratory tract. The efficacy of probiotics in several respiratory infections has been previously studied. Therefore, this study aimed to understand the available safety information provided by different species of probiotic bacteria in the process of improving the symptoms of respiratory infection caused by the COVID-19 virus.
... O vírus é capaz de se ligar a membrana externa da célula por meio de receptores e provocar danos a função estrutural celular. (1) Múltiplas comorbidades podem piorar o desfecho clínico dos pacientes com coronavírus. Doenças como hipertensão, HIV, câncer, Doença Pulmonar Obstrutiva Crônica (DPOC), asma, alterações renais e diabetes mellitus são fatores de risco potenciais para a gravidade da doença e elevam as taxas de mortalidade em unidades de terapia intensiva relacionadas ao SARS-CoV-2. ...
Article
Introdução: A obesidade é considerada um fator de risco importante para piora das condições clínicas do paciente internato por COVID-19. Objetivo: investigar qual o desfecho clínico dos pacientes obesos diagnosticados com COVID-19 em Unidades de Terapia Intensiva. Metodologia: Revisão Integrativa da Literatura com pesquisa nas bases de dados Pubmed. Resultados: Foram analisados 17 artigos para este estudo. Discussão: O tecido adiposo se torna propenso a invasão viral, vulnerabilizando órgãos como coração e pulmão. Associado a isso, esses pacientes possuem movimento torácico limitado, função respiratória comprometida e pressão abdominal aumentada, o que implica ainda mais na gravidade das infecções pelo COVID-19. Há maior risco para tromboembolismo venoso, de Coagulação Intravascular Dissemina (CIVD) e choque, sendo ainda considerada como fator independente para o agravamento de doenças pré-existentes, como hipertensão arterial e diabetes mellitus. Considerações finais: A obesidade é um fator de risco independente e, modifica o curso da infecção pelo coronavírus. Pacientes com IMC> 30kg/m² e IMC>40kg/m² foram mais associados a pior gravidade e mortalidade, indicando que, quanto maior o IMC, maior a gravidade do quadro clínico e pior o desfecho.
... This virus is mainly transmitted from symptomatic patients by aerosol-like droplets that are produced during coughing or sneezing. 6 This virus does not only affect the respiratory system but also affects the heart, kidneys, eyes, gastrointestinal system, immune system, skin, endothelium, and the coagulation system. 7 In this case report, two patients with positive laboratory results for COVID-19 who had visual symptoms are presented. ...
Article
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Coronavirus disease 2019 (COVID-19) is caused by the virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the literature, this virus has been associated with coagulation dysfunction and arterial thromboembolism. In clinical practice, corpus callosum infarcts are very rare, and the incidence of isolated splenium infarct is very low. Here, two cases of isolated splenium infarct after COVID-19 are reported with clinical and imaging findings. These findings are thought to be useful in daily practice for our colleagues. In addition, differential diagnoses of this entity will also be discussed in this case report.
Conference Paper
In the past years, since 2020, the outbreak of COVID-19 has alarmed the world with the speed and its spread around the world. This raised the demand for early, accurate and automated detection systems for COVID-19 as there is a scarcity of manpower in the medical field. This attracted many researchers using deep learning to build a COVID-19 detection model. For the diagnosis of COVID-19, computed tomography scanning is being used as a more accurate, non-invasive and efficient method in real-time. In this work, we have proposed a model using six different image classification techniques of deep learning on CT scan images and compared the accuracy to find the most suitable and reliable model for transfer learning to achieve the best result on ResNet50 as 97.19% training and 98.05% testing accuracy. The model will automate the process of detection of COVID-19, leading to the advancement in the field of smart health care.
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During March 2022 to January 2023, two Omicron waves hit Shanghai and caused a massive number of reinfections. To better understand the incidence and clinical characteristics of SARS-CoV-2 reinfection in Shanghai, China, we conducted a multicenter cohort study. COVID-19 patients first infected with BA.2 (March 1, 2022-May 23, 2022) who were quarantined in Huashan Hospital, Renji Hospital, and Shanghai Jing'an Central Hospital were followed up for reinfection from June 1, 2022 to January 31, 2023. Of 897 primary infections, 148 (16.5%) experienced reinfection. Incidence rate of reinfection was 0.66 cases per 1000 person-days. Female gender (adjusted odds ratio [aOR]= 2.19, 95% confidence interval [CI]: 1.29-3.83) was a risk factor for reinfection. The four most common symptoms of reinfections during the circulation of BA.5 sublineages were cough (62.59%), sore throat (54.42%), fatigue (48.98%), and fever (42.57%). Having received a booster vaccination was not associated with reduced severity of reinfection in comparison with not having received booster vaccination. After matched 1:1 by age and sex, we found that reinfections with BA.5 sublineages had significantly lower occurrence and severity of fever, fatigue, sore throat, and cough, as compared to primary infections with BA.5 sublineages. SARS-CoV-2 Omicron reinfections were less severe than Omicron primary infections during the circulation of the same subvariant. Protection offered by both vaccination and previous infection was poor against SARS-CoV-2 reinfection. K E Y W O R D S clinical characteristic, cohort study, COVID-19, incidence, multicenter, Omicron, reinfection, SARS-CoV-2 J Med Virol. 2023;95:e28997. wileyonlinelibrary.com/journal/jmv
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Background and Aim Coronavirus is still a life-threatening disease around the world. In patients with this disease, having an underlying disease reduces the effectiveness of treatment and increases mortality. This study aimed to examine the effect of cancer history on mortality rates in patients with COVID-19. Materials and Methods This study was a case-control study involving 60 cancer patients with COVID-19 as the case group and 180 non-cancer patients with COVID-19 as the control group. A matching method based on propensity score was used to select patients in the control group. The effect of treatment on the outcome (recovery death) was studied with logistic regression, and the factors affecting patient survival were analyzed with Cox models. R software was used to analyze the data. Results The mean (SD) age of patients in the case and control groups was 61.37 (13.47) and 63.19 (13.95) years, respectively. In the case group, 37 patients (61.7%), and in the control group, 114 patients (63.3%) were male. 23 cancer patients (38.3%) and 26 non-cancer patients (14.4%) died. The results of logistic regression as well as the Cox model showed the variables of age, blood oxygen level (SpO2), admission to the intensive care unit, and cancer history as significant for patient death (P <0.05). Conclusion To study the effect of demographic, clinical, and laboratory results on the risk of death among COVID-19 patients with and without a cancer history, control group in this study was selected by PSM method. The results of this study have indicated cancer history to be one of the factors affecting the mortality of patients with COVID-19 in addition to age variables, blood oxygen levels (SpO2), and admission to the intensive care unit (ICU).
Article
No fim de 2019 iniciou-se uma das maiores crises da saúde pública global em Wuhan, China. Essa emergência foi o aparecimento do SARS-CoV-2 e da doença COVID-19, uma síndrome respiratória aguda de alta transmissibilidade. A declaração da pandemia pela OMS em março de 2020 fez com que o mundo tomasse diversas medidas para o combate e contenção da doença. Inicialmente o isolamento social e lockdown foram as principais iniciativas, já que não havia formas de tratamento ou prevenção da doença. Essas medidas restritivas geraram uma mudança de hábito da população que deflagrou sérios comprometimentos físicos e psicológicos. Uma das consequências foi o aumento do uso de substâncias de abuso e, consequentemente, do transtornos por uso de substâncias, dentre elas o tabaco. Durante a pandemia o consumo de cigarro aumentou de 10 a 30% no mundo, o tabagismo é a principal causa de morte evitável e fator de risco para diversas doenças. Conjuntamente ao álcool, a nicotina têm um poder aditivo superior a muitas drogas ilícitas. A combinação dos transtornos por uso de substâncias e a COVID-19 acabam por ter um efeito sinérgico, dessa forma, buscamos integrar aspectos neuroquímicos, cognitivos e comportamentais que levaram ao aumento do consumo e/ou recaída nicotina e a terapêutica utilizada.
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The current pandemic caused by SARS-CoV-2 originated in the city of Wuhan, China with an outbreak of pneumonia. The reported symptoms were mostly respiratory, but mounting evidence began to indicate that COVID-19 could reach other organs and systems. Among the gastrointestinal symptoms, liver involvement appears to be more common, with changes in liver enzymes (ALT and AST) being the first sign. Therefore, the present study aims to evaluate and discuss the hepatic manifestations in COVID-19 as the infection, manifestations, and drug effects. The study was based on a literature review, of a qualitative nature and an exploratory type. The mechanism that SARS-CoV-2 uses to reach the liver is still uncertain, there are currently 3 hypotheses: ACE2 receptors in cholangiocytes, cytokine storm, and drug-induced liver injury, due to the increase in the indiscriminate use of hepatotoxic drugs without scientific comprovation, hydroxychloroquine can lead to fulminant hepatic failure and azithromycin potentiates these effects, the role of remdesivir on the liver are still uncertain. Liver damage in mild cases of COVID-19 can be transient, but doctors should monitor and be alert to any changes in liver enzymes. When severe liver damage occurs, liver protective drugs have usually been given to these patients. Thus, this review provides a review of hepatic impairment and the management of patients considering the main studies carried out to date.
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Coronavirus disease 2019 (COVID-19) was first detected in Mexico in February 2020. Even though health authorities did not perceive then the value of viral detection tests, we anticipated the demand for them. We set up to develop an expeditious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular diagnostic service through the implementation of standardized protocols for biospecimen sampling, transportation, biobanking, preanalytical validation, and nucleic acids (NA) testing (NAT). Nasopharyngeal and oropharyngeal swabs collected in a special transportation medium were the biospecimens from which NAs were purified either manually or automatically. Viral RNA genome presence was determined using commercial SARS-CoV-2 detection kits (based on reverse transcription coupled with real-time PCR [RT-PCR]). Improvements in laboratory processing speed and reliability resulted from semi-automatizing laboratory processes and adopting a quality control/quality assurance system (QC/QA), respectively. NAs that were purified, either manually or automatically, were validated by preanalytical spectrophotometric characterization. Automated purification was less prone to contamination and reduced the processing time. The following six RT-PCR kits were evaluated for their convenience, specificity, sensitivity, time consumption, and required materials (in order, starting with the kit with the best results): RIDA gene and Viasure (tied), Vircell, LightMix, 1copy, and Logix Smart. Redesigning the laboratories' working areas, equipment, fluxes of personnel and material, and personnel skills, and overemphasizing biosafety safeguards were major challenges encountered in the middle of the sanitary crisis. Adopting a QC/QA system, utilizing automatization processes, and working closely with health authorities were key factors in our success. IMPORTANCE Rearranging our diagnostic laboratories to improve the fight against a new unexpected, unpredictable, and sudden public health threat demanded that we move quickly to redesign not only the laboratory processes but also the distribution of space, personnel activities, and fluxes of material coming in and out. We also had to work closely with governmental health authorities to gain their trust in our technical competence. Gaining the confidence of the clients, i.e., mainly individuals, the human resource departments of factories and corporations sending employees for testing, and medical institutions, and implementing as much automatization as possible of processes, in which only officially approved reagents (for extraction and analysis of NA) were used to generate opportune trustable testing results, were key factors. Our laboratories have gathered a considerable amount of experience and significant number of solutions, considering our geographic contexts alongside this continuously morphing pandemic, validating many techniques that might help other laboratories find a better and more precise workflow.
Preprint
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We report an asymptomatic child who was positive for a 2019 novel coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.
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Facing the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), high-volume respiratory testing is demanded in laboratories worldwide. We evaluated the performance of a molecular assay for the detection of SARS-CoV-2 on a high-throughput platform, the cobas 6800, using the 'open channel' for integration of a laboratory-developed assay. We observed good analytical performance in clinical specimens. The fully automated workflow enables high-throughput testing with minimal hands-on time, while offering fast and reliable results.
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On 31 st December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated Coronavirus Disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time RT-PCR assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 TCID 50 /ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRd-P2-negative specimens [119/273 (43.6%) vs 77/273 (28.2%), P<0.001], including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21×10 ⁴ RNA copies/ml (range, 2.21×10 ² to 4.71×10 ⁵ RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.
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The currently available data suggests that many laboratory parameters are deranged in patients with COVID-19, and some of these may also be considered significant predictors of adverse clinical outcomes. The most frequent abnormalities were lymphopenia (35–75% of cases), increased values of CRP (75–93% of cases), LDH (27–92% of cases), ESR (up to 85% of cases) and D-dimer (36–43% of cases), as well as low concentrations of serum albumin (50–98% of cases) and hemoglobin (41–50%). Many laboratory abnormalities were instead predictive of adverse outcome, including increased white blood cell count, increased neutrophil count, decreased lymphocyte count, decreased albumin, increased LDH, ALT, AST, bilirubin, creatinine, cardiac troponins, D-dimer, prothrombin time, procalcitonin and CRP values.
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The outbreak of the novel coronavirus disease (COVID‐19) quickly spread all over China and to more than 20 other countries. Although the virus (SARS‐Cov‐2) nucleic acid RT‐PCR test has become the standard method for diagnosis of SARS‐CoV‐2 infection, these real‐time PCR test kits have many limitations. In addition, high false negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point‐of‐care lateral flow immunoassay which can detect IgM and IgG antibodies simultaneously against SARS‐CoV‐2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID‐19 patients and 128 negative patients at 8 different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM‐IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS‐CoV‐2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories. This article is protected by copyright. All rights reserved.
Article
An epidemic of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in China and has spread to other countries.¹ Real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) of nasopharyngeal swabs typically has been used to confirm the clinical diagnosis.² However, whether the virus can be detected in specimens from other sites, and therefore potentially transmitted in other ways than by respiratory droplets, is unknown.
Article
Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.
Article
OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The "reversed halo" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.
Article
The emergence and spread of 2019 novel coronavirus–infected pneumonia (COVID‐19) from Wuhan, China, it has spread globally. We extracted the data on 14 patients with laboratory‐confirmed COVID‐19 from Jinhua Municipal Central hospital through 27 January 2020. We found that compared to pharyngeal swab specimens, nucleic acid detection of COVID‐19 in fecal specimens was equally accurate. And we found that patients with a positive stool test did not experience gastrointestinal symptoms and had nothing to do with the severity of the lung infection. These results may help to understand the clinical diagnosis and the changes in clinical parameters of COVID‐19. Highlights • To determine the accuracy of COVID‐19 diagnosis in stool samples, we analyzed 14 laboratory‐diagnosed patients with COVID‐19 pneumonia. • The results showed that fecal specimens were as accurate aspharyngeal specimens. • COVID‐19 nucleic acid positive in fecal specimens was not related to the severity of pneumonia and gastrointestinal symptoms.