3.3. Radiographic imaging
Radiological examinations are of great importance in the early detection
and management of COVID-19. According to current experience, lung
imaging manifests can be found earlier than clinical symptoms, so
imaging examination is vital in preclinical screening
(Sohrabi et al., 2020). Therefore, the
suspected cases should undertake chest examination as soon as possible.
In the early stage, multiple small patchy shadows and interstitial
changes were detected in the extrapulmonary zone. And then, it developed
into multiple ground-glass infiltrations
(Dawei Wang et al., 2020).
In
severe and critically cases,
lung
lesions usually involved most commonly 4-5 lobes in the bilateral lower
and upper lobes.
The
first report of COVID-19 patients described that bilateral lung
involvement was detected in 80% of patients, and consolidative pattern
changes were always observed in most patients in an intensive care unit
(ICU), but ground-glass pattern always showed in patients not in the
ICU
(Bernheim et al., 2020). Shi et al.
analyzed the CT changes and found that most patients even the
asymptomatic patients showed dynamic changes from focal unilateral to
diffuse bilateral ground-glass opacities and then progressed to
consolidations within 1-3 weeks (X. W. Xu
et al., 2020). In general, combining assessment of imaging features
with clinical and laboratory findings can facilitate the diagnosis of
COVID-19 pneumonia and evaluate the severity of the disease.
4.Thepathological
changes in COVID-19 patients
Pathological examination of patients with COVID-19 would confirm
laboratory and radiological findings and contribute to further study and
a better understanding of mechanisms of the disease
(Z. Xu et al., 2020).
A
recent study reported the biopsy results from two patients who underwent
surgery for malignancy and then were found to have been infected with
SARS-CoV-2, which provided first opportunities to study the pathology of
COVID-19. It revealed that the lungs of patients exhibited edema,
proteinaceous exudate, focal reactive hyperplasia of pneumocytes with
patchy inflammatory cellular infiltration, and multinucleated giant
cells, but hyaline membranes were not prominent
(Tian et al., 2020). This study may
describe early phase changes of the lung pathology of COVID-19
pneumonia.
After
that pathologist from Huazhong University of Science and Technology,
Wuhan, China performed
autopsy
from 12 dead patients and the results were released by the national
health commission, China (Wang, Du, Yue,
& Chen, 2020). The histopathological changes for different organs are
summarized below:
Lung The lungs showed evident multi-pulmonary consolidation,
acute interstitial inflammatory infiltrates and congestion in the
alveolar septae. The lumina of alveoli and bronchioles were variably
filled with protein-rich edema fluid, erythrocytes, cellular debris, and
lymphocytes. Type II alveolar epithelial cells proliferated obviously
with inclusion bodies inside. The blood vessel of the alveolar septum
had congestion and edema, in which the infiltration of lymphocytes and
monocytes, and intravascular hyaline thrombosis can be seen. Focal
hemorrhage and necrosis of the lung tissue caused hemorrhagic
infarction. Diffuse interstitial pulmonary fibrosis would be presented
with the disease progress.
Bronchial
epithelial cells were degenerated, necrosis and fell off. Mucus plugs
were visible in the bronchial lumen. Due to the over-inflation of the
alveoli, a small number of the alveolar septum was broken, or the cysts
were formed. SARS-CoV-2 particles could be observed in the cytoplasm of
bronchial mucosal epitheliums and type II alveolar epithelial cells
under an electron microscope. Immunohistochemical staining showed that
some alveolar epitheliums and macrophages were positive for SARS-CoV-2
antigens. These tissue types also tested positive for nucleic acids on
RT-PCR.
Immune systemThe
volume of the spleen decreased
significantly
and the number of lymphocytes was significantly
reduced.
There were focal patchy hemorrhages, necrosis and proliferation, and
phagocytosis of macrophages in the splenic tissue, with atrophy of white
pulp lymphoid aggregates. The number of lymphocytes decreased obviously,
and necrosis was visible in lymph nodes. Immunohistochemical staining
showed that CD4 + T and CD8 + T cells were reduced in the spleen and
lymph nodes. The number of three cell lines in the bone marrow was
reduced.
Cardiovascular system There was
notable
degeneration and necrosis
in
the myocardial cells, and a few monocytes, lymphocytes and neutrophils
infiltrated in the interstitium. Endothelial shedding, endovascular
inflammation and thrombosis were visible in the blood vessel.
Liver and gallbladder The volume of the liver increased and its
color was dark red. There were degeneration of hepatocytes, congestion
of hepatic sinus, focal necrosis with neutrophil infiltration and
microthrombosis, which feature the repeated interchange of these kinds
of pathological course. The gallbladder was filled with bile.
Kidney There was proteinaceous exudate in the glomerular
cavity
and degeneration and necrosis in renal tubular epitheliums. Hyperemia,
microthrombus and focal fibrosis can be observed in the renal
interstitium.
Further,
a cohort study conducted by Dominic Wichmann from Intensive Care
Medicine University Medical Center Hamburg, demonstrated that 4 (4/12,
33.3%) patients died of pulmonary embolism, and 8 (8/12, 66.7%)
exhibited substantial histomorphological diffuse alveolar damage. This
study revealed that SARS–CoV-2 RNA could be detected at high
concentrations in the lung of all the patients.
And
more than half of the patients demonstrated high viral RNA titers
SARS–CoV-2 RNA was detected in the liver, kidney, or heart
(Wichmann et al., 2020).
5.
Treatment of COVID-19
Patients
should be allocated to designated treatment areas according to the
disease severity. Confirmed and suspected patients should be isolated in
hospitals with applicable protective equipment and special conditions
(e.g. negative pressure ward.). The confirmed cases can be admitted in
the same ward, but the suspected cases would be better isolated in a
single room to avoid transmission. Besides, critical cases should be
treated in ICU as soon as possible (N. H.
C. S. A. o. T. C. Medicine, 2020).
Until now, no medicine or anti-virus vaccine has yet been officially
recommended for COVID-19 infection (J. Sun
et al., 2020). In fact, many countries are focusing on investigating
specific medicine to control the infections of SARS-CoV-2 such as
vaccines, antibodies, and interferon, which may require a long time of
clinical trial (Amanat & Krammer, 2020).
Currently available treatment approaches include symptomatic and
supportive therapies including supplementary oxygen, mechanical
ventilation, glucocorticoids and infection prevention and control
(Jin et al., 2020).
Antibiotics
have no role in treating COVID-19 patients, but they can be used in the
case of a secondary bacterial infection. As for antiviral therapy,
several agents previously used to treat SARS and Middle East Respiratory
Syndrome (MERS) and HIV have been considered as the most potential
candidates for COVID-19 patients in China firstly
(Kang et al., 2020). With the spread of
COVID-19, a large number of pre-clinical and clinical studies all over
the world have been underway to investigate the potential agents for
COVID-19.
Lopinavir/Ritonavir were the first two antivirals extensively applied
for treatment of the COVID-19 in china. Though
lopinavir/ritonavir have been used
for the treatment of human immunodeficiency virus (HIV) infection with a
generally good safety profile, clinical feasibility and safety require
further investigation (Kaplan & Hicks,
2005). As has been pointed out, lopinavir/ritonavir usually has
compromised interactions with many drugs commonly used in severe
patients, which
made
it less promising for the treatment of COVID-19 patients. Nevertheless,
this antivirus has been recommended by the available guidelines in many
other countries including the US, Japan
(Cao et al., 2020;
Stower, 2020). Favilavir was another
anti-virus drug that has been effective in relieving the symptoms
COVID-19 patients in Japan and China (Abd
El-Aziz & Stockand, 2020; Elfiky,
2020). However, this antivirus is not currently approved by the Food
and Drug Administration (FDA) of the US
(Guan et al., 2020;
Li G Fau - De Clercq & De Clercq,
2020).
Remdesivir,
a monophosphoramidate prodrug of an adenosine analogue, could inhibit
viral replication through incorporating into nascent viral RNA chains
resulting in
pre-mature
termination (M. Wang et al., 2020). A
variety of studies have confirmed that remdesivir showed a significant
antiviral activity against a broad variety of RNA viruses including
SARS-CoV, MERS-CoV and Ebola virus in cultivated cells, mice and
non-human primates (NHP) models (de Wit et
al., 2020; Warren et al., 2020;
Xie & Chen, 2020). Therefore,
remdesivir has emerged as the most promising candidate based on the
broad antiviral spectrum for the treatment of SARS-CoV-2 infection
(Marto & Monteiro, 2020). Meanwhile, a
large number of randomized clinical trials have been strictly conducted
to investigated its antiviral and safety profile in patients with
COVID-19 such as: NCT04252664 and NCT04257656 in many countries
(Esposito, Noviello, & Pagliano, 2020;
Y. Wang et al., 2020). Recently, a
randomized, double-blind clinical trial conducted in China revealed that
remdesivir could not improve the time to clinical cure and elimination
of viruses, as well as the mortality in patients with COVID-19
(Y. Wang et al., 2020). However, the
preliminary clinical study of compassionate use of remdesivir released
in England Journal of Medicine
came
to diametrically opposed conclusions, which demonstrated that 68%
(36/53) of patients showed significant clinical improvement with a
mortality rate of 18% (Grein et al.,
2020). Similarly, the National Institutes of Health of the US reported
the findings from a randomized, placebo-controlled trial of remdesivir
among 1,063 patients, which suggested that patients who received
remdesivir tend to improve faster
than patients without, and remdesivir could significantly reduce the
mortality rates.
Therefore,
additional studies with the multicenter and large samples are required
to evaluate the safety and efficiency of this antiviral agent.
Chloroquine
(CQ)
and hydroxychloroquine (HCQ), belonging to the class of aminoquinolines,
have been approved for the treatment of malaria, chemoprophylaxis, and
autoimmune diseases including lupus and rheumatoid arthritis
(Jakhar & Kaur, 2020;
Rempenault et al., 2020). In addition,
these small-molecule agents have been identified as a promising
broad-spectrum antiviral. Previous studies have shown that
CQ
and HCQ could inhibit the activity of RNA virus such as HIV, HCV, SARS,
MERS, Ebola, Hendra viruses in vitro via targeting endosomal
acidification as the major determinant of antiviral activity and
affecting glycosylation of ACE2 receptor that are required for viral
entry (Costanzo, De Giglio, & Roviello,
2020; Lentini, Cavalluzzi, &
Habtemariam, 2020; Pereira, 2020;
Savarino A Fau - Di Trani, Di Trani L Fau
- Donatelli, Donatelli I Fau - Cauda, Cauda R Fau - Cassone, & Cassone,
2020). A recent study also supported the potent activity of CQ and HCQ
against SARS-CoV-2, which suggesting the inhibiting effect of viral
replication during the initial phases of viral infection. Therefore,
they have been approved by the FDA and currently recommended for the
treatment of COVID-19 patients.
The
China National Health Commission reported that CQ may be one of the
three drugs with a promising profile for treatment of SARS-CoV-2, but
not for infection prevention due to the frequent side effects including
severe nausea, polymorphic ventricular tachycardia, digestive disorders,
long QT syndrome, and increased risk for sudden
death
(Juurlink, 2020). A France study among 36
patients reported that single-agent HCQ or combination with azithromycin
therapy holds the promise of shortening the clearance of SARS-CoV-2 RNA
in the upper respiratory tract (CHEN Jun,
2020). Another report with a larger trial of 84 patients treated with
hydroxychloroquine
and 97 cases for control suggested that there was no evidence of
improvement in patient outcomes between the two groups
(Marto & Monteiro, 2020). According to
the latest report released by European Medicines Agency (EMA) in April,
CQ and HCQ should be only used in clinical trials or emergency use
programs (Ferner & Aronson, 2020).
Therefore, they are currently presented as an option for the treatment
of hospitalized COVID-19 patients in several countries, including the
United States, Portugal, Brazil, and France
(Health., 2020;
P. S. o. c. medicine, 2020;
Wilson KC, 2020).
According to the previous reports, SARS-CoV-2 induced aberrant immune
responses and excessive infection cytokine storm with increased plasma
concentrations of interleukins IL-6, IL-2, IL-7, and IL-10 and tumor
necrosis factor are believed to play major roles in disease severity
(Yang et al., 2020). Zhou et al
confirmed that the value of IL-6 was significantly elevated in patients
with ARDS who died compared with patients who
survived(Wu et al., 2020). Tocilizumab,
a humanized IL-6-receptor (IL-6R) monoclonal antibody, has been
experimentally administered in the treatment of COV-ID-19 patients with
the severe form of the disease and elevated IL-6 levels in China and
Italy (Commission., accessed 2020 Apr
12). In March, The Italian Medicines Agency (AIFA) announced the launch
of the clinical phase 2 study named to evaluate the efficacy and safety
of TCZ in the treatment of COVID-19
(Esposito et al., 2020). Up to now, many
multicenter clinical trials have been registered and spanning the United
States, Canada, China, and Europe. Therefore, the WHO has not given a
positive response for the use of tocilizumab in
COVID-19,
due to insufficient evidence.
Convalescent
plasma has been applied to treatment of infectious diseases for more
than one century. Based on the initial successful experience in the
treatment of SARS and MERS, convalescent plasma therapy may be another
potentially promising option for COVID-19 patients by providing passive
immunity against infectious agents (Cheng
et al., 2020; van Griensven et al.,
2020).
Researches
from China have demonstrated that convalescent plasma could
significantly improve the symptoms and reduce the mortality rate
(Duan et al., 2020;
C. Shen et al., 2020). Recently, the FDA
has approved convalescent plasma therapy for emergency use to treat
COVID-19 patients especially patients with severe condition. Inevitably,
convalescent plasma may increase the risks of blood-borne pathogen
transmission such as HIV, HBV, HCV and so on
(Bhimraj et al., 2020).
Corticosteroids have been previously used in SARS, MERS, H1N1 viral
pneumonia with possible immunomodulatory properties
(Arabi et al., 2020;
Booth et al., 2020). However, reports have
confirmed that instead of improving of the mortality among patients with
SARS and MERS, corticosteroids increased risk of extended hospital
lengths of stay, delayed viral clearance and secondary infections
(Coondoo, Phiske, Verma, & Lahiri,
2014). One study among 31 patients from China showed that
corticosteroid use did not influence the outcome of patients with mild
COVID-19 (Zha et al., 2020). And
systematic use of corticosteroids is even higher in critically ill
patients with ARDS. However, a multicenter study of 213 patients from
the University of Maryland Medical Center demonstrated that low-dose
glucocorticoid treatment during the early stages of COVID-19 could
significantly reduce the likelihood of being admitted to ICU, the
requirement for mechanical ventilation and mortality. Therefore, the
treatment of COVID-19 with glucocorticoids is rather controversial, and
the
WHO has recommended against routinely administering systemic
corticosteroids to patients with COVID- 19.
6.The
physical and mental health of medical staff
During
the spread of the epidemic, COVID-19 prevention and control attracted
considerable attention. The highly pathogenic and infectious COVID-19
undoubtedly poses a great challenge to the health of front-line medical
staff who were testing for and treating patients with COVID-19 are at a
higher risk of contracting it than the general publication (Magellan
Health Insights, 2020). According to the existing study results,
medical
staffs were at high risk of infection during the MERS and SARS
outbreaks, with 18.6% of MERS cases occurring in medical staff and 21%
of SARS cases occurring in medical staff
(Chan-Yeung, 2004;
Kim et al., 2020). Due to insufficient
understanding of the characteristics of pathogenic and insufficient and
unequally-distributed medical resources at the beginning of the epidemic
outbreak, a large number of medical staff were infected during the
battle against COVID-19. According to the International Council of
Nurses (ICN), there have been more than 90,000 health workers were
infected, and 260 nurses died from this contagious disease
(Nurses, 2020). Health care
professionals, particularly those working in emergency units and
resuscitation departments, were most often infected during the operation
with
high
level of exposure levels such as
endotracheal
suction and intubation, nasogastric feed, cardiopulmonary resuscitation
and high flow-rates of oxygen and so on
(Gamage et al., 2005). In addition, many
professionals may consistently experience a high intensity of work with
the need of wearing Personal Protective Equipment (PPE), which usually
cause physical discomfort and difficulty breathing
(Huang, Han, Luo, Ren, & Zhou, 2020;
Shigemura, Ursano, Morganstein, Kurosawa,
& Benedek, 2020).
Apart from physical suffering, health professionals were suffered from
great psychological pressure and other psychological-related problems.
Frontline medical staff, especially those in the most severely affected
city: New York, Madrid, London, are highly vulnerable to experiencing
physical exhaustion, fear, emotion disturbance, sleep problem and
concern for themselves, their families and colleagues
(Kisely et al., 2020;
Malta, Rimoin, & Strathdee, 2020). In
one study of 1563 health medical staffs, 50.7% of the participants
experienced serious depression symptoms, 44.7% anxiety, and 36.1%
sleep disorders (Chersich et al., 2020).
Another multicenter study conducted in Singapore and India demonstrated
that 19.8% of healthcare workers exhibited varying degrees of
psychological discomfort: moderate to very-severe depression, anxiety,
psychological distress, and 32.3% always experienced with headache,
panic (Cullen, Gulati, & Kelly, 2020).
Early evidence indicates that medical staff especially the ones who
participated in the treatment of SARS patients was more susceptible to
psychological disorders. Therefore, healthcare organizations should
adopt following key strategies urgently to protect the mental health of
employees with their duty: enhanced decision making support to provide
sufficient medical resources; the provision of time and space for
clinicians to decompress; and staff working consistently in the same
team (Kisely et al., 2020). At the same
time, the National Health Commission of China (NHC) has integrated
psychological crisis intervention into the general deployment of disease
prevention, and released the clinical practice guideline of emergency
psychological crisis interventions, psychological counseling for health
staff. Recently, the platform for remote health counseling services has
been established with psychological professionals in Wuhan, Macao and
Rome,which made it easier and safer to provide mental health education
for both patients and front-line medical staff
(W. Li et al., 2020;
Macau., 2020).
Therefore, we cannot ignore providing psychological counseling and
crisis intervention training for medical staff. In addition, reasonable
schedules, adequate sleep, and appropriate diet and exercise are also
the keys to improving the body’s immunity and reducing the risks of
suffering.