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An Insight of comparison between COVID-19 (2019-nCoV disease) and SARS in pathology and pathogenesis

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COVID-19, a novel pathogenic coronavirus (2019-nCoV, now named SARS-CoV2) induced disease, emerged in China and spread globally rapidly. 2019-nCoV(SARS-CoV2) shares above 85% identity in genome with SARS-CoV. Patients infected by 2019-nCoV and SARS-CoV also reveal similar clinical characteristics. Here we compare the clinical and pathological features between patients of COVID-19 and SARS respectively. Conclusions: 1. Older patients refer to a higher case fatality rate (CFR) than young. 2. Males show a higher CFR than females, and this difference may converge as age increase. 3.COVID-19 may cause a kidney and testis damage. Combined with higher CFR in males, genitourinary system disorder caused by the COVID-19 needs to be cautioned. 4. It is critical to control the cytokine release syndrome(CRS) in COVID-19. IL-6, IL-10 and their receptors may be the drugable target. 5.Consistently to decrease of CD4+T and CD8+T cells, spleen damage, and lymphocyte depletion may exist inCOVID-19 patients. Approaches for T cell rescued may be considered. 6. Compared with SARS-CoV’s Spike protein, 2019-nCoV(SARS-CoV2) Spike protein present a higher binding affinity to ACE2, which suggests that soluble ACE2 might be a potential candidate for COVID-19 treatment. Other receptors, such as L-SIGN and DC-SIGN, need to be investigated in the future.
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An Insight of comparison between COVID-19 (2019-nCoV disease) and SARS in
pathology and pathogenesis
Xiaolong Cai1,2,*
1.Hanbio Research Center, Hanbio Tech Co. Ltd., Shanghai, P.R. China (www.hanbio.net)
2.R&D Center, GeneMedi Co.Ltd., Shanghai, P.R. China
*Corresponding authors: E-mail: cxl@hanbio.net
Abstract: COVID-19, a novel pathogenic coronavirus (2019-nCoV, now named SARS-CoV2)
induced disease, emerged in China and spread globally rapidly. 2019-nCoV(SARS-CoV2)
shares above 85% identity in genome with SARS-CoV. Patients infected by 2019-nCoV and
SARS-CoV also reveal similar clinical characteristics. Here we compare the clinical and
pathological features between patients of COVID-19 and SARS respectively.
Conclusions:
1. Older patients refer to a higher case fatality rate (CFR) than young.
2. Males show a higher CFR than females, and this difference may converge as age increase.
3.COVID-19 may cause a kidney and testis damage. Combined with higher CFR in males,
genitourinary system disorder caused by the COVID-19 needs to be cautioned.
4. It is critical to control the cytokine release syndrome(CRS) in COVID-19. IL-6, IL-10 and
their receptors may be the drugable target.
5.Consistently to decrease of CD4+T and CD8+T cells, spleen damage, and lymphocyte
depletion may exist inCOVID-19 patients. Approaches for T cell rescued may be considered.
6. Compared with SARS-CoV’s Spike protein, 2019-nCoV(SARS-CoV2) Spike protein
present a higher binding affinity to ACE2, which suggests that soluble ACE2 might be a
potential candidate for COVID-19 treatment. Other receptors, such as L-SIGN and
DC-SIGN, need to be investigated in the future.
Introduction
A novel coronavirus pneumonia (NCP) caused by a novel coronavirus, 2019-nCoV, which named
COVID-19 by WHO recently, emerged in Wuhan, Hubei province, China in December 2019. The
COVID-19 then broke-out aggressively in Jan 2020 following the human flow from Wuhan to
other cities during the vocation of the Chinese Spring Festival.
Several coronaviruses can cause light respiratory disease in humans [1]. In contrast, the
SARS-CoV, which emerged in 2003 in Guangdong Province, China, and MERS-CoV, in 2012,
both proved host by bat and transmitted from other animals to humans, can cause severe
respiratory diseases respectively[2].
Genetics Similarity of 2019-nCoV and SARS-CoV
The 2019-nCoV is also a novel coronavirus transmitted from uncertain wild animals, that can
cause acute respiratory disease (ARD) with complicated clinical characteristics[3-7]. According to
the whole genome sequence analysis, the 2019-nCoV is closer to the SARS-like bat CoVs
(MG772933) than the SARS-CoV[8], which is descended from SARS-like bat CoVs
However, 2019-nCoV share above 85% identity with SARS-CoV[8], but less related to
MERS-CoV[9]. Importantly, within high similarity of RBD in Spike-protein, several analyses
reveal that 2019-nCoV uses the same receptor of SARS-CoV - the angiotensin-converting enzyme
2 (ACE2)[10-12]. Meanwhile, DPP4 (dipeptidyl peptidase 4, also known as CD26), the
MERS-CoV’s primary receptor, is proved not to be a receptor of 2019-nCoV[11].
Case fatality rate (CFR) of COVID-19 and SARS both affected by age and gender.
Age and gender distinction affect the CFR of COVID-19 and SARS respectively(Table1). It is
certain that older patients refer to higher CFR than young both in COVID-19[3] and SARS[13, 14]
respectively. Consistently to SARS, Males seem to have a higher CFR than females in
COVID-19[3, 13, 14]. Meanwhile, a SARS related study in Hongkong indicates a gradual
decrease of gender-depended difference in CFP as the age increase, which may also be likely to
exist in COVID-19[14].
Comparison of Major Pathological Characteristics between COVID-19 and SARS
We summarize the major Major Pathological Characteristics between COVID-19 and SARS in
Table2. Since lots of mentions in other articles, COVID-19 induced acute respiratory distress
syndrome(ARDS) will not be discussed in this article.
The high rate of renal impairment was observed in COVID-19 patients, indicating the
development of kidney dysfunction[15], which was consistent with SARS patients[16-20]. As is
shown in Figure1, ACE2, the co-receptor of 2019-nCoV and SARS-CoV, presents a high
expression level in the gastrointestinal tract, kidney, and testis. Since SARS induce severe testis
damage[21], it holds a high risk that 2019-nCoV infection may also lead to testicular lesions in
males,which need further clinical investigation. Considering the higher CFR of COVID-19 and
SARS in younger males than females, with the high ratio of kidney damage[12, 15](worthy of
future investigation in gender), we should pay attention to the genitourinary system disorder
caused by the 2019-nCoV infection.
Cytokine release syndrome(CRS) remains a core factor that aggravates disease
progression[22]. A higher value of IL-6 and IL-10 was observed in COVID-19 patients parallel
with the severity of the disease[22]. IL-6 and IL-10 are the core cytokines that are consistently
found to be elevated in patients with CRS(23,24). Tocilizumab, a monoclonal antibody targeting
the IL-6 receptor, was already registered for a Clinical Trials in Anhui Provincial Hospital now
(Chinese Clinical Trials Registration number: ChiCTR2000029765).
Necrosis of the spleen and atrophy of the white pulp with severe lymphocyte depletion have
been mentioned in SARS patients[16-18, 25, 26]. Consistently, the amount of various immune
cells including CD4+T, CD8+T, dendritic cells(DCs), macrophages, and natural killer cells(NKCs)
decrease respectively[26]. Since a significant decrease of CD4+T and CD8+T cells number were
also found in COVID-19 patients respectively[22], the spleen impairment needs to be further
confirmed. Meanwhile, it was reported that CD4+T cells, but not CD8+T cells are Important in
control of SARS-CoV infection[27]. We might further consider different approaches for T cell
rescuing within the control of CRS.
Receptors
ACE2 is proved a co-Receptor of 2019-nCoV and SARS-CoV. Structure analysis of 2019-nCoV
and SARS-CoV recently indicated that 2019-nCoV Spike protein (S-protein) binds ACE2 with
above 10 folds higher affinity than SARS-CoV[28]. This discovery further explains the more rapid
transmission characteristic of the 2019-nCoV in humans than SARS-CoV. Referring to the higher
affinity of 2019-nCoV S-protein and ACE2, soluble ACE2 might be a potential candidate for
COVID-19 treatment.
Recognized ACE2 as the receptor of 2019-nCoV, now scientists find important an ACE2
downstream target-TMPRSS, which maybe drugable[11, 29]. Besides ACE2, the L-SIGN
(CD209L, gene symbol: CLEC4M) and DC-SIGN (CD209, gene symbol: CD209) have been
identified as alternative SARS-CoV receptors respectively [30, 31]. The organ-specific expression
of L-SIGN and DC-SIGN is present in Figure1C, D respectively. It is unknown if L-SIGN and
DC-SIGN can act as alternative receptors of 2019-nCoV . Regarding 14 amino acid sequences of
RBD of SARS-CoV S-protein, 2019-nCoV reveals 8 strictly conserved residues and 6 amino acid
mutations, which may affect the tropism and transmission property. Excluding ACE2, other
receptors may also be available.
Concluding remarks of COVID-19 compared with SARS
1. Older patients refer to higher case fatality rate (CFR) than young.
2. Males show a higher CFR than females, and this difference may converge as age increase.
3.COVID-19 may refer to a kidney and testis damage. Combined with higher CFR in males,
genitourinary system disorder caused by the COVID-19 need to be cautioned.
4. It is critical to control the cytokine release syndrome(CRS) in COVID-19. IL-6, IL-10 and their
receptors may be the drugable target.
5.Consistently to decrease of CD4+T and CD8+T cells, spleen damage, and lymphocyte depletion
may exist inCOVID-19 patients. Approaches for T cell rescued may be considered.
6. Compared with SARS-CoV’s Spike protein, 2019-nCoV(SARS-CoV2) Spike protein present a
higher binding affinity to ACE2, which suggests that soluble ACE2 might be a potential candidate
for COVID-19 treatment. Other receptors, such as L-SIGN and DC-SIGN, need to be investigated
in the future.
Acknowledgement
Tribute to the medical staff fighting against the COVID-19 in China. You are the angels.
Thanks for the helps from my colleagues from Hanbio Tech Co. Ltd., Shanghai, P.R. China
(www.hanbio.net) and GeneMedi Co.Ltd., Shanghai, P.R. China (www.genemedi.net) respectively.
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Table 1
Age and gender distinction may affect the CFR of COVID-19 and SARS
COVID-19 [3]
SARS in China
Mainland [13]
SARS in China
Hongkong [14]
R0
3.78
2-3
CFR
No.of case
CFR
CFR
All
3.06%
5327
6.40%
17.04%
Gender
Male
4.45%
2607
7.20%
21.90%
Female
1.25%
2720
5.60%
13.20%
Age group
<60
1.43%
4777
4.35%
Age 0-44:
CFR=7.7%(male);
CFR=3.7%(female);
Age 45-74:
CFR=32.6%(male);
CFR=24.5%(female)
Age>=75,
CFR=64.7%(male);
CFR=63.6%(female)
>=60
5.30%
548
24.64%
SARS, severe acute respiratory syndrome; CFR, case fatality rate; R0,reproductive number
Table 2
Comparation of Major Pathological Characteristics between COVID-19 and SARS-CoV
COVID-19
SARS-CoV
Respiratory Tract
Pneumonia, ARDS
Pneumonia, ARDS
Gastrointestinal Tract
Diarrhea
Diarrhea
Kidney
Reported a 63% proteinuria, indicative of
renal impairment.
Focal necrosis and vasculitis of small veins in the renal
interstitial tissue.
Testis
Unknown, worthy of future investigation
Testes damage, germ cell destruction
Spleen
Unknown, worthy of future investigation
necrosis of the
spleen with severe lymphocyte depletion
Immune system
Reduction of CD4+T,CD8+T,
B cell,NK cell,especially CD4+T and CD8+
Reduction of CD4+T,CD8+T,Macrophages, DCs,NKCs cells;
Increased size of macrophages
Cytokines & chemokines Release
higher value of IL-6, IL-10
IL-6,TNF-alpha,IL-2,IL-5,CXCL10,CCL2,CCL3,CCL5
ARDS, acute respiratory distress syndrome; DCs,dendritic cells; NKCs,natural killer cells;
Figure 1. ACE2, L-SIGN(CLEC4M), DC-SIGN(CD209) Protein & RNA expression in organs in
Protein Atlas
A. ACE2, L-SIGN(CLEC4M), DC-SIGN(CD209) gene expression in organs classified by gender;
B. ACE2 (the Co-receptor of COVID-19 and SARS-CoV) Protein & RNA expression in organs in
Protein Atlas;
C. L-SIGN(CLEC4M, alternative SARS-CoV receptors) Protein & RNA expression in organs in
Protein Atlas;
D. DC-SIGN(CD209, alternative SARS-CoV receptors) Protein & RNA expression in organs in
Protein Atlas;
Figure 1
A
B
C
D
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The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2’s molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.
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The World Health Organisation declared Covid-19 as a pandemic on 11th March 2020. The main approach to tackle Covid-19 worldwide is to screen and provide supportive care to patients. For screening purpose RT-qPCR- based test are used as an initial detections assay. The test is expensive, time consuming and not suitable for mass scale screening/ confirmation requirement. A recent advancement is development of Immunoassay procedures (liquid Phase tests or bed side 10-20 minute strip test). In order to help and accelerate bringing life to normal after lock down, Pakistan is in dire need to develop and adopt the immunoassay procedures for mass scale screening and confirmation of COVID-19 infection. It is cheap and easy to perform without a lab requirement.
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An outbreak of severe acute respiratory syndrome (SARS), an infectious disease attributed to a novel coronavirus, occurred in Singapore during the first quarter of 2003 and led to 204 patients with diagnosed illnesses and 26 deaths by May 2, 2003. Twenty-one percent of these patients required admission to the medical intensive care unit. During this period, the Center for Forensic Medicine, Health Sciences Authority, Singapore, performed a total of 14 postmortem examinations for probable and suspected SARS. Of these, a total of 8 were later confirmed as SARS infections. Our series documents the difficulties encountered at autopsy during the initial phases of the SARS epidemic, when the pattern of infection and definitive diagnostic laboratory criteria were yet to be established. Autopsies were performed by pathologists affiliated with the Center for Forensic Medicine, Health Sciences Authority, Singapore. Tissue was accessed and read at the Tan Tock Seng Hospital, Singapore, and at the Armed Forces Institute of Pathology, Washington, DC. Autopsy tissue was submitted to the Virology Department, Singapore General Hospital, for analysis, and in situ hybridization for the SARS coronavirus was carried out at the National Institute of Infectious Diseases, Tokyo, Japan. Thirteen of 14 patients showed features of diffuse alveolar damage. In 8 patients, no precipitating etiology was identified, and in all of these patients, we now have laboratory confirmation of coronavirus infection. Two of the 8 patients presented at autopsy as sudden unexpected deaths, while the remaining 6 patients had been hospitalized with varying lengths of stay in the intensive care unit. In 3 patients, including the 2 sudden unexpected deaths, in situ hybridization showed the presence of virally infected cells within the lung. In 4 of the 8 SARS patients, pulmonary thromboemboli were also recognized on gross examination, while one patient had marantic cardiac valvular vegetations. It is unfortunate that the term atypical pneumonia has been used in conjunction with SARS. Although nonspecific by itself, the term does not accurately reflect the underlying dangers of viral pneumonia, which may progress rapidly to acute respiratory distress syndrome. We observed that the clinical spectrum of disease as seen in our autopsy series included sudden deaths. This is a worrisome finding that illustrates that viral diseases will have a spectrum of clinical presentations and that the diagnoses made for such patients must incorporate laboratory as well as clinical data.