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Molecular immune pathogenesis and diagnosis of COVID-19

Xiaowei Li a, b, Manman Geng a, b, Yizhao Peng a, b, Liesu Meng a, b, *, Shemin Lu a, b, *
a
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi,
710061, China
b
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, Shaanxi, 710061, China

a r t i c l e i n f o a b s t r a c t

Article history: Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan,
Received 24 February 2020 China, in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-
Received in revised form CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic
1 March 2020
coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-
Accepted 1 March 2020
Available online xxx
CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In
this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss
current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base
Keywords:
Coronavirus
of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering
SARS-CoV-2 novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.
SARS-CoV © 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article
MERS-CoV under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Pathogenesis

1. Introduction the World Health Organization (WHO) announced that COVID-19

Novel coronavirus-induced pneumonia, which was named as
coronavirus disease 2019 (COVID-19) by the WHO on the February
11, 2020, has rapidly increased in epidemic scale since it first
appeared in Wuhan, China, in December 2019 [1]. On the same day,
the international virus classification commission announced that
the novel coronavirus was named as severe acute respiratory syn-
drome coronavirus 2 (SARS-CoV-2). COVID-19 is not the first severe
respiratory disease outbreak caused by the coronavirus. Just in the
past two decades, coronaviruses have caused three epidemic dis-
eases, namely, COVID-19, severe acute respiratory syndrome (SARS)
and Middle East respiratory syndrome (MERS) [2]. At present, the
cases of COVID-19 have been found in many countries around the
world [3]. According to the latest data, up to the March 1, 2020, the
number of confirmed cases in China reached 79,968, of which 2,873
were dead, and 41,681 were cured. In addition to China, the number
of confirmed cases in other countries also reached 7,041, of which
105 were dead, and 459 were cured. On the 31st of January 2020,
* Corresponding authors at: Department of Biochemistry and Molecular Biology,
School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center,
Xi’an, Shaanxi, 710061, China.
E-mail addresses: mengliesu@xjtu.edu.cn (L. Meng), lushemin@xjtu.edu.cn
(S. Lu).
Peer review under responsibility of Xi’an Jiaotong University.
was listed as the Public Health Emergency of International
Concern (PHEIC), meaning that it may pose risks to multiple
countries and requires a coordinated international response. The
review tries to explain the molecular immune pathogenesis and
diagnosis of COVID-19 and provide a reference for the prevention
and drug development of SARS-CoV-2 infection, based on the
recent research progress of SARS-CoV-2 and the knowledge from
researches on SARS-CoV and MERS-CoV.
2. Virology of SARS-CoV-2
Coronaviruses are enveloped viruses with a positive sense
single-stranded RNA genome (26e32 kb) [4]. Four coronavirus
genera (a, b, g, d) have been identified so far, with human coro-
naviruses (HCoVs) detected in the a coronavirus (HCoV-229E and
NL63) and b coronavirus (MERS-CoV, SARS-CoV, HCoV-OC43 and
HCoV-HKU1) genera [5]. In late December 2019, patients present-
ing with cough, fever, and dyspnea with acute respiratory distress
syndrome (ARDS) due to an unidentified microbial infection were
reported in Wuhan, China. Virus genome sequencing of five pa-
tients with pneumonia hospitalized from December 18 to
December 29, 2019, revealed the presence of a previously unknown
b-CoV strain in all of them [6]. This isolated novel b-CoV shows 88%
identity to the sequence of two bat-derived severe acute respira-
tory syndromes (SARS)-like coronaviruses, bat-SL-CoVZC45 and

https://doi.org/10.1016/j.jpha.2020.03.001
2095-1779/© 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.
org/licenses/by-nc-nd/4.0/).

Please cite this article as: X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://
doi.org/10.1016/j.jpha.2020.03.001
2 X. Li et al. / Journal of Pharmaceutical Analysis xxx (xxxx) xxx

bat-SL-CoVZXC21, and about 50% identity to the sequence of MERS-
CoV [6]. The novel b-CoV was then named “SARS-CoV-2” by the
International Virus Classification Commission. The phylogenetic
tree of SARS-like coronaviruses complete genome sequences is
clearly depicted in Fig. 1A.
The genome of SARS-CoV-2 is similar to that of typical CoVs and
contains at least ten open reading frames (ORFs). The first ORFs
(ORF1a/b), about two-thirds of viral RNA, are translated into two
large polyproteins. In SARS-CoV and MERS-CoV, two polyproteins,
pp1a and pp1ab, are processed into 16 non-structural proteins
(nsp1-nsp16), which form the viral replicase transcriptase complex
[7]. Those nsps rearrange membranes originating from the rough

Fig. 1. The phylogenetic tree of SARS-like coronaviruses complete genome sequences and genome of SARS-CoV, MERS-CoV and SARSCoV- 2.
(A) This phylogeny shows evolution of SARS-like b-coronaviruses including samples from human (n ¼ 20), bat (n ¼ 22), civet (n ¼ 3) and pangolin (n ¼ 6). The phylogenetic tree of
complete genome sequences of coronaviruses was obtained and analyzed with Nextstrain (https://github.com/blab/sars-like-cov). (B) Coronaviruses form enveloped and spherical
particles of 100e160 nm in diameter. They contain a positivesense single stranded RNA (ssRNA) genome of 26e32 kb in size. In SARS-CoV, MERS-CoV and SARS-CoV-2, the 50 -
terminal two-thirds of the genome ORF1a/b encodes polyproteins, which form the viral replicase transcriptase complex. The other ORFs on the one-third of the genome encode four
main structural proteins: spike (S), envelope (E), nucleocapsid (N) and membrane (M) proteins, as well as several accessory proteins.

Please cite this article as: X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://
doi.org/10.1016/j.jpha.2020.03.001
 X. Li et al. / Journal of Pharmaceutical Analysis xxx (xxxx) xxx
endoplasmic reticulum (RER) into double-membrane vesicles
where viral replication and transcription occur [8,9]. The other
ORFs of SARS-CoV-2 on the one-third of the genome encode four
main structural proteins: spike (S), envelope (E), nucleocapsid (N)
and membrane (M) proteins, as well as several accessory proteins
with unknown functions which do not participate in viral replica-
tion (Fig. 1B).
Several groups of scientists in China have all discovered that
SARS-CoV-2, just like SARS-CoV, requires the angiotensin-
converting enzyme 2 (ACE2) [1] as a receptor to enter cells [10].
The binding of the virus with host cell receptors is a significant
determinant for the pathogenesis of infection. SARS-CoV most
likely originated in bats [11]and adapted to non-bat ACE2 variants
as it crossed species to infect humans [12]. Dipeptidyl peptidase 4
(DPP4, also known as CD26) was identified as a functional receptor
for MERS-CoV, because the receptor-binding S1 domain of the
MERS-CoV spike protein was copurified with DPP4 specifically from
lysates of susceptible Huh-7 cells [13]. MERS-CoV can bind DPP4
from multiple species, which promotes the transmission to humans
and other species, and infection of cells from a large number of
species [14]. A better understanding of the relative effects of re-
ceptor binding and protease action will help predict whether spe-
cific zoonotic coronaviruses infect humans and the possibility of
adaptation.
3. Pathogenesis of COVID-19
Patients with COVID-19 show clinical manifestations including
fever, nonproductive cough, dyspnea, myalgia, fatigue, normal or
decreased leukocyte counts, and radiographic evidence of pneu-
monia [15], which are similar to the symptoms of SARS-CoV and
MERS-CoV infections [16]. Hence, although the pathogenesis of
COVID-19 is poorly understood, the similar mechanisms of SARS-
CoV and MERS-CoV still can give us a lot of information on the
pathogenesis of SARS-CoV-2 infection to facilitate our recognition
of COVID-19.
3.1. Coronavirus entry and replication
Coronavirus S protein has been reported as a significant deter-
minant of virus entry into host cells [2]. The envelope spike
glycoprotein binds to its cellular receptor, ACE2 for SARS-CoV [10]
and SARS-CoV-2 [17], CD209L(a C-type lectin, also called L-SIGN)
for SARS-CoV [18], DPP4 for MERS-CoV [13]. The entry of SARS-CoV
into cells was initially identified to be accomplished by direct
membrane fusion between the virus and plasma membrane [19].
Belouzard et al. [20] found that a critical proteolytic cleavage event
occurred at SARS-CoV S protein at position (S20 ) mediated the
membrane fusion and viral infectivity. MERS-CoV also has evolved
an abnormal two-step furin activation for membrane fusion [21].
Besides membrane fusion, the clathrin-dependent and -indepen-
dent endocytosis mediated SARS-CoV entry too [22,23]. After the
virus enters the cells, the viral RNA genome is released into the
cytoplasm and is translated into two polyproteins and structural
proteins, after which the viral genome begins to replicate [5]. The
newly formed envelope glycoproteins are inserted into the mem-
brane of the endoplasmic reticulum or Golgi, and the nucleocapsid
is formed by the combination of genomic RNA and nucleocapsid
protein. Then, viral particles germinate into the endoplasmic
reticulum-Golgi intermediate compartment (ERGIC). At last, the
vesicles containing the virus particles then fuse with the plasma
membrane to release the virus [2].
Please cite this article as: X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://
doi.org/10.1016/j.jpha.2020.03.001
3
3.2. Antigen presentation in coronavirus infection
While the virus enters the cells, its antigen will be presented to
the antigen presentation cells(APC), which is a central part of the
body’s anti-viral immunity. Antigenic peptides are presented by
major histocompatibility complex (MHC; or human leukocyte an-
tigen (HLA) in humans) and then recognized by virus-specific
cytotoxic T lymphocytes (CTLs). Hence, the understanding of anti-
gen presentation of SARS-CoV-2 will help our comprehension of
COVID-19 pathogenesis. Unfortunately, there is still lack of any
report about it, and we can only get some information from pre-
vious researches on SARS-CoV and MERS-CoV. The antigen pre-
sentation of SARS-CoV mainly depends on MHC I molecules [24],
but MHC II also contributes to its presentation. Previous research
shows numerous HLA polymorphisms correlate to the susceptibil-
ity of SARS-CoV, such as HLA-B*4601, HLA-B*0703, HLA-DR
B1*1202 [25] and HLA-Cw*0801 [26], whereas the HLA-DR0301,
HLA-Cw1502 and HLA-A*0201 alleles are related to the protec-
tion from SARS infection [27]. In MERS-CoV infection, MHC II
molecules, such as HLA-DRB1*11:01 and HLA-DQB1*02:0, are
associated with the susceptibility to MERS-CoV infection [28]. Be-
sides, gene polymorphisms of MBL (mannose-binding lectin)
associated with antigen presentation are related to the risk of SARS-
CoV infection [29]. These researches will provide valuable clues for
the prevention, treatment, and mechanism of COVID-19.
3.3. Humoral and cellular immunity
Antigen presentation subsequently stimulates the body’s hu-
moral and cellular immunity, which are mediated by virus-specific
B and T cells. Similar to common acute viral infections, the antibody
profile against SARS-CoV virus has a typical pattern of IgM and IgG
production. The SARS-specific IgM antibodies disappear at the end
of week 12, while the IgG antibody can last for a long time, which
indicates IgG antibody may mainly play a protective role [30], and
the SARS-specific IgG antibodies primarily are S-specific and N-
specific antibodies [2]. Comparing to humoral responses, there are
more researches on the cellular immunity of coronavirus. The latest
report shows the number of CD4þ and CD8þ T cells in the periph-
eral blood of SARS-CoV-2-infected patients significantly is reduced,
whereas its status is excessive activation, as evidenced by high
proportions of HLA-DR (CD4 3.47%) and CD38 (CD8 39.4%) double-
positive fractions [31]. Similarly, the acute phase response in pa-
tients with SARS-CoV is associated with severe decrease of CD4þ T
and CD8þ T cells. Even if there is no antigen, CD4þ and CD8þ
memory T cells can persist for four years in a part of SARS-CoV
recovered individuals and can perform T cell proliferation, DTH
response and production of IFN-g [32]. Six years after SARS-CoV
infection, specific T-cell memory responses to the SARS-CoV S
peptide library could still be identified in 14 of 23 recovered SARS
patients [33]. The specific CD8þ T cells also show a similar effect on
MERS-CoV clearance in mice [34]. These findings may provide
valuable information for the rational design of vaccines against
SARS-CoV-2.
3.4. Cytokine storm in COVID-19
The report in Lancet shows ARDS is the main death cause of
COVID-19. Of the 41 SARS-CoV-2-infected patients admitted in the
early stages of the outbreak, six died from ARDS [15]. ARDS is the
common immunopathological event for SARS-CoV-2, SARS-CoV
and MERS-CoV infections [31]. One of the main mechanisms for
ARDS is the cytokine storm, the deadly uncontrolled systemic in-
flammatory response resulting from the release of large amounts of
pro-inflammatory cytokines (IFN-a, IFN-g, IL-1b, IL-6, IL-12, IL-18,
4 X. Li et al. / Journal of Pharmaceutical Analysis xxx (xxxx) xxx
IL-33, TNF-a, TGFb, etc.) and chemokines (CCL2, CCL3, CCL5, CXCL8,
CXCL9, CXCL10, etc.) by immune effector cells in SARS-CoV infec-
tion [15,35e37]. Similar to those with SARS-CoV, individuals with
severe MERS-CoV infection show elevated levels of IL-6, IFN-a, and
CCL5, CXCL8, CXCL-10 in serum compared to those with the mild-
moderate disease [38]. The cytokine storm will trigger a violent
attack by the immune system to the body, cause ARDS and multiple
organ failure, and finally lead to death in severe cases of SARS-CoV-
2 infection, just like what occurs in SARS-CoV and MERS-CoV
infection [31].
3.5. Coronavirus immune evasion
To better survive in host cells, SARS-CoV and MERS-CoV use
multiple strategies to avoid immune responses. The evolutionarily
conserved microbial structures called pathogen-associated molec-
ular patterns (PAMPs) can be recognized by pattern recognition
receptors (PRRs). However, SARS-CoV and MERS-CoV can induce
the production of double-membrane vesicles that lack PRRs and
then replicate in these vesicles, thereby avoiding the host detection
of their dsRNA [39]. IFN-I(IFN-a and IFN-b) has a protective effect
on SARS-CoV and MERS-CoV infection, but the IFN-I pathway is
inhibited in infected mice [40,41]. Accessory protein 4a of MERS-
CoV may block the induction of IFN at the level of MDA5 activa-
tion through direct interaction with double-stranded RNA [42].
Besides, ORF4a, ORF4b, ORF5, and membrane proteins of MERS-
CoV inhibit nuclear transport of IFN regulatory factor 3 (IRF3) and
activation of IFN b promoter [43]. The antigen presentation can also
be affected by the coronavirus. For example, gene expression
related to antigen presentation is down-regulated after MERS-CoV
infection [44]. Therefore, destroying the immune evasion of SARS-
CoV-2 is imperative in its treatment and specific drug development.
4. Diagnosis of COVID-19
Clinical diagnosis of COVID-19 is mainly based on epidemio-
logical history, clinical manifestations and some auxiliary exami-
nations, such as nucleic acid detection, CT scan, immune
identification technology (Point-of-care Testing (POCT) of IgM/IgG,
enzyme-linked immunosorbent assay (ELISA)) and blood culture.
However, the clinical symptoms and signs of patients infected with
SARS-CoV-2 are highly atypical, including respiratory symptoms,
cough, fever, dyspnea, and viral pneumonia. Therefore, auxiliary
examinations are necessary for the diagnosis of COVID-19, just as
the epidemiological history.
4.1. Nucleic acid detection technology
The two commonly used nucleic acid detection technologies for
SARS-CoV-2 are real-time quantitative polymerase chain reaction
(RT-qPCR) and high-throughput sequencing. The authoritative
identification method for SARS-CoV-2 is virus blood culture and
high-throughput sequencing of the whole genome [1]. However,
the application of high-throughput sequencing technology in
clinical diagnosis is limited because of its equipment dependency
and high cost. So RT-qPCR is the most common, effective and
straightforward method for detecting pathogenic viruses in respi-
ratory secretions and blood [45].
After the outbreak of SARS-CoV-2 in China, many companies
soon launched RT-qPCR test kits for clinical diagnosis. The Chinese
Center for Disease Control and Prevention (China CDC) recom-
mends the use of specific primers and probes in the ORF1ab and N
gene regions for SARS-CoV-2 detection by RT-qPCR. The patient is
defined as having a laboratory-confirmed infection when both
targets are positive (http://ivdc.chinacdc.cn/kyjz/202001/
Please cite this article as: X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://
doi.org/10.1016/j.jpha.2020.03.001
t20200121_211337.html). Chu et al. [46] described two 1-step RT-
qPCR assays (TaqMan-based fluorescence signal) to detect two
different regions (ORF1b and N) of the viral genome separately. The
negative control samples were all confirmed as negative ones,
while samples from two SARS-CoV-2 infected patients were
confirmed as positive ones in respiratory specimens by this
method. Another study showed that the positive rate of SARS-CoV-
2 was 91.7% (11/12) in the patients’ self-collected saliva by using RT-
qPCR (non-probes SYBR based fluorescence signal), which suggests
that saliva is a promising non-invasive specimen for the diagnosis,
monitoring, and infection control of patients with SARS-CoV-2
infection [47]. RT-qPCR detection also showed high sensitivity
and specificity for SARS-CoV and MERS-CoV infection [48]. How-
ever, five patients with negative results of RT-qPCR for SARS-CoV-2
may present with positive chest CT findings, and repeated swab
tests (RT-qPCR) eventually confirmed that all patients were infec-
ted by SARS-CoV-2 [49]. The detection of SARS-CoV using RT-qPCR
can only achieve a sensitivity of 50%e79%, depending on the pro-
tocol used the sample type and number of clinical specimens
collected [50]. Thus, it is essential to improve the detection rate of
RT-qPCR for SARS-CoV-2 infection. Besides, RT-qPCR has some
other shortcomings, including certain biological safety hazards
brought by the retention and operation of patient samples,
cumbersome nucleic acid detection operations, and long waiting
time for results.
4.2. CT scans and other diagnostic methods
For the diagnosis of COVID-19, although RT-qPCR is specific, its
false-negative rate cannot be ignored because of the severe con-
sequences of missed diagnosis. So many clinicians proposed CT
scans should be one necessary auxiliary diagnostic method because
it is more sensitive. For individuals with a high clinical suspicion of
SARS-CoV-2 infection with negative RT-qPCR screening, a combi-
nation of repeated RT-qPCR tests and chest CT scan may be helpful.
Especially the high-resolution CT (HRCT) for the chest is essential
for early diagnosis and evaluation of disease severity of patients
with SARS-CoV-2 [51]. Several studies have analyzed chest CT im-
ages of patients infected with SARS-CoV-2 [52,53]. The typical CT
images show bilateral pulmonary parenchymal ground-glass and
consolidative pulmonary opacities, sometimes with a rounded
morphology and a peripheral lung distribution. Lung involvement
with a peripheral predominance was also seen in patients with
SARS-CoV and MERS-CoV infections, and the chest CT showed that
disease progressed with ground-glass opacities and consolidation,
which is similar to that of SARS-CoV-2 infection [54,55]. According
to those findings, CT scans have a great clinical diagnostic value for
COVID-19, especially in the high prevalence area of SARS-CoV-2
infection. However, CT scans also have some shortcomings, such
as indistinguishability from other viral pneumonia and the hys-
teresis of abnormal CT imaging.
Given the shortcomings of the currently used nucleic acid
detection and CT scans for the diagnosis of COVID-19, clinical lab-
oratories should apply some immunological detection kits that
target viral antigens or antibodies as soon as possible. Currently,
POCT of IgM/IgG and ELISA kits for SARS-CoV-2 have been devel-
oped and pre-tested by some companies and have shown higher
detection rates than nucleic acid detection, but there is still no
product or published article. The sensitivity of SARS-CoV N-based
IgG ELISA (94.7%) is significantly higher than that of SARS-CoV S-
based IgG ELISA (58.9%) [48], but the sensitivity of SARS-CoV-2 IgG/
IgM remains to be studied. Hence, developing other sensitive and
specific auxiliary methods is necessary and urgent for the diagnosis
of COVID-19.
 X. Li et al. / Journal of Pharmaceutical Analysis xxx (xxxx) xxx
5. Current treatment strategies for COVID-19
Just like SARS-CoV and MERS-CoV [2,56], there is currently no
clinically proven specific antiviral agent available for SARS-CoV-2
infection. The supportive treatment, including oxygen therapy,
conservation fluid management, and the use of broad-spectrum
antibiotics to cover secondary bacterial infection, remains to be
the most important management strategy [15]. According to the
research on molecular mechanisms of coronavirus infection [57]
and the genomic organization of SARS-CoV-2 [6], there are several
potential therapeutic targets to repurpose the existing antiviral
agents or develop effective interventions against this novel
coronavirus.
5.1. Virally targeted inhibitors
Remdesivir, an adenosine analogue that can target the RNA-
dependent RNA polymerase and block viral RNA synthesis, has
been a promising antiviral drug against a wide array of RNA viruses
(including SARS/MERS-CoV) infections in cultured cells [58], mice
[59] and nonhuman primate models [60,61]. The Washington
Department of Health administrated remdesivir intravenously first
and found that remdesivir might have potential protection from
SARS-CoV-2 infection [62]. Then remdesivir and chloroquine have
been demonstrated to inhibit SARS-CoV-2 effectively in vitro [63].
Hence, other nucleoside analogues, such as favipiravir, ribavirin and
galidesivir [56,64], may be potentially clinically applicable against
SARS-CoV-2. Chymotrypsin-like (3C-like protease, 3CLpro) and
papain-like protease (PLP) are non-structural proteins, which have
an essential function for coronaviral replication and can inhibit the
host innate immune responses [65]. So 3CLpro inhibitors, such as
cinanserin [66] and flavonoids [67], and PLP inhibitors, such as
diarylheptanoids [68], are other attractive choices to fight against
SARS-CoV-2. ACE2 mediates SARS-CoV-2 entry into the cell as a
functional receptor of coronaviruses. So blocking the binding of S
protein with ACE2 is also a meaningful strategy against SARS-CoV-2
infection [10].
5.2. Antibody and plasma therapy
It has also been reported that there are many convalescent pa-
tients donating plasma against SARS-CoV-2, just as SARS-CoV [69]
and MERS-CoV [70] trials. It has preliminary acquired favorable
results in acute, severe SARS-CoV-2 patients. Moreover, the gen-
eration of recombinant human monoclonal antibody (mAb) is a
fairly straightforward path to neutralize SARS-CoV. CR3022, a SARS
coronavirus-specific human monoclonal antibody, can bind
potently with the receptor-binding domain(RBD) of SARS-CoV-2
and has the potential to be developed as candidate therapeutics
of SARS-CoV-2 infections [71]. Other monoclonal antibodies
neutralizing SARS-CoV, such as m396, CR3014, could be an alter-
native for the treatment of SARS-CoV-2 [72].
5.3. Vaccines
Effective SARS-CoV-2 vaccines are essential for reducing disease
severity, viral shedding and transmission, thus helping to control
the coronavirus outbreaks. There are several vaccination strategies
against SARS-CoV, MERS-CoV tested in animals, including a live-
attenuated virus, viral vectors, inactivated virus, subunit vaccines,
recombinant DNA, and proteins vaccines [73]. These studies are in
progress, but it requires months to years to develop the vaccines for
SARS-CoV-2.
Currently, there may be many promising targets for SARS-CoV-2,
but more laboratory and clinical evidence still should be explored.
Please cite this article as: X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://
doi.org/10.1016/j.jpha.2020.03.001
5
The WHO is working with Chinese scientists to launch more than
80 clinical trials on potential treatments for SARS-CoV-2. Tradi-
tional Chinese medicine seems to have some effects in the sup-
portive treatments. Some new pharmaceutical drugs, including HIV
drugs and stem cells, were testified in those clinical trials.
6. Conclusion
In conclusion, the occurrence and development of SARS-CoV-2
depend on the interaction between the virus and the individual’s
immune system. Viral factors include virus type, mutation, viral
load, viral titer, and viability of the virus in vitro. The individual’s
immune system factors include genetics (such as HLA genes), age,
gender, nutritional status, neuroendocrine-immune regulation, and
physical status. These factors all contribute to whether an indi-
vidual is infected with the virus, the duration and severity of the
disease, and the reinfection. In the early stages of the epidemic,
accurate diagnosis helps control the spread of the disease. It is
imperative to develop new, safe, accurate, fast and simple new
technologies for detecting SARS-CoV-2. Of course, physicians will
intentionally intervene in the two factors to make them develop
into a direction beneficial to human health, which can help patients
recover as soon as possible. However, it must not be considered that
medical intervention can achieve a 100% curative effect.
Conflicts of interest
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (project No.81970029) and Fundamental
Research Funds for the Central Universities of China (The Emer-
gency Projects on COVID-19. project No.xzy032020042). We
sincerely thank the individuals who contributed to this work
including Xudong Yang, Wenhua Zhu, Jing Xu, Fumeng Huang,
Muhammad Saadiq Khan, Jiajun Ren, and Xipeng Wang.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.jpha.2020.03.001.
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Another random document with
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 Pyscomancy, or Sciomancy,

An art among the ancients of raising or calling up the manes or souls

of deceased persons, to give intelligence of things to come. The witch
who conjured up the soul of Samuel, to foretel Saul the event of the
battle he was about to give, did so by Sciomancy.

Rhabdomancy,

Was an ancient method of divination, performed by means of rods or

staves. St. Jerome mentions this kind of divination in his
Commentary on Hosea, chap. vi. 12.; where the prophet says, in the
name of God: My people ask counsel at their stocks; and their staff
declareth unto them: which passage that father understands of the
Grecian Rhabdomancy.
The same is met with again in Ezekiel, xxi. 21, 22. where the
prophet says: For the king of Babylon stood at the parting of the
way, at the head of the two ways, to use divination; he made his
arrows bright; or, as St. Jerome renders it, he mixed his arrows; he
consulted with images; he looked in the liver.
If it be the same kind of divination that is alluded to in these two
passages, Rhabdomancy must be the same kind of superstition with
Belomancy. These two, in fact, are generally confounded. The
Septuagint themselves translate ‫ חצים‬of Ezekiel, by ῥαβδος, a rod;
though in strictness it signifies an arrow. So much however is
certain, that the instruments of divination mentioned by Hosea are
different from those of Ezekiel. In the former it is ‫ עצו‬etso, ‫מקלו‬
maklo, his wood, his staff: in the latter ‫ חצים‬hhitism, arrows. Though
it is possible they might use rods or arrows indifferently; or the
military men might use arrows and the rest rods.
By the laws of the Frisones, it appears that the ancient inhabitants
of Germany practised Rhabdomancy. The Scythians were likewise
acquainted with the use of it: and Herodotus observes, lib. vi. that
the women among the Alani sought and gathered together fine
straight wands or rods, and used them for the same superstitious
purposes.
 Among the various other kinds of divination, not here mentioned,
may be enumerated: Chiromancy, performed with keys;
Alphitomancy or Aleuromancy, by flour; Keraunoscopia, by the
consideration of thunder; Alectromancy, by cocks; Lithomancy, by
stones; Eychnomancy, by lamps; Ooscopy, by eggs; Lecanomancy,
by a basin of water; Palpitatim, Salisatio, παλμος, by the pulsation
or motion of some member, &c. &c. &c.
All these kinds of divination have been condemned by the fathers
of the Church, and Councils, as supposing some compact with the
devil. Fludd has written several treatises on divination, and its
different species; and Cicero has two books of the divination of the
ancients, in which he confutes the whole system. Cardan also, in his
4th Book de Sapientia, describes every species of them.
 ORACLE.

The word oracle admits, under this head, of two significations:

first, it is intended to express an answer, usually couched in very
dark and ambiguous terms, supposed to be given by demons of old,
either by the mouths of their idols, or by those of their priests, to
those who consulted them on things to come. The Pythian[36] was
always in a rage when she gave oracles.
Ablancourt observes that the study or research of the meaning of
Oracles was but a fruitless thing; and they were never understood
until they were accomplished. It is related by Historians, that Crœsus
was tricked by the ambiguity and equivocation of the oracle.
Κροισος Άλυν διαβας μεγαλην αρχην καταλνσει. rendered thus in
Latin:—
Crœsus Halym superans magnam pervertet opum vim.
Oracle is also used for the Demon who gave the answer, and the
place where it was given. (Vide Demon.)
The principal oracles of antiquity are that of Abæ, mentioned by
Herodotus; that of Amphiarus; that of the Branchidæ, at Didymus;
that of the Camps, at Lacedemon; that of Dodona; that of Jupiter
Ammon; that of Nabarca, in the Country of the Anariaci, near the
Caspian sea; that of Trophonius, mentioned by Herodotus; that of
Chrysopolis; that of Claros, in Ionia; that of Mallos; that of Patarea;
that of Pella, in Macedonia; that of Phaselides, in Cilicia; that of
Sinope, in Paphlagonia; that of Orpheus’s head, mentioned by
Philostratus in his life of Appolonius, &c. But, of all others, the oracle
of Apollo Pythius, at Delphi, was the most celebrated; it was, in
short, consulted always as a dernier ressort, in cases of emergency,
by most of the princes of those ages.—Mr. Bayle observes, that at
first, it gave its answers in verse; and that at length it fell to prose, in
consequence of the people beginning to laugh at the poorness of its
versification.
Among the more learned, it is a pretty general opinion that all the
oracles were mere cheats and impostures; calculated either to serve
the avaricious ends of the heathen priests, or the political views of
the princes. Bayle positively asserts, they were mere human artifices,
in which the devil had no hand. In this opinion he is strongly
supported by Van Dale, a Dutch physician, and M. Fontenelle, who
have expressly written on the subject.
There are two points at issue on the subject of oracles; viz. whether
they were human or diabolical machines; and whether or not they
ceased upon the publication and preaching of the Gospel?
Plutarch wrote a treatise on the ceasing of some oracles: and Van
Dale has a volume to prove that they did not cease at the coming of
Christ; but that many of them had ceased long before the coming of
that time, and that others held out till the fall of Paganism, under the
Empire of Theodosius the Great, and when it was dissipated, these
institutions could no longer resist.
Van Dale was answered by a German, one Mœbius, professor of
Theology, at Leipsic, in 1685. Fontenelle espoused Van Dale’s
system, and improved upon it in his history of oracles; wherein he
exposed the weakness of the argument used by many writers in
behalf of Christianity, drawn from the ceasing of oracles.
Balthus, a learned Jesuit, answered both Van Dale and Fontenelle.
He labours to prove, that there were real oracles, and such as can
never be attributed to any artifices of the Priests or Priestesses; and
that several of these became silent in the first ages of the Church,
either by the coming of Jesus Christ, or by the prayers of the Saints.
This doctrine is confirmed by a letter from Father Bouchet,
missionary to Father Balthus; wherein it is declared, that what
Father Balthus declares of the ancient oracles, is experimented every
day in the Indies.
It appears, according to Bouchet, that the devil still delivers
oracles in the Indies; and that, not by idols, which would be liable to
imposture, but by the mouths of the priests, and sometimes of the
bye-standers; it is added that these oracles, too, cease, and the devil
becomes mute in proportion as the Gospel is preached among them.
 It was Eusebius who first endeavoured to persuade the christians
that the coming of Jesus Christ had struck the oracles dumb; though
it appears from the laws of Theodosius, Gratian, and Valentinian,
that the oracles were still consulted as far back as the year 358.
Cicero says the oracles became dumb, in proportion as people,
growing less credulous, began to suspect them for cheats.
Two reasons are alleged by Plutarch for the ceasing of oracles: the
one was Apollo’s chagrin, who, it seems, “took it in dudgeon,” to be
interrogated about so many trifles. The other was, that in proportion
as the genii, or demons, who had the management of the oracles,
died and became extinct, the oracles must necessarily cease. He adds
a third and more natural cause for the ceasing of oracles, viz. the
forlorn state of Greece, ruined and desolated by wars. For, in
consequence of this calamity, the smallness of the gains suffered the
priests to sink into a poverty and contempt too bare to cover the
fraud.
Most of the fathers of the church imagined it to be the devil that
gave oracles, and considered it as a pleasure he took to give dubious
and equivocal answers, in order to have a handle to laugh at them.
Vossius allows that it was the devil who spoke in oracles; but thinks
that the obscurity of his answers was owing to his ignorance as to the
precise circumstances of events. That artful and studied obscurity,
wherein, says he, answers were couched, shew the embarrassment
the devil was under; as those double meanings they usually bore
provided for the accomplishment. When the thing foretold did not
happen accordingly, the oracle, forsooth, was always misunderstood.
Eusebius has preserved some fragments of a Philosopher, called
Oenomaus, who, out of resentment for having been so often fooled
by the oracles, wrote an ample confutation of all their impertinences,
in the following strain: “When we come to consult thee,” says he to
Apollo, “if thou seest what is in the womb of futurity, why dost thou
use expressions that will not be understood? if thou dost, thou takest
pleasure in abusing us: if thou dost not, be informed of us, and learn
to speak more clearly. I tell thee, that if thou intendest an equivoque,
the Greek word whereby thou affirmedst that Crœsus should
overthrow a great Empire, was ill-chosen; and that it could signify
nothing but Crœsus’ conquering Cyrus. If things must necessarily
come to pass, why dost thou amuse us with thy ambiguities? What
dost thou, wretch as thou art, at Delphi; employed in muttering idle
prophesies!”
But Oenamaus is still more out of humour with the oracle for the
answer which Apollo gave the Athenians, when Xerxes was about to
attack Greece with all the strength of Asia. The Pythian declared, that
Minerva, the protectress of Athens, had endeavoured in vain to
appease the wrath of Jupiter; yet that Jupiter, in complaisance to his
daughter, was willing the Athenians should save themselves within
wooden walls; and that Salamis should behold the loss of a great
many children, dead to their mothers, either when Ceres was spread
abroad, or gathered together. At this Oenamaus loses all patience
with the Delphian god: “This contest,” says he, “between father and
daughter, is very becoming the deities! It is excellent, that there
should be contrary inclinations and interests in heaven! Poor wizard,
thou art ignorant who the children are that shall see Salamis perish;
whether Greeks or Persians. It is certain they must be either one or
the other; but thou needest not have told so openly that thou
knewest not which. Thou concealest the time of the battle under
these fine poetical expressions, either when Ceres is spread abroad,
or gathered together: and thou wouldst cajole us with such pompous
language! who knows not, that if there be a seafight, it must either be
in seed-time or harvest? It is certain it cannot be in winter. Let things
go how they will, thou wilt secure thyself by this Jupiter, whom
Minerva is endeavouring to appease. If the Greeks lose the battle,
Jupiter proved inexorable to the last; if they gain it, why then
Minerva at length prevailed.”
 OURAN, OR URAN, SOANGUS,

The name of an imaginary set of magicians in the island

Gromboccanore, in the East Indies.
The word implies men-devils; these people, it seems, having the
art of rendering themselves invisible, and passing where they please,
and, by these means, doing infinite mischief; for which reason the
people hate and fear them mortally, and always kill them on the spot
when they can take them.
In the Portuguese history, printed 1581, folio, there is mention of a
present made by the king of the island to a Portuguese officer, named
Brittio, ourans, with whom, it is pretended, he made incursions on
the people of Tidore, killed great numbers, &c.
To try whether in effect they had the faculty ascribed to them, one
of them was tied by the neck with a rope, without any possibility of
disengaging himself by natural means; yet in the morning it was
found he had slipped his collar. But that the king of Tidore might not
complain that Brittio made war on him with devils, it is said he
dismissed them at length, in their own island.
 DREAMS, &c.

The art of foretelling future events by dreams, is called

 Brizomancy.
Macrobius mentions five sorts of dreams, viz. 1st, vision; 2d, a
discovery of something between sleep and waking; 3d, a suggestion
cast into our fancy, called by Cicero, Vesum; 4th, an ordinary dream;
and 5th, a divine apparition or revelation in our sleep; such as were
the dreams of the prophets, and of Joseph, as also of the magi of the
East.
 Origin of Interpreting Dreams.
The fictitious art of interpreting dreams, had its origin among the
Egyptians and Chaldeans; countries fertile in superstitions of all
kinds. It was propagated from them to the Romans, who judging
some dreams worthy of observation, appointed persons on purpose
to interpret them.
The believers in dreams as prognostics of future events, bring
forward in confirmation of this opinion, a great variety of dreams,
which have been the forerunners of very singular events:—among
these are that of Calphurnia, the wife of Julius Cæsar, dreaming the
night before his death, that she saw him stabbed in the capitol: that
of Artorius, Augustus’s physician, dreaming before the battle of
Philippi, that his master’s camp was pillaged; that of the Emperor
Vespasian dreaming an old woman told him, that his good fortune
would begin when Nero should have a tooth drawn, which happened
accordingly.
Cæsar dreaming that he was committing incest with his mother,
was crowned Emperor of Rome; and Hippias the Athenian Tyrant,
dreaming the same, died shortly after, and was interred in his
mother earth. Mauritius the Emperor, who was slain by Phocas,
dreamed a short time previous to this event, that an image of Christ
that was fixed over the brazen gate of his palace, called him and
reproached him with his sins, and at length demanded of him
whether he would receive the punishment due to them in this world
or the next; and Mauritius answering in this, the image commanded
that he should be given, with his wife and children, into the hands of
Phocas. Whereupon Mauritius, awakening in great fear, asked
Phillipus, his son-in-law, whether he knew any soldier in the army
called Phocas, he answered that there was a commissary so called;
and Phocas became his successor, having killed his wife and five
children. Arlet, during her pregnancy by William the Conqueror,
dreamed that a light shone from her womb, that illumined all
England. Maca, Virgil’s mother, dreamed that she was delivered of a
laurel branch.
 The ridiculous infatuation of dreams is still so prominent, even
among persons whose education should inform them better, and
particularly among the fair sex, that a conversation seldom passes
among them, that the subject of some foolish inconsistent dream or
other, does not form a leading feature of their gossip. “I dreamed last
night,” says one, “that one of my teeth dropped out.”—“That’s a sign,”
replies another, “that you will lose a friend or some of your
relations.”—“I’m afraid I shall,” returns the dreamer, “for my cousin
(brother, or some other person connected with the family or its
interests,) is very ill,” &c.
 Opinions on the cause of dreams.
Avicen makes the cause of dreams to be an ultimate intelligence
moving the moon in the midst of that light with which the fancies of
men are illuminated while they sleep. Aristotle refers the cause of
them to common sense, but placed in the fancy. Averroes places it in
the imagination. Democritus ascribes it to little images, or
representations, separated from the things themselves. Plato, among
the specific and concrete notions of the soul. Albertus to the superior
influences which continually flow from the sky, through many
specific mediums. And some physicians attribute the cause of them
to vapours and humours, and the affections and cares of persons
predominant when awake; for, say they, by reason of the abundance
of vapours, which are exhaled in consequence of immoderate
feeding, the brain is so stuffed by it, that monsters and strange
chimera are formed, of which the most inordinate eaters and
drinkers furnish us with sufficient instances. Some dreams, they
assert, are governed partly by the temperature of the body, and
partly by the humour which mostly abounds in it; to which may be
added, the apprehensions which have preceded the day before; which
are often remarked in dogs, and other animals, which bark and make
a noise in their sleep. Dreams, they observe, proceeding from the
humours and temperature of the body, we see the choleric dreams of
fire, combats, yellow colours, &c.; the phlegmatic, of water, baths, of
sailing on the sea, &c.; the melancholics, of thick fumes, deserts,
fantasies, hideous faces, &c.; the sanguines, of merry feasts, dances,
&c. They that have the hinder part of their brain clogged with viscous
humours, called by physicians ephialtes incubus, or, as it is termed,
night-mare, imagine, in dreaming, that they are suffocated. And
those who have the orifice of their stomach loaded with malignant
humours, are affrighted with strange visions, by reason of those
venemous vapours that mount to the brain and distemper it.
Cicero tells a story of two Arcadians, who, travelling together,
came to Megara, a city of Greece, between Athens and Corinth,
where one of them lodged in a friend’s house, and the other at an
inn. After supper the person who lodged at the private house went to
bed, and falling asleep, dreamed that his friend at the inn appeared
to him, and begged his assistance, because the innkeeper was going
to kill him. The man immediately got out of bed much frightened at
the dream but recovering himself and falling asleep again, his friend
appeared to him a second time, and desired, that as he would not
assist him in time, he would take care at least not to let his death go
unpunished; that the innkeeper having murdered him, had thrown
his body into a cart and covered it with dung; he therefore begged
that he would be at the city gate in the morning, before the cart was
out. Struck with this new dream, he went early to the gate, saw the
cart, and asked the driver what was in it; the driver immediately fled,
the dead body was taken out of the cart, and the innkeeper
apprehended and executed.
 FATE.

Fate, in a general sense, denotes an inevitable necessity,

depending on some superior cause. It is a term much used among
the ancient philosophers. It is formed a fando, from speaking; and
primarily implies the same with effatum, i. e. a word or decree
pronounced by God; or a fixed sentence, whereby the deity has
prescribed the order of things, and allotted every person what shall
befal him. The Greeks called θμαρμενη, quasi, θρμος, nexus, a
change, or necessary series of things, indissolubly linked together;
and the moderns call it Providence. But independent of this sense of
the word, in which it is used sometimes to denote the causes in
nature, and sometimes the divine appointment, the word Fate has a
farther meaning, being used to express some kind of necessity or
other, or eternal designation of things, whereby all agents, necessary
as well as voluntary, are swayed and directed to their ends.
Some authors have divided Fate into Astrological and Stoical.
Astrological fate, denotes a necessity of things and events,
arising, as is supposed, from the influence and positions of the
heavenly bodies, which give law to the elements and mixed bodies, as
well as to the wills of men.
Stoical fate, or FATALITY, or FATALISM, is defined by Cicero, an
order or series of causes, in which cause is linked to cause, each
producing others; and in this manner all things flow from the one
prime cause. Chrysippus defines it a natural invariable succession of
all things, ab eterno, each involving the other. To this fate they
subject the very gods themselves. Thus the poet observes, that the
“parent of all things made laws at the beginning, by which he not
only binds other things, but himself.” Seneca also remarks, Eadem
necessitas et deos alligat. Irrevocabilis divina pariter et humana
cursit vehit. Ipse ille omnium conditor et rector scripsit quidam
fata, sed sequitur; semel scripsit, semper paret. This eternal series
of causes, the poets call μοιραι, and parcæ, or destinies.
By some later authors Fate is divided into Physical and divine.
The first, or Physical fate, is an order and series of physical causes,
appropriated to their effects. This series is necessary, and the
necessity is natural. The principal or foundation of this Fate is
nature, or the power and manner of acting which God originally gave
to the several bodies, elements, &c. By this Fate it is that fire warms;
bodies communicate motion to each other; the rising and falling of
the tides, &c. And the effects of this Fate are all the events and
phenomena in the universe, except such as arise from the human.
The second, or divine Fate, is what is more commonly called
Providence. Plato, in his Phædo, includes both these in one
definition; as intimating, that they were one and the same thing,
actively and passively considered. Thus, Fatum Est ratio quædam
divina, lexque naturæ comes, quæ transiri nequeat, quippe a causa
pendens, quæ superior sit quibusvis impedimentis. Though that of
Bœtius seems the clearer of the two:—Fatum, says he, est inhærens
rebus molilibus despositio per quam providentia suis quæque nectet
ordinibus.
 PHYSIOGNOMY[37], ΦΥΣΙΟΓΝΩΜΙΑ.

There seems to be something in Physiognomy, and it may perhaps

bear a much purer philosophy than these authors (see Note,) were
acquainted with. This, at least, we dare say, that of all the fanciful
arts of the ancients, fallen into disuse by the moderns, there is none
has so much foundation in nature as this. There is an apparent
correspondence, or analogy between the countenance and the mind;
the features and lineaments of the one are directed by the motions
and affections of the other: there is even a peculiar arrangement in
the members of the face, and a peculiar disposition of the
countenance, to each particular affection; and perhaps to each
particular idea of the mind. In fact, the language of the face
(physiognomy,) is as copious, nay, perhaps, as distinct and
intelligible, as that of the tongue, (speech.) Thanks to bounteous
nature, she has not confined us to one only method of conversing
with each other, and of learning each other’s thoughts; we have
several:—We do not wholly depend on the tongue, which may
happen to be bound; and the ear, which may be deaf:—but in those
cases we have another resource, viz. the Countenance and the Eye,
which afford us this further advantage, that by comparing the reports
of the tongue, (a member exceedingly liable to deceive,) with those of
the face, the prevarications of the former may be detected.
The foundation of Physiognomy is the different objects that
present themselves to the senses, nay, the different ideas that arise
on the mind, do make some impression on the spirits; and each an
impression correspondent or adequate to its cause,—each, therefore,
makes a different impression. If it be asked how such an impression
could be effected, it is easy to answer; in short, it is a consequence of
the economy of the Creator, who has fixed such a relation between
the several parts of the creation, to the end that we may be apprized
of the approach or recess of things hurtful or useful to us. Should this
not be philosophical enough for our purpose, take the manner of the
Cartesian language, thus: the animal spirits moved in the organ by
an object, continue their motion to the brain; from whence that
motion is propagated to this or that particular part of the body, as
is most suitable to the design of nature; having first made a proper
alteration in the face by means of its nerves, especially the
Pathetici and Motores Occulorum. See Dr. Gurther’s work, anno
1604.
The face here does the office of a dial-plate, and the wheels and
springs, inside the machine, putting its muscles in motion, shew
what is next to be expected from the striking part. Not that the
motion of the spirits is continued all the way by the impression of the
object, as the impression may terminate in the substance of the
brain, the common fund of the spirits; the rest Dr. Gurther imagines,
may be effected much after the same manner as air is conveyed into
the pipes of an organ, which being uncovered, the air rushes in; and
when the keys are let go, is stopped again.
Now, if by repeated acts, or the frequent entertaining of a private
passion or vice, which natural temperament has hurried, or custom
dragged on to, the face is often put in that posture which attends
such acts; the animal spirits will make such passages through the
nerves, (in which the essence of a habit consists,) that the face is
sometimes unalterably set in that posture, (as the Indian religious
are by a long continued sitting in strange postures in their pagods,)
or, at least, it falls, insensibly and mechanically, into that posture,
unless some present object distort it therefrom, or some
dissimulation hide it. This reason is confirmed by observation: thus
we see great drinkers with eyes generally set towards the nose; the
abducent muscles (by some called bibatorii, or bibatory muscles,)
being often employed to put them in that posture, in order to view
their beloved liquor in the glass, at the time of drinking. Thus, also,
lascivious persons are remarkable for the oculorum mobilis
petulantia, as Petronius calls it. Hence also we may account for the
Quaker’s expecting face, waiting the spirit to move him; the
melancholy face of most sectaries; the studious face of men of great
application of mind; revengeful and bloody men, like executioners in
the act; and though silence in a sort may awhile pass for wisdom, yet
sooner or later, St. Martin peeps through the disguise to undo all. “A
changeable face,” continues Dr. Gurther, “I have observed to show a
changeable mind, but I would by no means have what has been said
be understood as without exception; for I doubt not but sometimes
there are found men with great and virtuous souls under very
unpromising outsides.”
“Were our observations a little more strict and delicate, we might,
doubtless, not only distinguish habits and tempers, but also
professions. In effect, does there need much penetration to
distinguish the fierce looks of the veteran soldier, the contentious
look of the practised pleader, the solemn look of the minister of state,
or many others of the like kind?”
A very remarkable physiological anecdote has been given by De La
Place, in his “Pièces Interrestantes et peu connues.” Vol. iv. p. 8.
He was assured by a friend that he had seen a voluminous and
secret correspondence which had been carried on between Louis
XIV. and his favourite physician De la Chambre on this science: the
faith of the monarch seems to have been great, and the purpose to
which this correspondence tended was extraordinary indeed, and
perhaps scarcely credible. Who will believe that Louis XIV. was so
convinced of that talent, which De la Chambre attributed to himself,
of deciding merely by the physiognomy of persons, not only on the
real bent of their character, but to what employment they were
adapted, that the king entered into a secret correspondence to obtain
the critical notices of his physiognomist. That Louis XIV. should
have pursued this system, undetected by his own courtiers, is also
singular; but it appears by this correspondence, that this art
positively swayed him in his choice of officers and favourites. On one
of the backs of these letters De la Chambre had written, “If I die
before his majesty, he will incur great risk of making many an
unfortunate choice.”
This collection of Physiological correspondence, if it does really
exist, would form a curious publication. We, however, have heard
nothing of it.
De la Chambre was an enthusiastic physiognomist, as appears by
his works: “The Characters of the Passions,” four volumes in quarto;
“The art of Knowing Mankind;” and “the Knowledge of Animals.”
 Lavater quotes his “vote and interest” in behalf of his favourite
science. It is no less curious, however, to add, that Phillip Earl of
Pembroke, under James I., had formed a particular collection of
portraits, with a view to physiognomonical studies.
The great Prince of Condé was very expert in a sort of
Physiognomy which shewed the peculiar habits, motions, and
positions of familiar life, and mechanical employments. He would
sometimes lay wagers with his friends, that he would guess, upon the
Pont Neuf, what trade persons were of that passed by, from their
walk and air.
The celebrated Marshal Laudohn would have entered when young,
into the service of the great Frederick, King of Prussia; but that
monarch, with all his penetration, formed a very erroneous judgment
of the young officer, (as he himself found in the sequel,) and
pronounced that he would never do; in consequence of which
Laudohn entered into the service of the Empress-Queen, Maria
Theresa, and became one of the most formidable opponents of his
Prussian Majesty. Marshal Turrene was much more accurate in his
opinion of our illustrious John Duke of Marlborough, whose future
greatness he predicted, when he was serving in the French army as
Ensign Churchill, and known by the unmilitary name of the
“handsome Englishman.”
In the fine arts, moreover, we have seen no less accurate
predictions of future eminence. As the scholars of Rubens were
playing and jesting with each other, in the absence of their master,
one of them was accidentally thrown against a piece on which
Rubens had just been working, and a considerable part of it was
entirely disfigured. Another of the pupils set himself immediately to
repair it, and completed the design before his master returned.
Rubens, on reviewing his work, observed a change, and a difference
that surprised and embarrassed him. At last, suspecting that some
one had been busy, he demanded an explanation; adding, that the
execution was in so masterly a manner, that he would pardon the
impertinence on account of its merit. Encouraged by this declaration,
the young artist confessed, and explained the whole, pleading, that
his officiousness was merely to screen a comrade from his master’s
anger. Rubens answered, “if any one of my scholars shall excel me, it
will be yourself.” This pupil was the great Vandyck.
 Lavater, who revived physiognomy, has, unquestionably, brought
it to great perfection. But it may justly be doubted whether he is not
deceived in thinking that it may be taught like other sciences, and
whether there is not much in his system that is whimsical and
unfounded. Every man, however, has by nature, something of the
science, and nothing is more common than to suspect the man who
never looks his neighbour in the face. There is a degree of cunning in
such characters, which is always dangerous, but by no means new.
“There is a wicked man that hangeth down his head sadly; but
inwardly he is full of deceit. Casting down his countenance, and
making as if he heard not. A man may be known by his look, and one
that hath understanding, by his countenance, when thou meetest
him.”—In several of Lavater’s aphorisms, something like the
following occurs: “A man’s attire, and excessive laughter, and gait,
shew what he is.”