2. HISTORY OF MAIN PLAGUES
Plagues are as certain as death.
Over the last century several important
human microbes causing severe acute
respiratory disease have emerged.
SARS CoV-2 is not the first, and nor will it
be
the last of its kind.
Outbreak
Year
Great flu pandemic, worldwide
1918
Legionnaires’ disease, Philadelphia,
1976
Hanta virus pulmonary syndrome,
1993
Hendra virus infection, Australia
1994
H5N1 influenza infection, Hong Kong
1997
Nipah virus encephalitis/pneumonitis,
Malaysia
1999
History of epidemics over the last century
9. CORONAVIRUS
The genus Coronavirus belongs to the family
Coronaviridae in the order Nidovirales.
Coronaviruses (CoVs) infect a variety of livestock,
poultry, and companion animals, in which they can
cause serious and often fatal respiratory, enteric,
cardiovascular, and neurological diseases.
Coronaviruses
are the causative agents of an estimated 30%
of upper and lower respiratory tract
infections in humans resulting in :
rhinitis, pharyngitis, sinusitis, bronchiolitis,
and
pneumonia .
10. CORONAVIRUS DEFINITIVE HOST
Host Genus Virus
Human Alpha Human CoV-229E
Human CoV-NL63
Beta Human CoV-HKU1
Human CoV-OC43
SARS-CoV
MERS-CoV
Pig Alpha PRCV/ISU-1
TGEV/PUR46-MAD
PEDV/ZJU-G1-2013
SeACoV-CH/GD-01
Dog Alpha Canine CoV/TU336/F/2008
Camel Alpha Camel alphacoronavirus isolate Camel/Riyadh
Cat Alpha Feline infectious peritonitis virus
Cow Beta Bovine CoV/ENT
Horse Beta Equine CoV/OBIHIRO12-1
Mice Beta MHV-A59
Chicken Gamma IBV
Whale Gamma Beluga whale CoV/SW1
Bulbul Delta Bulbul coronavirus HKU11
11.
12. ANIMAL CORONAVIRUS
Historical Background
Coronaviruses were first identified from
domestic and laboratory animals before they
were identified in humans. Infectious
bronchitis virus of chickens was actually
isolated in embryonated eggs in the
1940s.And in human the first case of human
coronavirus was found in the 1960s.
13. EMERGING OF HUMAN CORONA
VIRUS (SARS)
Before the first outbreak of severe acute respiratory
syndrome (SARS), a limited number of coronaviruses
were known to be circulating in humans, causing only
mild illnesses, such as the common cold.
Following the 2003 SARS pandemic, it became
apparent that coronaviruses could cross the species
barrier and cause life-threatening infections in
humans.
14. THE EMERGENCE MERS-COV.
In June 2012, 10 years after the first emergence of
SARS-CoV, a man in Saudi Arabia died of acute
pneumonia and renal failure by A novel coronavirus,
Middle East respiratory syndrome coronavirus
(MERS-CoV).
At that time, MERS-CoV was the sixth human
coronavirus identified.
MERS is a highly lethal respiratory disease and had
a higher case fatality rate than SARS .It caused
large nosocomial outbreaks in Jeddah,
Kingdom of Saudi Arabia
Moreover, MERS-CoV-specific antigens
were detected in camel serum samples collected in
1983 ,suggesting that MERS-CoV was present
in camels at least 30 years ago.
18. WHY CHINA?
several bat CoVs caused outbreaks in China; it is thus
urgent to study the reasons to avoid future
outbreaks.
China is the third largest territory and is also the most
populous nation in the world.
A vast homeland plus diverse climates bring about great
biodiversity including that of bats and bat-borne
viruses.
19. WHY CHINA?
The majority of the CoVs can be
found in China.
most of the bat hosts of these CoVs
live near humans, potentially
transmitting viruses to humans and
livestock.
Chinese food culture maintains
that live slaughtered animals are
more nutritious, and this
belief may enhance viral
transmission.
20. Coronavirus Species Abbreviations Human Bats Other Animals Reported in China
Bat coronavirus HKU10 BtCoV-HKU10 Yes Yes [7,8,26,27]
α-CoV
Bat coronavirus CDPHE15 BtCoV-CDPHE15 Yes No
Rhinolophus
ferrumequinum alphacoronavi
rus HuB-2013
BtRfCoV-HuB13 Yes Yes [8]
* Human coronavirus 229E HCoV-229E Yes Yes [28,29]
Lucheng Rn rat coronavirus LRNV Yes (rat) Yes [30]
Ferret coronavirus FRCoV Yes (ferret) No [31]
* Mink coronavirus 1 MCoV Yes (mink) No [14]
Miniopterus bat coronavirus 1 BtMiCoV-1 Yes Yes [7,8,32,33,34,35,36,37]
Miniopterus bat coronavirus
HKU8
BtMiCoV-HKU8 Yes
Yes
[7,8,33,34,35,37,38,39,40,41]
Myotis
ricketti alphacoronavirus Sax-
2011
BtMy-Sax11 Yes Yes [8,37]
Nyctalus
velutinus alphacoronavirus
SC-2013
BtNy-Sc13 Yes Yes [8]
* Porcine epidemic diarrhea
virus
PEDV Yes (pig) Yes [42]
Scotophilus bat coronavirus
512
BtScCoV-512 Yes Yes [37]
* Rhinolophus bat
coronavirus HKU2 (SADS)
BtRhCoV-HKU2 Yes Yes Yes [2,7,8,38,43,44,45]
* Human coronavirus NL63 HCoV-NL63 Yes Yes [28,29]
NL63-related bat coronavirus
strain BtKYNL63-9b
BtKYNL63 Yes No [24]
* Alphacoronavirus 1
(Transmissible gastroenteritis
virus)
TGEV Yes (pig) Yes [42]
22. LINKING BATS TO CORONAVIRUSES
Bat are the only mammals with the capability of powered
flight, which enables them to have
a longer range of migration compared to land mammals.
bats were linked to a few highly pathogenic human diseases,
Some of these well characterized bat viruses, including:
bat lyssaviruses (Rabies virus)
henipaviruses (Nipah virus and Hendra virus)
(SARS-CoV, MERS-CoV, and SADS-CoV)
filoviruses (Marburgvirus, Ebola virus, and Mengla virus)
all these pose a great threat to human health
23. VIROLOGY OF SARS- AND MERS-COV
Coronaviruses are spherical, enveloped,
positive-sense, single-stranded RNA
viruses
SARS- and MERS-CoV transcribe 12 and 9
subgenomic RNAs, respectively,
which encode for:
the spike (S).
envelope (E).
membrane (M).
nucleocapsid (N).
24. VIROLOGY OF SARS- AND MERS-COV
the spike (S) facilitates
host cell attachment to
angiotensin converting
enzyme (ACE)-2 receptors
for SARS-CoV .
the spike (S) in MERS-
CoV facilitates host cell
attachment to dipeptidyl
peptidase
(DPP)-4 receptors.
The N protein
encapsulates the viral
genome to form the helical
nucleocapsid.
27. SARS AND MERS: EPIDEMIOLOGY
Both viruses infect the lower airways and cause
severe respiratory syndromes in humans.
Animal-to-human transmission likely occurs
following direct contact with intermediate hosts.
During the 2003–2004 SARS epidemic, there
were 8096 cases and 774 deaths were reported from
26 countries with no cases reported since .
Human-to-human transmission of SARS-CoV
occurred primarily in healthcare settings with
healthcare workers comprising 22% and 40% of
reported cases in China and Canada, respectively .
28. SARS AND MERS: EPIDEMIOLOGY
During 2012 MERS cases in Saudi Arabia
reached>2000 cases and >800 deaths and it
reported that the virus spread in 27 countries in
2020.
While most cases have been reported from the
Arabian Peninsula, an imported case to South
Korea in 2015 resulted in a large outbreak in
multiple healthcare facilities .
MERS and SARS transmission occurs primarily
in healthcare facilities and to a lesser degree
within households.
29.
30.
31. SARS- AND MERS-COV TRANSMISSION AND
MECHANISMS
OF DISEASE
SARS-CoV is transmitted by large
respiratory droplets and by contact with
infected
surfaces.
Epidemiologic data also support small
droplet airborne transmission of SARS-
CoV .
MERS-CoV is transmitted by large
respiratory droplets and by contact with
infected surfaces .
Viral shedding from the lower respiratory
tract may persist for weeks .
32. SARS AND MERS ILLNESS AND COMPLICATIONS
Following an average 5-day incubation
period, SARS-CoV infection presents
with :
fevers .
Chills.
dry cough.
headache.
malaise.
dyspnea which commonly followed by
watery diarrhea .
Age >60 years and pregnancy are
associated with severe disease
manifested by progressive respiratory
failure within 2 weeks of illness onset .
33. SARS AND MERS ILLNESS AND COMPLICATIONS
Initial symptoms of MERS-CoV infection include:
fever.
chills .
cough .
shortness of breath .
myalgia .
following a mean incubation period of 5 days.
Gastrointestinal symptoms, including vomiting and
diarrhea, occur in one third of patients .
MERS patients present with a rapidly progressing
pneumonia requiring mechanical ventilation and
additional organ support with the first week of illness
.
34. SARS AND MERS: INFECTION CONTROL AND LAB
DIAGNOSIS
SARS is no longer circulating.
MERS should be suspected in individuals
with a febrile illness and an epidemiological risk factor .
Risk factors include travel to the Arabian Peninsula or contact with
a confirmed or suspected case within 14 days of symptom onset.
Confirmatory testing and infection control should be coordinated
through local or state health authorities.
MERS may be confirmed in designated public health laboratories by
RT-PCR testing of lower respiratory tract specimens .
Multiple other specimen types including upper respiratory tract
samples, serum, and stool should also be collected for testing.
Serologic testing can be used to evaluate for
suspected infection among individuals with no longer shedding
virus .
35. SARS AND MERS TREATMENT
There are currently no licensed therapeutics
or vaccines for SARS or MERS.
supportive care is the mainstay of treatment .
Renal replacement therapy is frequently
required in severe illness .
Empiric antibiotics are often administered
given potential for secondary bacterial
infection.
Ribavirin and pegylated alpha interferon
have been administered to MERS patients,
although effectiveness data is lacking .
37. THE EMERGENCE COVID-19.
The origin of the SARS-CoV-2 genome has been
linked to bats akin which is the host for the SARS-
CoV-1 and MERS-CoV viruses .
The SARS-CoV-2 whole-genome aligned with the
genomes of viruses (pangolins and Bat-CoV
RaTG13) with 96% similarity .
it suspected that in SARS-CoV-2 pangolins is the
natural reservoir.
38. THE EMERGENCE COVID-19. (THE LINK BETWEEN COVID-19
AND PANGILON )
The link between covid-19 and pangolin was
based on the analysis of the genome alignment
between SARS-CoV-2 and Pangolin-CoV
harbored in the lung tissue of two dead Malayan
pangolins .
the Pangolin-CoV’s whole genome had 91.02%
similarity with SARS-CoV-2 and 90.55%
similarity with Bat-CoV RaTG13 .
genomic analysis revealed that the S1 subunit
of Spike glycoprotein (S) was more closely
related to that of SARS-CoV-2 compared to
BaT-CoV RaTG13.
43. CLINICAL PRESENTATION OF COVID-19
Clinical presentation in adults Approximately 15% of
patients present with the symptom triad of fever,
cough, and dyspnea, and 90% present with more
than one symptom.
Some patients may be minimally symptomatic or
asymptomatic, while others may present with severe
pneumonia or complications such as acute
respiratory syndrome, septic shock, acute
myocardial infarction, venous thromboembolism,
or multi-organ failure.
44. MOLECULAR TESTING OF COVID-19
Molecular testing is required to confirm the
diagnosis. Order a nucleic acid amplification test,
such as real-time reverse-transcription polymerase
chain reaction (RT-PCR).for SARS-CoV-2 in patients
with suspected infection whenever possible .
Tests should be performed according to guidance
issued by local health authorities and adhere to
appropriate biosafety practices.
45. WHO TO TEST
People with symptoms of new continuous cough, high temperature, or altered sense of smell/ taste.
People with acute respiratory infection, influenza-like illness, clinical or radiologic evidence of
pneumonia, or acute worsening of underlying respiratory illness, or fever without another cause (whether
presenting in primary or secondary care).
People with symptoms, even if they are mild
People who are asymptomatic and have been in close contact (less than 6 feet [2 meters] for a total of 15
minutes or more over a 24-hour period) with a person with documented infection.
People who are asymptomatic and have not been in close contact with a person with documented infection
only if required by a healthcare provider or public health official.
46. SEROLOGIC TESTING
Serology cannot be used as a standalone
diagnostic test for acute SARS-CoV-2
infections. However, it may be useful in
various settings (e.g, negative molecular
testing, diagnosing patients with late
presentation or prolonged symptoms,
serosurveillance studies).
47. RAPID DIAGNOSTIC TESTS
Antigen testing relies on direct detection of SARS-CoV-2 viral
proteins in nasal swabs and other respiratory specimens using a
lateral flow immunoassay.
Results are usually available in less than 30 minutes. While
antigen tests are substantially less sensitive than RT-PCR, they
offer the possibility of rapid, inexpensive, and early detection of
the most infectious cases in appropriate settings.
testing should occur within the first 5 to 7 days following the
onset of symptoms
48. INFECTION PREVENTION AND CONTROL (IPC) FOR COVID-19
Infection prevention and control (IPC) is the practice of
preventing or stopping the spread of infections during
healthcare delivery in facilities like hospitals.
Outpatient clinics, dialysis centres, long-term care
facilities, or traditional practitioners. IPC is a critical part
of health system strengthening and must be a priority
to protect patients and healthcare workers.
49. INFECTION PREVENTION AND CONTROL (IPC) FOR COVID-19 (PRIORITIES)
1- Rapid identification of suspect cases.
Screening/Triage at initial healthcare facility encounter and rapid implementation of source control.
Limiting the entry of healthcare workers and/or visitors with suspected or confirmed COVID-19.
2- Immediate isolation and referral for testing.
Group patients with suspected or confirmed COVID-19 separately.
Test all suspected patients for COVID-19.
3- Safe clinical management.
Immediate identification of inpatients and healthcare workers with suspected COVID-19.
4- Adherence to IPC practices.
Appropriate use of Personal protective equipment (PPE).
50. TREATMENT
Most people who become ill with COVID-19 will be able to recover at home.
For patients who recovering at home, there are some measures can help reduce symptoms:
They most take plenty of rest.
They most Stay well hydrated.
acetaminophen To reduce fever and ease aches and pains.
51. TREATMENT
For people hospitalized with COVID-19.
Remdesivir
In October 2020, the FDA approved the antiviral drug remdesivir to
treat COVID-19. Clinical trials suggest that in these patients,
remdesivir may modestly speed up recovery time.
Baricitinib in combination with remdesivir
In November 2020, the Food and Drug Administration (FDA) issued
an emergency use authorization (EUA) for the use of baricitinib in
combination with remdesivir in hospitalized adults and children 2
years and older who require respiratory support.
52. REFERENCES
Vijayanand P, Wilkins E, Woodhead M. Severe acute respiratory syndrome (SARS): a review. Clin Med (Lond). 2004;4(2):152-160. doi:10.7861/clinmedicine.4-2-152
doi: 10.7861/clinmedicine.4-2-152
Cong, Y.; Verlhac, P.; Reggiori, F. The Interaction between Nidovirales and Autophagy Components. Viruses 2017, 9, 182. https://doi.org/10.3390/v9070182
Jorge Hidalgo, Laila Woc-Colburn (Eds.), Highly Infectious Diseases in Critical Care, 69-96 - January 2020
https://doi.org/10.1007/978-3-030-33803-9_5
Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020 Mar 16;24:91-98.
doi: 10.1016/j.jare.2020.03.005. PMID: 32257431; PMCID: PMC7113610. DOI: 10.1016/j.jare.2020.03.005
Song, Z.; Xu, Y.; Bao, L.; Zhang, L.; Yu, P.; Qu, Y.; Zhu, H.; Zhao, W.; Han, Y.; Qin, C. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses 2019, 11, 59.
https://doi.org/10.3390/v11010059
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019 Mar;17(3):181-192. doi: 10.1038/s41579-018-0118-9. PMID: 30531947; PMCID:
PMC7097006.
Chang L, Yan Y, Wang L. Coronavirus Disease 2019: Coronaviruses and Blood Safety. Transfus Med Rev. 2020 Apr;34(2):75-80. doi: 10.1016/j.tmrv.2020.02.003. Epub 2020
Feb 21. PMID: 32107119; PMCID: PMC7135848.
XIAOJUN LI, ELENA E. GIORGI, MANUKUMAR HONNAYAKANAHALLI MARICHANNEGOWDA, BRIAN FOLEY, CHUAN XIAO, XIANG-PENG KONG, YUE CHEN, S.
GNANAKARAN, BETTE KORBER, FENG GAOSCIENCE ADVANCES01 JUL 2020 : EABB9153
53. REFERENCES
de Wit, E., van Doremalen, N., Falzarano, D. et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14, 523–534 (2016).
https://doi.org/10.1038/nrmicro.2016.81
Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci. 2020 Mar 15;16(10):1753-
1766. doi: 10.7150/ijbs.45134. PMID: 32226295; PMCID: PMC7098028.
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
Prabhu G. Suresha, Chameettachal Akhil, Aithal Anjali, Dsouza R. Giselle, Bhaskar Revti, Govindakarnavar Arunkumar
J Med Virol. 2016 Jan; 88(1): 163–165. Published online 2015 Oct 29. doi: 10.1002/jmv.24296
Gabutti, G., d’Anchera, E., Sandri, F. et al. Coronavirus: Update Related to the Current Outbreak of COVID-19. Infect Dis Ther 9, 241–253 (2020).
https://doi.org/10.1007/s40121-020-00295-5
Patrick Dawson, Mamunur Rahman Malik, Faruque Parvez, and Stephen S. Morse.Vector-Borne and Zoonotic Diseases.Mar 2019.174-
192.http://doi.org/10.1089/vbz.2017.2191
Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, Liu W, Bi Y, Gao GF. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016
Jun;24(6):490-502. doi: 10.1016/j.tim.2016.03.003. Epub 2016 Mar 21. PMID: 27012512; PMCID: PMC7125511.
Kakodkar P, Kaka N, Baig M (April 06, 2020) A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019
(COVID-19). Cureus 12(4): e7560. doi:10.7759/cureus.7560
All these infections, with theexception of Legionnaires’ disease, have one thing incommon: the origin of the infective agent is in animals, either domestic or wild. Chlamydia pneumoniae
Vijayanand P, Wilkins E, Woodhead M. Severe acute respiratory syndrome (SARS): a review. Clin Med (Lond). 2004;4(2):152-160. doi:10.7861/clinmedicine.4-2-152
doi: 10.7861/clinmedicine.4-2-152
https://doi.org/10.1007/978-3-030-33803-9_5
Cong, Y.; Verlhac, P.; Reggiori, F. The Interaction between Nidovirales and Autophagy Components. Viruses 2017, 9, 182. https://doi.org/10.3390/v9070182
The key reservoirs and mode of transmission of coronaviruses (suspected reservoirs of SARS-CoV-2 are red encircled); only a and b coronaviruses have the ability toinfect humans, the consumption of infected animal as a source of food is the major cause of animal to human transmission of the virus and due to close contact with aninfected person, the virus is further transmitted to healthy persons. Dotted black arrow shows the possibility of viral transfer from bat whereas the solid black arrowrepresent the confirmed transfer.
https://doi.org/10.1016/j.jare.2020.03.005
https://doi.org/10.3390/v11010059
https://doi.org/10.1038/s41579-018-0118-9
Animal origins of human coronaviruses. Severe acute respiratory syndromecoronavirus (SARS-CoV) is a new coronavirus that emerged through recombination ofbat SARS-related coronaviruses (SARSr-CoVs)20. The recombined virus infected civetsand humans and adapted to these hosts before causing the SARS epidemic42,62.Middle East respiratory syndrome coronavirus (MERS-CoV) likely spilled over frombats to dromedary camels at least 30 years ago100 and since then has been prevalentin dromedary camels. HCoV-229E and HCoV-NL63 usually cause mild infections inimmunocompetent humans. Progenitors of these viruses have recently been foundin African bats133,134, and the camelids are likely intermediate hosts of HCoV-229E134,135.HCoV-OC43 and HKU1, both of which are also mostly harmless in humans, likelyoriginated in rodents. Recently, swine acute diarrhoea syndrome (SADS) emerged inpiglets. This disease is caused by a novel strain of Rhinolophus bat coronavirus HKU2,named SADS coronavirus (SADS-CoV)34; there is no evidence of infection in humans.Solid arrows indicate confirmed data. Broken arrows indicate potential interspeciestransmission. Black arrows indicate infection in the intermediate animals, yellow arrowsindicate a mild infection in humans, and red arrows indicate a severe infection in humansor animals
Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci. 2020 Mar 15;16(10):1753-1766. doi: 10.7150/ijbs.45134. PMID: 32226295; PMCID: PMC7098028.
COVID-19: what has been learned and to be learned about the novel coronavirus disease - PubMed (nih.gov)
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
https://doi.org/10.3390/v11030210
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
https://doi.org/10.3390/v11030210
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
https://doi.org/10.3390/v11030210
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
https://doi.org/10.3390/v11030210
Fan, Y.; Zhao, K.; Shi, Z.-L.; Zhou, P. Bat Coronaviruses in China. Viruses 2019, 11, 210. https://doi.org/10.3390/v11030210
https://doi.org/10.3390/v11030210
DOI: 10.3390/v11010059
The N protein encapsidates the viralgenome to form the helical nucleocapsid.
MERS-CoV binds dipeptidyl peptidase 4 (DPP4) onrespiratory epithelial cells and pneumocytes where it undergoes productive replication during a 2–14 days incubation period . Viral shedding from the lower respiratory tract may persist for weeks .
DOI: 10.3390/v11010059
https://doi.org/10.1007/978-3-030-33803-9_5
Coronavirus: Update Related to the Current Outbreak of COVID-19 | SpringerLink
https://doi.org/10.1007/s40121-020-00295-5
https://doi.org/10.1007/978-3-030-33803-9_5
Map of countries having at least one laboratory-confirmed human MERS-CoV case, 2012–2016. Darkershades indicate greater numbers of laboratory-confirmed cases. (B) Inset of Fig. 1A showing Gulf countries having at leastone laboratory-confirmed human MERS-CoV case. Darker shades indicate greater numbers of laboratory-confirmed cases.Data Source: World Health Organization
Patrick Dawson, Mamunur Rahman Malik, Faruque Parvez, and Stephen S. Morse.Vector-Borne and Zoonotic Diseases.Mar 2019.174-192.http://doi.org/10.1089/vbz.2017.2191
1Global Distribution of Human Coronaviruses. (A) Green, blue, brown, and purple represent the global distribution of the NL63, HKU1, OC43, and 229E human coronaviruses, respectively. (B) Red and yellow represent the global distribution of MERS-CoV and SARS-CoV, respectively.
https://doi.org/10.1016/j.tim.2016.03.003
https://doi.org/10.1007/978-3-030-33803-9_5
https://doi.org/10.1007/978-3-030-33803-9_5
https://doi.org/10.1007/978-3-030-33803-9_5
https://doi.org/10.1007/978-3-030-33803-9_5
https://doi.org/10.1016/j.molmed.2020.02.008
https://www.cureus.com/articles/29670-a-comprehensive-literature-review-on-the-clinical-presentation-and-management-of-the-pandemic-coronavirus-disease-2019-covid-19
Kakodkar P, Kaka N, Baig M (April 06, 2020) A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19). Cureus 12(4): e7560. doi:10.7759/cureus.7560
https://doi.org/10.1016/j.molmed.2020.02.008
https://www.cureus.com/articles/29670-a-comprehensive-literature-review-on-the-clinical-presentation-and-management-of-the-pandemic-coronavirus-disease-2019-covid-19
Kakodkar P, Kaka N, Baig M (April 06, 2020) A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19). Cureus 12(4): e7560. doi:10.7759/cureus.7560