SARS, MERS, COVID-19
Svatava Snopková, 4/2020
• coronavirus – kopie
(2coronavirus – kopie
(2))
The family Coronaviruses
Constitute the subfamily Orthocoronavirinae
• Is divided into 4 genera
1. Alphacoronavirus
2. Betacoronavirus
3. Gammacoronavirus
4. Deltacoronavirus
Coronaviruses
• Enveloped RNA viruses with positive-sense, single
stranded RNA genomes
• With a crown-like appearance under an electron
microscope (coronam is the Latin term for crown)
• Diameter of approximately 60-140 nm
• The genomic structure is organized in 30 000 bases (the
larges known RNA viruses)
• Circulate among animals with some of them also known to
infect humans
• These viruses can cross species barriers and can cause
illness in human
Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiologyn2020;00:1-8. doi.org/10.1148/radiol.2020200274. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro. Cell Research. 2020;30:269-271.
• coronavirus – kopie
(2coronavirus – kopie
(2))
The family Coronaviruses
• Are responsible for about 5%-10% of acute
respiratory infections in hunans
• Bads – are considered as natural hosts of these
viruses, several other species of animals are also
known to be a source
• Three zoonotic CoVs-β cause severe respiratory
diseases
• SARS-CoV
• MERS-CoV
• SARS-CoV-2
• Is genetically closely related to the SARS-CoV
• CoV genome is highly conserved. SARS-CoV-2 and
SARS-CoV share similar key protein include the
spike protein, RdRp, 3CLpro and PIpro
Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiologyn2020;00:1-8. doi.org/10.1148/radiol.2020200274. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro. Cell Research. 2020;30:269-271.
Severe Acute Respiratory Syndrome (SARS)
• Etiologic agent – SARS-CoV (SARS-CoV-1)
• Was transmitted to humans from the Himalayan civet cats
• Appeared in the Guangdong province of southern China in 2002
• These epidemic was in 2-7/2003 (8437 patients/813 deaths)
• It was mainly characterized by flu-like symptoms, including high fevers
exceeding 38 C, myalgia, dry nonproductive dyspnea, lymphopaenia,
infiltrate on chest radiography
• In 38 % of all cases, the resulting pneumonia led to acute breathing
problems requiring artificial respirators
• The overall mortality rate was about 10%, but mortality rate in the
elderly was as high as 50%
• SARS affected relatively few children and generally appeared to be
milder in the paediatric age group
• Reproduction number (R) = 3
• On average, each patient transmits the infection to an additional 3 individuals
Stadler K, Masignani V, Eickmann M, et al. SARS-beginning to understand a new virus. Nature reviews, microbiology. 2003;1:209-218.
Middle East Respiratory Syndrome (MERS)
• Etiologic agent – MERS-CoV
• Was transmitted to humans from the
dromedary camel
• This epidemic began in Saudi Arabia
in 2012 and still causes as sporadic
cases
• It is now seen sporadically yearround
but more so during wintertime
• There were 2494 cases/858 deaths in
2012
• The overall mortality rate was about
34%, but mortality rate in the elderly
was as high as 50%
• R = 1
Stadler K, Masignani V, Eickmann M, et al. SARS-beginning to understand a new virus. Nature reviews, microbiology. 2003;1:209-218.
• Currently, the whole world is facing the largest epidemic caused by
coronaviruses, which has been identified as
• Coronavirus disease 2019 (COVID-19)
- is the name given to the disease associated with the new virus
• SARS-CoV-2
• Severe Acute Respiratory Syndrome Coronavirus-2
• Is the name given to the 2019 novel coronavirus
• Is a new strain of coronavirus that has not been previously
identified in humans
• Is the third documented spillover of an animal coronavirus to
humans in 2 decades that has resulted in a major epidemic
• Available data suggested that the SARS-CoV-2 may be less
virulent than the SARS-CoV and MERS-CoV.
COVID-19
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers; Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 /COVID-19) outbreak – an update on the status. Military Medicine Research. 2020:7:11.
COVID-19
Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiologyn2020;00:1-8. doi.org/10.1148/radiol.2020200274. https://www.1who.int/emergencies/diseases/novel-coronavirus-2019
• In December 2019, a cluster of pneumonia cases, caused by a newly
identified β-coronavirus, occurred in Wuhan, in China
• The epidemic broke out possibly related to a seafood market from where it
then spread from person to person
• This new virus seems to be very contagious and has quickly spread globally
• The WHO declared a global pandemic on March 11, 2020
COVID-19 transmission
• The first cases of the COVID-19 disease were linked to direct
exposure to the seafood market of Wuhan
• The animal-to-human transmission was presumed as the main mechanism
• Subsequently, virus was transmitted from person-to-person
• The virus seems to be transmitted mainly via respiratory droplets that
people sneeze, cough, or exhale
• Particles can be detected in upper and lower respiratory tracts
• A relatively low infective dose is required to transmit the infection
• Transmission can still occur during asymptomatic stage
• This transmission may represents 25-50% of total infections.
• The virus can also survive for several hours on surfaces such as tables, door
handles…
• More stable on plastic and stainless steel than on copper and cardboard,
and viable virus was detectable ≤72 hours
• More over SARS-CoV-2 was isolated from fecal swabs and blood – indicating
the possibility of multiple routes transmission
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers; Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military medical Research, 2020; Guo………
COVID-19
• SARS-CoV-2 exhibits strong infectivity but less virulence, compared
to SARS and MERS
Contagiousness
• Is probably higher than for seasonal influenza
• The basic reproduction number (R)
• Of SARS-CoV-2 to be around 2.2 or even more
(range from 1.4 to 6.5)
• It means, that one infected person will infect between 2-3 another
people
ECDC estimats that mortality rate
• Seasonal influenza
• Approximately 1 people die in every 1000 people who are infected
• The current estimated mortality rate for COVID-19
• Is 20-30 per 1000 people
• It is significantly less than the 2003 SARS outbreak
• But it is much higher than the mortality rate for seasonal influenzawww.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers; Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military medical Research, 2020;
Angiotensin converting enzyme II (ACE2)
• Is a known cell receptor for SARS-CoV
• It is clear now that SARS-CoV-2 could use
angiotensin-converting enzyme 2 (ACE2), the
same receptor as SARS CoV
• The binding of SARS-CoV-2 spike (S)
glycoprotein and ACE2 receptor is a critical
step for virus entry
Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military medical Research, 2020; Guo……….
ACE2 protein presents in abundance on lung alveolar
epithelial cells and enterocytes of small intestine
COVID-19
The incubation period for COVID-19
• The time between exposure to the virus and onset of symptoms
• Is currently estimated at between 2 and 14 days
The clinical manifestations
• Mild disease
• Fever, cough, flu-like illness….
• This occurred in 81% of cases and most patients have a good
prognosis
• Severe disease
• With severe pneumonia
• This occurred in 18% of cases
• Critical disease
• Respiratory failure, septic shock, multiple organ dysfunction…
• This occurred in 5% cases
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers. Huang et al. Lancet 2020.
Fever and cough
• are the dominant symptoms
Gastrointestinal symptoms
• Herald more serious disease and suggesting the differences in viral tropism as
compared with SARS-CoV, MERS-CoV and influenza
COVID-19 complications
• Most patients have a good prognosis
• About 20% of patients have severe illness with complications
• Acute respiratory distress syndrome (ARDS)
• Arrhytmia
• Shock
• Acute kidney injury
• Acute cardiac injury
• Liver dysfunction
• Secondary infection…
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers; Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 /COVID-19) outbreak – an update on the status. Military Medicine Research. 2020:7:11.
Elderly people
• And those with underlying health conditions (e.g. hypertension, diabetes,
cardiovascular disease, chronic respiratory disease, cancer…)
• Are considered to be more at risk of developing severe symptoms
• Developed rapidly into acute respiratory distress syndrome, septic shock, metabolic
acidosis hard to correct and coagulation dysfunction, even leading to the death
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers; Guo et al. The origin, transmission and clinical therapies on coronavirus disease 2019 /COVID-19) outbreak – an update on the status. Military Medicine Research. 2020:7:11.
COVID-19 CT imaging
Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiologyn2020;00:1-8. doi.org/10.1148/radiol.2020200274.
Hosseiny M et al. Radiology perspectives of coronavirus disease 2019 (COVID-19). Am J Roentgenology, 2020; DOI: 10.2214/AJR.20.22969
• After an incubation period of 2-14 days - very early changes on CT of the lungs
• Abnormalities are already at an early stage in most patients
• The main findings
• Pure ground-glass opacities (GGO), GGO with reticular and/or interlobular septal
thickening, and GGO with consolidation
• The absolute number of lung findings increased with the time from symptom onset
• The younger patients tended to have more GGOs, while older patients tended to have
more areas of lung involvement and more consolidation
• A part of confirmed patients appeared the normal CT image presentations
CT scan COVID-19
Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiologyn2020;00:1-8. doi.org/10.1148/radiol.2020200274.
Hosseiny M et al. Radiology perspectives of coronavirus disease 2019 (COVID-19). Am J Roentgenology, 2020; DOI: 10.2214/AJR.20.22969
Consolidation
• Indicated disease progression or more severe disease
Most pulmonary lesions involved
• Bilateral lungs with multiple lung lobes
• With predominant distribution in posterior and paripheral part of the lungs
• The posterior and paripheral lung predominant distribution – ussually is charakteristic
Patients with fever and/or cough and with GGO-prominent lesions in the peripheral and posterior part of
lungs on CT images, combined with normal or decreased white blood cells should be highly suspected of
having COVID-19 pneumonia.
ELISA tests
• Tests are currently in development detection of IgM
and IgG antibodies against SARS-CoV-2 proteins
• Seroconversion for IgM antibodies occurs a few days
earlier than IgG
• IgM: 5 days (3-6)
• IgG: 14 days (10-18)
Most but not all patients recovered from COVID-19
producing neutralizing antibodies that are likely
sufficiently protective against infection.
But immunity may not be long-lasting (1-3 years) based
on work with routine coronaviruses, SARS and MERS.
COVID-19 laboratory examination
Most of the patients had
• Normal or decreased neutrophil count
• Lymphocyte count was low (or normal) or continued decrease
• Elevate D-dimer
• LDH may be modestly elevated
• Elevated IL-6
• C-reactive protein is elevated
• Thirty-one patients had a low CD4+ cell count
• with a range of 72-408 cells/μl
• Elevations in IL-6, CRP, ferritin suggested correlating with a cytokine
storm and impending ARDS.
www.ecdc.europa.eu/en/novel-coronavirus-china/questions-answers
COVID-19 therapy
SARS-CoV-2 = as it is a new virus
• Nobody has prior immunity
• which in theory means, that entire human population is potentially
susceptible to COVID-19 infection
• Unlike influenza, there is no vaccine
• No specific treatment for the disease
• Healthcare providers treat the clinical symptoms of patients
• Supportive care
• e.g. fluid management
• oxygen therapy – major treatment intervention
• intubation and protective mechanical ventilation – may be
necessary in cases of respiratory failure refractory to oxygen
therapy
• ECMO (extracorporeal membrane oxygenation) – to patients with
refraktory hypoxemia
• hemodynamic support – is essential for managing septic shock
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
COVID-19 candidate therapies
• Currently there are no licensed therapeuticm agents for the treatment of
COVID-19
• There is an increasing number of antiviral agents being investigated in
clinical trials for the treatment of COVID-19
• Remdesivir (anti-SARS-CoV-2 nukleoside inhibitor)
• Shows broad spectrum antiviral aktivity against several RNA viruses
• Remdesivir is a prodrug, an adenosine analog that acts as an inhibitor of
RNA-dependent RNA polymerases (RdRps). Remdesivir-TP competes with
adenosine-triphosphate for incorporation into nascent viral RNA chains.
Once incorporated into the viral RNA. Because RDV-TP does not cause
immediate chain termination, the drug appears to evade proofreading by
viral exoribonuclease (an enzyme thought to excise nucleotide analog
inhibitors).
• Hydroxychloroquine (antimalaria)
• Mechanisms may include inhibition of viral enzymes or processes such as
viral DNA and RNA polymerase, viral protein glycosylation, virus assembly,
new virus particle transport, and virus release. Other mechanisms may also
involve ACE2 cellular receptor inhibition, acidification at the surface of the
cell membrane inhibiting fusion of the virus, and immunomodulation of
cytokine release.
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
COVID-19 candidate therapies
• Lopinavir/ritonavir (boosted HIV protease inhibitor)
• Lopinavir and ritonavir may bind to Mpro, a key enzyme for coronavirus
replication. This may suppress coronavirus activity
• + /- interferon beta (immunomodulator)
• Various protease inhibitors, oseltamivir (neuraminidase inhibitor), favipiravir
(RdRp inhibitor), chloroquine… are investigatet to treatment COVID-19
• Azithromycin
• Macrolides may have immunomodulatory properties in pulmonary
inflammatory disorders. They may downregulate inflammatory responses
and reduce the excessive cytokine production associated with respiratory
viral infections; however, their direct effects on viral clearance are
uncertain. Immunomodulatory mechanisms may include reducing
chemotaxis of neutrophils (PMNs) to the lungs by inhibiting cytokines (i.e.,
IL-8), inhibition of mucus hypersecretion, decreased production of reactive
oxygen species, accelerating neutrophil apoptosis, and blocking the
activation of nuclear transcription factors.
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
COVID-19 candidate therapies
• Tocilizumab
• Tocilizumab inhibits IL-6-mediated signaling by competitively binding to
both soluble and membrane-bound IL-6 receptors. IL-6 is a proinflammatory
cytokine that is involved in diverse physiological processes such as T-cell
activation, immunoglobulin secretion induction, hepatic acute-phase
protein synthesis initiation, and hematopoietic precursor cell proliferation
and differentiation stimulation. IL-6 is produced by various cell types,
including T- and B-cells, lymphocytes, monocytes, and fibroblasts.
• COVID-19 Convalescent Plasma or serum-containing neutralizing antibodies
against SARS-CoV-2
• Plasma collected from persons who have recovered from COVID-19 that
may contain antibodies to SARS-CoV-2. Clinical trials are being conducted to
evaluate the use of COVID-19 convalescent plasma to treat patients with
severe or immediately life-threatening COVID-19 infections. COVID-19
convalescent plasma is not intended for prevention of the infection.
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
COVID-19 therapy
• Corticosteroids
• Corticosteroid therapy is not recommended for viral pneumonia; however,
use may be considered for patients with refractory shock or acute
respiratory distress syndrome.
• NSAIDs
• The FDA continues to investigate the use of NSAIDs in patients with COVID-
19 symptoms.
• Concern for potential worsening of COVID-19 symptoms has been
suggested, but confirmatory clinical data is lacking at this time. There is an
anecdotal published letter that suggests a link between ibuprofen and
increased ACE2 expression that may lead to worse outcomes in COVID-19
patients.
• Acetaminophen may be considered for temperature control.
• Various research efforts are currently underway to develop
effective drugs and a vaccine against COVID-19
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
Prevention
How can I avoid getting infected
• Personal protection and hygiene measures
• Wearing masks
• Hygiene and desinfection
• The virus enters into the human body via eyes, nose and/or mouth
• So, it is important to avoid touching your face with unwashed hands
• Washing of hands with soap and water for at least 20 seconds
• Cleaning hands with alcohol-based solutions, gels or tissues is
recommended in all settings
• Desinfect frequently touched household objects
www.genengnews.com/a-lists/how-to-conquer-coronavirus-top-35-treatments-in-development/
The epidemiological measures
Public health measures aimed at reducing contact rates in a population and
thereby reducing transmission of the virus
• Isolation of patients and quarantine of exposed contacts
• Social distancing measures
• Maintaining distance from others min. 2 meters
• Avoid crowding
• Closing scholls and childcare centers
• Simultaneous use of multiple measures to reduce social mixing
• Measures for persons entering or exiting an infected area
Conclusion
Unfortunately, it is not possible to predict
• how long the outbreak will last and how the epidemic will unfold.
We are dealing with a new virus and therefore a lot of uncertainty
remains.
For instance, it is not known whether transmission within the EU/EEA
will naturally decrease during the northern hemisphere
summer, as is observed for seasonal influenza.