James Cook University - Associate Professor Peta-Ann Teague Dr … · 2020. 4. 24. · jcu.edu.au JCU COVID-19 WEBINAR SERIES EP 1 RNA Viruses for Dummies Presented by: Associate

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RNA Viruses for DummiesJCU COVID-19 WEBINAR SERIES EP 1

Presented by:

Associate Professor Peta-Ann TeagueDirector of JCU GP Training

Dr Robert NortonPathologist (Microbiology) and Director of Microbiology at Townsville University Hospital

Professor John McBrideInfectious Diseases Physician and Clinical Microbiologist, Cairns Hospital and Professor in Medicine, James Cook University

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RNA viruses and respiratory tract infections

Dr Robert NortonClinical Microbiologist

Townsville Hospital

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The “common” viruses

DNA virusesHSVVZVCMVEBV

RNA virusesInfluenzaRSVMeaslesHIVCoronavirusHuman metapneumovirus

Usual QLD picture• RSV – 9.2%

• hMPV – 7.1%

• Influenza A – 3.5%

• Parainfluenza 3 – 2.3%

• Adenovirus – 1.3%

Expressed as a percentage of all swabs taken (Emerg Inf Dis 2006)

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So what are the RNA viruses?

• A large heterogenous group with multiple levels of infectivity and pathogenicity.

• Most are single stranded RNA

• Unlike most DNA viruses, RNA viruses replicate in the cytoplasm.

• The method of replication varies between RNA viruses

o Eg : Positive stranded, negative stranded , retroviruses

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And then there was.........

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Coronaviruses• A single stranded, positive sense, enveloped RNA virus

• A large group of veterinary pathogens

o Cats, dogs, birds, bats, pigs, mice etc.

o Enteric disease in animals

• Corona from the “crown like” appearance of the surface projections.

• Respiratory coronaviruses

o Common cold – similar to rhinovirus , occasional severe disease

o Severe Acute Respiratory Syndrome (SARS)

SARS CoV – China 2002- 2003 – Mortality of 7-17%

Middle Eastern Respiratory Syndrome (MERS-CoV) – Mortality of 30-50%

o Gastrointestinal coronavirus infection

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Coronavirus attachment to Respiratory epitheliumInteraction between virus and host cellPenetration and DisassemblyPrimary Genome replicationReassembly and spreadCell tropismSecondary replicationCell injuryHost response – variable and is related to inherited Toll-like receptors, cytokine and cellular responses

• Attachment• Multiple, sequential, interactions

occur between the virus and host cell during the attachment step.

• For coronaviruses• Carcinoembryonic antigen

glycoprotein family• Aminopeptidase N• Angiotensin converting enzyme 2

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The cytokine “storm”• Subgroup of patients with severe COVID-19 may have a cytokine storm syndrome.

• Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality.

• Secondary haemophagocytic lymphohistiocytosis (sHLH)

• hyperinflammatory syndrome characterised by a fulminant hypercytokinaemia with multiorganfailure

• sHLH triggered by a variety of pathogens.

• Occurs in 3·7–4·3% all cases of sepsis.

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The cytokine “storm”• Cardinal features of sHLH:

• unremitting fever, cytopenias,hyperferritinaemia; • pulmonary involvement (including ARDS) occurs in approximately 50% of patients.

• A cytokine profile resembling sHLH is associated with COVID-19 disease severity: • increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10,

monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α.

• Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin and IL-6

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The assessment of a cytokine storm and consideration of immunosuppression• A number of parameters

• Temp• Organomegaly• Cytopenias• Fibrinogen• Ferritin

• An H score is determined and based on this, immunosuppression MAY be of some benefit.

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Viral detection• Pharyngeal virus shedding was very high during the first week of symptoms

(peak at 7.11 × 108 RNA copies per throat swab, day 4).

• Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples.

• Blood and urine never yielded virus.

• Shedding of viral RNA from sputum outlasted the end of symptoms.

• Seroconversion occurred after 7 days in 50% of patients (14 days in all) but was not followed by a rapid decline in viral load.

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Survival of the virus on inanimate objects• Human coronaviruses (HCoV) can persist on inanimate surfaces like

metal, glass or plastic for up to 9 days

• They can be efficiently inactivated by surface disinfection procedures with

o 70% ethanol OR

o 0.5% hydrogen peroxide OR

o 0.1% sodium hypochlorite within 1 minute

o Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective.

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Emerging therapeutic options under investigation: All unproven!Is immunosuppression of benefit if there is a cytokine storm?• Lopinavir/Ritonavir – Protease inhibitor• Remdesivir – Nucleoside analogue - Used in Ebola• Chloroquine/Hydroxychloroquine• ACE inhibitors• Interferon• Ivermectin• If immunosuppression is being considered because of a ‘cytokine storm”

o Tocilizumabo IL-1 blockade (Anakinra)o Steroids

• Avoid NSAIDS

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Gunnison, Colorado, USA 1918

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Personal Protective EquipmentWhat about masks for GPs?ED staff?The public?

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COVID-19 What the curves tell us

Professor John McBrideJames Cook University

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China – lag between cases and deaths

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USA

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An estimated additional 180 - 195 deaths per day occurring at home in New York City due to COVID-19 are not being counted in the official figures.

"Early on in this crisis we were able to swab people who died at home, and thus got a coronavirus reading. But those days are long gone. We simply don't have the testing capacity for the large numbers dying at home. Now only those few who had a test confirmation *before* dying are marked as victims of coronavirus on their death certificate. This almost certainly means we are undercounting the total number of victims of this pandemic."

Mark Levine, Chair of New York City Council health committee

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“Unless we get this globally under control, there is a very good chance that it will assume a seasonal nature in the sense that if - and I hope it's not only if but when - we get it down to a point where it is really at a low level, we need to be prepared. Since it will be unlikely to be completely eradicated from the planet, as we get into next season, we may see the beginning of a resurgence. And that's why we're pushing so hard to get our preparedness much better than it was but, importantly, pushing on a vaccine and doing clinical trials for therapeutic interventions so that hopefully, if in fact we do see that resurgence, we will have interventions that we did not have in the beginning of the situation that we're in right now.”Dr. Fauci

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The researchers used a new approach to deliver the drug, called a microneedle array, to increase potency.This array is a fingertip-sized patch of 400 tiny needles that delivers the S protein pieces into the skin, where the immune reaction is strongest. The patch is applied similarly to a plaster and then the needles, made entirely of sugar and the protein pieces, dissolve into the skin.

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Italy

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Scenario 4. Suppression, Reff = 0.8 In Scenario 4, we assume a reproduction ratio of 0.8. This means that, on average, people transmit infection to less than one other person. This would be consistent with some transmission events and even a few links in a chain of transmission, but would not result in large ongoing clusters of transmission in the community. In the suppression scenario, herd immunity is not achieved during the initial epidemic (see Figure 5). The result is that as soon as restrictions are lifted, secondary epidemic waves are almost inevitable. Therefore, successful elimination in this context requires several intermittent periods of strong interventions.

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UK

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Documents

James Cook University - Associate Professor Peta-Ann Teague Dr … · 2020. 4. 24. · jcu.edu.au JCU COVID-19 WEBINAR SERIES EP 1 RNA Viruses for Dummies Presented by: Associate