The COVID-19 Pandemic - Prof. Dr. Hortense Slevogt - ZIK Septomics - Host Septomics
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ZIK Septomics – Host Septomics
Klinik für Innere Medizin I
The COVID-19 Pandemic
imago images/Ralph Peters
Prof. Dr. Hortense Slevogt
March 25th, 2020
The Virus:
Severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) Basic biology:
SARS-CoV-2 is a RNA virus and part of the family of
coronaviruses
Coronaviruses contains:
• (i) 4 coronaviruses, widely distributed and usually cause
the common cold
• (ii) SARS and MERS
• (iii) COVID-19 is most closely related to SARS
The virus is called “SARS-CoV-2”
The clinical illness is called “COVID-19.”
December 30th, 2019:
Dr. Li Wenliang: “A new coronavirus infection has been
confirmed and its type is being identified.
Inform all family and relatives to be on guard!”
First
Case in
the USA
Dr Wenliang died
Outbreak in Italy
Li Wenliang (Chinese: 李文亮; pinyin: Lǐ Wénliàng; 12 October 1986 – 7 February 2020)
COVID-19 = Coronavirus Disease 2019
Symptoms
Absence of fever does not exclude COVID-19.
RKI 2020
Modes of transmission
• Droplet infection = main mode of transmission
• Also smear infection possible
• Infection through the conjunctiva of the eye possible
• No Transmission from infected mother to her child
(before, during, after birth):
• Up to now few studies proved that in previously examined newborns of COVID-positive
mothers no transmission was been detected
https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Steckbrief.html#doc13776792bodyText11 (22.03.2020)
COVID-19: Course of disease
Courses of disease vary widely from asymptomatic infection to
severe pneumonia with respiratory failure and death
Data from China:
• Ca. 80% mild to moderate course
• No pneumonia, no dyspnoea, oxygen saturation of the blood > 93%,
no pulmonary infiltrates affecting more than half of the lung
• Ca. 10-20 % severe course admitted to ICU
• dyspnoea, oxygen saturation 94% or
pulmonary infiltrates in more than half of the lung, but NOT life-threatening
• Ca. 6% critical to life-threatening course require intubation
• ~ 1-5% die
https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Steckbrief.html#doc13776792bodyText11 (22.03.2020)
„Typical“ course of severe disease • Incubation period is a median of ~4 days (interquartile range of 2-7 days), with a range up to 14 days • Typical evolution of severe disease Dyspnea ~ 6 days post exposure. Admission after ~8 days post exposure ICU admission/intubation after ~10 days post exposure.
March 25th, 2019, 9.07 AM
WHO, March 24th,2020
R⌀ = Reproduction number
R⌀ is the average number of people that an infected person
transmits the virus to.
• If R⌀ is 1, the epidemic will increase exponentially
• Current estimates put R⌀ at ~2.5-2.9
This is a bit higher than seasonal influenza.
• R⌀ is a reflection of both the virus and also human
behavior.
https://emcrit.org/ibcc/COVID19/Germany: March, 24th, 2020
Moderate/ severe cases:
Age distribution of patients and
interval from onset of symptom to death of patients with confirmed COVID-19
(Wuhan, China)
Ruan et al. Intensive Care Med, 2020Case fatality ratio (CFR): The proportion of deaths from a certain disease compared to the total number of people diagnosed with the disease for a certain period of time.
From: Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy
JAMA. Published online March 23, 2020. doi:10.1001/jama.2020.4683
Case-Fatality Rate by Age Group in Italy and Chinaa
Date of download: 3/24/2020 Copyright 2020 American Medical Association. All
Rights Reserved.Factors affecting the case fatality rate
• Variability in the number of cases detected by testing
• Severe disease are being preferentially tested
• Delays between symptoms onset and deaths
• Factors that account for increased death rates:
• Coinfection
• Poorer healthcare
• Patient demographics
• Comorbidities
• Smoking
2020 Centre for Evidence-Based MedicineThe Importance of the Diamond Princess
Passengers: 3711
Confirmed cases: 619
Death: 7
Russel et al, medRxiv 2020The Importance of the Diamond Princess
The only true controlled experiment where 100% of passengers
were tested: Is a reliable numerator and a complete 100%
accounted for denominator
Case fatality ratios for COVID-19 on the Diamond Princess ship: 1.2% (0.38–2.7%)
Russel et al, medRxiv 2020COVID-19: Fatality Rate/ Spreading Potential
Updated Feb. 28, 2020Providing medical resources: Flattening the curve! https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930567-5; https://voxeu.org/article/it-s-not-exponential-economist-s-view-epidemiological-curve
Situation in England
Prediction Model
March 2020:
Ferguson et al. 16 March 2020: Imperial College COVID-19 Response TeamSituation in England
Prediction Model
March 2020:
Ferguson et al. 16 March 2020: Imperial College COVID-19 Response TeamSituation in England
Prediction Model
March 2020:
Ferguson et al. 16 March 2020: Imperial College COVID-19 Response TeamSituation in the USA
Prediction Model
March 2020:
95% reduction of infection rate (moderate 75% reduction of infection rate (severe
szenario) scenario)
80% asymptomatic 80% asymptomatic
20% require health care 20% require health care
8% require hospital admission 8% require hospital admission
6% require ITS treatment 6% require ITS treatment
0,5% death rate 3% death rate
Ezekiel et al NEJM, March 2020Ethical guidelines for the allocation of
Scarce Medical Resources in the COVID-19 Pandemic
Conclusions of this study:
• Governments and policy makers must do all they can to
prevent the scarcity of medical resources.
• If resources do become scarce, we believe the six
recommendations should be used to develop guidelines that
can be applied fairly and consistently across cases.
• Guidelines should be provided at a higher level of authority
• to alleviate physician burden and to ensure equal treatment.
Ezekiel et al NEJM, March 2020Situation in Italy
Prediction Model
February 2020:
Grasselli, Jama, March 2020Slow Infection Rate - Gain Time!
Getting prepaired for the COVID-19 Pandemic
• Doubling of the capacity of available ICU beds
• Central plannings of the available ICU capacity (Registry)
• Increase nummer of Respirators
• Increased production of face masks, etc.
• Centralized storage of drug that might be effective in treating COVID-19
• Ensure availability of trained staff
• Teaching of new staff
• Multicenter-based Research:
Treatment strategies
Vaccination!
Epidemiology (Effectivity of containment measures)
Mutations of the virus
Protection strategies
Future strategies …Example Germany I:
Example Germany II: The ZEO- Scenario Counter
Der ZEQ-Szenariorechner zum Strukturbedarf im Rahmen
der COVID-19-Pandemie 2.0
Berechnung von Anhaltswerte zu durch Corona-Patienten belegten Betten auf der
Normal- und Intensivstation, zu benötigten Schutzmasken, zu invasiv beatmeten
mit extrakorporaler Membranoxygenierung (EMCO) sowie zu den notwendigen
Personalressourcen zur Versorgung der Patienten berechnet.
https://www.zeq.de/covid-19/corona-virus-covid-19/covid-19-szenariorechner.htmlThe COVID-19 Patient:
Course of disease and therapeutic strategies
https://emcrit.org/ibcc/covid19/Remdesivir
• Remdesivir might be an excellent antiviral, based on a study involving in vitro and animal
data with MERS (e.g. Sheahan 2020).
• Unfortunately, remdesivir is not commercially available. Remdesivir was used on the basis
of “compassionate use” for one of the first patients with COVID-19 in the United States
(Holshue 2020).
• Remdesivir is being used in trials in the United States being sponsored by NIH.
• Alternative approach – compassionate use program GileadLopinavir/Ritonavir (Kaletra) • This is a combination of antiviral agents used in treatment of HIV • Lopinavir and ritonavir are protease inhibitors, which block viral replication. • Lopinavir seems to be the agent which actually acts on the virus. • Ritonavir is a CYP3A inhibitor which functions primarily to reduce metabolism of lopinavir, thereby boosting lopinavir levels. • Known activity against Corona viruses
CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was
observed with lopinavir–ritonavir treatment beyond standard care.
Cao et al., NEJM, March 2020Chloroquine
• Used for treatment of malaria and amebiasis.
• Anti-viral activity in vitro, but no established track record in treatment of
viral disease.
• Appears to work via multiple mechanisms, including:
Interference with the cellular receptor ACE2 (potentially making it
particularly effective against SARS and COVID-19).
Impairment of acidification of endosomes, which interferes with virus
trafficking within cells.
• Chloroquine also has immunosuppressive activities. It's unknown
whether such immunosuppressive action could be beneficial or harmful
• In vitro data using cell lines shows that chloroquine can inhibit COVID-19
with an 50% inhibitory concentration of 1 uM, implying that therapeutic
levels could be achieved in humansChloroquine
Expert consensus China
Cave: QTc-prolongationProtection against infection
March 25th,2019 COVID-19: The numbers are constantly rising
9.07 AM
10.14 AMThank you for your attention!
hortense.slevogt@med.uni-jena.deConclusion: Our results in-dicate that aerosol and fomite transmission
of SARS-CoV-2 is plausible, since the virus can remain viable and infectious
in aerosols for hours and on surfaces up to days
Morris et al. NEJM, March 2020You can also read
