COVID-19 in the Valley Ric ichard C. . Boucher, M.D .D. Mar - - PowerPoint PPT Presentation

COVID-19 in the Valley

Ric ichard C. . Boucher, M.D .D.

Mar arsic ico Lung ung Ins Instit itute – Cystic ic Fib Fibrosis is Cen enter Th The e Univ niversit ity of

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arolin ina at t Cha hapel l Hill ill Mer erced Rot

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SARS-CoV-2: A Key (Spike Protein) and Lock (ACE2) Infectious Mechanism Produces COVID-19

Fischetti et al, Scientific American, 2020 Berkeley Lights, 2020

A B

98% Water 0.9% Salt 0.7% Globular proteins 0.4% Mucins

MUC5AC MUC5B Overlay

What Normally Protects Us against Vir iruses? Mucus.

Mucus composition:

Ehre/Biogels.MIT.edu Mucus Layer PCL Cells

SARS-CoV-2: Extraordinarily “Smart” Virus

Penetrates mucus Attacks prevalent cell Attacks high abundance receptor Shuts down host defense

Created with BioRender.com

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How We Acquire COVID-19 Nasal and Lung Infections

Hou et al, Cell, 2020

Relative expression

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ACE2 TMPRSS2

Nasal epithelium Trachea Bronchiole Alveoli

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• Fig. 4

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Nasal epithelium

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ACE2 FOXJ1 ACE2 MUC5B ACE2 FOXJ1 ACE2 MUC5B

Bronchi Alveoli

ACE2 FOXJ1 ACE2 SFTPC HOPX ACE2

i ii iii iv v vi vii

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The Target (A (ACE2) Profile in in the Human Respiratory ry Tract

Hou et al, Cell, 2020

Human Nasal Mucosa (Epithelium) Is the Most Fertile Ground for SARS-CoV-2 Infection

HNE LAE SAE AT2-like AT1-like

A B i

ii iii

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iv

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Ciliated Cell Is the SARS-CoV-2 Target in Human Nasal Epithelium

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icSARS-CoV-2-GFP infected HNE

Loss of f Smell in in COVID-19 19: U Unfortunately Reflects Dir irect In Infection of f Olf lfactory ry Cells

How We Acquire COVID-19 Nasal and Lung Infections

Hou et al, Cell, 2020

The SARS-CoV-2 Infected Human Lung, Part I

B SARS-CoV-2

SARS-CoV-2 MUC5B SARS-CoV-2 MUC5AC SARS-CoV-2 α-Tub

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H&E SARS-CoV-2 SARS-CoV-2 sense

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The Cause of f COVID-19 Shortness of f Breath: In Infection and Loss of f Key Lung Cell Type

Control

We Are All Different: Differential Infectivity of Human Airway Epithelium

icSARS-CoV-2-GFP infected LAE at 72hpi

Donor 1 Donor 2 Donor 3 Donor 4 Donor 5

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GFP cilia staining

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SARS-CoV-2 Infecting Human Airway Epithelia: The Numbers Game Is Not on Our Side!

Ehre, NEJM, In Press

How Is Is SARS-CoV-2 Transmitted: The Worst Way, Small Aerosol Part rticles

Long-Range (> 2 m) Close-Range Only (< 2 m)

WHAT Is “Small”?

“Small” Referenced to Things We Know

How Do We Produce These In Infectious Aerosols?

Morowska et al, J Aerosol Sci, 2009

Im Important Lessons

The Givens:

• Wear a mask – test/trace/isolate
• Maintain distance – fewer people (reduces potential total source)
• Do not linger
• Outdoors is safer than indoors

Aerosol Transmission Suggests:

• CDC “exposed” definition (> 15 min within 6 feet) is not adequate
• COVID patients can infect family members when recovering at home?
• Plexiglass shields only protect against droplets, not aerosols

Save singing for the shower : )

Cover Your Nose: E Even If If You Are the Next xt Pri rime Min inister

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f Germany!

How Good Are Mask Materials?

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1 2 50 100

(Log µg/ml)

% Neutralization

MERS-27 m336 EDE1-C10

µ

µ

% Neutralization

A

µ

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1 2 50 100

(Log µg/ml)

% Neutralization icSARS-CoV-nLuc

S230 S230.15 S227.9 MERS-27 m336 EDE1-C10

µ

% Neutralization

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B

Candidate Vaccine: Novel and Traditional Approaches

• 1. Moderna: mRNA
• 2. Roche/Oxford: Adenovirus DNA
• 3. China/Russia: Protein (spike)

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Pre-Immune Immune Vaccine Candidates 1 2 3 4 5 6 (Log10) Test Survey (Log10) Test Survey

Hou et al, Cell, 2020

THANK YOU!

richard_boucher@med.unc.edu