MCB55 Midterm 2 - Modules 4-6

SARS CoV1, MERS-CoV, SARS CoV2

The 3 highly pathogenic human coronaviruses (all causing severe respiratory syndrome)

HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1

Four human coronaviruses (mild upper respiratory diseases in immunocompetent hosts), their high lethality reduces transmission

7th

SARS CoV-2 is the ___ coronavirus known to infect humans

Coronavirus

(CoV) — a large family of viruses that can cause disease in humans and animals

SARS CoV-2

(Severe Acute Respiratory Syndrome Coronavirus-2) — the strain of virus causing the current pandemic

COVID-19

(Coronavirus Disease 2019) — the set of symptoms caused by SARS-CoV-2

corona

latin for crown

Coronavirus virus structure

Spike, membrane, envelope, nucleocapsid, RNA viral genome

Neutralization

one mechanism of antibody functions

targeting spikes

Antibodies neutralize coronaviruses by

ACE2 (Angiotensin-converting enzyme 2)

helps regulate blood pressure

ACE2 receptors

Covid-19 spikes attach to

Week 1 of COVID

Virus finds home in nasal lining (many ACE2), lots of it found due to copying, some people are asymptomatic, fever, dry cough, sore throat, loss of smell/taste, headaches, body aches

Lungs in COVID

virus moves windpipe to lungs, virus attacks alveoli (many ACE2)

alveoli

thin lung sacks that pass oxygen into the capillaries

Pneumonia

Virus replicates in alveoli, lung cells release cytokines, virus 2 cells kill each other leaving behind puss, coughing, fever, shallow rapid respiration, nasal prongs can be used to breathe in oxygen

ARDS (Acute Respiratory Distress Syndrome)

can develop from pneumonia, oxygen levels plummet (makes it hard to breathe) patients go on ventilators, alveoli stuffed with/(fluid, white blood cells, mucus, dead cells), many die

accounted for

to fight off covid both disease phases must be

antiviral therapies

viral response phase needs

anti inflammatory drugs

host inflammatory phase needs

ACE2 expressions

some of covid-19s symptoms accounted for by

Nasal (initial infection, spread, loss of smell)

how ACE2 effects nose

pneumonia ARDS

how ACE2 effects lungs

inflammation, oxygen loss, blood clots cause damage

how ACE2 effects heart

gastrointestinal symptoms, virus is shed in feces (waste water monitoring can be an early warning for future outbreaks)

how ACE2 effects ileum

Chronic condition, that occurs after Covid, 10-30% incident rate (higher for people who were hospitalized), many symptoms

Long Covid

possibly caused by antigen persistence, herpesvirus reactivation, dysbiosis, or microvascular dysfunction

how is long covid created

10-30%

non-hospitalized cases of long covid

50-70%

hospitalized cases of long covid

10-12%

vaccinated cases of long covid

5 weeks

SARS-CoV2 was identified and sequenced in

700 million

confirmed covid-19 cases worldwide

7 million

confirmed covid-19 deaths

19-36 million

total deaths due to covid-19 (including excess mortality) (Many people were confirmed to be positive at their deaths but not all deaths were attributed to COVID)

4% of global population but >15% of all cases

U.S. during covid-19

age, comorbidity and social inequities

Hospitalization and Death increase according to

vaccines cause autism, false claim from Andrew Wakefield, study reacted

Vaccine misinformation spread by government

6,000+ false narratives, 80% of adults encountered false info, microchip vaccine conspiracy, misinformation spreads faster than official updates, emphasized importance of media literacy and trust in science

Infodemic

14 billion

vaccine doses administered worldwide

25%

U.S. vaccine hesitancy

over 50%

Africa/Eastern Europe vaccine hesitancy

coronaviruses were a concern, Worldwide collaboration, Funding for COVID-19 vaccine research Close collaboration between pharmaceutical companies and governmental agencies, Very high infection rate in the population and no difficulty recruiting volunteers

COVID vaccine developed incredibly fast

fatality reduction

vaccine rate for covid had a huge impact on

mRNA vaccine

Pfizer-BioNTech and Moderna

chimpanzee-derived adenovirus

AstraZeneca-Oxford and Covishield

human adenovirus (Ad26)

Johnson & Johnson/Janssen

inactivated/killed SARS-CoV2 virus

Sinovac and Sinopharm

protein subunit vaccines

Novavax

14.8 billion

how many doses of the covid-19 vaccine were administered?

2.5 million deaths (benefit was limited to manly older people)

COVID-19 vaccinations averted

Mimics the spike protein (Knew the spike protein from SARS CoV1), Make the RNA (Transcription and purification, Mix RNA with lipids to form a thingy that traps the RNA, Filtration)

mRNA vaccines

cytokines

RNA from viruses are recognized by innate sensors and release

antigen-presenting cells

Injected mRNA vaccines are endocytosed by

ribosomes

After entering the cytosol, the mRNA (from the vaccine) is translated into protein by the

immune system

The translated antigenic protein (from the vaccine) stimulates the

innate sensors and elicit release of cytokines

RNA from viruses (or lipid mRNA particles) are recognize by

decreased activation of TLR signaling and cytosolic RNA sensors

Incorporation of modified nucleotides into the mRNA strongly reduces the innate immune signaling through

Global anxiety and depression increased by 25%

Mental Health & Social Shifts

Global GDP fell 3.1% in 2020, one of the largest declines in history, U.S. unemployment surged from 3.5% → 14.7%, IMF estimates $12 trillion in global output losses, 100 million people pushed into extreme poverty

Economic ripple effect

Global CO₂ emissions fell 6.4% (2.3 billion tons) in 2020, Air pollution dropped up to 60% in major urban centers

environmental impact of the pandemic 

enveloped RNA virus with a helical capsid

Rabies virus is an

75 nm in diameter and 180 nm long

Rabies is approximately

Glycoprotein, envelope membrane, matrix protein, ribonucleoprotein

Structure of rabies virus

to rabies virus

Several others Lyssaviruses are closely related

a bite from an infected (“rabid”) animal.

These viruses are also usually transmitted via

Rabies virus

It is a virus from the genus Lyssavirus. Lyssa is derived from the greek word for “rage” and “furry”

60,000 people a year

rabies kills about

Dogs, Bats, Raccoons, foxes

Rabies virus is transmitted by a rabid animal

Transmission is almost always a bite, 

Rabies transmission

Saliva from a rabid animal comes into contact with someone’s mucous membranes (eyes, noses, mouth) or fresh skin lesions

Non-bite rabies transmission

Inhalation of virus-containing aerosols, Human to human transmission through transplantation

rare ways to get rabies

dog bites

98% of human rabies cases caused by

40-60%

What percent of all animal bites cases are reported to occur in Children?

Due to their short stature, children are susceptible to bites on
face & scalp, playing in open ground or in streets, can not ward
off animals easily, more likely to provoke an animal, might not report a bite or scratch

Why are children more susceptible to getting rabies?

2-3 months

The incubation period for rabies is typically

from 1 week to several years, dependent upon factors such as the location of virus entry and viral load

incubation period for rabies may vary

fever with pain and unusual or unexplained tingling, pricking, or burning sensation (paraesthesia) at the wound site

Initial symptoms of rabies are not very specific

furious rabies

people exhibit signs of hyperactivity and hydrophobia (Death occurs after a few days due to cardio-respiratory arrest)

paralytic rabies

20% of the total number of human cases. A coma slowly develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the under-reporting of the disease

Hydrophobia

fear of water

• Since the virus is spread through saliva. it increases spit production.

• Painful spasms also develop in the muscles that control breathing and swallowing

• they feel like they are drowning hence the fear of water

Why does rabies cause hydrophobia?

Delirium, Aggression, Drooling, Muscle spasms, Drooling, Dizziness, Hallucinations

symptoms of furious rabies

Post-exposure prophylaxis (PEP)

The immediate treatment of a bite victim after rabies exposure. This prevents virus entry into the central nervous system, which results in imminent death

extensive washing and local treatment of the wound, a course of potent and effective rabies vaccine, the administration of rabies
immunoglobulin (RIG)

PEP consists of 

Any person who could be exposed to the
live rabies virus (including laboratory staff, veterinarians, animal and bat handlers, and wildlife officials), Children traveling to or living in a rabies-endemic area, Travelers who may be more than 24 hours from a medical centre with a post-exposure vaccine

Preventive immunization in people

1-3 cases reported annually, 25 cases in the past decade (7 of which were acquired outside of the U.S.), over 90% of animal rabies cases occur in wild animals, Rabies annual prevention costs ~$300 million

Rabies in the U.S.

infected bats

most rabies exposure in the US are from

The bite wound is so small (about the size of a
hypodermic needle) that the person may not know they
were bitten therefore, they don’t seek medical
attention and PEP

Why do people bitten by bats not realize it?

control of animal vectors

the primary strategy for the prevention of rabies in humans

Management of stray dog populations to reduce numbers, Vaccination

Typically targets dogs (most important animal vector for
transmission to humans) and involves

70%

Rabies can be controlled in the canine population if ___ are vaccinated using inactivated virus vaccine.

3 years

Immunity lasts for approximately _______ in the animals

Trap/vaccinate/release (TVR), Oral baits w/antivirus

Rabies Control in Wildlife

Majority of victims do not receive rabies vaccination,
and a few of those who do do not complete the full course, use of rabies immunoglobulins (RIG) is abysmally low

Why so many death by RABV when treatment is available and effective?

lack of awareness about the potential seriousness of animal bites and the need for prompt PEP in the community as well as among medical professionals and an irregular supply of antirabies vaccines and RIG, particularly in primary health care facilities. In addition, some dog bite victims cannot afford the cost of PEP

serious lapse in PEP can be attributed to

Medical (Doctors, Nurses) - Human treatment, PEP, awareness
Veterinary - Dog vaccination, surveillance
Legal - Policy, regulation, animal control laws
Design / Architecture / Planning - Safer, cleaner spaces reducing stray dog presence
Public Health / Governance -Coordination, financing, and data systems
Education / Communication - Awareness and community engagement
Research / Academia - Evidence, innovation, modeling

Zero death by 30