COVID Lecture

What does cover-19 stand for? How did it get its name?

- Coronavirus disease 2019 - WHO gave it

What are the symptoms of Covid-19

- Some are asymptomatic - Others: fever, dry cough, body ache, etc. - No sense of taste or smell or other neurological symptoms - GI symptoms in some - Shortness of breath -Secondary infection (pneumonia) - Blood clotting - Heart attack

List the main components of a human coronavirus.

- Spike protein - Membrane - Envelope + Envelope protein - RNA Viral Genome - Nucleocapsid

What is the fatality rate of SARS-CoV-2 infection?

1-3% In Shelby County, it's 1.5%

When and where did MERS-CoV-2 originate? What is the mortality rate of MERS-CoV-2? Cause and symptoms?

1. MERS-CoV-2 originated from Saudi Arabia in 2012 and spread to many other countries, including the US. 2. There is a mortality rate of 70% in those above the age of 65, but the overall rate is around 34%. 3. The virus mainly complicates stopping transmission, but some are just asymptomatic or mildly ill. It's mainly hospital acquired. It is primarily causes and transmitted by camels, which introduce it into the human population.

Where did SARS-CoV-2 originate from? Is it similar to any other viruses?

1. SARS-CoV-2 originates rom bats. The virus may have jumped from bats to humans, or through another unknown intermediate host. 2. SARS-CoV-2 is 96% identical to a coronavirus discovered in 2013 in a horseshoe bat in Yunnan Province of China. SARS-CoV-2 has 80% genetic identity to SARS-CoV-1 and 50% genetic identity to MERS-CoV.

What does the spike protein do? In the case of a typical human coronavirus, where does it bind to?

1. The spike protein mediates membrane fusion by binding to cellular receptors. 2. The spike protein on a viral envelope protein binds to the ACE-2 receptor, which is found on the surface on many cell types.

What does ARDS result from?

A cytokine storm, basically uncontrolled immune activation

What syndrome is fatality linked to?

ARDS (Acute Respiratory Distress Syndrome)

What're some risk factors to mortality from SARS-CoV-2?

Advanced age Obesity Diabetes Hypertension

What is a virus?

An intracellular, obligate, infectious parasite that consists of genetic material (either DNA or RNA) and is surrounded by a protein coat (capsid) and sometimes a membrane.They are passive agents that rely on hosts for processes like energy, protein synthesis, etc.

What family does the coronavirus belong to?

Coronaviridae

What is herd immunity?

If enough people are vaccinated (or have been infected), spread of disease stops as there are fewer and fewer "targets" for the virus

How many people need to be vaccinated to get to herd immunity?

It depends. Partly a function of "R naught" (R0) value.

How to get herd immunity for covid-19?

Need 70-80% of population to be vaccinated

Describe Covid-19 progression.

Once the virus is detected through PCR, there's an incubation period that lasts from 2-14 days. During that period, the viral RNA increases, rising above the infectious level til the beginning of the viral symptom phase. During this phase, viral RNA levels fall and antibody levels rise. They continue to rise through the early inflammatory phase , secondary infection phase, and multi system inflammatory phase.

Why was vaccine production so fast?

One thing that helped speed vaccine production for SARS-CoV-2: the study of other coronaviruses. Scientists knew that the spike protein was highly immunogenic and was targeted by neutralizing antibodies

When and where did SARS-CoV-1 appear?

SARS-CoV-1 appeared in 2002 in China and left 2004.It mainly originated from animals (specifically bats); it's been replicated in civets and dogs.

What type of infection does SARS-CoV-1 involve? What's the mortality rate?

SARS-CoV-1 involves droplet infection. SARS-CoV-1 generally has an infection rate of about 10%. Yet, it increases to over 50% for those over 65. Those infected had serious disease and are mostly hospital acquired.

How did SARS-CoV-2 originate?

SARS-CoV-2 is of zoonotic origin (bats) and first found in Wuhan City, Hubei Province, China in December 2019.

What does SARS-CoV-2 do?

SARS-CoV-2 is the cause of COVID-19. It is primarily a positive sense single strand RNA virus. Positive sense just means that the genome of the virus can function for mRNA once. It enters the host cell.

Why are two doses separated by 3-4 weeks?

See notes on phone

What does SARS-CoV-2 stand for?

Severe Acute Respiratory Syndrome Coronavirus 2

Describe the article she gave on coined 19 being a case of autoimmunity.

The article suggested that severe cover is a case of autoimmunity, A group at Rockefeller U reported that more than 10% of 987 people with severe COVID 19 had antibodies that attacked/blocked type1 interferon, which normally functions to bolster the immune response again foreign pathogens

What causes Covid-19?

The disease is caused by SARS-CoV-2.

When was the coronavirus discovered and how did it get its name?

The first scientific encounter occurred in the early 1900s when vets noticed bronchial infections in animals, such as pigs, chickens, and cats. Human coronaviruses were discovered in the early 1960s.

How is SARS-CoV-2 transmitted?

The primary route of transmission is through droplets (5-10 micrometers in diameter) and aerosols (less than 5 micrometers). Basically airborne transmission

What is R0?

The reproduction number tells you how contagious an infectious disease is. For the virus, it's around 2-2.5. However in other populations, it may be as high as 4.5.

How many coronaviruses cause the common cold?

There are four among all the viruses that cause the common cold. The three that infects humans are not innocuous.

What is the Johnson-Johnson vaccine?

• Also adenovirus-based, engineered to deliver the SARS-CoV-2 spike protein • Technology is same they used to produce an Ebola vaccine • Early studies report at least 70% efficacy•possibly higher with 2nd dose • A plus: may be a one dose vaccine • Cost is also reasonable: about 10$ per dose • Another plus: doesn't require ultra-cold storage, refrigeration okay for 3 months • No severe adverse side effects reported

What're the benefits of neutralizing antibodies?

• Bind to specific part of a pathogen • In lab setting, shown to decrease SARS-CoV-2 viral infection of cells • May block interactions with host cell receptors • Might bind to viral capsid and inhibit the "freeing" of the viral genome in the host cell

What're inactivated vaccines?

• May be referred to as "killed" • Among earliest developed • Don't cause infection • Stimulate a B cell response (= antibodies) • Usually require "boosters" • Generally, fewer side effects than live attenuated • Tend to evoke less robust immune response • The influenza vaccine that is injected is this type

What're the phases/criteria that the FDA uses to approve vaccines?

• Phase I: done on small number (20-100) of healthy volunteers•Serious side effects? Dose? Does it result in immune response? • Phase II: hundreds of volunteers, not just the healthy - Side effects? Optimal dose? Immune response? • Phase III: hundreds to thousands - Comparison between vaccinated vs non-vaccinated - Effective (are neutralizing antibodies produced)? - Side effects? • FDA approval only if vaccine is SAFE, EFFECTIVE and benefits outweigh risks

What's the future for SARS-CoV-2?

•According to a January 2021 article in Science magazine: Infection-blocking immunity wanes fairly quickly, BUT•Disease-reducing immunity is long-lived •SARS-CoV-2 may thus just become (once endemic phase is over) another cold virus •Most people will get it as children, with the possibility of mild reinfections later

What is the chimpanzee adenovirus vectored vaccine?

•Adenoviruses cause colds •Adenovirus used in the AstraZeneca vaccine infects chimpanzees, not people •thus we should not have antibodies against this virus •The chimp virus was engineered to carry a piece of the SARS-CoV-2 spike protein •When delivered into human cells, the engineered virus triggers an immune response to spike, leading to production of antibodies and memory cells that recognize SARS-CoV-2 •To date, an adenovirus vaccine has yet to be approved for use in the U.S.

What is the Oxford-AstraZeneca vaccine?

•Developed at the University of Oxford (UK) •"non-profit"; 2-3$ per dose •Type of vaccine: chimpanzee adenovirus vectored •For adults 18 and older •Two-dose regimen, 28 days apart •Some trial participants accidentally got only ½ dose with first vaccination •Tested in both UK, South Africa and Brazil •Approved for use in UK •A plus: requires only usual refrigerator storage•Efficacy overall about 70% •In trial group that got a lower first dose, efficacy was much higher than in groups that got two "standard" doses

Describe the Moderna vaccine

•EUA is for persons 18 years and older •two injections given 28 days apart •Efficacy rate 94.1% •Cost 25-37$/dose •Contraindication: those with known history of severe allergic reaction (anaphylaxis) to any component in the vaccine•Immunocompromised persons may have a diminished response to the Moderna vaccine •Most common adverse reactions: pain at injection site, fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, axillary swelling and tenderness, fever, swelling and erythema at injection site •Seems more likely after 2nd dose

Benefits of the mRNA vaccines

•Moderna says "mRNA is the best platform to make vaccines" •They can be very rapidly developed •Clinical trials of nine different mRNA vaccines have shown neutralizing antibodies were elicited •Several mRNA vaccines in early phases of development are targeting: hMPV, RSV, influenza, CMV, EBV, Zika

Describe the Pfizer vaccine

•Recommended for 16 and over •two injections given 21 days apart •Efficacy rate 95% 7 days after 2nd dose •Unclear at this point: is this "sterilizing immunity" or does it just protect from disease? •A downside of this vaccine: strict temp requirements - Has to be kept at minus 70oC - Cost about 19$/dose - Side effects were mostly "flu-ish"; more common after second dose •Contraindication: those with known history of severe allergic reaction (anaphylaxis) to any component in the vaccine

How many vaccines for SARS-CoV-2 are in development, and which ones are approved?

•Remarkably, 58 vaccines are being developed/are in some point in clinical trials •Presently, just two are approved (emergency use authorization) in the U.S. (Pfizer +Moderna) •Both of these are "mRNA vaccines" •AstraZeneca vaccine may come on-line in the spring in U.S. •Also likely to be approved soon is Johnson and Johnson vaccine

What're subunit/conjugate/recombinant vaccines?

•Specific macromolecule (protein, polysaccharide, lipid) from virus •The macromolecule stimulates an immune response •This type cannot cause disease •hepatitis B, Hib, HPV vaccines are this type

What're mRNA vaccines?

•Technology is new, but has in fact been studied for more than a decade •The mRNA molecule is coated with a lipid vesicle ("liquid nanoparticle") that protects the nucleic acid •The lipid vesicle is not the same in the two mRNA vaccines currently being given •An advantage of mRNA vaccines over the conventional categories: cheaper, less time to develop •No need to pass viruses in cell culture

Describe the Novavax vaccine.

•The company is "tiny"! 18 months ago, a lot of people thought the company was going to go under •Worked on vaccines for 20 years but never brought one to market •Their vaccine, funded in part by Operation Warp Speed (as are the other 4 I've shown you) is a protein subunit vaccine•vaccine is their version of spike protein mixed with an additional compound ("adjuvant") that helps stimulate a strong protective immune response •Phase III trials going on now, Memphis is one location •Two injections, 21 days apart •89% efficacy in U.K, but less potent in South African trials (new variants are circulating in both of these locations •Will only require normal refrigeration - Another important note: the efficacy numbers refer to ability to prevent disease; there may be higher efficacy in preventing SEVERE disease. This is important in South African trials, as there's a new variant there.

How do mRNA vaccines do their magic?

•The mRNA in its lipid coating enters dendritic cells and macrophages (cells of the immune system) in lymph nodes near the vaccination site•In host cells, ribosomes translate the mRNA into the viral spike protein •Dendritic cells and macrophages "display" the spike protein piece, kind of like a billboard, on their surface•B cells and T helper cells "see" bits of spike protein (the "antigen"), and then do their thing.

What're vector vaccines?

•These begin with a weakened version of a live virus, the "vector" •This virus does not cause illness •A piece of genetic material from a viral target (e.g., SARS-CoV-2) is spliced into the genetic material of the live virus • Once the vector is injected into the host, the genetic material that was inserted into the vector evokes an immune response

What're live vaccines?

•Virus is weakened ("attenuated") • Cause infection without symptoms • Generally, stimulate both a memory B cell and memory T cell response • Can cause illness in the immunosuppressed • Measles, mumps, rubella vaccines of this type (MMR) • Nasal spray influenza vaccine is of this type