4.7 COVID-19

Commercial Antibody Treatment

synthesized antibodies against covid many different ones to ensure viral resistance does not happen

SARS-CoV-2 utilizes the [Spike Protein] protein to interact with

the [ACE‑2] protein on human host cells.

Prevention: Vaccination

0 approved preclinical --> phase 1 --> phase 2 --> phase 3

Replication Cycle

1. Attachment/Entry 2. Replication, Transcription, Translation 3. Assembly and Packaging 4. Release

Sporadic

Disease that occurs infrequently and irregularly

SARS-CoV-2

Enveloped, RNA Virus Classification: Class IV, +ssRNA Size: 26.4 to 31.7 kilobases Open Reading Frames: 14

Assembly, Packaging, and Release

1. Newly synthesized viral proteins sent to the Golgi where new viruses are created*The virus acquires is envelope from the Golgi membrane 2. New viruses are then released into the environment to infect new neighboring cells 3. Host cells are not immediately killed, they continue to produce viruses; however, over time the cell will eventually die.

Transcription and Translation

1. Viral RNA is initially translated by host cell ribosomes to make the viral RNA Replicase 2. RNA Replicase copies viral RNA *Viral Protein *RNA Dependent RNA Polymerase *Make RNA from RNA 3. Newly copied Viral RNA is then translated by host proteins to make viral proteins

Attachment and Entry

1. Virus attaches to host cells via Spike protein 2. Spike (viral protein) attaches to ACE2 (host receptor) 3. The viral envelope fuses with the host cell membrane releasing the nucleocapsid into the host cell

Spike Protein

A Virus needs a host to replicate Viral genomes do not encode all the machinery (proteins) required to make new viruses For a virus to infect a cell it must be able to attach/bind to that cell Specific proteins on the viral surface interact with specific proteins on a host cell allowing for attachment or "docking" and eventual infection of that cell If the host cell doesn't express that protein receptor, the virus will not be able to attach/bind and will not infect that cell The SARS-CoV-2 Spike Protein directly binds to the ACE2 protein on human cells ACE2 is mainly found in vascular endothelial cells, the kidneys, and in the testes. It's also expressed in the lung and gastrointestinal tract; tissues shown to be infected by SARS-CoV-2 Remember that host cell receptors have their own function independent of viral binding. These receptors did not evolve as viral docking stations allowing for viral infection. ACE2 is a Type I transmembrane metallocarboxypeptidase involved in the vascular system.

Asymptomatic Carriers

An asymptomatic carrier is someone who has SARS-CoV-2 virus but does not show any symptoms of disease Infection is term reserved for describing a scenario where someone has the infectious agent, resulting in disease (damage to host) Based on current reporting, it's estimated that ~31% of individuals may be asymptomatic carriers (ranging from 24- 38%) Wearing a mask helps ensure that if you are an asymptomatic carrier than you are not unknowingly exposing others to the virus

Pandemic

An epidemic that has spread over many countries or continents

Flatten the Curve

At the start of the pandemic in March 2020, the number of new COVID-19 cases was overwhelming many hospitals and critical care centers, including Intensive Care Units (ICU) The purpose of social distancing is to limit close interactions of individuals which lead to increased risk of transmission of the virus Social distancing aides in decreasing the rate of the number of newly infected individuals as well as the number of those needing hospitalization

SARS-CoV-2 & COVID-19

Coronavirus Disease first appeared in 2019 (COVID-19) The disease is caused by the viral pathogen Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) It is genetically related to the coronavirus that caused the SARS outbreak in 2003, thus the "2" designation. Pathogens don't always have the same name as their associated disease Example: The Human Immunodeficiency Virus (HIV) causes the disease AIDS Acquired immunodeficiency syndrome) Example: The bacterial pathogen Yersinia pestis causes the disease plague

COVID-19 is the [Disease]SARS-CoV-2 is the [Pathogen]

Coughing and shortness of breath are [Symptoms/Clinical Signs of Disease]

Transmission

Droplet Transmission: • Large respiratory droplets that typically fall to the ground within ~6-8 feet Airborne Transmission: • Small respiratory droplet nuclei (aerosols) that remain suspended in air and travel in air currents Fomite Transmission:• Transmission of virus from contaminated, inanimate surfaces (e.g. doorknob, pen)

Treatments

FDA Approved The drug is safe and effective for its intended use Benefits outweigh risks Based on substantial research & clinical trials Investigational Treatments A potential drug that may help treat or cure a disease These drugs have been tested in a lab and shown to have potential in humans Drugs must then go through rigorous clinical trials to determine safety and effectiveness in humans Expanded Access AKA: Compassionate Use A patient with an imminent, life- threatening condition may apply to use an investigational drug (prior to approval) if no other treatments are available Emergency Use Authorization (EUA) A drug may be used in advance of full approval based on current scientific evidence Allows promising safe and effective drugs to be used in emergency situations when no approved therapies are available Off-Label Use Using an approved drug for treating conditions not tested in initial approval Example: hydroxychloroquine preclinical --> phase 1 20-80 drug approved for testing in humans --> phase 2 100-200 --> phase 3 1000-3000 drug submitted for FDA approval --> FDA Review drug approved--> phase 4 1000+ participants

Outbreak

Increase, often sudden, in the number of cases of a disease above what is normally expected in that population in a specific (small/confined) area.

Infectious Dose and R0

Infectious Dose: How much of an infectious agent is needed to cause an infection in a host How much virus must an individual intake to become infected? Currently not know for SARS-CoV-2 R-naught (R0): Basic Reproduction Number How many un-infected individuals can one infected individual infect? SARS-CoV-2 estimated to be 2.5 (1.8-3.6)

Adenovirus Vaccine

Johnson & Johnson/Janssen Pharmaceuticals AstraZeneca/University of Oxford Adenoviruses are double-stranded DNA Viruses Group of viruses that cause the common cold Viruses are modified so they can no longer replicate & cause disease (termed vectors) Viral vectors are engineered to encode a gene for a protein that the immune system will recognize and induce an immune response • Example: spike gene from SARS-CoV-2 When the engineered viral vector is given to humans as a vaccine, the engineered viral gene (DNA) is released into the host cell, the spike gene is transcribed and translated by the host into an independent Spike Protein. The Spike Protein is then processed by the host cell and displayed to activate the immune system The viral vector cannot replicate and cannot cause disease in the host. basically delivery system The only gene from SARS-CoV-2 is the spike gene, The vaccine does not include the SARS-CoV-2 virus It is impossible to contract COVID-19 from this vaccine

Masks

Masks help stop the spread Main purpose is to stop infected individuals from releasing high numbers of virus into the environment Also help decrease the amount of virus an un-infected individual may be exposed to Face-shields are excellent secondary measures to help inhibit droplet transmission. Must be worn with a mask to be most protective. cloth, disposable, KN95

RNA Dependent RNA Polymerase

RNA Dependent RNA Polymerase Viral protein that makes an RNA copy from an RNA template RNA à RNA Required by many RNA viruses to make copies of their RNA genomes Host cells (like human cells) don't encode this protein thus it must be encoded for on the viral genome

Epidemic

Similar to an outbreak but affecting a much larger number of individuals in a larger geographic area

Viral Test

Tests for active infection or those who are current asymptomatic carriers RT-PCR-based test Detects presence of viral RNA AKA: Nasal Swab Test

Antibody Test

Tests for previous infection Detects presence of SARS-CoV-2 antibodies in blood Does not directly test the presence of virus AKA: Antigen Test, Blood Test

Endemic

The constant presence of a disease or infectious agent in a population within a geographic area

Everyday Preventive Actions

Wear a mask Social distance Refrain from closed/confined spaces especially when wearing a mask is not possible Wash your hands withs oap and water*Hand sanitizer is a good alternative when soap and water are not available Avoid touching yourf ace Stay home when not feeling well, contact your health care provider, and get tested

[Viral Test (Nasal Swab)] detects replicating virus and current/active infections, or current asymptomatic carriers

[Antibody Test (Blood Test)] detects the presence of an immune response indicating a previous infection

Symptoms

cough, shortness of breath or difficulty breathing fever or chills muscle or body aches vomiting or diarrhea new loss of taste or smell

Once SARS-CoV-2 genome enters into human host cells, the host RNA Dependent RNA polymerase enzyme will copy viral RNA into new RNA copies to eventually be packaged into new viruses.

false

Convalescent Plasma

from donors who had covid-19 to those who currently have it APO compatible matching SARS-CoV-2 neutralizing antibodies seriously ill patients

Dexamethasone

lower 28-day mortality corticosteroid antiinflammatory critically ill patients ventilators no benefit for mild symptoms

Which potential SARS-CoV-2 Vaccine does not utilize engineered viruses, but formulations, to deliver SARS-CoV-2 spike transcript which will be translated by host cells into Spike Protein to initiate an immune response?

mRNA Vaccine

Currently there is no FDA approved treatments for COVID-19. Which of the following potential treatments uses a nucleoside analogue to block viral transcription and thus production of new viruses?

remdesvir

Wearing a mask helps prevent the spread of SARS-CoV-2.

true

Recombinant Vesicular Stomatitis Virus (VSV) Vaccine

• Merck, Sharpe & Dohme/International AIDS Vaccine Initiative natural VSV Virus expressing VSV-glycoprotein does not cause disease recombinant VSV Virus expressing SARS-CoV-2 Spike Protein infects cows, rare in humans

mRNA Vaccine

• Moderna • BioNTech/Fosun Pharma/Pfizer closely mimics a native viral infection leading to B and T cell responses no virus used spike protein mRNA translated into spike protein

Remdesvir

• Nucleoside analogue, antiviral chemotherapeutic Mimics adenine and is incorporated into viral RNA during replication Incorporation of Remdesivir results in pre- termination of viral transcription Inhibition of transcription results in an inability to create viral proteins and new viruses. Broad-spectrum activity against many viruses including EBOLA, Marburg, SARS, MERS and SARS-CoV-2 broad spectrum activity