SARS-CoV-2 & Covid-19

**What 2 genetic features of SARS-CoV2 differ from other alpha and betacoronaviruses?

1. "Mutations in the receptor-binding domain of the Spike (S) Protein" -Six receptor-domain amino acids have been shown to be critical for binding of S1 to ACE2 receptors. -Five of these six residues differ between SARS-CoV-2 versus SARS-CoV (the SARS virus). 2. "SARS-CoV-2 has a polybasic cleavage site at the junction of S1 and S2" -This allows effective cleavage by TMPRSS2 and other proteases. -This plays a role in determining host range. -A proline is also inserted at this site in SARS-CoV-2 that results in the addition of carbohydratesm (glycoprotein).

1. SARS-CoV-2 often spreads in clusters and during ______________________ events? **2. The Ro for SARS-CoV-2 is 2.39 - 3.44. What does this mean?

1. "Superspreader" 2. It means it is HIGHLY CONTAGIOUS

1. How long is the average incubation period for a person with SARS-CoV-2? 2. How many percent will present with neurologic symptoms?

1. 5 days (range = 1 to 14 days) 33%

1. In the Enteric Neuronal Route, the virus can travel from the gut to the brain via what? 2. Which nerve provides a direct connection of the enteric nervous system with the brain? 3. ______________ receptor is found in high amounts on the enterocyte cells of the gut? 4. (True/False) SARS-CoV2 can directly infect and replicate within intestinal cells that further triggers a cytokine storm within the gut that may expand into the brain as neuroinflammation?

1. A Neural Route 2. The Vagus Nerve 3. ACE2 4. True

Describe Stage 3 (Hyperinflammation Phase) of Cytokine Storm Syndrome?

1. A worsening inflammation response even with diminishing virus load 2. Hyperproduction of TNF-Alpha and granulocyte colony stimulating factor

1. SARS-CoV-2 binds to target cells through ____________? 2. The expression of ACE2 is substantially increased in patients with ______________ or _______________ diabetes who are treated with angiotensin II type-1 receptor blockers? 3. ACE2 expression is increased by _________________? 4. _________________ is also treated with angiotensin II type-1 receptor blockers? 5. ________________ and _________________treatment with ACE2-stimulating drugs may increase the risk for developing severe and fatal COVID-19?

1. ACE2 2. Type 1 or Type 2 3. Ibuprofen 4. Hypertension 5. Diabetes & Hypertension

1. What is the primary transmission for SARS-CoV-2? 2. (True/False) It may be possible for a person to become infected through indirect contact by touching a contaminated surface and then touching their mouth, nose, or possibly their eyes? 3. It may be possible for a person's ______________ to be infected via infected respiratory droplets or aerosols and be a source for infection of the mouth or nose after touching a contaminated cornea? 4. Is there any evidence for virus spread via feces, urine, breast milk, food, wastewater, drinking water, or mother-to-baby during pregnancy?

1. Contact of the mucous membranes with virus-infected respiratory droplets or aerosols. 2. True 3. Cornea 4. No

*****Rank the Mortality rates of SARS, MERS, Covid-19 from low to high?

1. Covid-19 (2.2%) 2. SARS (9.7%) 3. MERS (36%)

1. Critically ill patients with COVID-19 may exhibit significant increases in amounts of inflammatory cytokines such as TNF- Alpha and develop this type of syndrome? 2. Cytokine Storm Syndrome is a hyperimmune response induced by SARS-CoV-2 that results in an imbalance of _______________? 3. Cytokine Storm Syndrome caused by SARS-CoV-2, SARS-CoV, and MERS-CoV are different how?

1. Cytokine Storm Syndrome 2. Cytokine levels 3. With respect to the patterns of cytokines stimulated

1. COVID-19 predisposes patients to a _________________ state. Severe thrombotic complications may cause significant mortality? 2. (True/False) Vascular endothelial cell injury is an important observation in the lungs of patients with COVID-19 and primary blood clot formation occurs directly in the lungs. SARS-CoV-2 directly infects endothelial cells through ACE2?

1. Hypercoagulable (Blood-Clotting) 2. True

What factors play into the reason older people have a higher mortaliy rate for SARS-CoV-2?

1. Hypertension 2. Diabetes 3. Cardiovascular Disease 4. Asthma 5. Smoking

Rank the R-naught of SARS-CoV, MERS-CoV, & SARS-CoV-2 from low to high?

1. MERS-CoV (0.29 - 0.80) 2. SARS-CoV (1.7 - 3.6) 3. SARS-CoV-2 (2.39 - 3.44)

1. In the Respitory Neuronal Route, the virus can travel to the respiratory system of the brain known as the ___________ ______________ by neurons which innervate and regulate the respiratory system? 2. Porcine coronavirus CoV HEV 67N experimentally shown to invade the brain of ___________ via peripheral nerves? 3. (True/False) CoV HEV 67N shown to be cross synapses and be transmitted from neuron to neuron?

1. Medulla Oblongata 2. Pigs 3. True

*****What are the clinical symptoms of a person with SARS-CoV-2?

1. Most people have mild or asymptomatic disease, -some develop acute respiratory distress syndrome. -Multiorgan failure -Septic shock vascular complications including blood clots, and/or neurologic disease. 2. A significant number of people who have recovered from the acute phase of the disease continue to experience a range of symptoms such as: -severe fatigue -memory loss and other cognitive issues, low grade fever, muscle weakness, and breathlessness for many months.

These 2 scenarios can plausibly explain the origin of SARS-CoV-2?

1. Natural selection in an animal host before zoonotic transfer. 2. Natural selection in humans following zoonotic transfer.

1. _________________________ is one of the major pathways associated with a variety of CNS complications? 2. How can SARS-CoV-2 inflict structural and metabolic damage within the CNS? 3. IL-6 production is stimulated from microglial cells and _________________ within the brain? 4. The virus can also activate CD4+ T cells to secrete IL-6 that in turn activate ____________________?

1. Neuroinflammation 2. By overly stimulating inflammatory cytokines (TNF-Aplha, IL-6) 3. Astrocytes 4. Macrophages

1. In the Neural Route, the virus travels to the brain via ______________ _______________ to the Olfactory Bulb? 2. _____________ receptors are present on olfactory rods? 3. The virus can reach the Cerebrospinal fluid within how many days? 4. (True/False) Removal of the olfactory bulbs of mice restricts entry of virus into the central nervous system?

1. Olfactory Neurons 2. ACE2 3. 7 Days 4. True

Describe Stage 1 (Early Infection Phase) of Cytokine Storm Syndrome?

1. SARS-CoV-2 infiltration to the lung parenchyma and its proliferation occurs. 2. The immune response is initiated by monocytes, macrophages, and neutrophils.

1. This system is affected broadly by SARS-CoV-2 infection? 2. Direct virus infection of the _______________ tissue? 3. Lung injury that leads to an oxygen supply-demand ________________ to the heart? 4. Microvascular dysfunction that results in microvascular thrombosis/ the formation of what?

1. The Cardiovascular System 2. Myocardial 3. Imbalance 4. Blood Clots

***1. In the Hematogenous Route, the high expression of ACE2 receptor on blood-brain barrier endothelial cells suggests what? 2. It also suggests what?

1. The virus can cause blood-brain barrier damage and infect the central nervous system. 2. The virus can enter the central nervous system via infected circulating monocytes using the "Trojan Horse" mechanism.

1. Why is their a higher mortality rate in men than women for SARS-CoV-2? 2. Why have there been a greater proportion of death among African Americans?

1. This may be attributable to lifestyle choices (smoking and drinking alcohol). 2. Possibly due to a lack of health insurance and underlying conditions of hypertension, diabetes, & cardiovascular disease. Similar issues affect Latino and Native American communities.

Describe Stage 2 (Pulmonary Phase) of Cytokine Storm Syndrome?

1. Tissue injury, vasodilation, endothelial permeability, and edema occurs. 2. Additional leukocytes are recruited from the blood

1. Is it possible that a progenitor of SARS-CoV2 jumped to humans, acquiring its genomic features through adaptation during undetected human-to-human transmission? 2. True/False) All SARS-CoV-2 genomes sequenced so far have the same genomic features and are therefore derived from a common ancestor? 3. The presence in pangolins of a receptor-binding domain very similar to that of SARS-CoV-2 means that this was probably the virus that jumped to humans?

1. Yes, it is possible 2. True 3. True

SARS-CoV-2 initiates infection by binding of its Spike (S) Protein to ________________- Converting Enzyme 2 (ACE2) on Protein the host cell surface?

Angiotensin

Why can't Covid-19 just be considered as a disorder of the pulmonary system?

Because it has a significant central nervous system involvement

***What is Covid-19 "Long haulers"

COVID-19 patients who often suffer from lingering persist symptoms -Extreme fatigue (chronic fatigue syndrome) -Shortness of breath and chest pain -Chills and sweats (low grade fever) -Body aches -Chronic Headaches -Diarrhea

_____________ _______________ is central to the pathogenesis of SARS-CoV-2 infection?

Cytokine Storm

R-naught (R0) Number is an indicator of what?

How contagious a disease is in a population -On average, how many people one infected person can infect in a population where all persons are susceptible to in a population.

What are the 2 routes for SARS-CoV-2 Dissemination to the Central Nervous System?

Neural Route & Hematogenous Route

**What may be the reason for SARS-CoV-2 high infectivity and highly contagious nature?

The affinity between the S protein of SARS-CoV-2 and the target cell ACE2 is 10 to 20 times stronger than that of SARS-CoV

****Covid-19 is caused by what?

The betacoronavirus known as SARS-CoV-2

(True/False) Neither bat nor pangolin viruses have polybasic cleavage sites?

True

(True/False) SARS-CoV-2 directly infects the endothelial cells that make up the blood-brain barrier. The tight junctions in these endothelial cells are destroyed providing monocytes, macrophages, neutrophils, proinflammatory cytokines (TNF-a), and even access to the brain parenchyma or cerebrospinal fluid?

True

(True/False) SARS-CoV2 is an RNA containing virus?

True

There is growing evidence that Cytokine Storm Syndrome is one of the major pathways through which SAR-CoV-2 induces damage to the brain?

True