Viruses and COVID-19

• What is a virus? – Viruses are infectious agents composed of some type of

genetic material (either DNA or RNA) surrounded by a protein coat (known as a capsid)

– Click on my picture below for a brief video intro

• How are viruses different from cells? – Viruses are not surrounded by a self-generated

plasma membrane (although some viruses have phospholipid “envelopes” surrounding them, which largely come from their host cell’s plasma membrane)

– Viruses cannot grow, metabolize food or reproduce on their own • They must infect a host cell, and use its cellular machinery to

make copies of themselves

• So are viruses alive? – That depends on your definition of “alive”! – Some say that, because they evolve, they should be

considered living things – Others say that, because they can’t reproduce on their

own, they are not alive

• Viral Reproduction and Genetics – Viruses lack the “machinery” to make proteins from their

own genetic material; therefore, they must insert their DNA or RNA into a host cell

– The host cell then reads the viral genetic instructions and makes the viral proteins

– Some viruses have RNA as their genetic material • Cold, influenza (aka flu), measles and coronaviruses

– Others have DNA as their genetic material • Herpes and smallpox viruses

– Some viruses have a single molecule of genetic material (these are called “unsegmented” viruses) • Coronaviruses • Human rhinoviruses

– Others have multiple molecules of genetic material (these are called “segmented” viruses) • Influenza viruses • Rotaviruses

• How do viruses evolve? – Viruses can undergo mutations over time, which can

either increase or decrease the severity of disease, and can also require the development of new vaccines • New strains of the flu virus, for example

– Genetic mutations • A replacement, insertion, or deletion of one or more letters

from the viral genome may have various effects – Mutations that harm the virus will be eliminated

– Silent mutations and beneficial mutations will persist

• DNA viruses have genetic mutation rates similar to that of eukaryotic cells, because DNA viruses also have proof-reading enzymes that correct mistakes – Mutation rate is therefore low, at about once in several hundred

or several thousand genome replications

• RNA viruses lack proof-reading enzymes, and therefore accumulate mutations more quickly than DNA viruses

– Recombination • If viruses from two different

strains infect the same host cell, they may interact during replication and result in progeny that have some genes from both viral strains

• In segment reassortment, viruses with segmented genomes swap genetic segments – For example, consider the

influenza virus, which is segmented with 8 RNA molecules

– If a human cell is infected by two influenza viruses from two different strains, new viruses can be produced that have some segments from each of the “parent” viral strains

– This type of mutation is common in segmented viruses and can produce dramatic changes (leading to relatively rapid evolution)

Source: Viral Genome Evolution. https://viralzone.expasy.org/4136

• Recombination in incompletely linked genes – If two non-segmented viruses co-infect the same host cell,

pieces of their genomes may “break” and swap places with each other in the progeny

– This type of mutation is less common than segment reasortment

Source: Gomez, C., Gonzalez, G., & Meneses, E. (2018). Algorithm for history reconstruction of viral recombination events: Preliminary results. Conference paper available online at https://www.researchgate.net/publication/327636116_Algorithm_for_History_Reconstruction_of_Viral_Recombination_Events_Preliminary_Results

• Origins of the Novel Coronavirus – The current pandemic is caused by a new coronavirus

called SARS-CoV-2, which causes the disease known as COVID-19 (from coronavirus disease 2019)

– Epidemic originated in Wuhan, China – Evidence suggests the most likely origin of SARS-CoV-2

is a bat • Genetic sequence from a betacoronavirus in the

Intermediate Horseshoe Bat found in Asia is 96% identical to SARS-CoV-2

• The receptor binding domain (RBD) of the virus spike protein in the novel coronavirus is genetically very similar to the RBD protein in a betacoronavirus found in pangolins

• One possibility is that the virus spread from bats to pangolins to humans in “wet markets” in Wuhan, where wild animals are sold for food and Traditional Chinese Medicine

Source: Anderson et al. (March 17, 2020 ) The proximal origin of SARS-CoV-2. Nature Medicine

• In February, China implemented a ban on sale of many species of wildlife at these markets, including civets, pangolins, and bats

• But regulation has loopholes and enforcement has been lax

Sources: “Coronavirus: Revenge of the Pangolins?” (March 5, 2020) New YorkTimes; “Indonesia’s Scariest Market Takes Bat off Menu Over Virus Fear” (February 5, 2020 ) Bloomberg.com

• What is a coronavirus? How is it different from a flu virus? – Coronaviruses are a family of RNA viruses that

frequently cause respiratory tract infections in mammals • Examples of diseases caused by coronaviruses include:

– The common cold may be caused by many different viruses, including some types of coronaviruses

– Middle East Respiratory Syndrome (MERS-CoV)

» First detected in Saudi Arabia in 2012, MERS-CoV had a case fatality rate of 35%

– Severe Acute Respiratory Syndrome (SARS-CoV)

» First reported in Asia in 2003, SARS-CoV had a case fatality rate of 11%

– Severe Acute Respiratory Syndrome-2 (SARS-CoV2) – this is the current COVID-19 pandemic; estimates of case fatality rate are preliminary, variable and should be interpreted with caution

» World Health Organization on March 5, 2020, estimated the world-wide case fatality rate to be about 3.4%

» Note that the seasonal flu typically has a case fatality rate of less than 0.1%

Click here for audio

– Both influenza viruses and coronaviruses have RNA as their genetic material

– Influenza viruses are “segmented RNA” viruses • Their genomes are composed of 8 RNA strands

• Evolve quickly through segment reassortment

– Coronaviruses are “unsegmented RNA” viruses • They possess just one strand of RNA

• So far, mutation rates appear low, indicating that once a vaccine is developed, it should offer long-term protection

– COVID-19 is caused by SARS-CoV-2, a virus that is closely related to SARS-CoV, which caused the SARS outbreak in 2003 • SARS stands for Severe Acute Respiratory Syndrome • SARS-CoV was initially identified as causing severe cases of

pneumonia in southern China in 2003 • It is believed to have originated in bats, and then spread to other

animals (civets) and humans • The SARS-CoV and SARS-CoV-2 viral genomes are about 80%

identical, but one important difference has been identified: – SARS-CoV-2 binds more easily to cell membranes than SARS-CoV

» The “spike” proteins on SARS-CoV-2 enable the virus to attach to ACE2 proteins on human cells (including respiratory tract cells, blood vessel cells, and kidney cells)

» This enables SARS-CoV-2 to better infect cells and spread more easily from person to person (making it more infectious)

» This makes the spike proteins a prime target for scientists working to develop a vaccine

Sources: WHO: SARS --https://www.who.int/ith/diseases/sars/en/ CDC: SARS Response Timeline -- https://www.cdc.gov/about/history/sars/timeline.htm Live Science: https://www.livescience.com/why-coronavirus-attaches-stronger-human-cells.html

• Another possible therapy: use a decoy ACE2 – Scientists have created a genetically modified version of the

ACE2 protein , called human recombinant soluble ACE2 (hrcACE2)

– When hrcACE2 was added to tissue cultures and infected with the novel coronavirus, the virus bound to the decoy and infection of the tissue was reduced by a factor of 1,000 to 5,000

» According to Dr. Mirazimi (lead researcher in this study) “We believe adding this enzyme copy, hrsACE2, lures the virus to attach itself to the copy instead of the actual cells… It distracts the virus from infecting the cells to the same degree and should lead to a reduction in the growth of the virus in the lungs and other organs.”

Source: Drug Target Review -https://www.drugtargetreview.com/news/59290/decoy-ace2-receptors-could-be-promising-covid-19-infection-preventing-drug/

• COVID-19: Symptoms and Prevention – Symptoms include fever, tiredness, and a dry cough

• In severe cases, can be fatal – especially in older patients, and those with underlying medical conditions such as diabetes, asthma, or heart disease

– Primarily spread through respiratory droplets (released when someone coughs, sneezes, or even talks) • Staying at least 6 feet away from other people reduces

chances of coming into contact with respiratory droplets • About 10% of cases are spread by people who have no

symptoms (according to a study from the University of Texas at Austin, https://www.medicalnewstoday.com/articles/covid-19-study-estimates-rate-of-silent-transmission#The-serial-interval)

• Wearing a mask can help prevent spread of respiratory droplets

• You can even make a fashion statement with your mask!

– Can also be spread through contact with contaminated surfaces • If you touch a contaminated surface, and then rub your

eyes, nose or mouth, you can become infected

• Avoid touching your face, wash your hands frequently with soap and water (or use hand sanitizer), and disinfect surfaces before you touch them

• The virus can live up to: – 5 days on metal and glass

– 4 days on wood

– 3 days on plastic

– 24 hours on cardboard

» Source: WebMD, https://www.webmd.com/lung/how-long-covid-19-lives-on-surfaces

• Social distancing to curb the spread – Because we currently lack a cure or vaccine for SARS-

CoV-2, our options to reduce the spread and severity of the pandemic are: • Intensive testing, and quarantining and contact tracing for

those infected – This has been successful in South Korea, Germany, Singapore and

Hong Kong – South Korea, for example, very quickly instituted widespread

testing, and quarantined infected people and asked close contacts of infected people to self quarantine

• When tests aren’t readily available, social distancing (including closing of schools and limiting sizes of gatherings) can curb the spread – The goal here is to “flatten the curve” – reduce the number of

people who are infected at the same time and require hospitalization, in order to prevent exceeding the capacities of our health care system

– This is the strategy currently in use in the US

• This article provides a good explanation for variation in “case fatality rates” between countries: https://www.vox.com/2020/4/1/21203198/coronavirus-deaths-us-italy-china-south-korea

– How long will we need to practice social distancing?

• It depends.

• Here are some factors that could decrease the duration of the pandemic: – Increasing our critical care capacity (for example, increasing the

number of ventilators and ICU beds), which would allow population immunity to be accumulated more quickly (i.e., sick people being treated and released more efficiently)

– If people who recover from infection are permanently immune

– Development of treatments: therapeutic drugs can reduce the duration of illness, and therefore the length of time someone is infectious

– Development of vaccines, which would dramatically increase the proportion of people who are immune

Source: Kissler, S., Tedijanto, C., Lipsitch, M., and Grad, Y.H. (2020). Social distancing strategies for curbing the COVID-19 epidemic. https://www.medrxiv.org/content/10.1101/2020.03.22.20041079v1

– Ultimately, we need to build “herd immunity” to stop the spread of the coronavirus • Herd immunity is when a large proportion of the

population is immune to a disease, and therefore the disease can no longer spread – In most cases, it requires 80- 95% of the population to be

immune

• Can be acquired through a large number of people getting sick and the recovering, and thus gaining natural immunity – This would unfortunately also result in our hospitals being

overwhelmed and many people dying from COVID-19

• Or, can be induced through vaccination – The optimal solution, but will likely require at least a year to

develop a vaccine

– In a worst-case scenario, a number of factors may increase the length of time the pandemic lasts

• Critical care capacity exceeded – Hospitals are unable to care for sick people, who continue to spread

the infection

• No treatments or vaccines developed soon

• If those who recover from COVID-19 quickly lose their immunity to it (unlikely, but we just don’t know how long immunity will last)

• Seasonal forcing: – Many respiratory pathogens vary in their prevalence seasonally in

temperate climates like ours, peaking in the winter months when people are indoors and spread infections more efficiently

– If SARS-Cov-2 undergoes seasonal forcing, and if we stop social distancing in the summer and fall, we may experience a dramatic rise in cases over the winter, which may exceed critical care capacity

Source: Kissler, S., Tedijanto, C., Lipsitch, M., and Grad, Y.H. (2020). Social distancing strategies for curbing the COVID-19 epidemic. https://www.medrxiv.org/content/10.1101/2020.03.22.20041079v1

• So how long will the COVID-19 pandemic last? – Researchers from Harvard believe that a one-time

period of social distancing (as we are in right now) will not be sufficient to prevent COVID-19 from overwhelming our hospitals

– Their models show that, in a worst-case scenario, we may have to undergo recurring periods of social distancing into 2022

– However, if we develop new treatments, vaccines, and implement aggressive testing and quarantining of infected people, we can reduce the length of time we’ll need to use stringent social distancing

Source: Kissler, S., Tedijanto, C., Lipsitch, M., and Grad, Y.H. (2020). Social distancing strategies for curbing the COVID-19 epidemic. https://www.medrxiv.org/content/10.1101/2020.03.22.20041079v1

We’re In This Together!

A final note from Dr. Weyrauch (click above)

• Helpful Resources to Keep Informed – Ohio State University “Keep Learning” – tips to

help you stay engaged in learning online: • https://keeplearning.osu.edu/

– Ohio Department of Health’s coronavirus information: • https://coronavirus.ohio.gov/wps/portal/gov/covid-

19/home

– Center for Disease Control and Prevention’s (CDC) coronavirus information: • https://www.cdc.gov/coronavirus/2019-

ncov/index.html