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COVID CONWAY COMMUNICATIONS REBOOT #5
Q&A FEBRUARY 2022
Hi Colleagues and Community! I’m Dr. Kate Conway (she/her) and I have been writing CCC since Summer 2020. I now have a team with me ready and excited to bring you answers to your questions every month. I am a Family Physician specializing in Global Health and Medical Education. I have been working hard during the pandemic to take care of my family, my patients, my coworkers, and my students. I believe in the power of relationships and sharing our stories to empower positive change in this world. I will share my own personal reflections along with introducing our monthly Q&A topics. Stay Well, Stay Safe, Stay Smart!
In this February edition we will be answering questions on What are the new outpatient treatments available for COVID-19? Why is Omicron more contagious and less dangerous? Why did the CDC change guidelines for isolation/quarantine? Will there be more variants and why? When will this pandemic be over? Each question is first answered with Take Home Points for quick and easy reference. This is followed by More of the Story when our writers have provided a deeper dive on the topic and then Resources Used to Answer this Question with the primary references listed, including links to take you there. We hope to include infographics and other visual aids along the way and will make sure to highlight multi-media resources when we can.
We will always strive to answer the question with the best information available. It is our goal to provide information from trusted sources and balanced perspectives. We will also be honest when a question can’t fully be answered because science is still trying to answer it and may only have partial data available for review and interpretation. I am humbled by how much we have learned in such a short amount of time. Asking questions is one important way we all stay tuned in together. Please continue to submit COVID questions here:
Google Form COVID Q&A. You can also reach me if you have any questions or need clarifications on material published here katharine.conway@wright.edu.

Please share this with others! We hope to continue working together to build back our communities’ health, safety, knowledge, and informed engagement with trusted connections.

~ The BSOM CCC Reboot Team
What are the new outpatient treatments available for COVID-19? – Dr. Conway
Take Home Points
  • All patients should be offered symptomatic management. Symptomatic treatment includes using over-the-counter antipyretics, analgesics, or antitussives for fever, headache, myalgias, and cough.
  • Patients who are at high risk of progressing to severe COVID-19 can be considered for the following listed in preferred order based on efficacy and convenience of use:
    • Paxlovid (nirmatrelvir+ritonavir) – combination antiviral, 3 pills twice daily for 5 days
    • Sotromivab – a single IV infusion of monoclonal antibodies that work for Omicron
    • Remdesivir – IV infusion antiviral, 200mg on Day 1 and 100mg on Day 2 and 3
    • Molnupiravir – antiviral pill, 800mg twice daily for 5 days
  • Supplies are still limited and not all treatments are available everywhere. All these treatments need a clinician to prescribe/order and confirm a positive COVID-19 test.
  • All of these treatments need to be started as close to onset of symptoms as possible and have a range of 5-10 days from diagnosis to treatment initiation.
  • There are many drug-drug interactions to consider when prescribing (especially Paxlovid) and patients need to work closely with their physician/pharmacist to determine best approach for managing chronic medications during treatment.
  • Eligible patients can receive the treatment free of charge during this public health emergency.
  • Patient friendly Q&A article to share with family and friends Mayo Clinic article here.
More of the Story
Before December 2021, most targeted treatment for COVID-19 infection was limited to hospitalized patients.  As a Family Physician trying to keep my patients OUT of the hospital, it has been so hard to feel so limited in my available interventions for patients when first diagnosed with COVID-19. My toolkit has now been expanded, but there is still much to learn and understand about how best to utilize what we have while maximizing prevention through the vaccines.

Emergency Use Authorization (EUA) was granted to Paxlovid in late December 2021 after clinical trials showed it cut the risk of hospitalization and death for people at high risk of severe COVID-19 by nearly 90%. Paxlovid can be prescribed for eligible adults and children age 12 and older who weigh at least 88 pounds. Patients would take 3 pills (2 nirmatrelvir pills and 1 ritonavir pill) by mouth twice a day for 5 days. This treatment needs to be started within the first 5 days of feeling COVID-19 symptoms and a confirmed positive COVID-19 test. Paxlovid has significant and complex drug-drug interactions, primarily due to the ritonavir component of the combination since it is a strong cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent that has been used to boost HIV protease inhibitors.
Coadministration of ritonavir is required to increase nirmatrelvir concentrations to the target therapeutic range. Before prescribing ritonavir-boosted nirmatrelvir, clinicians should carefully review the patient’s medication list, including over-the-counter medications and herbal supplements, to evaluate potential drug-drug interactions. The EUA fact sheet for ritonavir-boosted nirmatrelvir and the Liverpool COVID-19 Drug Interactions website (there is an app you can download here!) should be utilized to identify and manage drug-drug interactions. A quick reference guide is also provided in the Panel’s statement on the drug-drug interactions for ritonavir-boosted nirmatrelvir. Medications like blood thinners, statins, seizure medications, anti-hypertensives, and anti-depressants are just a few examples of the many drugs that can be elevated or diminished when taking Paxlovid and may require alternative considerations or discontinuation/titration plans.

Four monoclonal antibody products (bamlanivimab plus etesevimab, casirivimab plus imdevimab, sotrovimab, and bebtelovimab) have received EUAs from the FDA for the treatment of nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease. In the clinical trials for these agents, monoclonal antibodies reduced the risk of hospitalization or death by 70% to 85% compared to placebo. Sotrovimab and Bebtelovimab are the only ones that work with Omicron currently. Both require a person to have an order to go to an infusion center for the treatment.

Remdesivir is currently approved by the FDA for use in hospitalized patients with COVID-19 and in nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression. Clinical trials showed that 3 consecutive days of IV Remdesivir resulted in an 87% relative reduction in the risk of hospitalization or death compared to placebo. This also requires an order to go to an infusion center 3 days in a row for treatment, which can present logistical issues for many patients who are ill and may have limited resources.

Molnupiravir reduced the rate of hospitalization or death only by 30% compared to placebo in nonhospitalized patients with COVID-19. Molnupiravir is recommended only when Paxlovid, Sotrovimab, and Remdesivir are not available or cannot be used. Molnupiravir has lower efficacy than the other options and the potential for genotoxicity is still being watched closely.

Paxlovid and Sotrovimab and Remdesivir can be considered in pregnancy (limited data) if threat of severe disease outweighs the risk of medication use.

Not everyone who tests positive for the coronavirus will be eligible for these treatments at this time. The COVID-19 pills are in short supply in some areas, while other areas may have plenty in stock. So far, more courses of Molnupiravir have been delivered to states than Paxlovid. Eligible patients can receive the treatment free of charge during this public health emergency. An interactive map and tables of supply and locations can be found at GoodRx here.
 
Although I am grateful to have options to finally offer my patients when considering the best approach to prevent hospitalization, I am acutely aware of the limitations and complications these treatments currently present. This makes prevention of severe disease with vaccination + booster THE way to go for as many of my patients as possible!
From NIH COVID-19 Treatment Guidelines
Resources Used to Answer this Question
Website: National Institutes of Health – COVID-19 Treatment Guidelines, accessed 2/25/22. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/nonhospitalized-adults--therapeutic-management/
Article: Gerencher, Kristen, COVID-19 Pills Tracker: Live Updates on How to Find Paxlovid and Molnupiravir, February 24, 2022, Good Rx Health, https://www.goodrx.com/conditions/covid-19/covid-pill-cost-availability.
Website: COVID-19 Drug Interactions – University of Liverpool, accessed 2/25/22. https://www.covid19-druginteractions.org/
Website: Mayo Clinic Q and A: COVID-19 treatment options, accessed 2/28/22. https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-covid-19-treatment-options/
Team Member Introduction: Who am I and Why do I COVID Care?
Hi! My name is Maneesh Chidambaram and I am a first year medical student. I am writing for this publication because in the past year I have witnessed how misinformation has affected our community and the lives of people we care about. I believe the best way to combat this misinformation is through evidence-based information which I hope to share.

Question I am answering: “Why is Omicron more Contagious but less Dangerous?”

Take Home Points
1. Omicron is more contagious due to spike protein mutations allowing for better transmission from person to person.
2. Omicron is showing less severity of illness than the previous Delta variant, hence it is depicted as less dangerous.
3. Omicron has the ability to better break through both disease and vaccine-given immunity.
4. Vaccination and mask wearing remain a key component of fighting the virus.
5. Vaccinated + Boosted individuals are more likely to have mild illness associated with Omicron.

More of the Story
The Omicron variant was identified in South Africa and reported to the World Health Organization who designated it as a variant of concern (VOC). The VOC names follow the Greek alphabet Alpha, Beta, Gamma, Delta and Omicron. The names Nu and Xi were skipped because Nu can be confused with “New” and Xi is a common surname. But for the average individual, the real worry is not the naming convention but the virulence (or contagiousness) of the Omicron variant1.

Reports have since come out saying the Omicron variant is more contagious but less dangerous, especially for those who are vaccinated + boosted. When we ask ourselves how this is possible, it all comes down to the viral proteins and how they are used. Although exact mechanisms are still being studied, research indicates that enhanced contagiousness may be linked to Omicron’s increased affinity and ability to bind the human angiotensin-converting enzyme 2 (ACE2) protein 2. Additionally, there are an increased number of hydrophobic amino acids on the spike protein, which further stabilize the spike protein at the binding site 2. This means Omicron has an increased potential to transmit and “stick” to human cells more than the Delta variant. The spread of COVID-19 infections can be indicated by the value “R”, which represents the number of new cases caused by a single infected person. For the Delta variant, R is approximately 2, and Omicron has an R value approximately 3 to 6 times higher1.

While the infectivity shows high levels of transmission, the data does suggest that Omicron is a less dangerous strain. This can be extrapolated from the data of previously infected individuals. Studies comparing Omicron to Delta have shown that hospitalizations occurred in 0.5% of Omicron vs 1.3% of Delta. Medical hospital stays were 3.4 days shorter for Omicron than Delta, and within the Kaiser Permanente Study, zero Omicron cases required a ventilator versus 11 Delta cases requiring ventilators3.

While vaccination is the best way to beat the virus, the Omicron variant has been a challenging foe. Due to its spike protein mutations, it is twice as likely than the Delta variant to escape the antibodies produced by the Moderna and Pfizer vaccines4. To combat this, vaccine manufacturers are working towards creating an Omicron vaccine and a future vaccine to protect against multiple variants all in one5.

In summary, the omicron variant is more transmissible due to its spike protein mutations, but less deadly. It is better able to evade immunity provided by previous infection or vaccines, but efforts are underway to develop future vaccines that will be more effective against Omicron and future variants. Still, the best way to avoid COVID-19 is to make sure you receive your vaccinations + booster and wear masks in public spaces until the community spread is diminished to a safer level.

Resources used to answer this question:
1. Ren SY, Wang WB, Gao RD, Zhou AM. Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance. World Journal of Clinical Cases. 2022;10(1):1. doi:10.12998/WJCC.V10.I1.1
2. Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G. Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein. Journal of medical virology. 2022;94(4). doi:10.1002/JMV.27526
3. Lewnard JA, Hong VX, Patel MM, Kahn R, Lipsitch M, Tartof SY. Title: Clinical outcomes among patients infected with Omicron (B.1.1.529) SARS-CoV-2 variant in southern California. doi:10.1101/2022.01.11.22269045
4. Chen J, Wang R, Gilby NB, Wei GW. Omicron (B.1.1.529): Infectivity, vaccine breakthrough, and antibody resistance. ArXiv. Published online December 1, 2021. Accessed February 17, 2022. https://pubmed.ncbi.nlm.nih.gov/34873578/
5. Araf Y, Akter F, Tang Y dong, et al. Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines. Published online 2022. doi:10.1002/jmv.27588
Team Member Introduction: Who am I and Why do I COVID Care?
Kyle Henneke, BSN-RN, MPH, CEN, TCRN
I am a third-year MD/MPH student here at BSOM with experience in public health and a lot of interest. I completed my MPH in May 2021 with a certificate in Emergency Public Health and have done a number of things with COVID-19 response here in the U.S. including humanitarian deployment, contact tracing program leadership, and clinical research on vaccine hesitancy.
I care very much about the goals of public health which include education and advocacy. As a future physician with public health training, I feel I share in the responsibility of combatting misinformation to give people the opportunity to make wiser decisions for the health of themselves, their loved ones, and their communities.

Question I am answering: Why is the Isolation/Quarantine Period Shorter?

Take Home Points
• Disclaimer: This will be a lengthy article with links to many resources. It is based off the 1-hour-long COCA call that took place on January 13, 2022. The primary points are at the end of the article, but it is important to keep in mind context. If curious with further questions and cannot find the time to listen to the recorded call, it is suggested you read this full synopsis. Diagrams/pictures are not my own and are generally cited. They are all from the COCA Call presentation. I hope you find clarity amongst the gritty details!

More of the Story
The COVID-19 pandemic is constantly evolving, and the recent Omicron variant wave first detected by scientists in South Africa in early December prompted some changes in isolation and quarantine of those with or potentially exposed to COVID-19. The changes have resulted in quite a lot of confusion and controversy, so it begged the question: Why did the guidelines recommend shorter isolation/quarantining? The simple response from their December press release described a data-driven approach guiding their recommendations, but in all fairness, that seemed vague. You can see the original media release here: CDC media release

I think many can understand that when trying to convey a succinct message to the public it must be simple and without too many details. As a scientist, though, the itch that I needed to scratch involved those very details! What data? What were the considerations? Is Omicron really so different from its predecessors?

So, I thought on it for a long while as the media storm whipped up a frenzy, and eventually, our patience was rewarded. The CDC regularly engages the public with Clinician Outreach and Communication Activity (COCA) Calls to discuss in further detail any updates and provide an opportunity to answer questions. The COCA Call on January 13 of this year focused an hour of time on the background information and data, considerations made for healthcare institutions and staffing, as well as the continued economic and mental health burdens on individuals documented throughout the last two years.

I will be attempting to summarize the information, but it is important to understand before reading on that the long-and-short of the presentation is IT’S EXTREMELY COMPLICATED. There is no single diagram, list of bullet-points, or brief explanation of the takeaways that will make you feel wholly convinced that a lot of thought went into these changes

I highly suggest giving the video a listen as the COCA Call was recorded and you can view the entire presentation here: COCA Presentation

The first part of the presentation was given by Dr. Lauri Hicks, a Captain in the United States Public Health Service and the CDC’s Chief Medical Officer of COVID-19 Response. It involved the background that stimulated the considerations for changing guidelines, beginning with the new variant that served as the impetus for conversation – Omicron. The concerns laid out involved how transmissible the new variant was, its virulence or severity, how well vaccines or prior infection effect these variables, and whether other therapeutics available for Delta would be effective in Omicron infection.
This photo describes the mutations mapped in the B.1.1.529 (Omicron) variant of the SARS-CoV-2 virus which included around 45-52 noted mutations – 15 of which involved the virus’s ability to bind to host cell receptors for invasion. A virus’s genotype describes the pattern of genetic material unique to the organism and a phenotype describes how this collection of genes presents itself and interacts with the world around it. It was clear based on a lot of experience with prior variants that, phenotypically, Omicron would be far more transmissible than Delta and more resistant to antibodies formed by previous infection or vaccination, treatment resistant to available therapeutics, and good at evading innate immunity.
The graph above describes data on the secondary attack rate of Omicron based on a study in Denmark. It’s important to remember that Omicron was already working its way well through the European Union and other parts of the world like South Africa when it was detected, and this data was available to American epidemiologists in advance of the wave that they knew had to be coming. She then went on to describe the rapid climb in reported cases and hospitalizations that were being tracked throughout the month of December here in the U.S. However, she did cite a pre-print study that had been released by Kaiser-Permanente for the evaluation of clinical outcomes of Omicron. It used mathematical modeling to estimate risk of hospitalization in the health system, which serves ~19% California’s population, and the data suggested a substantially reduced risk of severe illness when compared to the Delta variant. Dr. Hicks went on to describe the resistance of the virus to antibodies produced from vaccination or prior infection as well as the futility of nearly all available therapeutics currently used for severe illness associated with Delta. The bad news is that Omicron was found to be resistant to every monoclonal antibody that was being used for Delta, except for Sotrovimab which demonstrated promise. The good news is that those that received a full vaccine series with a booster showed much greater vaccine efficacy than those who only received a 2-dose, and even greater still than those unvaccinated at all. This is demonstrated in the graph below:
Other graphical representations of the data can be viewed in the original COCA Call presentation recorded and available at the link provided above.

Dr. Alexander Allen, Chief of the Prevention and Response Branch then went on to explain the recommended changes to healthcare specific guidance and why it was necessary to make those changes. He acknowledged that healthcare-specific guidance needs to be different from guidance provided to the community and that this nuanced incongruence between what healthcare personnel (HCPs) were being told and what the general population was seeing in media reports could have served as a nidus for confusion. The media may report the updates, but they may not get into the weeds of which guidance applies to which groups of people. This can be highlighted in the picture below which serves as just one example of how HCPs should be approaching work restrictions:
As you can see, this level of complexity is not great for recommendations to the public as it leads to confusion and is contingent on the context of the situation your community is experiencing (i.e., clinical staff shortages, vaccination status). Many of the changes that apply to HCPs are designed to mitigate staff shortages (contingency) or address shortages as they happen (crisis). The primary recommendation remains, however, under the conventional column so the situation that applies to HCPs will change based on hospital needs and resources. The other complicating factor to recommendations is that for those visiting patients in the health care setting or undergoing outpatient procedures they should be following criteria for discontinuing isolation/quarantine that apply to HCPs – NOT the general community. As you can probably see, this can be highly confusing as HCP guidelines are far more complex and people may not readily understand why they must follow a different set of guidelines than perhaps a neighbor! For this reason, I highly recommend the Coronavirus Self-Checker widget on their website as it will walk you through exactly what recommendations will apply to you based on your risk factors and situation. Just answer the questions and it will provide you a brief summary of recommendations! See the link here: Self Checker

If you’re curious about the details or specific recommendations concerning health care providers, I highly recommend the following links as they are updated regularly: The following is a summarization of specifically WHY the CDC shortened their isolation/quarantine period guidelines in the context of what I’ve already discussed in this article.
  • Consideration #1: Impact of large increase in cases
    • Omicron wave in South Africa and UK preceded the U.S. – which was still working through its Delta wave
    • Individual factors: mental health and personal economic factors
    • Critical societal factors: supply chain challenges and staffing shortages
  • Consideration #2: Period of infectiousness
    • Review of 113 studies from 17 countries indicated most SARS-CoV-2 transmission occurs early in course of infection
    • Peak infection ~1 day prior to symptom onset and declines within 1 week
  • Consideration #3: Severity of disease
    • Omicron has shorter incubation (2-4 days) with less severe individual disease course and shorter hospital stays (3-4 days vs 7-8 days) and lower death rate (0.8% vs 5.3%) when compared to other variants
    • Data from South Africa showed much smaller Omicron wave compared to Delta
    • Caveat: unsure if shorter incubation corresponds to shorter infectious period but that was another consideration
  • Consideration #4: Testing in symptomatic patients
    • Optimal time for using antigen test (rapid) for diagnosis is much earlier (demonstrated in graph below)
  • Consideration #5: Vaccine Effectiveness (VE)
    • Similar infection rates of Omicron between fully vaccinated and unvaccinated and breakthrough cases much higher compared to other variants
      • However, much more increased vaccine efficacy if individual considered “up-to-date” or fully vaccinated plus a booster
  • Consideration #6: Neutralization after Booster Dose
    • Boosters effectively neutralize infection with Omicron
And there you have it – a synopsis of the reasoning behind the recent CDC updates. It’s vital to keep in mind a couple of points:
  • The recommendations are contingent on strict adherence to masking and social distancing AFTER a 5-7 day isolation/quarantine for a full 10 days- Clearing individuals with testing was not recommended as this would be a misuse of tests – they are designed to diagnose, NOT comment on infectiousness of an individual
  • Cycle thresholds (CT numbers) associated with some COVID-19 tests are not the optimal proxy for determining infectiousness (how easily a positive individual can spread the virus), viral cultures remain the gold-standard
  • Viral cultures are impractical, but CT numbers may correlate fairly well with cultures in days 0-10 of the COVID-19 infection cycle, assuming it is timed correctly
  • Low CTs mean high viral load (and vice-versa) but do not necessarily mean an individual is infectious
  • Median day of viral shedding is day 6, days 3-6 are most infectious on average, by day 8 ~11% of people are infectious and by day 10 ~5% are infectious
Again, I highly recommend you watching the COCA Call presentation at the link provided and hope that your questions/concerns have been answered! See below for even MORE resources provided in the presentation that you can provide patients, friends, and family:
Resources:
Team Member Introduction: Who am I and Why do I COVID Care?
Cynthia Sheppard Solomon, RPh is a Clinical Associate Professor, Department of IM/Neurology, WSU-BSOM. A registered pharmacist providing consulting expertise around the country, Ms. Solomon is nationally certified in tobacco treatment practice, heads the department’s medical marijuana task force, and facilitates the COVID19 educational task force. Ms. Solomon is mom to a border collie-lab rescue dog, BB King Solomon.

Question I am answering: “Will there be more variants of SARS-CoV-2 that come along during the pandemic?”

Take Home Points
• The answer to this question is YES. As long as some people remain unvaccinated and are being infected in this country and elsewhere, there are more chances for variants to occur.
• The mathematical equation for this is: Decrease spread of SARS-CoV-2 = Decrease number of variants

More of the Story
Changes or mutations to the gene of a virus creates variants. All RNA viruses, including the coronavirus SARS-CoV-2 that causes COVID19, mutate over time. Some viruses, like those that cause influenza, change quite often, creating a need for new yearly influenza vaccination.

With the SARS-CoV-2 coronavirus, we are seeing variants emerge fairly often. Not all come to the attention of the public unless they show characteristics of interest, or concern, or of high consequence (1).
• “Interest” is defined as genetic characteristics of greater transmissibility, evasion of immunity, diagnostic testing, or more severe disease.
• “Concern” means more infectious, more likely to cause re-infection in vaccinated or previously infected individuals.
• “High consequence” means current vaccines do not offer protection.

How are new variants different?
Since the beginning of the pandemic, different variants have come and gone. Some have had an increased ability to re-infect people who have recovered from earlier versions of coronavirus, and some are somewhat resistant to some of the coronavirus vaccines (2). However, the vaccines currently available in the U.S., when given fully as primary vaccines along with later booster doses, provide protection against hospitalization and death from currently widespread SARS-CoV-2 variants. People should be fully boosted, as recommended by medical experts. Following guidance to fully protect children with the primary vaccine series and recommended boost interval is highly recommended at this time, as are the special circumstances of boost intervals for individuals who are immunocompromised.

There is evidence that a genetic change in SARS-CoV-2 could result in a more contagious variant, particularly in the delta or omicron family. In fact, the BA.2 sub-variant of omicron is currently being tested for this type of behavior in a hamster model (3). We do not yet know how it will pan out worldwide. But, it appears to have the ability to be more contagious than the original omicron, and may be more resistant to vaccines (3). Researchers also have some new evidence suggesting some variants, including BA.2, seem to bind more tightly to our cells, making some new strains “stickier”, and more transmissible, due to changes in the spike protein (2). Although designs are months away from fruition, researchers are diligently working on multi-faceted vaccines to cover new variants, as well as creating one vaccine to cover all variants.

What can be done to slow the variant changes?
The more advantageous it is for a respiratory virus, the more it evolves and spreads. Some mutations enable the coronavirus to spread faster between people, overwhelming our hospitals and health care facilities. As long as SARS-CoV-2 spreads through a population, mutations continue to happen, and the delta and omicron families continue to evolve (2). New variants are detected each week. What is of great concern is that changes to the spike protein of SARS-CoV-2 are arising independently on multiple continents.

We must stay focused on using the precautions already shown to be effective (1):
• Full vaccination with appropriate booster shots with goal of vaccinating as many people around the world as possible
• Utilizing well-fitting high-quality masks as recommended
• Physical distancing while avoiding large gatherings
• Demonstrating proper hand hygiene

These protections work to continue to interrupt virus spread, decreasing the impact of more infectious variants if they do occur.

We must remain vigilant to decrease the spread of the virus, and therefore the variants.

Resources used to answer this question:
Toolkit for finding the facts on SARS-CoV-2 variants:
1) COVID19: About Variants. Center for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/variants/about-variants.html {accessed 02-14-2022}
2) Bollinger R, Ray S. COVID Variants: What You Should Know. Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/a-new-strain-of-coronavirus-what-you-should-know?amp=true {accessed 02-13-2022}
3) BioRXiv—preprint manuscript. https://doi.org/10.1101/2022.02.14.480335. 2/15/2022.
Team Member Introduction: Who am I and Why do I COVID Care?
Kyle Henneke, BSN-RN, MPH, CEN, TCRN
I am a third-year MD/MPH student here at BSOM with experience in public health and a lot of interest. I completed my MPH in May 2021 with a certificate in Emergency Public Health and have done a number of things with COVID-19 response here in the U.S. including humanitarian deployment, contact tracing program leadership, and clinical research on vaccine hesitancy.
I care very much about the goals of public health which include education and advocacy. As a future physician with public health training, I feel I share in the responsibility of combatting misinformation to give people the opportunity to make wiser decisions for the health of themselves, their loved ones, and their communities.

Question I am answering: When will this pandemic turn endemic and be done?

Take Home Points
• The virus that causes COVID-19 is here to stay. It will still take time for it to become less and less harmful as one major goal.
• There are many factors to consider when trying to “live with” the virus ever-present.
• Pacing ourselves with “the long view” rather than hoping for it to all be over yesterday can help us all manage expectations.

More of the Story
As we roll into the start of year three of the COVID-19 pandemic this coming March, I think I speak for many when saying that “COVID-Fatigue” doesn’t even begin to adequately describe how ready we are for the curtain to finally fall and the show to be over. However, a “return to normal life” isn’t so simple. COVID-19 has become a regular part of our lives and will continue to be so – full stop. It may continue to mutate, hopefully becoming less and less virulent as we’ve discussed with previous editions of the CCC Reboot but we’re always going to have to consider how best to live alongside this new addition to Earth’s ecosystem.

Something I hear quite a lot from people is the idea that once the virus has been deemed “endemic” rather than “pandemic”, COVID-19 will be officially done. This sentiment is likely rooted in the desire to return to a world where we aren’t constantly reminded about masking, and we can freely go about our activities without concerns for social distancing or isolating and quarantining. I know, personally, with the rampant rise of mental health issues, students throughout the nation would feel better with less online, distance-learning and return to all the socialization perks that come with in-class participation. But how can we know when a viral pandemic is considered “under control” or, in epidemiological terms, endemic? The answer isn’t quite so simple but there are a couple of things to look out for and we first must understand a few epidemiological concepts/terms.

Epidemiology 101:
  • Outbreak = higher than expected increase in cases in a specific location at a specific time
  • Epidemic = a sudden rise in the number of cases of a disease
  • Pandemic = event during which a disease spreads and affects multiple countries and lots of people
  • Endemic = constant presence of a disease within a population generally specified by geographic area
  • R0 (“R-naught”) = the reproductive number of a contagion or, more specifically, the number of people that one infected person is likely to spread that contagion to.
If you had to define a “turning point” by a specific number in a pandemic, you’d probably use the pandemic contagion’s R0. It is generally accepted that pandemics and epidemics reverse when the R0 is less than 1, or basically when one infected person passes the infection onto one or less people. However, this isn’t as clear of an answer as I think people are looking for and here’s why:
To calculate: R0 = infection/contact (transmissibility) x contact/time (average rate of contact) x time/infection (duration of infectiousness)
 
Each of these things can be considered naturally inherent to a contagion, which will give you a raw R0 if you’re considering the introduction of the virus to a completely naïve population. Over the past two years I’ve read literature estimating the R0 of the original SARS-CoV-2 wild-type strain to be 2-3, the Delta variant to be between 5-7, and the current Omicron variant to be as much as three times that of the Delta variant. The issue with using R0 as our magical sign that the pandemic is “over” is that we have several mitigating factors that could be affecting these numbers. This number is not infallible, and you can see why if you consider how we calculate it.

Viral mitigating strategies are designed specifically to target the three parts that make up the reproducibility factor of a contagion. Masks and social distancing measures affect the transmissibility, limiting contact/quarantining/travel bans affect the average rate of contact, and the duration of infectiousness changes with each variant. We use viral mitigating strategies to help bring down the R0 in this way, but we must do it well-before the virus has an opportunity to mutate into something more infectious that brings its R0 back up. What’s increasingly frustrating about COVID-19 is its rapid mutation rate and its ability to overcome our vaccines’ antibody responses. When you combine this with economic, social, and mental health considerations deeply affected by these well-known mitigation strategies, the situation becomes more and more complicated. It seems like R0 isn’t really the helpful answer we’re looking for.

At the end of the day, what’s likely going to determine when COVID-19 is considered “endemic” will be what losses we as a society have decided will be acceptable. It’s a risk-benefit analysis, like all things in medicine. If we stopped all viral mitigation strategies instituted in our everyday lives since the beginning of the pandemic and let the virus move freely, are we going to be okay with the results? What mortality level is acceptable? What morbidity, or complications, are we okay with? What risks are we willing to take on for the benefit of interacting with one another like we used to? The truth is, we don’t have the full picture with which to make these decisions. We don’t and can’t truly understand the long-term effects of a COVID-19 infection right now. The many presentations of a phenomenon we frequently call “Long-COVID Syndrome” can be quite debilitating for those who were once perfectly healthy people.

I recall reading an article in Vox that aptly described the difficulty of deciding when COVID-19 moves from a “pandemic” situation to one more closely resembling an endemic. It’s only a commentary, but if you’re trying to get a sense of the nuances behind this ultimate question it’s well-worth a quick read and some thought (referenced below).

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