COVID-19: Overview of Our Response to the Pandemic

    Because of COVID-19, our approach to patient care has changed dramatically bringing Dr. Bretsky’s dual roles as a Primary Care Physician and Epidemiologist into sharp focus. The pandemic also led us to dramatically reduce our patient population moving us into a fully concierge model.  Because of the lack of federal and local oversight, Dr. Bretsky became a de facto testing site, contact tracer, COVID educator, treating physician and vaccine advocate – efforts that were impossible to maintain across a large practice. That in addition to maintaining the preventive care milestones for patients during the 2 plus years. Post-COVID, our approach to patient care will be irrevocably altered.

    When discussing the profound impact of COVID-19, one analogy seems particularly apt – that of a critically ill Intensive Care Unit (ICU) patient. In such a patient, multiple organ systems may be failing at once. The heart may be in an unstable rhythm, the lungs working ineffectively so a ventilator is needed, the kidneys failing and electrolytes becoming dangerously depleted. In this type of situation, one begins with the most critical issues first – stabilizing a heart rhythm that will lead to death in 20 minutes, adjusting ventilatory flow to keep oxygen levels high enough to maintain tissue perfusion and delaying dialysis knowing that the kidneys can be addressed in 24-48 hours. A similar situation arose with COVID-19 except the entire population was crashing in the ICU. As such, decisions to protect the most vulnerable were paramount while sometimes deferring care and even transforming our practice into a full time testing site. Those who have not or did not change how they practice Medicine from the COVID-19 experience did not fully appreciate the gravity of what occurred.

    Below we highlight our initial response and our practical approach to COVID-19. We cover testing access, the importance of vaccines, school reopening strategies and what we see as a reasonable path forward. With climate change profoundly affecting our planet, emerging infections (particularly zoonoses) will become more often the norm rather than the exception. We cover specific concerns of Long COVID and the potential consequences of being infected with multiple strains of the virus. From Ebola to SARS to Zika and COVID-19, we must have strategies in place to effectively respond to such in the future. Here is our story and our approach.

    In the Office

    As noted above, our patients’ office experience will be different from that to which you are historically accustomed. We begin your visit a day or two beforehand, with a call from our clinical staff to discuss your upcoming visit, verify medications, identify any need for vaccinations and understand any other concerns you may have. We may even set up routine imaging such as Mammograms, Bone Density or cancer screening scans. Upon arrival, you will first notice that while we have a waiting room, very little if any time will be spent there. Examination rooms are each equipped with ceiling-based ventilation and HEPA filters scrub the air.

    About 30% of our visits now take place outside of the office – either by telemedicine of FaceTime video. 

    Because time and proximity are the two key elements in COVID-19 spread, we take advantage of the large size of the office. We have two separate entrances and a wide clinical wing. Generally, only one patient will be in the office at a time. In the rare instances that there are two, they will be in separate areas and will be staggered in terms of time.  We also have a dedicated room for patients who are actively ill with symptoms such as fever, cough, or congestion. This room will often be sealed then for the remainder of the office day to allow any airborne particles to circulate out. Staff members are separated from patients and one another by extensive plexiglass barriers and doorways. While there has been some debate as to the effectiveness of these barriers, we have kept them in place until there exist compelling data to remove them.

     

    We have taken great effort to change the flow of patients in the office to eliminate contact with non-clinical staff. 

    What Are Your Recommendations for COVID-19, Annual Flu and Other Vaccinations ?

    COVID-19: We recommend COVID-19 vaccinations without reservation given their strong protective effect against severe disease, hospitalization and mortality. Initial data suggested that these vaccines would be protective against mild disease and would halt transmission. However, the genesis of variants such as Delta, Omicron, BA.2 and other variants of concern led to frequent breakthrough infections (typically mild) as well as vaccinated to vaccinated spread. The definition of ‘fully vaccinated’ remains in flux but our recommendation is in line with those of the CDC which states that everybody eligible should have a primary series plus at least one booster. Recommendations will be different depending on your age, health status, what vaccine you first received and when you first got vaccinated. COVID-19 vaccines must be administered at a pharmacy or a municipal vaccination site as we still do not have Health Department clearance to provide a primary vaccination series or boosters.

    Influenza: Each season the WHO, CDC and other health agencies unequivocally recommended the seasonal flu shot as a measure to protect against a ‘twindemic’ of COVID-19 and influenza. Interestingly, in the first two seasons during which COVID-19 and influenza coexisted (2020/2021 and 2021/2022), coinfections with these two viruses was not generally seen. This may have been due to widespread mask use that led to remarkable declines in influenza cases. Moving forward as mask mandates relax, these two viruses may indeed coexist in both the individual and the population.

    Flu shots are formulated during the Spring and Summer, come to market in the Fall and are administered through the Fall and Winter. Traditionally in Los Angeles, the greatest spike in influenza cases occurs in the last two weeks of December and the first week of January. We recommend having your annual seasonal influenza by the end of October to provide protection during Thanksgiving gatherings. Flu vaccinations are available in our office seasonally.

    Shingles: The shingles vaccine prevents the reactivation of Varicella, the chicken pox virus, which can lead to significant and unpleasant symptoms with a painful, itchy rash. Most patients describe a deep ‘burning’, ‘throbbing’, or ‘stabbing’ sensation which alone is a reason to prevent such. The current shingles vaccine (Shingrix) is a series of two shots, separated by 2 to 6 months. For Medicare patients, this vaccine must be administered at a pharmacy (there was not sufficient money in the Medicare budget to pay for Shingrix, but funding was available in the pharmacy benefit program). For those with private insurance, it can be given in the office.

    Other Routine Vaccines: Other routine vaccines like Tetanus, Pertussis, Hepatitis A&B and Measles/Mumps/Rubella are given according to adult vaccination schedules. International travel may be one instance in which these vaccines are given sooner. All are available in our office.

    I’m Interested in More Background. How Did Your COVID-19 Response Start ?

    With a formal educational background in Infectious Disease Epidemiology, I had long been concerned that a respiratory pandemic would occur. I had believed that it would be a particularly deadly influenza strain. I began to take notice of reports from Wuhan in January and February of 2020, but thought that a similar situation to SARS would emerge – wherein it would remain largely confined regionally with sporadic cases worldwide.

    Since Los Angeles is a critical transportation hub, I purchased a small amount of PPE concerned that we would have some travel related cases in patients who were returning to the US. (Ironically enough the US pandemic was touched off by cases from Europe, not China).  However, what really got my attention was Dr. Nancy Messioner’s statement on February 25th 2020.  Dr. Messonnier, the director of the CDC’s National Center for Immunization and Respiratory Diseases said that it was inevitable that novel coronavirus disease (COVID-19) would spread through U.S. communities, given the virus’s increasing incidence outside of China. “Disruption to everyday life may be severe,” she warned.

    At that point, everything changed.  We immediately stopped seeing patients with acute illness in the office and, two weeks later, stopped routine office visits – switching entirely to video and telehealth modalities. It became obvious quickly that we would not have sufficient PPE to maintain safe protocols in the office.

    Testing kits and laboratory reagents were hard to come by in the early days of the pandemic – and shortages persisted in the months that followed (disappointingly, test kits were scarce again during the Omicron surge in January of 2022). We performed our first PCR test on March 11th sending a nasal swab to our laboratory partners at LabCorp – results returned 5 days later:  Negative.  

    Our first positive test was March 18th 2020.

    We began testing patients with a makeshift drive up alongside our building on 20th and Arizona. We still do this today so that patients can rapidly access a test without having to come into the office.

    Soon after starting testing, we began to experience shortages in swabs, tubes and the solution (viral transport media) used to preserve the viral sample during transport from our clinic to the lab.  At no point did we turn anybody away, however, as we were able to fashion our own viral test kits from materials in the office.  I rummaged through every cabinet, every exam room and our two in office laboratories to find the materials needed to keep testing.  Our commercial laboratory provider, LabCorp, to their great credit ran all the samples we sent them – even if not collected with one of their own kits.  As our laboratory representative put it, “if you send it, we will run it.”

    We have never once turned a patient away for testing.

    Rapid antigen testing (“lateral flow” tests) came to market in the summer of 2020 but access was restricted to those sites designated as a priority by the federal government. We searched high and low for tests and, at one point, were even designing our own based on a protocol published by MIT researchers based on CRISPR technology. Ultimately the solution came from a surreptitious discovery of an older generation Quidel SOFIA machine in a cabinet. The firmware was updated and we were able to source tests, not from the manufacturer, but from a third party. Our first tests cost $56 a test to run. Today the cost of a rapid antigen test is about $5.

     

    How Do You Test Now ? Does Insurance Cover It ?

    At this point in time we are not experiencing any shortages of testing kits and we run both a rapid antigen test (with 15 minute results) as well as viral PCR (with results in 36-48 hours). There was a nationwide shortage of tests in January of 2022 during the Omicron spike. We had stockpiled tests (and also run them on multiple platforms), so again never had to turn anybody away from testing if they wanted such. 

    Rapid antigen testing has long been the mainstay of our test / treat / isolate policy – one which is simply good public health practice. We have used many different iterations of these tests which are called ‘lateral flow’ tests in Europe as the testing solution “flows” along a test paper.

    PCR testing is sent out to our commercial laboratory partner, LabCorp.  

    All tests (both antigen and PCR) are billed to commercial insurance providers. We do not charge (and have never charged) any amount above what insurance covers.  It is always important to check with your provider regarding coverage but, so far, we have not had any denials or non-coverage of COVID-19 testing.  This includes both the rapid antigen test and the send-out PCR.

    Can I Get A Test Today ?

    Absolutely.  In terms of things that we are most proud about our response to COVID-19 is that at no point did we ever turn a patient away for testing.  If you want a test for any reason – recent or upcoming travel, exposure to a known or possible case, concerning clinical symptoms or because you are going to visit a high risk relative – we will provide you with a test.  We perform both rapid antigen testing (15 minute result, on multiple separate platforms: BD Veritor and Quidel Sofia among them) as well as PCR (which we send out to LabCorp).  For patients with high risk exposure or concerning symptoms we also provide self-directed testing, which limits healthcare worker exposure.  We also test patients in a drive-through motif using the three car cutout next to our building.

    We do not charge any additional fee for testing. To date, LabCorp has accepted insurance payment for PCR testing as payment in full. Private insurance carriers also reimburse the rapid antigen tests, although typically below our actual cost of sourcing the test, reagents and optical readers to ensure accurate results. This cost is not passed on to patients, however.  

    Tell Me More About Antibody Testing?

    In general, testing for antibodies is used as a marker of prior infection and recovery. In some cases, such as HIV antibody testing, it can be used to identify an infection (HIV viral load can also be tested to quantify viral activity, the goal being an ‘undetectable’ viral level with treatment). Antibodies are generally long lasting but their interpretation is more complicated than it first appears. They can provide clues about the following:

    1. When was the person exposed?
    2. Has immunity waned or never formed?
    3. Was the person exposed or vaccinated?
    4. Did the person have the disease or just infection?

    When antibody testing for SARS-CoV-2 is considered, two main antibody classes are considered:

    1. Nucleocapsid: The viral “coat” that packages the SARS-CoV-2 RNA genome in a protective covering. Antibodies to this protein motif indicates prior community acquired exposure and likely clinical infection with the virus. I have had rare cases of individuals who do not recall having COVID-19 but have positive nucleocapsid antibodies but this is quite unusual. These individuals likely had very mild symptoms and, therefore, went unnoticed. These antibodies do seem to be very long lived as I can still detect nucleocapsid antibodies among those with documented clinical infection as early as March 2020.

    2. Spike: This antibody test is used primarily to detect an adaptive immune response to the SARS-CoV-2 vaccine. In some instances, this antibody level may return detectable levels as a result of community acquired infection alone (I have seen this in some patients who were unvaccinated but had the infection). However, SARS-CoV-2 vaccines preferentially target the spike protein of the virus and typically generate a robust quantitative response beyond that seen from infection alone

    Using both the nucleocapsid and spike protein antibody results can distinguish between vaccination alone, community-acquired infection alone or infection (primary or breakthrough) and vaccination together.

    Adding further complexity to this picture is the fact that the spike protein antibody returns a numeric value which can be different based on the performing laboratory. LabCorp for instance returned values up to a maximum of 2500 from the test inception (Summer 2021) through early 2022. However, in 2022 the test parameters changed to accommodate values up to 25,000. Theoretically higher levels of antibody should provide “better” protection against infection but, again, there is significant nuance to the role of these neutralizing antibodies. What we do know is that they protect against severe disease, hospitalization, need for mechanical ventilation and death. 

    What Has Your Experience Been Like with COVID-19 Cases? How Do You Treat Them?

    In the practice we have had a lot of COVID-19 cases. About 70 of these occurred prior to vaccination and, without any treatment beyond supportive care, these were admittedly very scary times. We had two inpatient hospitalizations for COVID-19 associated pneumonia but, fortunately, no deaths. We have had patients become quite ill (but not requiring hospitalization) in some instances and several continued to have residual symptoms months after their acute illness has resolved.

    We initially approached treatment primarily with supportive care – rest, hydration, and Tylenol (not Motrin / Ibuprofen). Steroid treatment, both inhaled and systemic treatments, seemed to provide initial benefit and subsequent clinical studies have supported the role of such in severe COVID disease.  We have also been a strong supporter of clinical trials and, early on, referred patients (both with disease and recently exposed) to a number of clinical studies – including those of the widely (and appropriately) maligned Hydroxychloroquine..  These studies both showed that Hydroxychloroquine had no effect on either COVID-19 acquisition or progression.  We also referred patients to trials of Regeneron’s REGN-COV2 antibody and anti-inflammatory trials with Indomethacin. We also recommended that recovered patients donate convalescent plasma as a potential treatment modality. While there remains an Emergency Use Authorization (EUA) for convalescent plasma among hospitalized patients with impaired immunity, there is no clear evidence of benefit.

    Vaccination was a game-changer – and this cannot be emphasized enough. The likelihood of severe disease, hospitalization, mechanical ventilation, ICU admission or death was significantly reduced. Of course, there was a lot of worry when patients 85 years and older acquired an infection, but soon afterwards treatment options emerged including monoclonal antibodies and antivirals. Prior to the Omicron variant emerging in the US in December of 2021, monoclonal antibodies provided significant and rapid clinical benefit in our experience, with some patients feeling improved within 6-12 hours. However, accumulating evidence showed a relative lack of efficacy when it came to the Omicron variant and sublineages – so, again , while there is an EUA for monoclonal antibody combinations of casirivimab-imdevimab or bamlanivimab-etesevimab for those over the age of 12, these have largely fallen out of favor.

    Instead, Paxlovid (a combination of two oral protease inhibitors) is the currently preferred COVID-19 specific therapy for symptomatic adult patients who have mild to moderate COVID-19 AND risk factors for progression to severe disease (e.g. age, immune status and/or comorbidities associated with progression). Whereas Paxlovid was extremely difficult to find in Los Angeles County in early 2022 (only two pharmacies stocked in across a County of 10 million people), it is now widely available – often at your local national-chain pharmacy. While patients generally feel better in about 2 days after starting therapy, we have seen some cases of rebound symptoms and test positivity – typically about 2 weeks after the therapy was begun. This phenomenon was highlighted in a 27 April 2022 Washington Post article which cited Dr. Bretsky’s clinical experience.

    https://www.washingtonpost.com/health/2022/04/27/paxlovid-second-case-covid/

    How Did You and How Do You Manage Isolation and Quarantine?

    In March 2020, the United States was already lagging behind other countries in terms of a coordinated response. The Centers for Disease Control (CDC) was slow to develop testing kits and establish clear protocols for case isolation and quarantine (the debacle of the CDC’s COVID testing development is covered in clear detail in Michael Gottlieb’s book “Uncontrolled Spread” although the 493 book itself is far too long and descends into self-aggrandizement). Because of this, we began to look to other countries for guidance.

    Before continuing further, two definitions are in order. 

    Isolation: The separation of a person or group of people known or reasonably believed to be infected with a communicable disease and potential infectious from those who are not infected

    Quarantine: The separation of people who are not yet symptomatic but have been exposed to a contagious person and are believed to be at risk of developing an infection. Exposed people are separated from others to rapidly identify onset of illness if it occurs and to keep them away from susceptible people. Once a person in quarantine develops signs or symptoms of disease, it should be assumed that they are infected and they would need to be isolated (see above).

    Ottawa, Canada provided clear, accurate and comprehensive materials on topics ranging from self-isolation to contact tracing (Link:  https://www.ottawapublichealth.ca/en/public-health-topics/novel-coronavirus.aspx).  The only aspect that needed clarification for US patients is that 2 meters = 6 feet.

    We initially looked to Singapore for testing and quarantine guidelines but their public health department actually sends an epidemiologic services officer to your home in the event of COVID-19 exposure or infection. So there was nothing published that would help our efforts.

    South Korea had an early and effective COVID-19 response, partially shaped by their disastrous experience with a different, but far more deadly), coronavirus – Middle East Respiratory Syndrome (MERS).  Their website (Link: http://www.cdc.go.kr/cdc_eng/) outlines their detailed methodology for case isolation and quarantine.  In it, a person testing positive for COVID-19 is isolated for two weeks beginning the day of their first positive test.  To be considered for release from isolation, they must meet both clinical (no fever without taking fever reducers and show improvement symptoms for at least 72 hours) and testing criteria At the end of 10 days (initially this was two weeks), the patient is tested twice in a row with at least 24 hours between tests.  If both are negative, the patient is released from isolation.  If positive, the patient may retest at their physician’s discretion – all are released from isolation after 21 days. Until rapid antigen testing was developed and became widely available, our office followed the South Korean test, trace and isolate policy.

    Rapid antigen tests represented a fundamental shift in how we approached COVID-19 testing and isolation policy as this test denotes both infection and infectiousness. Unlike the PCR which can remain positive for weeks after an infection even if the patient is no longer able to spread the virus, a positive rapid antigen test indicates that SARS-CoV-2 is not only detectable but that it is transmissible to others.

    At this time, rapid antigen tests are widely available but, at critical junctures of the pandemic, they have been scarce. This occurred most acutely during the Winter surge of 2020/2021 and again during the Omicron surge of 2020/2021. Our own office supply dwindled into the single digits despite having stockpiled 600 tests prior to the surge. For future planning, the December/January time period is one traditionally associated with exponential increases in viral respiratory illnesses, and it would be reasonable for each household to have at least 10 rapid antigen tests stored in anticipation of this risk period. The US Government has a mechanism by which free home tests can be ordered (link: https://www.covid.gov/tests).

    We take a conservative approach to managing quarantine and isolation and one that departs from the current CDC recommendations.

    Quarantine: For those individuals that have been exposed to a known COVID-19 case we recommend quarantine at home for 5-7 days post-exposure. Avoid the workplace and any gatherings. If errands or medical appointments are necessary, these can still be performed while wearing a N95 or KN95 mask. If having symptoms, most certainly avoid these activities. Rapid antigen and PCR testing between Day #5 and Day #7 from the exposure (last contact with a known case) are most accurate. Some individuals may test positive as early as Day #2 or Day #3 from exposure. However, if a PCR or rapid antigen test obtained between Day #5-7 results as negative then quarantine can be lifted and normal activities resumed.

    Isolation: For those individuals testing positive for COVID-19, they should anticipate a 7-10 day isolation period. As we take a conservative approach, we begin the isolation ‘clock’ with Day #0 being the day of the first positive test (some will count from the day of first symptoms but for our purposes, the date of the first positive test is a more accurate starting point). At a minimum, one should isolate for 5 days from the first positive test meaning not going to work, not performing errands or not participating in any social gatherings. If an urgent matter must be attended to, an N95 or KN95 mask should be worn and being outdoors is preferable to indoor activities. For the purposes of release from isolation only a rapid antigen test should be performed, as a PCR can remain positive for weeks after the infection. If the rapid antigen test is negative at Day #5 and the individual is asymptomatic (especially no fever), then they are free to leave isolation without restriction. In our experience, most patients do not test negative until at least Day #7 with most having negative antigen tests between Day #7 and Day #10. Rarely patients test positive Day #11 or #12 but this is quite unusual. Those who are vaccinated and taking Paxlovid have some risk of recurrence (typically Day #14 or thereabouts) – this is covered more fully above. Often there will be some residual symptoms such as fatigue or a sore throat. Even with these, as long as one does not have a fever, they are free to resume all usual activities without restriction.

    What Is The Current Situation in the US and in Los Angeles ?

    We provide regular updates regarding COVID-19 prevalence rates and spread on our Facebook page (@santamonicaprimarycare) and Blog (www.drbretsky.com/blog) and encourage you to follow us on these social media outlets. There is a specific on Los Angeles County primarily but also compare our response to that of Riverside and Orange Counties as well as San Francisco.  Other times, we do look at hyper-local Santa Monica data as well.

    What Do You Think About Treatments ?

    If there has been one positive in the COVID-19 epidemic, it has been the significant improvement in hospital-based and outpatient treatments. While vaccination itself massively reduces the risk of severe disease and death, early intervention also plays a role – particularly among those at high risk (due to age, underlying conditions or immune status).

    Prior to vaccination, mortality rates were at their highest in early April and late July of 2020 when there were 0.43 daily deaths per 100,000 population in Los Angeles. By October 2020 that rate had decreased to 0.08. A number of factors have influenced this massive drop including decreasing incidence of cases and a case distribution towards younger individuals who, generally, fare better than those that are older. Efforts to ‘flatten the curve’ have prevented hospital ICUs from becoming overwhelmed so staff can provide comprehensive and effort-consuming care for each individual, rather than triaging critical cases. But improvements in-hospital treatment also played a significant role. Prone positioning, delaying intubation, early initiation of steroids, remdesivir (administered intravenously over three days) and supportive care have decreased mortality rates. 

    Vaccination without question significantly reduces, and essentially eliminates, the risk of severe disease, hospitalization and mortality. Additionally, in late 2021 two new treatment modalities emerged – monoclonal antibodies and antiviral treatments.

    At this time, the preferred treatment for individuals with active COVID-19 symptoms and with a risk of progression to more severe disease is Paxlovid (nirmatrelvir-ritonavir) which is a combination of two oral protease inhibitors. Ideally started within 5 day from the start of symptoms, these medications are given as 3 pills twice a day for a total of 5 days. Paxlovid is a strong inhibitor of metabolic enzymes and transporters such as the CYP3A enzyme and, as such, there exist a number of potential interactions. For a number of commonly prescribed medications, coadministration of Paxlovid is contraindicated. These include: alfuzosin, amiodarone, colchicine, cloazapine, lurasidone, lovastatin, simvastatin and triazolam.

    Anti-SARS-CoV-2 monoclonal antibodies represent an alternative option for those patients with risk of progression to severe disease. However, their use has been limited in 2022 due to their variable activities against different variants. As an example, sotrovimab has activity against the BA.1/BA.1.1 sublineages of Omicron but no activity against BA.2 sublineages. As such, it was no longer authorized to treat COVID-19 infection in the US once BA.2 became the predominant variant. One option that does exist is bebtelovimab which is active against all Omicron sublineages and is authorized for non-hospitalized patients who have mild to moderate COVID-19, are at risk for progression and cannot get other therapies.

    What About Vaccines? What About Boosters? What About Mixing and Matching?

    Very early on in the pandemic, Bill Gates wrote in his Gates Notes (well worth following) that a comprehensive response to COVID-19 would require a treatment that was at least 95% effective or a vaccine or both.

    We now have two FDA approved vaccines available in the United States – one from Pfizer/BioNTech and the other from Moderna. Although the initial publications suggested an efficacy of >90% in the prevention of even mild disease, we now know from practical experience that this is not the case. In some sense, breakthrough infections (of typically mild disease) may actually be the norm rather than the exception. What changed?  Variants.

    The initial vaccines were developed against the early strains of SARS-CoV-2 from Wuhan with the initial genome sequence being published in January of 2020. We have subsequently had a number of variants including Delta and the very infectious Omicron variants. Vaccines have not yet been modified to account for these newer variants and are necessarily less effective against breakthrough infections although they remain strongly protective against severe disease. 

    Two boosters are now recommended for all individuals over the age of 50 years as well as those that are younger with higher risk of progression to severe disease. There is some evidence from the NIH “Mix and Match” study that different primary vaccine / booster combinations may lead to higher spike protein antibody levels. The spike protein antibody quantifies the immunologic response to the vaccine + booster series. LabCorp offers a commercially available test that now can detect levels up to 25,000 and we do run this in the office.

     

    The table above shows the response after the first booster. Of the categories considered, three Moderna vaccines provide the best quantitative response (6799) followed closely by two Pfizers in a primary series plus one Moderna (6155). Note that the Moderna is a ‘full dose’ shot, not the booster dose of 50mcg.

    What Is Evushield and How Might It Be Useful?

    Reading the table above, one can see the wide difference in quantitative spike protein antibody levels that are generated, say, from one J&J shot (57) as compared to three Moderna shots (6799). Some subset of individuals, whether because of medications, chemotherapy, stem cell transplants or immunodeficiency, mount no response (or very little) to the vaccine series. It is for these individuals that Evushield (Tixagevimab/Cilgavimab) provides a pivotal role.

    Evushield, unlike other monoclonal antibodies medications used for COVID-19, is not a treatment but instead is a long-acting antibody given as a preventive medication. It is intended for those that have significant immune disorders or for those who have experienced a severe reaction to the COVID-19 vaccine and cannot receive additional doses.  It works by blocking viral entry into cells, thereby preventing illness

    It has been challenging finding a provider of Evushield but we were ultimately able to partner with IV League (http://www.ivleagueinc.com/) who has long been integral in supplying IV antibiotics and antimicrobials for our patients who need to go home with extended therapy. 

    What Is Your Outlook for the Future of COVID-19?

    Overall I remain optimistic about our response and continued management of COVID-19 – sometimes contrary to prevailing evidence it seems. But returning to Bill Gates’ original assessment of the pandemic (“comprehensive response to COVID-19 would require a treatment that was at least 95% effective or a vaccine or both”), we have all the tools we need to combat the illness. The first line of defense, vaccination and subsequent boosters, has been accepted by the US public to varying degrees which is unfortunate. In my clinical experience, widespread vaccination of a population (in my practice >95% of our patients have been vaccinated and received at least one booster) essentially eliminates the risk of severe disease, hospitalization, ICU admission, the need for mechanical ventilation and death.

    Further, available treatments bolster this response. Monoclonal antibodies, while less effective against Omicron, provided clear clinical benefit (I had some patients feeling better in 6-8 hours) during Delta and likely will have applicability for subsequent variants. Paxlovid, while best studied among the unvaccinated, significantly reduces the risk of hospitalization and death.

    *0.7% of patients receiving Paxlovid after SARS-CoV-2 infection were hospitalized through a 28 day follow-up period (5 of 697, no deaths) as compared to 6.5% who received placebo (44 of 682, 9 deaths). 

    *This is a 90% risk reduction (95% Confidence Interval: 76% to 95%).

    The efficacy of Paxlovid will undoubtedly be less efficacious among the vaccinated (who already have a lower risk of hospitalization and death) but will still have some role. Accessibility to medication will remain the primary challenge, especially in the US with a fractionated health care system. As the adage goes, the US healthcare system is “all breakthrough, no follow through.”

    Another major advance is in the availability and manufacture of rapid antigen (lateral flow) tests which now in the US retail for about $5 per test (1 Euro in the EU). Periodically, the US Government makes these available for free to households, shipping them by USPS. With results in about 10 minutes, these tests can identify those that are both infected and able to transmit the virus.

    A couple notes of caution about the future, the first and most obvious being the inevitable emergence of variants.  The figure below shows the progression of variants across the population over time through January 2022.

    Vaccine manufacturers need to be able to respond and even predict (much as we do for seasonal influenza which changes its formulation annually) which variants will emerge and circulate. Otherwise, vaccine efficacy will continue to decrease as will, potentially, the potency of antiviral treatments such as monoclonal antibodies and Paxlovid.

    Another concern will be the effect of COVID-19 infection with multiple variants. A cautionary tale comes from dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is a mosquito-borne infection known as a human disease for over 200 years but DHF and DSS have only been described since the 1980s.  There are 4 distinct serotypes of dengue and the more severe form of dengue is believed to be related to an infection with a second dengue serotype in an individual previously infected with another dengue virus. It carries a 5-15% mortality rate.

    The basics of viral containment are not difficult: case identification (test), following-up close contacts (tracing) and quarantine (isolation). Bookending this most basic Public Health function with widespread vaccination/boosting and effective treatments should reasonably eliminate the virus from the population. But as a global pandemic, these tools need to be available globally and widely integrated at the population level.