On Wednesday, June 10, 2020, the Infectious Diseases Division gathered to celebrate two outstanding fellows, Drs. Lindsey Rearigh and Randy McCreery. Both are graduating and moving on to amazing next steps. This year’s graduation was unprecedented for our program (and every other training program) due to the COVID-19 pandemic. But even though these graduating fellows capped off their year with zoom lectures and conferences, and we had to celebrate their graduation in a physically distant manner, we were grateful to be able to celebrate them nonetheless.
Physically distanced graduation dinner for our fellows and select faculty (Photo credit: Dr. Andrea Zimmer)
In 2018, our ID fellowship program was expanded to 4 fellows per year and both Dr. Rearigh and Dr. McCreery welcomed the opportunity to experience the program growth in live action. As a division, we were honored to help Drs. Rearigh and McCreery grow and develop their infectious diseases knowledge, leadership and team management skills, and most importantly, to expand their skills in delivering compassionate patient care. We also enjoyed getting to know them as amazing people, share laughs with them, and celebrate milestones with them.
UNMC ID Fellowship alumni dinner selfie at IDWeek2018 (Photo Credit: Dr. Jasmine Marcelin)
UNMC ID Fellowship Program Director Dr. Trevor Van Schooneveld with graduate Dr. Lindsey Rearigh (Inset: we did wear masks!) (Photo Credit: Dr. Andrea Zimmer)
UNMC ID Fellowship Program Director Dr. Trevor Van Schooneveld with graduate Dr. Randy McCreery (Inset: we did wear masks!) (Photo Credit: Dr. Andrea Zimmer)
We will certainly miss them both dearly, but wish them all the best in their journeys, and hope to keep sharing their news along the way!
*Thanks to Megan Hoesing for contributing some of the content for this post
*Disclaimer: the following represents my personal opinions only and do not represent the opinions of my employers*
Followers of the UNMC ID blog and Twitter accounts may have noticed that our accounts have not been very active lately. This is because as a Director of our Digital Innovation & Social Media Strategy, I have not been okay. Black men and women around our country have been killed as a result of racism in our country, at the hands of law enforcement and civilians alike. Here in Omaha, a young Black man named James Scurlock was killed last weekend during demonstrations about police brutality. It has been pretty overwhelming to watch all of this happening while having to presumably “go about life as normal”. So with this emotional exhaustion, I retreated; I stopped responding to emails, I rarely logged on to twitter on my personal account, and definitely did not log on to the blog or our divisional twitter account. The truth is, I have felt everything so deeply and personally, and while I have been speaking in an authentic voice on our divisional social media, I have never allowed myself to be this vulnerable.
Almost as soon as I knelt during the UNMC #WhiteCoats4BlackLives demonstration, I cried as I mourned George Floyd, Breonna Taylor, Ahmaud Arbery, James Scurlock, Sandra Bland, Tamir Rice, Trayvon Martin, and countless others whose lives were taken.
I wanted to share excerpts from a letter I wrote to my Department of Medicine last week about what all of this has been like. “Dear colleagues, I’m not sure how this message will be received, but I feel it needs to be said. I’ve been silent, even withdrawn, this past week. I lost a dear cousin to COVID-19 in Alabama. Then after reeling from shock of the devastating news of his death, I started seeing videos of a Black man [his name was George Floyd] being murdered by police in Minneapolis, only 90 minutes from where I used to live with my Black husband and my two Black sons…I have had feelings of despair, hopelessness, and wonder how it is that no matter what we do to overcome obstacles, this world, this country seems rigged against people that look like me. I am afraid for my family, and for my friends, and for the countless nameless people out there who live in fear too. …I want you all to know that for many of your colleagues and friends, it is very difficult to operate in the “business as usual” mode. We are in the midst of a pandemic that is disproportionately killing Black people, but that is not the only danger we fear. Almost on a daily basis, racism in this country results in reports of Black people being harassed, threatened, or killed, simply for existing. …If you are not Black, but these things bother you, you may also be struggling to process your own emotions and how to respond at a time like this. If you have a friend or a colleague who is Black, reach out to them and let them know that you care, that you are thinking about how they are doing and that you want to be there for them in whatever way they need from you. Try to just listen, and learn. It wasn’t until I randomly decided to pick up the phone and call a girlfriend yesterday to just talk about our shared distress, that I realized that keeping it in is not good for me, even though it hurts when I try to articulate the unbearable grief from it all. So I’m reaching out to let you know that you can reach out to me whenever you need if you just want to process this….
UNMC ID multidisciplinary team members participating in the demonstration
As the disease detectives of medicine who have dealt with countless epidemics riddled with healthcare inequities, Infectious Diseases experts should be busying themselves with the business of dismantling systemic racism and advocating for justice. I personally view that as part of my mission. I am having the hard conversations with those around me with privilege, and extending everyone around me an invitation to step into the discomfort of talking about racism. We need to have more of these conversations in public spaces, pledge to speak up despite the discomfort, but it cannot be the burden of Black people to always lead these conversations, because we are exhausted. I was glad to see over 300 UNMC/Nebraska Medicine employees turn out for a #WhiteCoats4BlackLives demonstration, including many of my colleagues from the division of Infectious Diseases. Keep the support going, and remember it must be multifaceted. The hashtags, demonstrations, and words of support are great for the movement and welcomed, but more important are the actions.
Almost 300 healthcare workers gathered at UNMC in solidarity of #BlackLivesMatter and in remembrance of George Floyd on 6.5.20
After you kneel, stand up, and be loudly antiracist.
As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID-19, there are lots of ongoing discussions about coronaviruses. Dr. Raquel Lamarche is a PGY1 Internal Medicine/Pediatrics resident at UNMC, who will be sharing her thoughts and information she learns about COVID-19. You can follow Dr. Lamarche on Twitter @LamarcheRaquel. This week Dr. Lamarche discusses “The Reopening”.
“The Reopening”
At this point, (at least) the more privileged members of society are aware of the benefits of social distancing. Now we are experiencing its negative offshoots, to mention a few: schools are closed, the economy is crumbling, and as Dr. Julia Marcus Ph.D. said, “Quarantine Fatigue is Real.” In her article, Dr. Marcus discusses sustainable risk reduction and how shaming risky behaviors drives them underground. My brother, a psychologist in the Dominican Republic interested in addiction and minorities, was often criticized for providing free needles and syringes to IV drug users to decrease their risk of bloodborne infectious diseases. Preventing all bad from happening, e.g., preventing people from physically socializing (ever), was never a realistic expectation. Harm reduction (secondary and tertiary prevention) are as valuable as primary and primordial prevention (trying to prevent the harm in the first place), in the sense that it meets our public health aspirations with public reality.
Since late April, the first states began to lift the restrictions placed to control the coronavirus pandemic. The lifting of restrictions has been controversial. Dr. Fauci testified before the Congress that reopening too soon could lead to unnecessary suffering and deaths. Here in Nebraska, we never had a formal “shelter in place” executive order shutting down the state; instead, there were a series of strict Directed Health Measures which are now gradually being relaxed. Following the news lately, there are many opinions on what “reopening the economy” means. (See which states are re-opening and which states are still shut down)
Even bacilli are social distancing!
What about herd immunity? In the US, the seroprevalence of SARS-CoV-2 is unknown, with obstacles including limited testing availability, and limited reliability of antibody tests. Scientists are still investigating how antibodies elicited by SARS CoV-2 may effectively neutralize the virus and for how long. The basic reproductive number, or R0, for SARS- CoV-2 is estimated to be 2, not as high as (real) airborne viruses such as varicella and measles (4, and 13, respectively). This means: one person with COVID-19 can spread the virus to 2 other persons (or more if they are singing in a choir). Herd immunity is the indirect protection provided to individuals in a community when most of the population is immune to that disease. Based on the R0 of SARS-CoV-2, it is thought that 60-70% of the population needs to have contracted SARS CoV-2 in order to start seeing the benefits of herd immunity, and it is unlikely that we have achieved this yet. We have achieved herd immunity to other infections like measles and chickenpox due to vaccine uptake in the community.
Vaccine? When? Vaccines can be hard to develop. There are over 60 vaccine trials right now. The hope is that with so many trials going, we will have at least one vaccine at some point, maybe 18 months from now, we are talking about 2021 perhaps. Moderna found that its experimental SARS CoV-2 vaccine was safe and provoked a strong immune response in 8 healthy volunteers.
How should we approach the re-opening? Due to a lack of widespread testing, the initial “containment” attempt to limit the spread of this virus is long gone as a feasible idea (adios). The virus is close to all of us. The conversation we are having right now is about harm mitigation. To re-open as safely as possible, certain conditions need to be met:
The rates of new cases should be low and remain low for at least two weeks.
There should be capacity to test anyone who has COVID-19 symptoms
Hospitals should be able to treat all cases.
Based on the above conditions, many states seem to be re-opening prematurely. But now that things are opening up, how can we stay safe? 1. (Sustainable) social distancing.Continue to stay 3-6 feet or more away from each other. Dr. Marcus talks about sustainable risk reduction strategies in her article, with some outdoor activities (such as walking, running, and cycling) posing less risk than indoor gatherings. 2. Hand Hygiene. We must wash hands as often as possible, especially every time we go into a new environment. Linking handwashing to mindfulness (e.g., acknowledging four tactile sensations while handwashing) has helped me reframe the experience. Also, clean surfaces at least once per day at the very minimum. 3. Perfect surveillance and contact tracing.The process should involve quarantining positive cases, followed by tracing then testing all of their contacts. In order to limit the spread of the virus, we must have the ability to test anyone who might have SARS-CoV-2. Dr. Atul Gawande, in his NewYorker article, described daily screening of all employees, patients, and visitors for symptoms of COVID-19 upon entry to any building in his healthcare system. UNMC has recently implemented a universal screening policy for all admitted patients. 4. Wear a mask! If worn appropriately, masks can help keep individuals from spreading their own droplets to others. The critical point is that these kinds of masks don’t create a perfect seal and are not meant to protect yourself: they are meant to protect those around you. If worn by everyone, we protect each other. N95 respirators block most airborne particles from being inhaled, therefore are designed to protect the wearer too. Throughout the pandemic there has been an N95 supply-demand mismatch. As ways to circumvent this problem, there have been great innovations that can help us safely reuse N95s, such as: • Ultraviolet germicidal irradiation by UNMC • Hydrogen peroxide decontamination system by Battelle
How do we re-open the economy and our physical social lives while still keeping each other healthy? What is going to save us, a vaccine, herd immunity, or a new treatment? I know that I did NOT provide you with perfect answers. Viruses are sometimes too smart for drugs. We continue to lack the capacity for widespread testing and contact tracing. We are far from being immune. A vaccine is many months away.
More powerful than putting our energy on hopes for a miracle, is a strong performance at applying what we already know: physical distancing, hygiene, screening, staying at home if we are ill, and wearing a mask (correctly).
The COVID-19 pandemic has changed lives all over the world, responsible for over 4 million infections and over 300,000 deaths worldwide. As we have progressed through this pandemic, it has become clear in the United States that we need to begin and continue conversations relating to the disturbing racial/ethnic disparities we are seeing emerging from cases, hospitalizations, and death due to COVID-19. We have identified risk factors for severe disease, developed multiple testing modalities, and tested several treatment options. It is time to address the generational inequities that have allowed these health disparities to exist.
Disparities exist With more than 80,000 deaths in the US, we are seeing higher rates of infection, hospitalizations, and death among African Americans, Hispanic Americans, and Native Americans. In certain states, these disparities are even wider; for example in Wisconsin and Kansas, Black residents are seven times more likely to die from COVID-19 than White residents; in Washington DC, the rate is six times higher, in Michigan five times higher, and in NY four times higher. In New York City, a disproportionate number of people dying from COVID-19 are Hispanic (Source: APM Research Lab). Navajo Nation (the largest community of Native Americans living on tribal homelands across Arizona, New Mexico, and Utah) has more coronavirus cases per capita than any US state.
Where does Nebraska stand? Here in Nebraska, over 10,000 people have been diagnosed, and over 120 people have died from COVID-19. However, Nebraska is the only state that is not only NOT reporting ANY demographic data at all about cases, so there’s no way we would be able to know race data at all on a statewide level. We do have demographic data from Douglas County and Lancaster County, where we see disproportionate numbers of cases in the Hispanic and Asian populations. In Douglas County, almost 50% of reported cases are among Hispanic persons, and 16% of reported cases are among people of Asian descent (that includes large Nepali immigrant/refugee communities). In Lancaster County, 33% of cases reported are among people of Asian descent, and 24% among Hispanic people. We are seeing these disparities play out in real time in our hospital, as a large number of our patients in COVID-19 units are minority and/or immigrant people.
Why is this happening? There are social, economic, and political structures embedded in our society that interact to create structural/social determinants of health, which in turn impact health outcomes. One cannot discount the disparities in the underlying medical conditions associated with higher risk of severe COVID-19. Heart disease, obesity and diabetes are risk factors for more severe disease and death, and these conditions are overrepresented in the Black, Hispanic, and Native American communities relative to their share of the population. However, generational patterns in development of these comorbidities is not proof of a purely biological explanation for the disparities.
What we are witnessing is the impacts of structural racism (systems that perpetuate and reinforce racial inequities) on minoritized communities. The differences we are seeing are a manifestation of the systemic differences in food insecurity, housing insecurity, financial insecurity, lack of access to healthcare, lower quality healthcare, and inability to shelter at home, that predispose these minority groups to have worse health outcomes. The virus, SARS-CoV-2/COVID-19 is NOT Racist. However, societal structural racism plays a significant role in creating conditions that put minority communities at risk.
What needs to be done now? There needs to be a structured, coordinated effort to collect and report data here in Nebraska (and more completely across the country) on COVID-19 that includes demographics. This will help with creating targeted testing strategies in communities that are most at risk. In Nebraska, we have several immigrant populations whose first language is not English, therefore as healthcare professionals and an organization, we must ensure that we are helping to provide communication/education in a culturally congruent manner. If a language does not have a reliable written component or most people cannot read, we must be innovative with videos, television, social media, and personal community outreach in the language that people understand. Couldn’t we leverage our own healthcare professionals who speak different languages to help with this?
In the long term, there are many more things that need to be done to address the impacts of structural racism in the community. Dealing with these will help to ensure that the next time we are dealing with a pandemic or major health crisis in our nation, we will not be talking about these kinds of disparities.
As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID-19, there are lots of ongoing discussions about coronaviruses. Dr. Raquel Lamarche is a PGY1 Internal Medicine/Pediatrics resident at UNMC, who will be sharing her thoughts and information she learns about COVID-19. You can follow Dr. Lamarche on Twitter @LamarcheRaquel. This week Dr. Lamarche discusses a pediatric Infectious Diseases primer on SARS-CoV-2.
Children are not tiny adults; thus, it is not surprising that many infectious diseases affect children differently from adults.
We don’t know why COVID-19 appears to be less frequent and severe in children compared to adults. Some considerations include a less vigorous immune response to the virus in children, potential viral interference in the respiratory tract of young children leading to a lower viral load, and perhaps the receptor for SARS-CoV-2, the angiotensin-converting enzyme 2 receptor, is expressed differently in the respiratory tract of children compared to adults. As the pandemic progresses, we expect to learn more from data being published.
Currently, the virus is not definitively known to be transmitted vertically.
Of note, there areisolated cases of potential vertical transmission as demonstrated by baby’s elevated IgM against SARS-CoV-2 (IgM does not cross the placenta). The latter is relevant because infants seem to be one of the most vulnerable groups for severe disease in the pediatrics population.
SARS-CoV-2 does not seem to be transmitted through breast milk. However, droplet transmission can occur through close contact during feeding.
One unknown is the impact on women who get sick early in pregnancy and their developing fetus. This is a new virus and nobody who was in the first trimester when they developed COVID-19 has delivered yet.
• 4% of virologically confirmed cases had asymptomatic infection [this rate could be underestimating the accurate scale of asymptomatic infection because many asymptomatic children are unlikely to be tested. On the other hand, children with congenital and chronic diseases are living longer in the US, which means we might have a larger population that is potentially vulnerable to symptomatic and severe disease]
• Among symptomatic children, 5% had dyspnea or hypoxemia, and 0.6% progressed to acute respiratory distress syndrome.
• Some children presented with only gastrointestinal symptoms
• It appears that children generally have a significantly milder disease
One caveat about this observational study:
• Out of the 2135 cases, 66% were “suspected cases” (not test confirmed) defined as a child who was exposed to COVID-19 within the last 2-weeks, or lived in an epidemic area, had 2 of the following conditions: (1) fever, respiratory, digestive symptoms (eg, vomiting, nausea, and diarrhea), or fatigue; (2) laboratory test white blood cell count was normal, decreased, or had a lymphocyte count or increased level of C-reactive protein; or (3) abnormal chest radiograph imaging result. Children often get sick multiple times per year with many of the above findings, completely unrelated to COVID-19 – could some of these “suspected cases” have had symptoms caused by other viral illnesses?
In a US case-series (n=296) the most common symptoms in children were:
• Fever (56%), Cough (54%), and Shortness of breath (13%)
• Less common symptoms: myalgia, fatigue, sore throat, rhinorrhea, nasal congestion, headache, diarrhea, and vomiting
• 73% of pediatric patients had symptoms of either fever, cough, or shortness of breath compared with 93% of adults aged 18–64 years
In another series of 171 children with confirmed SARS-CoV-2 infection,
• 42% had fever, median duration of 3 days (range 1-16 days)
• 49% had cough, and 16% were asymptomatic
• 19% had upper respiratory infection, but 65% had pneumonia.
• 29% had tachypnea, 42% had tachycardia on admission, and 2.3% had O2 sat <92% during hospitalization
• 77% of children with COVID-19 were in contact with a family member with confirmed SARS-CoV-2
Deaths in children with COVID-19
Although severe cases of COVID-19 in children, including fatal cases, have been reported, most children appear to have a mild or moderate disease and recover within one to two weeks of disease onset.
Laboratory findings
Laboratory findings in children with confirmed infection from Wuhan were variable.
25% had white blood cell count <5.5 x 109/L (5500/microL)
3.5 % had lymphocyte count 46 pg/mL)
20% had elevated C-reactive protein was elevated (>10 mg/L)
Radiographic findings
Radiographic findings may be present before symptoms. CT chest abnormalities noted were:
33% ground-glass opacity
19% patchy local shadowing
12% bilateral patchy shadowing
2% interstitial abnormalities
Risk factors for severe disease
• It appears that infants <1 year of age and children with certain underlying severe conditions are at higher risk for severe disease.
The most commonly reported underlying conditions were:
• Chronic pulmonary disease like asthma
• Cardiovascular disease
• Immunosuppression (cancer, chemotherapy, radiation therapy, hematopoietic cell or solid organ transplant, high doses of glucocorticoids)
• Based on data extrapolated from adults, other medical conditions that may increase the risk of severe disease in children include CKD undergoing dialysis, chronic liver disease, pregnancy, diabetes mellitus, and severe obesity.
Many of these risk factors are similar to adults. But while much of the conclusions about risk may be extrapolated from adults, children still appear to be affected differently than adults, and this is probably a good reason why more widespread testing, especially in children, may be a good idea, particularly as we look toward the fall and reopening of schools.
As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID-19, there are lots of ongoing discussions about coronaviruses. Dr. Raquel Lamarche is a PGY1 Internal Medicine/Pediatrics resident at UNMC, who will be sharing her thoughts and information she learns about COVID-19. You can follow Dr. Lamarche on Twitter @LamarcheRaquel. This week Dr. Lamarche discusses “Wellness in the time of COVID-19“.
Being a doctor is stressful. Whether you are an attending striving to set up a positive atmosphere for learning and patient care, a resident transitioning into a different work-environment every 4-weeks, or an immigrant trying to master a new language and healthcare system: This profession is no walk in the park. The COVID pandemic (and the political circus that has accompanied it) has caused a myriad of additional stressors. Here are some real quotes from healthcare professionals like you and me:
“I worry that my 1-year old might not be receiving all the stimuli he needs during this critical time of his development; he is not learning from the world… he has not seen other children in over five weeks.”
“I feel guilty that I am not in the frontlines [like some of my friends]; I am not helping out like they are.”
“Concern[ed] I might carry the virus to my family.”
“My loved ones are losing their sources of income.”
“I feel constricted. I wish I could travel and physically connect with my support system.”
“I can’t be there for my loved one who is sick with this virus.” “I am exhausted…we don’t have the supplies, the ventilators, the PPE, to take care of everyone. I don’t want to do this anymore.”
“It is just too much high priority information and e-mails. It feels impossible to stay up to date and adequately appraise available data.”
Even before the pandemic, physicians have been notorious for taking work anxieties home with them. Similarly, when I was in art school, I noted my teachers would live in a 24/7 state of unstoppable craft. I figured that certain professions are not merely an 8 am-5 pm appointment; they are part of who we are. It should also be within our power to make this journey a sustainable one. Knowing that healthcare is subject to VERY rapid and complex changes, the ability to adapt and heal is paramount, for it is when our wellbeing is most challenged that it is also most critical.
With this post, I don’t intend to generate more anxiety by linking to three thousand resources. My hope is that we learn to be well while we work, and that we share with each other our perspectives on wellness. Here are a few of the things that I am currently working on:
1. Be yourself. In healthcare, you cannot afford to waste any energy trying to be “conventional” in exchange for acceptance; chances are this won’t be gratifying. So, put your big girl/boy pants on and be proud of who you are. For example, I find small talk mentally draining; conversely, silence, and listening to the sounds in my environment are recharging; so I allow myself to be silent when I need to, and it feels is amazing. I also move a lot while I work; it is one of the ways I channel emotions. If I feel anger, anxiety, or sadness, I can process the emotion by doing some push-ups, or a sun salutation, and I try not to wait until I get home; it takes less than 2 minutes and it keeps me from accumulating body and mental tension. Also, during the virtual learning/zoom conferences, I am usually holding yoga postures or doodling – this further increases my resilience for that day, it helps me stay present, and have a better recall of the information later on. It’s like I am providing my brain with this extra association that feels very familiar (e.g. we spoke about sleep apnea treatment when I was holding a tree pose). The days that I allow myself to just be, I feel I am not in a rush to go home in order to relax. This takes courage since you don’t want to make others feel uncomfortable, but I think that as long as there is no objective harm, it is worth it to be yourself.
2. Master the boring stuff. These are the oh NOT so fascinating aspects about our jobs, but stuff that we need to know in order to have an efficient command of the health care system. In art school, this would be equivalent to an hour of drawing spheres or rectangles. In healthcare, this entails understanding policies/protocols, RVUs, peer to peers, institutional status quo, billing and coding, long excel sheets, coordination of care, who should I call first, and all that non -sense. First of all, I think reading about any of the above topics is excruciatingly painful and destroys my medicine-loving inner unicorn…So, to learn “the boring stuff” I go to my tribe of colleagues and attendings. I directly observe them during specific situations, and ask as many questions as an annoying intern possibly can. I feel it is easier to remember dry subjects when you had a micro-discussion about them. The end goal is to be at complete ease with the parts of medicine that you might dislike, but that your employer and third-party payers believe to be “essential”.
3. Minimalism plays a major role in my well-being. I believe in having things that add value and joy to life. Here are some examples of how I apply minimalism:
• I don’t accumulate tasks if I don’t need to; I get it done as soon as possible without thinking about it too much. • Avoiding wasting time on it if it has no value, for example: If I don’t have the energy to reply emails, I won’t look at my emails in that moment. • I try to have 1 small goal per day, only one. • Take care of what I have, even if I can afford new things.
4. Have a self-care affirmation ritual. It could be something that starts like, “wake up: today you are worthy of getting up and taking care of yourself”.
5. Protect yourself and your loved ones. The best you can do is using the appropriate precautions at work during your patient encounters. It is a good idea to change clothes once you get home and wash them as soon as you can. You are not required to separate from your family at home if this would create an unnecessary strain on your wellbeing, but if separating from them improves your wellbeing by removing concern that you carry the virus home to them, do what keeps you well.
At our institution, UNMC, we have access to many UNMC Wellness Resources, and hope that these kinds of resources are available across the country for all the healthcare professionals who may need them.
I believe that integrating all of you to any work you do is key! Feeling like you are neglecting some dimensions yourself by doing a job can generate more tension than needed. Drawing is one of my essential components of keeping myself well. I included some drawings of my little kid patients’ hearts. Drawing these hearts was fun and helped me commit to memory congenital heart disease physiology. I would love for you to share with me what works for you!
As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID-19, there are lots of ongoing discussions about coronaviruses. Dr. Raquel Lamarche is a PGY1 Internal Medicine/Pediatrics resident at UNMC, who will be summarizing updates about SARS-CoV-2 and hopefully make information easier to digest, with additional outlines of implications for graduate medical education. You can follow Dr. Lamarche on Twitter @LamarcheRaquel. This week Dr. Lamarche discusses “Innovation in the time of COVID-19: No idea is too small“.
I am a physician. The engine of my mind naturally shapes itself around problems, imagines its most likely origins, crafts hypotheses, and engineers experiments/plans. Sometimes I think to myself, “Raquel, make a decision, and please look confident.” Despite all the evidence gaps in medicine, a physician is trained to act like they know what they are doing; as if their intuition was conclusive. But the desire to always be right and prove ourselves through medicine could obscure great ideas.
A crisis awakens a collective sense of alertness, triggering us to appreciate each other’s stories and the contributions we make through them. We value life more than ever, and act to assuage fears and combat misinformation. We need bold people, who are not afraid of being imperfect who are willing to put their ideas to the test…because no idea is too small during these times.
The COVID-19 pandemic’s effect on the healthcare system has catalyzed a myriad of innovations. Prominent themes include: promotion of patient access with telehealth visits, disease screening with the use of apps, testing innovations (for instance, drive thru-testing, or creating the fastest test!), strategies to overcome the shortage of Personal Protective Equipment (PPE), and creative design of supplies/devices (e.g., face masks, ventilators). See below a summary with some of these innovations. Note: this is neither an exclusive nor exhaustive list; there are so many cool innovations out there, so feel free to comment on this post or connect with us on Twitter at @UNMC_ID to share more!
COVID19 SCREENING APPLICATIONS. University of Nebraska Medical Center (UNMC) created an app available for Apple users, 1-Check COVID, to help screen large populations for COVID. The user answers a series of questions, the app issues an assessment “low-risk,” “urgent risk,” or “emergent risk,” and guides the possible next steps. UK College also developed their own screening app, and Stanford university designed an app that helps first responders (police-officers, firefighters, paramedics) screen their symptoms, and, if needed, get high priority testing.
SARS-CoV-2 TESTING. The fastest molecular point of care test for COVID-19 is the Abbott ID NOW™ COVID-19, with positive results in five minutes, and negative results in 13 minutes. Abbott plans to produce 50,000 tests per day, and 5 million tests per month. Another rapid point of care test is the lateral flow immunoassay; it detects IgM and IgG antibodies against SARS-CoV-2 within 15 minutes. The University of Minnesota and Mayo Clinic also developed a SARS-CoV-2 antibody test. While scientists are still working out the kinks of the ideal COVID-19 test, the competition and race to innovation will ultimately give way to development of the test we need.
THE DIGITAL FORCE. The power of digital technology has also scaled up our traditional health care system with the sudden ability to do telehealth. “Clinical workflows and economic incentives have largely been developed to support and reinforce a face-to-face model of care, resulting in the congregation of patients in emergency departments and waiting areas during this crisis. This care structure contributes to the spread of the virus to uninfected patients who are seeking evaluation.” – Sirina Keesara, M.D
I CHALLENGE YOU. We need your ideas and innovative solutions to address this pandemic. Roche Canada, University of Chicago, Amazon, and others have all launched innovation challenges in the hopes of advancing in the fight against SARS-CoV-2.
This pandemic has been disastrous to thousands of individuals and families. Some of the innovations developed during this crisis will transform the way we practice medicine, and others may not make it past the idea stage. But there is a little bit of joy in watching humanity re-think their ways, collaborating, and innovating. When someone shares a well-thought out idea we should notice it, and encourage it, as creativity is very contagious.
Dr. Andre Kalil, our Director of Transplant Infectious Diseases, recently co-authored a reply to Geriak et al.: “Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia.” Debate around the findings of this article was recently featured by Dr. Razan El Ramahi in the IDSA ID journal club and on this blog.
In their reply to Geriak et al., Dr. Kalil and colleagues from Stanford and San Francisco General highlighted some important limitations to the study design. Dr. Kalil shared their reasoning for publishing a response the authors:
“Staphylococcus aureus bacteremia (SAB) is a common and serious infection with high morbidity and mortality. There are several different antibiotics that can be used to treat patients with SAB, and the current standard of care is based on the use of one of these antibiotics with proven efficacy, i.e. anti-staphylococcal monotherapy. However, there is a debate regarding the utility of two (combined) antibiotics compared to monotherapy. A new clinical trial was just published on the combination of Daptomycin plus Ceftaroline versus standard of care monotherapy. Our letter addresses the issues associated with this trial and proposes solutions to bring a resolve to this debate.”
In their response to Dr. Kalil and his colleagues, the original authors acknowledged the the points in their letter and conclude: “the results of our study should direct scientific leadership toward a next step to compare other treatments to vancomycin in MRSA bacteremia, such as daptomycin plus an anti-staphylococcal beta lactam or vancomycin plus ceftaroline, or perhaps even ceftaroline alone.” Clearly there is still much to be studied to determine the best medical management of SAB, and there will doubtless continue to be healthy debate about the best practices to treat our patients.
On March 20th, the International Journal of Antimicrobial Agents published Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial by Gautret et al. The president of the United States tweeted about the article the very next day, and on March 28th the FDA announced an emergency use authorization to allow the distribution of hydroxychloroquine and chloroquine from national stockpiles to treat patients hospitalized with COVID-19.
Since then, this study has come under intense scrutiny. On Friday the International Society of Antimicrobial Therapy released a statement of concern about the paper it’s journal had just published, writing that “[t]he ISAC Board believes the article does not meet the Society’s expected standard,” and “[while] it is important to help the scientific community by publishing new data fast, this cannot be at the cost of reducing scientific scrutiny and best practices.”
So what was the study, and what are the concerns?
First, some background. Chloroquine and hydroxychloroquine are antimalarial and antinflammatory drugs with in vitro activity against a number of viruses, including SARS-CoV-2 (hereafter, COVID-19). However, drugs that kill viruses in laboratory cell cultures frequently fail when used in patients. Chloroquine inhibits influenza in vitro, yet did not prevent influenza infection in a clinical trial; similarly, chloroquine inhibits the replication of chikungunya in vitro, but had no effect when prescribed to patients during a 2006 outbreak, and actually enhanced chikungunya infection in a primate model.
Gautret et al reported the viral PCR testing outcomes of 36 patients with COVID-19 in France, of whom 6 received hydroxychloroquine and azithromycin, 14 received hydroxychloroquine alone, and 16 received neither agent. The authors report that 100% of patients who received both hydroxychloroquine and azithromycin had a negative PCR by day six of the study, versus only 57% of the patients who received hydroxychloroquine and only 12.5% of the controls. They conclude that “hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.”
Let’s set aside the fact that we don’t know whether changes in viral load have anything to do with how patients fare clinically. This sounds great, right?
1. Six patients originally assigned to the drug treatment arms were described as “lost to followup” because their treatments were stopped early: of these, one died and three were moved to the ICU. Of course, any drug will look great for COVID-19 if you don’t count the patients who received it and then got worse or died.
2. Critical data is missing in a way that skews the reported outcomes. For example, the authors report that only 12.5% (2/16) of the control patients had negative viral PCRs at day 6, but what is left unsaid is that a third of the control patients didn’t have PCR testing on day 6, so there was no way to know if they were negative.
Further, the PCR data is reported strangely. First, some tests are reported with specific CT value (cycle threshold; the number of times you need to duplicate the RNA in a sample to generate a detectable amount), whereas others are reported as positive or negative. Are the authors using multiple different PCR tests and reporting them together? Second, CT values can vary widely between PCR tests, and even from batch to batch when using the same test platform – meaning that because the authors did not run each patient sample along side a standard curve of known quantities of SARS-CoV-2 RNA, the observed changes in CT values may not have any relation to changes in the patients’ viral loads (i.e. may be totally meaningless)
3. The study’s methods imply that the methodology was changed after the trial began. Note that the methods indicate that patients were to be treated for 10 days and that the power calculation for the study was based on reduction in the viral load at day 7. Yet the primary outcome is given as “viral clearance” at day 6. Moreover, the original study protocol submitted to the EU clinical trials registry stated that PCRs would be collected on days 1, 4, 7, and 14. Why the change? Note also that while the study states multiple clinical parameters would be secondary outcomes (e.g normalization of temperature and respiratory rate or length of hospital stay), none of these are reported in the results. The authors state that this is a preliminary report of an ongoing study, published early because their PCR findings were just so important – but isn’t how the patients fared clinically what really matters?
As an aside, this clinical trial was approved by the French ethics board on March 6th and submitted for publication on March 16th while reporting a total 7 days of data. Were the authors able to both enroll all of their patients and write their manuscript in less than 72 hours, or were they were recruiting patients into a clinical study before getting ethics approval?
4. Patients in the drug treatment and control arms were recruited from different medical centers (recruitment into the treatment arm occurred only in Marseille), and at the Marseille site patients who either refused treatment or who had one of the study’s exclusion criteria were recruited as controls. So, not only was the study non-randomized, the introduction of confounding factors was baked into the study’s design.
5. The paper was submitted for consideration on March 16th and accepted March 17th. For this paper to have passed peer review in less than 24 hours (indicating the reviewers had no substantive criticisms, which is not surprising given that the version published is essentially identical to the pre-print release) is truly remarkable, particularly given that the IJAA’s editor in chief is listed as a co-author on the paper.
Physicians and patients around the world are understandably desperate for treatments for COVID-19 infection. In my view, the study by Gautret et al is critically flawed and does not support hydroxychloroquine and azithromycin as an effective treatment for COVID-19 infection. Unfortunately, this study has created a fervor around hydroxychloroquine and azithromycin that has led to national shortages and anecdotal reports of patients with lupus and other autoimmune diseases (which hydroxychloroquine actually treat) being unable to fill their prescriptions. One person has already died after self-medicating with a chloroquine solution sold for aquariums in an attempt to prevent COVID-19 infection. How many deaths from wanton use of these two agents – both of which prolong the QT interval, promoting cardiac arrhythmias – will go unreported?
In a recent JAMA editorial, our UNMC ID colleague Dr. Andre Kalil put it best, arguing that the use of unproven drugs for COVID-19 outside of the context of randomized control trials not only risks harm to patients but delays the work of discovering which therapeutics actually work. He writes, “[a]lthough many drugs have in vitro activity against different coronaviruses, no clinical evidence currently supports the efficacy and safety of any drug against any coronavirus in humans, including SARS-CoV-2. Numerous drugs that have been highly promising in vitro for other infectious diseases have failed in clinical studies…. A common interpretation of off-label use and compassionate use of drugs is that is that if the patient died, they died from the disease, but if the patient survived, they survived because of the given drug. This is not true.” Studies like the trial by Gautret et al do not advance the science, and in kindling enthusiasm for drugs with potentially fatal side-effects, may well do harm.
Tell us a little about yourself. I’m a native Texan recently transplanted to the Midwest. I grew up in Austin, studied microbiology at the University of Texas, then moved to Houston to complete medical school, residency in Internal Medicine, and fellowship in Infectious Diseases at the Baylor College of Medicine. During that time I spent three years in Dr. Mary Este’s lab studying rotaviruses and noroviruses, the major causes of acute gastroenteritis in children and adults. In 2019 my wife and I moved to Omaha so that I could join the ID division at UNMC.
I spent most of my childhood wanting to be a virologist – my folks were physicians and very interested in HIV in the early 1990s, so the HIV life cycle was dinner table conversation at one point and I guess I latched onto that. In college my interests turned toward epidemiology and public health, but a mentor told me that if I wanted to be taken seriously in those fields I needed to go to medical school. For the record, that’s not true at all, but I’m glad to have gotten the advice because I fell in love with medicine once I got there.
What do you do now? Most of my time spent seeing patients is on the orthopedic ID service, which is devoted to treating bone and joint infections and particularly complicated infections involving prosthetic joints, screws and plates used to repair fractures, and other orthopedic ‘hardware’. The other big hat I wear is medical director of our Outpatient Parenteral Antimicrobial Therapy (OPAT; aka home IV antibiotic) program, which involves working with my PharmD colleague to help other medical teams identify patients who need OPAT and then monitor and manage those patients while they’re receiving it. While I’m not paid for this (yet), I also serve on our hospital’s ethics committee, as medical ethics is a longstanding passion of mine. Finally, I spend a little bit of time seeing patients on the general ID service, conducting clinical research, and teaching UNMC’s medical students, residents, and fellows.
Why UNMC? I decided to join UNMC primarily because of the unique clinical opportunities. The field of infectious diseases has a number of well-established subfields – transplant ID, oncologic ID, HIV disease – but ortho ID is more of an emerging field, and with UNMC’s ortho ID service having only recently started I thought this was a great opportunity to find my own career niche. There are few good data and lots of unanswered questions in bone and joint infections, and I think that’s really exciting!
The other thing that brought me here was my future colleagues. I knew Dr. Marcelin from the ID community on social media, and we talked at length before I’d even interviewed. It was a lot easier to make the decision to move halfway across the country knowing that other faculty here shared my interests and values, and that the division would offer strong mentorship and support for both my clinical and non-clinical activities.
Tell us something about yourself that isn’t related to medicine. I started college as a music major; as part of that I transcribed Bach’s third cello suite for the baritone saxophone, and somewhere out there is an out-of-print album where you can hear me playing Dvorák and Puccini and Saint-Saëns with the University of Texas Saxophone Ensemble.
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