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COVID-19 disproportionately impacts minority communities

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.

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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.

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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.

Want to learn more?
Here are some recent opportunities to hear or read more about this topic:
• North Omaha Information Support Everyone (NOISE) Facebook Live April 30,2020
• UNMC Internal Medicine Grand Rounds presentation May 8, 2020
• Infectious Diseases Society of America Podcast published May 12, 2020
• Omaha World Herald Opinion piece (co-authored with UNMC medical student Rohan Khazanchi) published May 14, 2020

Peer-reviewed references included in this post:

Here is a list of selected publications you can access to learn even more

The Weekly Corona with Dr. Raquel Lamarche

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.

Some Epidemiology
• In a case series of >2000 children from China, there was no statistically significant difference in incidence between girls and boys; another case series reported a higher COVID-19 case rate in boys (61%) compared with girls (39%)
• It appears that children are less affected by COVID-19 than adults. This could reflect a lack of widespread availability for SARS-CoV-2 testing or the fact that children are less likely to be tested due to milder disease.
• Coinfection of SARS-CoV-2 and multiple respiratory pathogens can occur in children
• Children account for 1 to 5 percent of diagnosed COVID-19 cases.

Transmission

  • Large droplets: this type of transmission can be prevented using face masks
  • Fomites: (objects on which the virus containing droplets have settled) the virus may remain on surfaces for up to 4 days.
  • Aerosols: it appears that the virus may also be aerosolized, with a UNMC study finding evidence of (noninfectious) viral particles in the air

Pregnancy and newborns

  • Data in pregnancy is minimal. The most extensive case series had 38 cases
  • Currently, the virus is not definitively known to be transmitted vertically.
  • Of note, there are isolated 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.
  • Healthy pregnant women seem to have the same risk as adults who are not pregnant; however, the CDC warns that contracting the coronavirus while pregnant could make you more vulnerable to severe respiratory problems. This is because pregnant women already have a physiologic restrictive lung disease and relative immunocompromised state.
  • 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.

Symptoms and signs in children

In case series of >2000 children from China:

• 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

Newborns and infants

In young infants, SARS-CoV-2 can cause fever without any other manifestations, including respiratory symptoms and signs. A 3-week old baby boy who tested positive for SARS-CoV-2 and developed hypercarbic respiratory failure. He had an otherwise negative sepsis workup.

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.

The Weekly Corona with Dr. Raquel Lamarche

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!

The Weekly Corona with Dr. Raquel Lamarche

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

PERSONAL PROTECTIVE EQUIPMENT INNOVATION. Medical University of South Carolina crafted a modular HEPA filtration system that can be fitted onto hospital masks. For those that are into doing it yourself, you can find innovative ideas on YouTube covering how to make an elastomeric respirator, or how to create an improvised droplet barrier to minimize the use of PPE. There is also the possibility for extended use and re-use of N95 respirators! Or to inactivate the virus by applying Ultraviolet germicidal irradiation (UVGI) to used N95s. A protective barrier developed at UNMC shields and protects health care workers from contagions and other contaminants during intubation procedures.

MISCELLANEOUS INNOVATIONS
• A wristband can track affected individuals, and trace their contacts. In the scenario of a future epidemic, the wristband could play a role in selectively quarantining the affected cases and the people that have been in contact with them. South Korea used smartphones to tag the movement of cases and alert the non-infected via real-time updates; this drove rapid testing of over 200,000 of its citizens.
• João Nascimento, a Portuguese Neurosciences and Philosophy student at Harvard University, launched an appeal to crowdsource ideas to produce more ventilators.  The project developed a proof of concept of a minimalist pressure-controlled emergency ventilator.
• Christian Fracassi and Alessandro Romano, two young Italian engineers specialized in 3D printing, in collaboration with Dr. Renato Favero, constructed an emergency respiratory mask for assisted ventilation,, by adjusting a snorkeling mask already available on the market.
• Artificial intelligence-powered drones, carry UV-C lights to disinfect rooms.
• Remote temperature monitoring patch.
• Expedited production with 3D printers.
• COVID-19 Lung Ultrasound simulation module.
• LED Bracelet that reminds you to wash your hands properly.

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.

Ongoing Debate on the Treatment of Staphylococcus aureus Bacteremia

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.

You can read the original article, the Kalil et al. letter to the editor, and the response from the authors.


 

A critical examination of the controversial study behind hydroxychloroquine and azithromycin for COVID-19

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?

Unfortunately, this study had problems. Academic watchdog and author of Science Integrity Digest Dr. Elizabeth Bik described several of the issues with this paper at length, but to summarize the key points:

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.

Meet our newest blog contributor: Dr. Nicolás Cortés-Penfield

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.

The Weekly Corona with Dr. Raquel Lamarche

As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID19, 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. Last week we started with a primer on Human Coronaviruses (HCoVs). This week we will look at what we know about treatment so far.

“(2003) In the event that SARS CoV re-emerges, we will need clarification of the effectiveness of treatments through controlled trials.” Red Book. 

We have generally treated HCoVs (Human Coronaviruses) with supportive care. Steroids, type-1 interferons, convalescent plasma, ribavirin, and lopinavir/ritonavir, were all used in the 2002 SARS-CoV-1 outbreak, albeit, without controlled data, thus NO proof of efficacy. Likewise, throughout this SARS-CoV-2 pandemic, patients from multiple countries have received off-label therapies mostly without controls. 

“(2020) This tragedy of not discovering new therapies during an outbreak cannot be repeated,” Dr. Andre Kalil, UNMC Infectious Diseases 

I discussed the need for quality evidence with my significant other, an ER-resident in NYC. “People are dying in front of our faces; I would try anything to save their lives. You just can’t be a strategic scientist while you are flooded, getting your hands dirty, Raquel, ” he said. Those words are enough to send a chill down the spine.  Physicians are wired to fight for their patients and may act instinctively when faced with death and uncertainty. 

But the fact remains: NO control groups = NO conclusions about clinical efficacy or safety.

Thankfully, there are some ongoing studies to help make decisions. Here’s what we know about potential treatments for SARS-CoV-2:

Remdesivir

MECHANISM

  • Broad-spectrum antiviral; an adenosine analog pro-drug that shuts down viral replication by inhibiting RNA-dependent RNA polymerase. Initially developed by Gilead Sciences to combat Ebola.

THE EVIDENCE

HOPE LEVEL: moderate-high

Lopinavir/ritonavir

MECHANISM.

  • Inhibition of viral protease, which results in inhibition of viral replication. Lopinavir is quickly broken down by human proteases; thus, it is given with low levels of ritonavir, another protease inhibitor, and potent CYP3A4 inhibitor that “boosts” lopinavir concentrations.

THE EVIDENCE

HOPE LEVEL: low

Chloroquine and hydroxychloroquine 

MECHANISM

  1. Inhibition of viral release into the host cell. Endosomal acidification blockade, which is required to activate proteases that release viral particles into the cell.
  2. Reduction of viral infectivity. Inhibition of protein glycosylation and proteolytic maturation of viral proteins.
  3. Immune modulation. Reduction of toll-like receptors, cGAS-STING signaling, and release of pro-inflammatory cytokines.

THE EVIDENCE

HOPE LEVEL: moderate

Anti-IL6 Agents (Tocilizumab, Siltuximab, Sarilumab)

MECHANISM.

  • IL-6 activates T cells and macrophages. May be of benefit for patients with cytokine storm.

THE EVIDENCE

HOPE LEVEL: maybe moderate in patient with cytokine storm

Steroids

THE EVIDENCE

  • “Early (replicative phase)” hydrocortisone treatment  associated with a higher SARS-CoV-2 plasma viral load.
  • Wu et al. found that among patients with ARDS due to SARS-CoV-2, using methylprednisolone correlated with reduced mortality.
  • Based on indirect evidence from critically ill patients in general, Surviving Sepsis guidelines weakly recommend steroids for intubated patients with ARDS and elevated C-reactive protein or patients with an independent indication for steroids.

HOPE LEVEL: 0. Use steroids only as indicated for co-existing processes.

Antibiotics 

THE EVIDENCE

HOPE LEVEL: 0 unless you are treating known bacterial co-infection (if you choose otherwise, you won’t go to ID heaven)

Convalescent plasma

MECHANISM

  • It is possible that convalescent plasma that contains antibodies to SARS-CoV-2 might be effective against the infection (if they are neutralizing antibodies).

THE EVIDENCE

HOPE LEVEL: low-moderate. It may seem intuitive that this would work, but it’s not always the case.

Here are some comprehensive reviews with more detailed information, all written by some phenomenal ID pharmacists:

  1. COVID-19 Treatment: A Review of Early and Emerging Options, By Erin McCreery, PharmD and Jason Pogue, PharmD
  2. UNMC COVID-19 Antiviral and Pharmacotherapy Information, by Bryan Alexander, UNMC PharmD and the UNMC Antimicrobial Stewardship Team
  3. Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies by Scott J Bergman, UNMC ID PharmD 

There are no answers yet. Nevertheless, we are hopeful and always learning. Now more than ever, it is crucial that we stay together, sharing our experiences, and supporting science.

#PharmToExamTable: What is the evidence for continuous infusion dosing of cefazolin?

The following is a clinical review written by Corey Paz, PharmD. Recent graduate of UNMC College of Pharmacy and new PGY1 Pharmacy Resident at Gunderson Health System in LaCrosse, Wisconsin. Follow him on Twitter @coreypaz.

Corey was supervised by Scott Bergman, PharmD, FCCP, FIDSA, BCPS. Pharmacy Coordinator for Antimicrobial Stewardship at Nebraska Medicine and Clinical Associate Professor in the UNMC Dept of Pharmacy Practice and Science. Follow him on Twitter @bergmanscott.

Cefazolin is a first-generation cephalosporin (ß-lactam antibiotic) used for the treatment of Gram-positive bacterial infections and some Gram-negative organisms.  It has potent activity against common Gram-positive bacteria including Staphylococcus aureus (methicillin-susceptible only, MIC90 = 2 mcg/mL)1 and beta-hemolytic Streptococci such as Streptococcus pyogenes (Group A) and Streptococcus agalactiae (Group B).  The volume of distribution of cefazolin is ~10 L, and it is 75-85% plasma bound.  In comparison to four other first-generation cephalosporins (cephaloridine, cephalothin, cephalexin, cephanone), cefazolin has the smallest apparent volume of distribution which in part explains its high levels in the blood and popularity over the others2.  The reported half-life of the drug in adults is 1.8 h (IV).

Based on its pharmacodynamic profile, cefazolin needs to be administered at least twice per day by IV bolus to achieve therapeutic concentrations for the most susceptible organisms1.  In patients with severe infection, the usual dosage range is 1 to 2 g IV every 8 h in patients when renal function is normal2.  Cefazolin is a preferred agent for patients being discharged from the hospital that require IV antibiotics due to its efficacy and safety.3,4  One option to avoid frequent re-dosing is to administer cefazolin as a constant infusion over 24 h.5

Due to time-dependent pharmacodynamics, the efficacy of cephalosporins is associated with time above the minimum inhibitory concentration (T>MIC)1.  The optimal bactericidal action of cephalosporins reportedly occurs at approximately four times the MIC for the infecting pathogen6.  Increasing the dose (>MIC) of a ß-lactam antibiotic does not improve bactericidal activity, but rather increases the risk of adverse effects.  Strategies utilized to maximize the efficacy of ß-lactams include (1) decreasing the dosing interval (2) extending the infusion time of the drug and (3) administering the drug as a continuous infusion following a loading dose.

Livingston & Wang (1992) first demonstrated the superiority of continuous infusion dose administration for cefazolin versus standard intermittent dose administration using rats.  The study explored identical quantities of cefazolin administered either intermittently or continuously after shock in a subcutaneous abscess model with 2×108 S. aureus.  Rats were divided into three groups: (1) controls, which received no drug treatment; (2) rats intermittently dosed at either 30 or 60 mg/kg intraperitoneally every 8 h for three doses daily, and (3) rats receiving continuous drug infusion consisting of 30 or 60 mg/kg intraperitoneally as a loading dose followed by 90 or 180 mg/kg continuously infused over a 24 h time period (Figure 1).

Administration of cefazolin as a loading dose (30 mg/kg) followed by a continuous infusion (90 mg/kg over 24 hours) resulted in significantly more drug being present in the tissue than the identical quantity of cefazolin given as intermittent bolus doses.6  Seven days after inoculation, abscess number, diameter, and weight were measured. Within the continuous infusion group, a standard quantity of cefazolin (120 mg/kg/day) significantly decreased the number and size of the abscess compared with intermittent dosing after hemorrhagic shock.

In a retrospective cohort study, Zeller et al. (2008) investigated the use of continuous intravenous cefazolin in patients who were discharged home with parenteral antibiotic therapy on an outpatient basis.  At home, antibiotic therapy was administered twice a day, over a 12 h period, by a visiting nurse through a portable infusion device, either a constant-infusion pump or an elastomeric infusion system (single-use).  Patients unable to discharge home were transferred to a rehabilitation center or remained inpatient until the end of parenteral therapy.  Drug therapy was initiated with a loading dose, infused over 10 minutes, of 1 g when the daily dose was ≤4 g or of 2 g when the daily dose was >4 g, followed immediately by the continuous infusion of 60 to 80 mg/kg of body weight.  For example, the dosing regimen of 70 kg individual would be as follows: 2 g of cefazolin infused over 10 minutes followed by 4200 mg (60 mg/kg * 70 kg) total daily dose divided twice a day (2100 mg/dose over 12 hours each).   The median treatment duration was 42 days, and the median daily cefazolin dose was 6 g.  The median follow-up time was 25 months.  Overall, 82 (93%) of the 88 patients were considered to have been cured (53 patients) or probably cured (29 patients)7.

In summary, cefazolin is a first-generation cephalosporin with bactericidal activity against methicillin-susceptible Gram-positive organisms and some Gram-negative organisms.  Two separate studies provided evidence favoring the administration of a continuous infusion of cefazolin following a loading dose compared to intermittent administration.  The emphasis for clinical application not only stems from the results of each study, but also from the pharmacodynamic profile of cefazolin.  The time-dependent efficacy plays an instrumental role in the flexibility of drug administration.  Doses ranging from 60 mg/kg/day to 120 mg/kg/day have demonstrated efficacy and fall within the suggested 12 g/day maximum dose whether administered over two 12 h intervals or one 24 h interval.

With appropriate clinical judgement, monitoring, and follow-up, administration of cefazolin (6g/d) by continuous infusion targeting susceptible pathogens may be considered in specific clinical scenarios.

References

  1. Howard, G., Begg, E., Chambers, S., Brincat, J., Zhang, M., & Kirkpatrick, C. (2002). Free and total cefazolin plasma and interstitial fluid concentrations at steady state during continuous infusion. Journal of Antimicrobial Chemotherapy, 50, 429-432.
  2. Kirby, W., Regamey, C. (1973). Pharmacokinetics of Cefazolin Compared with Four Other Cephalosporins. The Journal of Infectious Diseases, 128, S341-S346.
  3. Youngster, I., Shenoy, E., Hooper D., and Nelson S. (2014) Comparative evaluation of the tolerability of cefazolin and nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting. Clinical Infectious Diseases, 50, 369-375.
  4. Lee, B., Tam I., Weigel IV, B., Beeze, J., Paulus J., Nelson, J., Allison, G. (2015) Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches. Journal of Antimicrobial Chemotherapy, 70, 2389-2396.
  5. Harris, A., Shrestha, N., Allison. G., Keller, S., Bhavan, K., Zurlo, J., et al. (2019) 2018 IDSA Clinical Practice Guideline for the management of outpatient parenteral therapy. Clinical Infectious Diseases, 68, e1-e35.
  6. Livingston, D., Wang, M. (1992). Continuous Infusion of Cefazolin Is Superior to Intermittent Dosing in Decreasing Infection After Hemorrhagic Shock. The American Journal of Surgery, 165, 203-207.
  7. Zeller, V., Durand, F., Kitzis, M., Lhotellier, L., Ziza, J., Mamoudy, P., & Desplaces, N. (2008). Continuous Cefazolin Infusion To Treat Bone and Joint Infections: Clinical Efficacy, Feasibility, Safety, and Serum and Bone Concentrations. Antimicrobial Agents and Chemotherapy, 883-887.


     

The Weekly Corona with Dr. Raquel Lamarche

As our institution, state, country, and the world grapple with the impacts of SARS-CoV-2, causing COVID19, 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.

TODAY’S PRIMER: Human Coronaviruses (HCoVs)

Four HCoVs cause mild upper respiratory infections (common cold): 229E, OC43, NL63, and HKU1. Less frequently, these can be associated with lower respiratory tract infections, primarily in infants and the immunocompromised.

Three HCoVs are related to lower respiratory infections and responsible for recent epidemics:

1. SARS-CoV-1. This virus was responsible for the 2002-2003 global outbreak of severe acute respiratory syndrome (SARS). The virus causes a spectrum of disease, including asymptomatic infections and mild illness.

The outbreak lasted for 9-months, resulting in 8096 reported cases and 774 deaths. SARS-CoV disproportionately affected adults, who typically presented with fever, myalgia, headache, malaise, followed by dyspnea 5-7 days later. 25% of adults developed watery diarrhea. 20% developed respiratory distress requiring intubation and mechanical ventilation.

The overall mortality rate was 10%, with most deaths occurring in the 3rd week of illness. The case-fatality rate in people older than 60 approached 50%. Notably, no infant or child deaths were documented. The horseshoe bat is the natural reservoir of SARS-CoV-like viruses. The virus is thought to have evolved through civet cats or intermediate animal hosts in the wet markets of China.

The 2002-2003 global outbreak was controlled due to the rapid identification of cases, contact tracing, quarantine, and isolation. We always wondered whether a large scale re-emergence of SARS-CoV would ever occur and as Italians would say, “eccoci qui,” here we are.

2. MERS-CoV. This was a novel virus identified in 2012. The disease caused by this virus was called Middle-East respiratory syndrome (MERS).[It is important to note that while this virus and disease were unfortunately named for the region of the world where they were identified, it is generally recommended to avoid naming diseases after geographic regions, race/ethnicity, etc., as this can lead to stigma associated with the disease].

MERS is associated with a severe respiratory illness similar to that with SARS-CoV, resulting in 2494 cases and 858 deaths. Cases continue today but are primarily contained in the Middle East. Data suggests that the virus evolved from bats, with dromedary camels acting as intermediate hosts.

Preventing transmission from camels is challenging, given the prevalent use of camels in some Middle Eastern countries. The case-fatality rate is high, estimated at 35%, but may partially reflect surveillance bias for more severe disease. (Red Book, 31st edition)

3. SARS-CoV-2. This is the virus causing the current pandemic. The disease, now known as COVID-19, was first reported in Wuhan, China, in late December 2019. Click the link for the current number of US cases. This virus likely originated in chrysanthemum bats. There is probably an intermediate host between bats and humans, and preliminary data suggest it is the pangolin.

The virus uses a densely glycosylated spike (S) protein to enter host cells and binds with high affinity to the angiotensin-converting enzyme 2 (ACE2) receptor in humans like SARS-CoV. It is still unclear why SARS-CoV-2 is more easily transmissible than SARS-CoV-1 or MERS-CoV.

This virus is actively mutating, which means the virulence and transmission will shift over time in unpredictable ways. See genomic epidemiology of novel coronavirus. Genetic analyses of 103 SARS-CoV-2 genomes indicated that we have two different types of the virus:
• L Haplotype (∼70%) is more prevalent and causes more severe illness
• S Haplotype (∼30%), less prevalent, and causes milder illness

SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; COVID-19: coronavirus disease-2019; ACE-2: angiotensin converting enzyme-2; ARDS: acute respiratory distress syndrome; HLH: hemophagocytic lympho-histiocytosis; PRN: as needed, CPR: cardio-pulmonary resuscitation

Transmission is via LARGE D-R-O-P-L-E-T-S. Droplet transmission is prevented by using standard surgical-masks. If those droplets are aerosolized, the virus can prevail for up to 3 hours in the aerosols. The CDC recommends airborne precautions especially during aerosol-generating procedures (sputum induction, open suctioning of airways, intubation, tracheostomy, CPAP, bag-mask ventilation).

Contact transmission implies virus-containing droplets settling on surfaces, a person touching such contaminated surfaces/objects and transferring the virus to their faces and mucous membranes. The virus can survive for up to four days on surfaces. To prevent this form of transmission, you can:
• Avoid touching your face (I’m sure your face is itching now)
• Disinfecting surfaces with 0.5% sodium hypochlorite
• Cleaning hands with an alcohol-based sanitizer
• Be mindful of your stethoscope and sanitize it often

Clinical Overview: Incubation 2-14 days; median of 4-5 days. Rare patients may have a more prolonged incubation of up to 24 days; this potentially long incubation period could have implications for quarantine policies and prevention of spread. Clinical signs/symptoms include:
• Upper respiratory infection symptoms
• Lower respiratory symptoms (shortness of breath)
• Fever (may not be present in up to 50% of cases)
• Less commonly, gastrointestinal symptoms like diarrhea or nausea in 10% of patients
• The elderly may have hypoxemia with no increased work of breathing
• Physical examination is nonspecific
• Lymphopenia is present in ~80% of patients
• Elevated CRP in 60% of the patients. Poor prognostic factor
• SARS-CoV-2 is not associated with elevated procalcitonin (95% patients had pro-calcitonin below 0.5)

In future Weekly Corona posts, we will explore what we know about personal protective equipment for COVID-19, treatment options, impacts on medical education, and more. Stay tuned!

Endnote: As we sift through the mountains of information about COVID-19, it is helpful to keep a few reliable resources bookmarked. Review these often, at least weekly, for updates:
• World Health Organization https://www.who.int/emergencies/diseases/novel-coronavirus-2019
• Centers for Disease Control & Prevention https://www.cdc.gov/coronavirus/2019-ncov/index.html
• Infectious Diseases Society of America https://www.idsociety.org/public-health/COVID-19-Resource-Center/
• Nebraska Medicine https://www.nebraskamed.com/for-providers/covid19
• University of Washington https://covid-19.uwmedicine.org/Pages/default.aspx
• Our World in Data https://ourworldindata.org/coronavirus 

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