Provider Update for Thursday, April 2, 2020

Thursday, April 2, 2020

JoAnn Wood, MD, MHA, Chief Medical Officer - Baptist DeSoto
Jake Lancaster, MD, MSHA, MSACI, Chief Medical Information Officer - Baptist Memorial
Lillian Ogari, Ph.D., MPH., Associate Professor of Microbiology BCHS
Amanda Comer, DNP, FNP, ACNP, ENP, System Director Advanced Practice Providers
Jillian Foster, PharmD, MBA, System Pharmacy/Radiology Administrator
Stephen Threlkeld, MD, Medical Director Infectious Disease, Baptist Memorial Health Care
Steven Stroud, MD, Medical Director Infectious Disease, NEA Baptist, Jonesboro Arkansas
Manoj Jain, MD, Medical Director Infectious Disease and Infection Prevention, Baptist DeSoto
Bret Barrett, MD, Infectious Disease Consultant, Mississippi Baptist Medical Center

Update in Brief: 4-2-20

Coronavirus cases continue to rise across the mid-south. In our three state region, within the Baptist system, as of this morning we have tested 7825 symptomatic individuals. We have diagnosed 586 cases of COVID -19 using RT-PCR. Our current overall positive rate is 8.77% with individual local centers reporting rates as high as 24%. Over 90% of all individuals with COVID -19 positive results are being cared for at their homes under quarantine conditions. All hospitalized COVID -19 positive patients are in isolation or in an ICU bed in isolation.

We are very thankful for the expert guidance being given by Dr. Threlkeld, Dr. Jain, Dr. Stroud and Dr. Barrett. Based upon their recommendations and input we are focusing on the following actions across Tennessee, Arkansas and Mississippi: (1) Communicating broadly with the public and our team members about the Coronavirus threat and how important it is to adhere to social distancing behaviors and application of self-isolation for all symptom positive people. (2) Our teams are preparing for the surge of cases that lie ahead. This means we are preserving PPE and creating additional acute care and critical care bed capacity. Team members are developing plans to access more ventilators and devising ways to expand our current methods of ventilation support. (3) The Baptist leadership and clinical teams are fully supporting social distancing practices and government sanctioned travel and business lock-downs. (4) We are making every effort to support the work and leadership of the local and state health departments in identifying COVID -19 positive individuals through testing. (5) We are instructing COVID -19 positive individuals to comply with quarantine isolation parameters set forth by the State and local Health Departments. (6) We are supporting contact tracing to identify and isolate others who have had high risk exposure to a COVID  positive individual. (7) Finally, we are leading our teams to use PPE appropriately, per CDC guidelines, while practicing perfect hand hygiene at all times.

It remains imperative that physicians and their patients work together to avoid elective procedures, tests and routine medical care visits during the next 2-3 months. However, we are taking aggressive steps to support a wide variety of telemedicine options in our clinics and in our facilities. We continue to assertively, but compassionately limit visitors in all our facilities. It is important for our physicians and advanced practice providers to take this moment to reach out and encourage our bedside nursing colleagues who are working very hard and courageously to render direct patient care. Please contact your local CEO, CMO, or Clinic administrator with any specific questions or suggestions.

—Paul DePriest, MD, MHCM, EVP-COO Baptist Memorial Health Care

—Henry Sullivant MD, MHCM, VP- System CMO

—Mark Swanson MD, MHCM, VP-President Baptist Medical Group

Coronaviruses are a large family of lipid-enveloped RNA viruses. These viruses are commonly occurring in humans and many different species of animals, including camels, cattle, cats, and bats. Rarely, animal coronaviruses can mutate to infect humans and then spread between people such as with MERS-CoV, SARS-CoV, and now with this new virus (named SARS-CoV-2) COVID-19. The general evidence on MERS-CoV and SARS-CoV demonstrated that those pathogens were more difficult to transmit than common influenza but were much more clinically dangerous than the flu. COVID-19 is a novel virus; hence, there is precious little scientific data available about the infections it has now caused in scores of humans. There is also precious little herd immunity among humans to COVID -19. These infections were first discovered during late November –early December 2019 in and around Wuhan City in Hubei Province, China. The COVID-19 virus was able to efficiently infect thousands of Wuhan City residents in a matter of weeks leading to an epidemic. The WHO and CDC have both substantiated that COVID-19 causes SARS-CoV-2, and that an individual infection can quickly lead to community spread. This epidemiologic pattern has been particularly observed in China, Italy, Iran, Spain and now in the U.S. The virus has now spread around the world and meets the WHO classification as a pandemic.

The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. All three of these viruses have their origins in bats. The RNA sequences from COVID-19 viral particles detected in U.S. patients demonstrate a similar RNA sequence compared to the sequence that researchers from China initially posted. Early on, many of the patients at the epicenter of the outbreak in Wuhan City had some link to a large seafood and live animal market, suggesting animal-to-person spread. Later, a growing number of patients reportedly did not have exposure to animal markets, indicating community transmission via person-to-person spread. Within a matter of weeks from the first reported cluster of cases arising from the market-exposed patients, massive community transmission was reported. Collectively, this information strongly suggests the recent emergence of a novel coronavirus, arising from an animal reservoir, which upon mutation was capable of infecting humans.

Testing for the COVID-19 Virus

Current tests for COVID -19 consist largely of RT-PCR (Reverse Transcription Polymerase Chain Reaction) techniques. RT-PCR requires minute amounts of the RNA from a COVID -19 sample (i.e. nasal swab from a patient) which is then amplified to allow adequate detection of the viral type and sequence. This, in essence, allows identification of the viral type even if there are relatively small amounts of RNA within the collected sample. The sensitivity and specificity of RT-PCR is extremely high with low risk of false positives or false negatives. Baptist, through a relationship with AEL, is currently able to process over 2000 COVID -19 tests per day. The actual RT-PCR test takes 2 hours to run, but results reporting is usually a 1-3 day process. Other tests are available or are under development, but RT-PCR is the gold standard as of 3-24-20. Our current cost of the AEL RT-PCR is under$100.00.

On 3-21-20 the FDA approved the Cepheid point-of-service test platform for COVID -19 detection. This test is a form of RT-PCR which uses immunofluorescence technology to identify specific identifying RNA sequences of COVID -19. The test can be performed within the clinical setting and takes only 45 minutes to get results. Baptist has the Cepheid testing platform in many of our labs. However, it is still unclear when COVID -19 test kits for the testing platform will be available at scale. We have been told the cost of the test will be under $100.00.

Early Virology Understanding of COVID-19

Like other coronaviruses, COVID -19 can be spread by contact with droplets, by direct inhalation of aerosolized viral particles, or by contact with a contaminated surface. In a recent paper in the NEJM, researchers from Princeton found that the COVID -19 virus remained active at 3 hours in aerosol suspension and remained active for days on multiple types of contact surfaces including metals, plastics, cardboard and paper (3.). The virus can be inactivated with alcohol based and chlorine based cleansing agents. Alcohol-based hand sanitizers are an effective agent for hand hygiene in the healthcare setting. Most cleaning agents approved for the healthcare setting are sufficient for decontaminating solid surfaces.

Preventing COVID-19 infections

Currently there are no approved vaccines to prevent a COVID -19 infection. A worldwide effort is underway to develop a vaccine. However, it is realistic to assume that widespread immunization could not begin until late 2020 or early-mid 2021. The COVID -19 virus has been shown to use Angiotensin converting enzyme 2 (ACE 2) receptors as a point of entry into the human cell facilitated by type transmembrane serine proteases (2.). There are several drugs currently being tested which would target this pathway in an effort to prevent viral entry and possibly prevent overt infection.

The best way to prevent infection with COVID -19 is to limit one’s direct exposure to the pathogen. The most dangerous exposure is via direct droplet or aerosol transmission from an infected person. Contact with surfaces contaminated with secretions harboring COVID -19 particles also can effectively lead to infection. Avoiding large groups of people in close contact is imperative in preventing community spread of COVID -19. Avoiding close physical contact with others in the form of hugging, shaking hands, and kissing is also protective. In the healthcare environment every effort should be made to mask potentially infected patients, and for health care providers (HCP’s) to use proper application of the proper personal protective equipment (PPE). Careful hand hygiene using approved products and with soap and water can prevent transmission. Please see below.

Current Condition: 4-2-20

Prevalence in the World

World as of 4-2-20: Total cases: 1,002,159

PREVALENCE IN USA AND OUR REGION

USA as of 4-2-2020: 239,630 cases

COVID -19: U.S. at a Glance (CD and Johns Hopkins Coronavirus Resource)

  • Total cases: 239,630
  • Total deaths: 5,784
  • States reporting cases: 50
  • US Territories reporting cases: 4
  • TENNESSEE

    • Total cases: 2,845
    • Total deaths: 32

    MISSISSIPPI

    • Total cases: 1,177
    • Total deaths: 26

    ARKANSAS

    • Total cases: 625
    • Total deaths: 10

    LOUISIANA

    • Total cases: 9,150
    • Total deaths: 310

    Preparing for the Surge

    The USA, like countries across the world, has been quickly impacted largely due to mass transit of people around the globe who harbored the virus in an asymptomatic state or in an early symptomatic state. From what is understood at this time, there is little to no natural immunity to COVID -19 as it is a new variant of other coronaviruses. The population currently reported to be positive with the disease is likely to be a gross underestimation. Baptist leadership teams are quickly preparing for an influx of patients with COVID -19. This means opening additional acute care beds, increasing ICU capacity, increasing ventilator accessibility, and preparing off-site care centers where possible.

    So why all the hype?

    The main reason for immediate concern is that the virus has been able to spread very quickly leading to a sharp increase in the numbers of individuals requiring admission and acute care. The case counts rose so quickly in China and Italy that hospital capacity and ICU capacity were overwhelmed. Roughly 3.5-5% of patients required ICU care with many requiring ventilator support. In Italy, Spain and Iran many patients in need of care for a variety of non-COVID -19 medical or surgical conditions could not access appropriate support.

    Preventing or Blunting the Surge

    The best way to prevent a massive surge in hospital inpatient and ICU volume is to slow or limit spread of the disease in our communities. This is accomplished by strictly adhering to social distancing behaviors and supporting government mandated lock-downs. The healthcare systems can help by reinforcing these messages at every possible point of contact with the public. Next, we are encouraging individuals with ILI symptoms to STAY AT HOME in self-isolation or quarantine. If a symptomatic patient must be seen they should be directed to an outpatient screening and testing site or ambulatory clinic. If these are not available, then an emergency department is the next best option. These symptomatic individuals should have a mask placed on them upon arrival and they should be screened and tested for COVID -19. All ambulatory individuals should be returned home for self-isolation and self-care supported as needed with home health or telemedicine. The symptomatic individuals should remain in isolation for 14 days. If the individual tests positive for COVID -19, They are alerted by their physician who reinforces the message of isolation and quarantine for 14 days. The Health Department should be notified and contact tracing begun. All individuals with high risk exposure to a positive patient should be placed in self-isolation or quarantine and should be symptom monitored for 10-14 days. Patients requiring inpatient admission should be moved to an isolation room with negative pressure if available. All hospital staff should use PPE as CDC approved. All first responders and hospital/clinic staff are instructed to take their temperature daily and alert their manager if they develop any symptoms of flu –like-illness. Any symptomatic first responder or employee/provider should be seen and tested for COVID -19. They should be isolated in quarantine until the test returns. For more information on Healthcare Workers and COVID -19, please reach out to Baptist Employee Health or our 1-866 coronavirus hotline resource.

    In a recent white paper, Gottlieb and colleagues have outlined a strategy for the reopening of the U.S. after the COVID -19 pandemic (11). In this report the authors outline a four phase approach to dealing with the crisis immediately, but also how we will need to respond in the coming months to stabilize the communities we serve and develop vaccines, treatments and a better response to the next pandemic. This paper is a must-read for all those actively working to prevent a surge, react to the surge and plan recovery efforts after the surge.

    What can we do to immediately prepare for the surge

    First and fore most we can work together to cancel elective care during the ensuing surge in cases. We have asked each patient and each physician to work with local hospital and clinic administration to cancel elective office visits, elective testing and elective surgery. We can move to the use of telemedicine for many types of elective care that keeps the patients safely in their homes and the health care providers in a position to decrease their own exposure. By down regulating health resource utilization in a critical time we will open capacity for the patients that need care the most while decreasing the risk of exposing non-COVID -19 patients to a dangerous viral illness.

    We should work with our patients and administration to limit visitors and non-essential workers in the high risk hospital and clinic environments. We understand that compassionate care is usually rendered to a critically ill person and their loved ones. Limiting unnecessary visitation will be protective for other patients, for the families, for healthcare providers and for the community.

    Our teams are working diligently to open up additional bed access so that all patients can get the urgent and emergent care they need during this pandemic.

    Be frugal with the use of PPE. Identifying safe ways to avoid PPE wastage will help protect supplies for the weeks ahead when we will need every mask and gown we can find.

    How can Healthcare Providers be Protected?

    The most important thing we can do to protect healthcare providers is to use proper PPE in then proper way. Further below you will find the CDC recommendations on Personal Protective Equipment.

    Healthcare workers seem to have an increased risk of acquiring this virus and requiring hospitalization. One reason for this has been inadequate use of PPE. Studies have shown that when monitored, healthcare workers properly don and doff PPE only about 40% of the time. A second reason is that in this epidemic many hospitals have run out of PPE. Baptist is constantly working to ensure adequate supplies and will be updating you regularly with modified plans when/if they are needed. The last reason may be that healthcare workers are exposed to a higher load of viral particles because of the interventions performed on or near the airway. Therefore, all of our hospitals and medical staff have been working to reduce direct contact and exposure time with COVID -19 patients using telemedicine while also balancing the importance of providing excellent and compassionate care.

    The virus can be spread by individuals who are having few if any symptoms. As stated earlier, COVID -19 virus is extremely transmissible. Ying and colleagues reported that a COVID -19 positive patient can infect on average 2.2 people compared to influenza which on average is transmitted to 1.3 people. The virus is more contagious than the flu and leads to significantly higher rates of severe respiratory compromise and death compared to influenza.

    What should I do if I am caring for a patient with COVID-19?

    Caring for the COVID-19 patient should proceed as you would care for any other patient with a respiratory viral infection, but with greater caution regarding the highly infectious nature of this novel infection. A recent case study published in the NEJM can help you better understand the presenting signs and symptoms and early management (https://www.nejm.org/doi/full/10.1056/NEJMoa2001191?query=featured_home) (4).

    Healthcare personnel caring for patients with confirmed or possible COVID-19 should adhere to CDC recommendation for infection prevention and control (IPC):

    • Assess and triage patients with acute respiratory symptoms and risk factors for COVID-19 to minimize chances of exposure, including placing a face mask on the patient and placing them in an examination room with the door closed in an Airborne infection Isolation Room (AIIR) if available
    • Use standard precautions, contact precautions, and airborne precaution when caring for patients with confirmed or possible COVID-19.
    • Perform hand hygiene with alcohol-based hand rub before and after all patient contact, contact with potential infectious material, and before putting on and upon removal of PPE, including gloves.
    • Use soap and water if hand are visibly soiled.
    • Practice how to properly don, use and doff PPE in a manner to prevent self-contamination.
    • Perform aerosol-generating procedures, in AIIR, while following appropriate IPC practices, including use of appropriate PPE.

    What are the most frequent signs/symptoms of patients with COVID-19?

    Clinical characteristics of COVID-19 patients in China9

    • Median patient age 47 years
    • 0.9% younger than age 15
    • 41.9% female
    • 3.5% health care workers
    • Fever present in 43.8% on admission and 88.7% during hospitalization
    • Cough 67.8%
    • Nausea or vomiting 5%
    • Diarrhea 3.8%
    • 23.7% with comorbidity

    Lab Findings

    • Leukopenia 33.7%
    • Lymphopenia 83.2%
    • Thrombocytopenia 33.7%
    • Acute Kidney Injury
    • Mildly elevated AST, ALT, LDH and TBili
    • Low procalcitonin (May be elevated if a bacterial superinfection present)
    • Elevated Ferritin
    • Elevated IL-6
    • Elevated CRP 60.7%
    • Elevated D-Dimer 46.4%
    • Elevated LDH 41%

    CXR: Abnormalities on chest radiograph present on 59.1% of patients. Common abnormalities seen ground-glass opacities, local patch shadowing, bilateral patchy shadowing, interstitial abnormalities
    POCUS: Numerous B Lines; pleural lining thickening; consolidations with air bronchograms.
    CT: Abnormalities on chest CT see in 86.2% of patients. Most common finding ground-glass opacities.

    Clinical Characteristics of Critically ill Patients in Washington State8

    • Mean age: 70 years
    • Comorbidities present: 86% (most CKD and CHF)
    • Shortness of breath: 76%
    • Fever: 52%
    • Cough: 48%
    • Mean onset of symptoms: 3.5 days
    • 81% of patients admitted to ICU less than 24 hours after hospital admission

    Radiology findings:

    • Abnormal chest x-ray: 95%
      • Bilateral reticular nodular opacities: Initial: 52%, 72 hours: 86%
      • Ground-glass opacities: Initial: 48%, 72 hours: 67%

    Laboratory findings:

    • Normal WBC Count: 67%
    • Lymphopenia: 67%
    • Abnormal LFT’s: 38%

    Complications:

    • Mechanical Ventilation: 71%
      • Acute Respiratory Distress Syndrome: 100% of ventilated patients
      • Severe ARDS: 53% at 72 hours
    • Vasopressors used: 67%
    • Cardiomyopathy: 33%
    • Mortality: 67%

    Risk Factors for Mortality in COVID -19 Inpatients in Wuhan, China10

    • Older Age
    • Elevated d-dimer
    • Higher SOFA score on admission
    • Elevated levels of IL-6
    • Elevated high-sensitivity troponin I
    • Elevated lactate dehydrogenase
    • Lymphopenia

    Treatment options

    There are no proven effective treatment regimens. However, there are a growing number of reports citing efficacy of medications including, remdesevir, camostat mesylate, hydroxychloroquine and interventions such as ECMO. The therapeutic options will develop and change rapidly. Our infectious disease efforts led by Dr. Stephen Threlkeld and our pharmacists at Baptist led by Dr. Jillian Foster are vigorously working to stay abreast of the developing literature to help determine which medications and what support equipment is needed at any given time. Dr. Maggie DeBon, the Executive Director of the Baptist Clinical Research Institute (BCRI) is supporting the applications for compassionate use of investigational drugs such as remdesevir from Gilead Labs. Dr. DeBon also is leading oversight of clinical research trial applications and IRB approval processes.

    ACP COVID-19: Treatment- Pharmacology6

    While there are no proven beneficial targeted treatments, below are agents with initial reports of efficacy.

    Remdesivir: a prodrug of an adenosine analog with potent activity against an array of RNA virus families. Mechanism of action of remdesivir is through the targeting of the viral RNA dependent RNA polymerase. It is currently available for compassionate use from the manufacturer, Gilead. Patients considered by Gilead must be hospitalized with confirmed COVID-19 infections and significant clinical manifestations.

    Chloroquine and Hydroxychloroquine: Immunomodulant drugs that block the SARS virus infection by reducing virus/cell fusion. Has been shown effective in reducing viral replication of SARS-CoV and MERS-CoV. Early data suggests effectiveness in reducing viral infection in vitro.

    Chloroquine + Azithromycin: A small, open-label, non-randomized, practical study enrolled 26 patients [6 asymptomatic, 22 with URI symptoms, and 8 with LRTI symptoms] and 16 controls to observe outcomes on viral load at day 6 of treatment. Of the 26 patients in the treatment group, 6 also received azithromycin with daily electrocardiographic monitoring) and these 6 demonstrated more rapid resolution of viremia.

    Corticosteroid: Based on lessons learned form MERS-CoV patients, do not use corticosteroids due to the potential for prolonging viral replication unless otherwise needed to treat septic shock or other disease processes.

    ACEI/ARBs Controversy:

    Questions have arisen about the continued use of ACE inhibitors and ARBs due to the binding of SARS-CoV-2 to the ACE2 functional receptor. The American College of Cardiology issued a statement that is no data demonstrating beneficial or adverse effects among COVID -19 patients on ACE-I or ARB medications. The Council on Hypertension of the European Society of Cardiology strongly recommends that physicians and patients continue treatment with their usual anti-hypertensive therapy.

    NSAID Controversy:

    The FDA issued a statement on 3/19/20207 advising that there was not at the time of its posting any scientific evidence connecting NSAID use to worsening COVID-19 symptoms. The statement was in response to reports following a letter in the Lancet medical journal which hypothesized that an enzyme is increased by NSAIDs and could aggravate COVID-19 symptoms.

    Care for Critically Ill Patients with COVID -195, 8

    Approximately 5% of COVID-19 cases will result in severe disease requiring intensive care. Characteristics of COVID-19 patients that require intensive care include older age (median 60 years) and comorbid conditions such as diabetes and cardiac disease (40%). The median duration between onset of symptoms and ICU admission is 9-10 days. The most common reason for ICU admission is respiratory support. Two-thirds of ICU admitted patients have met criteria for acute respiratory distress syndrome (ARDS). Mortality ranges from 0.5% to 4% for all infected, 5% to 15% for those hospitalized, and 22% to 62% for those who become critically ill based on early data from Hubei.

    The management of severe COVID-19 infection is similar to the management of most viral pneumonia causing respiratory failure. In severe COVID-19 patients with ARDS, evidenced based treatment guidelines should be followed including conservative fluid strategies, empirical early antibiotics for suspected bacterial co-infection, lung-protective ventilation, prone positioning, and consideration of extracorporeal membrane oxygenation for refractory hypoxemia. To view the full article, click here.

    OK, what should physicians and advanced practice providers do?

    1. Ask that any patient with concerning symptoms be given a mask if available.
    2. Properly don and doff PPE.
    3. Protect your families by wearing your own scrubs and white coat to the hospital and taking them off and carrying them back home in a plastic bag which is immediately thrown into your washing machine and utilizing aggressive detergents and when possible bleach. Use careful hand hygiene before leaving the hospital and as you arrive home.
    4. Ask your direct family members to follow social distancing when in any public forum to avoid high risk social interactions during the next 2-4 months. This could help block community spread to your family and then to you. In the next 2-4 months your ability to continue service within the clinical setting is crucial for the patients who will need care.
    5. Personally practice immaculate hand sanitation in the hospital and clinic settings. Avoid touching your face, eyes, nose and mouth as much as possible. Encourage others to do the same.
    6. Wipe down your work surfaces with appropriate cleaning materials regularly.
    7. If you identify a concern, please quickly escalate it to the appropriate leadership immediately. Your CMO, CEO or Clinic Director will be able to address the issue most effectively with your assistance. As a physician, you are a leader within the clinical arena. The frontline staff look you for guidance, support and calm actions in critical situations.
    8. If you interact with a patient who eventually tests positive for the virus, and if you were using PPE appropriately, it is reasonable for you to monitor your symptoms and check your temperature twice daily. If you develop concerning symptoms or if your temperature rises above 100.4 please contact employee health. Otherwise, you should continue to work. If you were not wearing proper PPE, please contact employee health immediately for instructions.
    9. If sick, or symptomatic in any way please stay at home.
    10. Finally, knowledge is power. Check this website regularly for updates and changes in recommendations. “Up-to-Date” has a terrific page which is regularly being refreshed.

    References

    1. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020;27(2):taaa021. oi:10.1093/jtm/taaa021
    2. Cynthia Liu, Qiongqiong Zhou, Yingzhu Li, Linda V. Garner, Steve P. Watkins, Linda J. Carter, Jeffrey Smoot, Anne C. Gregg, Angela D. Daniels, Susan Jervey, Dana Albaiu. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. ACS Central Science, 2020; DOI: 10.1021/acscentsci.0c00272
    3. https://www.nejm.org/doi/full/10.1056/NEJMc2004973?query=featured_home
    4. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191?query=featured_home
    5. Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients with COVID-19. JAMA. Published online March 11, 2020. doi:10.1001/jama.2020.3633
    6. https://assets.acponline.org/coronavirus/scormcontent/?&_ga=2.79094743.2124121333.1585074648-211937735.1581348757#/lessons/anzGFkgpoH_6MkJZWAmio-svrvn8swCa
    7. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-COVID -19
    8. Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State [published online ahead of print, 2020 Mar 19]. JAMA. 2020;e204326. doi:10.1001/jama.2020.4326
    9. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China [published online ahead of print, 2020 Feb 28]. N Engl J Med. 2020;10.1056/NEJMoa2002032. doi:10.1056/NEJMoa2002032
    10. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID -19 in Wuhan, China: a retrospective cohort study [published online ahead of print, 2020 Mar 11] [published correction appears in Lancet. 2020 Mar 12;:]. Lancet. 2020;S0140-6736(20)30566-3. doi:10.1016/S0140-6736(20)30566-3
    11. Gottlieb S., Rivers C., McClellan M., et al. National Coronavirus Response: A Roadmap to Reopening, March 28, 2020; American Enterprise Institute