COVID-19 Update (Green 3/11/2020)

Great thanks to Dr. Gary Green, Infectious Disease specialist, for a well-attended Grand Rounds this week on COVID-19. Dr. Green's blend of  virology, epidemiology, and calm-ology left me feeling more confident and less panicky about our current situation with COVID-19. Hope you all feel the same!

Here's the down and dirty (recognizing that this is a dynamic situation-- it's very likely that information shared here will be out of date in a matter of days).

COVID-19 in our Community
As of 3/11/2020, Sonoma County has only three confirmed cases of COVID-19:

• 1 case of previously diagnosed COVID-19 transferred from Travis Air Force Base associated with the original Diamond Princess Cruise (Japan)
• 2 cases of COVID-19 associated with the Grand Princess Cruise (SF to Mexico)

As of this writing, there have been NO additional confirmed cases of COVID-19 in Sonoma County.

In fact, in the last two weeks, Dr. Green himself has tested 15 high risk symptomatic patients (high risk because of direct contacts to known COVID-19 cases and/or recent high risk travel history). All of these patients were symptomatic (i.e. cough, shortness of breath, fever) and all resulted NEGATIVE.

Dr. Green reassured us that currently, we have no evidence in Sonoma County of community transmission-- unlike many counties, including Santa Clara, San Francisco and Los Angeles. It doesn't mean we won't have community transmission in Sonoma County; we just don't yet.  

What Happened in Wuhan, China?

China "went through the wall first" explained Dr. Green--that is, because this novel Coronavirus originated in China, patients and healthcare workers have been literally on the front lines of a brand new disease. For this, they have suffered.

It has now been over three months since COVID-19 was first recognized, and we know a lot more about this virus than those brave healthcare workers-- many of whom gave their lives taking care of sick patients. 

China's experience is NOT necessarily our experience, but we can learn from them! 

• Chinese healthcare workers in Wuhan first recognized a string of strange respiratory cases and unusual pneumonias in early December 2019
• Just a few weeks later their scientists were able to identify a novel Coronavirus, and by January 7 the virus had been sequenced and shared with the world.
• Of note, SARS (2002-2003) and MERS (2012) were both novel Coronavirus outbreaks. Tons of Chinese research and prep done in response to these outbreaks are improving the global response to COVID-19.
• By Dr. Green's estimation, "this virus started in the right place"-- had such a virus emerged almost anywhere else in the world, we would not have been equipped to recognize it, identify it and study it so quickly. 

Healthcare Workers, what is our risk?
Of note, in China, over 3000 healthcare workers (HCW) have been infected with COVID-19, and at least 18 have died.  This scares many of us in the healthcare field. In one hospital, 29% of 138 confirmed cases were in HCW. This is likely because of inappropriate personal protective equipment (PPE) and underprepared infection control measures at the time COVID-19 was emerging. Also there was a tremendous strain on healthcare resources. Simultaneously, there was an abundance of community transmission in China due to insufficient infection control practices and large numbers of patients in crowded clinics in a crowded city.

(By the way, in the SARS epidemic, over 1/5 of confirmed cases were in healthcare workers).

In contrast, at Queen Mary Hospital in Hong Kong (a huge 1706-bed hospital) reported 42 COVID-19 confirmed cases. Of the 413 HCW who cared for confirmed cases, 11 had documented unprotected exposure. These HCW were all quarantined x 14 days. 

This is important: in this hospital, despite its massive size and the number of cases:

• No HCW becomes infected with COVID-19
• There were ZERO nosocomial transmission in the hospital

Dr. Green's take home: We can do this! We do this every year for flu and seasonal respiratory illness: wash your hands, don't come to work sick, use appropriate PPE and infection control practices when caring for sick patients. 

Flu vs. COVID-19: How worried should we be?

Dr. Green wants us to keep this in perspective. While COVID-19 is indeed a serious illness with global repercussions, the actual numbers of deaths (in the US and worldwide) are far lower than seasonal flu. And remember-- there have been no recorded pediatric deaths.

While initial studies from China were reporting a 2-3% mortality rates from COVID-19 those numbers now appear to be much much lower (on the order of ~0.6% from Korea). Initial reports were probably higher because China was really reporting a "case fatality" rate rather than a "mortality rate". While 0.6% is much higher than influenza mortality rates (typically ~0.1%), it is markedly lower than SARS, MERS or the Flu Pandemic of 1918.

See the slide below for the actual numbers, comparing (on the top) SARS, MERS and COVID-19 and (underneath the line) the 1918 flu pandemic and our current 2019-20 seasonal flu. Of note, in the US 136 children and over 20,000 people have died of influenza so far this season  (2018-2019, 80,000 people in the US died). Get your flu shot, please!

(sorry slide credit to Dr. Green, the formatting is a little off. First column=mortality rate, Second column= Ro; measure of infectivity (the higher the more infective), third column=case fatalities are actual counts of deaths)

What does COVID-19 actually look like?

While it does look a little like a common cold, there are a few things to note about COVID-19:

• This is primarily a virus of the LOWER respiratory tract (i.e. lungs), unlike most coronavirus infections, which are UPPER respiratory tract infections (i.e. head colds)
• This means that very few have rhinorrhea (aka a runny noses), ~4%
• Unlike influenza, which comes on abruptly, symptoms of COVID-19 seem to come on gradually over several days with worsening shortness of breath being a primary symptom after about 5 days of illness
• Fever is often present but often not very high 
• Cough is usually dry

We also know now that about 80% of people infected with COVID-19 have mild illness, 14% have severe and 5% have critical illness.

By far, the people most at risk are elderly with other chronic health conditions (especially cardio-pulmonary health conditions).

Who to test for COVID-19? (as of 3/8/2020)

Persons with symptoms (fever (T>100.3), cough, breathing difficulties or sore throat)

AND
Prioritize people who meet CDC criteria (https://www.cdc.gov/coronavirus/2019-ncov/travelers/index.html)

• any symptomatic person, including HCW with close contact with +COVID-19 patient in the last 14 days, including Grand Princess cruise ship passengers
• any symptomatic person who traveled to geographic area with CDC travel advisory 2/3 in the last 14 days of sx onset (China, Iran, Italy, Japan, South Korea)
• any person hospitalized with lower respiratory tract infection sx where an alternative etiology has not been identified

Don't test asymptomatic people!

US Healthcare system preparation:
Dr. Green assured us that even though we haven't experienced community transmission yet, COVID-19 will be coming to a community near you. Just like flu and RSV seasons. But this is going to be a long slog. We are just about the wrap up flu season, too bad, time to keep up the hard word. ,

Key goals for the US healthcare system per the CDC. These are our goals too in our local community!

1. Reduce morbidity and mortality
2. Minimize disease transmission
3. Protect healthcare personnel
4. Preserve our healthcare system functioning

So, healthcare workers, stay safe, wash your hands, wear PPE, don't come to work sick, and don't panic. 

A few extra super-interesting goodies:

On a vaccine: 

• During the 2002 SARS epidemic (which was also a novel coronavirus), there was a tremendous amount of work done to create a SARS vaccine. By the time the vaccine was ready, 20 months had passed, and the epidemic had died down. 
• However, the very substrate with which that vaccine was created is being used to fast-track a vaccine for COVID-19.
• That puts the world 20 months ahead of the game. 
• Look for vaccine trials for COVID-19 to start in the next couple months!

On antiviral medications: 

• During the SARS epidemic, it was noted that HIV+ patients on antiretrovirals (ARVs)-- particularly Kaletra-- did better than their counterparts, despite assumptions that they should be immunocompromised and do worse.
• This led to experimental use of ARVs for the SARS coronavirus
• Also, during the last Ebola outbreak, a new ARV was created (Remdemsivir), which didn't have great effect on Ebola but may work for coronavirus
• SO, in the US, China and other countries (and even locally) new and old ARVs are being used (experimentally) to treat people infected with COVID-19. So far with some good outcomes. So cool!

And finally, some additional resources

• Great map from Johns Hopkins with global data (but we can all agree that the black and red is a little overly dramatic, just what we don't need right now), Click here to go to live map: https://coronavirus.jhu.edu/map.html
• Local Sonoma County Department of Public Health website: https://socoemergency.org/emergency/novel-coronavirus/

2019 Practice Changing Papers: Ob, Peds & Medicine (2/19/2020)

Grand Rounds this week was a little bit like an average day in a primary care clinic: quite full, sometimes fun, and a little overwhelming. Definitely not boring! Three faculty members at the Santa Rosa Family Medicine Residency: Drs. Douglas Jimenez, Cherie Green, and myself presented a rapid medley of practice-changing papers from 2019 in obstetrics, pediatrics and adult medicine, respectively. Here are the the clinical questions, the papers, and a very abbreviated summary of each of our 2019 practice changers:

Obstetrics (Douglas Jimenez)

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The question: Does ursodiol improve adverse perinatal outcomes in cholestasis?

The paper: Ursodeoxycholic Acid: versus placebo in intrahepatic cholestasis of pregnancy: A Randomized Controlled Trial (PITCHES), Chappell et al, Lancet 2019

Bottom line: In this study of ~600 women with cholestasis, ursodiol was safe (we knew this) but did NOT improve maternal itching symptoms or lead to a decrease in bile acids. Ursodiol also did not reduce the incidence of stillbirth, spontaneous preterm birth, or NICU admission. Ursodiol might reduce total preterm birth (iatrogenic plus spontaneous). The authors’ conclusions: the only intervention to affect adverse perinatal outcomes is delivery.

The question: What can bile acid levels tell us about adverse perinatal outcomes?

The paper: Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses, Ovadia et al, Lancet 2019

Bottom line: The risk of stillbirth with cholestasis (usually quoted at 1-3%) increases markedly when bile acids are >100milimol/L. Most women with bile acids <100 can be reassured and should be rechecked weekly until delivery. For women with bile acids>100, delivery should occur between 35 and 36 weeks EGA.

The question: Does hydroxyprogesterone prevent recurrent preterm birth in singleton pregnancies?

The paper: 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG), Blackwell et al, American Journal of Perinatology, January 2020

Bottom line: In this study of 1700 women with a history of preterm labor, progesterone did NOT decrease recurrent preterm birth. There was also NO difference in any of the individual components that were part of the composite neonatal morbidity and mortality. Despite these findings, American College of Obstetricians and Gynecologists (ACOG) and Society for Maternal and Fetal Medicine (SMFM) have not changed their recommendations; they continue to recommend hydroxyprogesterone supplementation in all pregnant women with a singleton gestation and a history of a prior spontaneous preterm delivery.

Pediatrics (Cherie Green)

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The question: Is high dose oral dexamethasone our only option for croup?

The paper: Prednisolone versus Dexamethasone for Croup: A Randomized Control Trial, Parker et al, Pediatrics, September 2019

Bottom line: Oral steroids are an effective treatment of croup, and the type of steroid  (high dose dex (0.6mg/kg), low dose dex (0.15mg/kd), prednisolone (1mg/kg)) seems to have NO significant impact on efficacy either acutely or in the week after treatment. 

The question: How accurate is the M-CHAT/F as a screening tool for autism?

The paper: Accuracy of Autism Screening in a Large Pediatric Network, Guthrie et al, Pediatrics, October 2019

Bottom Line: In this “real world” use of the MCHAT in 26,000 children, sensitivity was quite low at 39% with a positive predictive value of 15%; this is much lower than previous studies. However children who screened positive and were ultimately diagnosed with autism, were caught 7 months earlier than those who screened negative. Children of color and those from low income homes were found to have lower rates of screening, screen positive more often, and have more false positives. Be aware of the low sensitivity, and be SURE to follow-up positive MCHAT screens in a sensitive manner.

The question: Which leads to speedier recovery in sport-related concussion: rest or a bit of exercise? 

The paper: Early Subthreshold Aerobic Exercise for Sport-related Concussion: a Randomized Clinical Trial, Leddy et al, JAMA Pediatrics February 2019

Bottom Line: Though the standard of care for sport-related concussion has been sustained rest until resolution of symptoms, this study of 100 teenage athletes shows that sub-symptom threshold aerobic exercise during the first week after injury safely speeds recovery in adolescents with concussion symptoms. 

Adult Medicine (Veronica Jordan)

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The question: Should we prescribe intermittent inhaled corticosteroids for mild asthma?

The paper: Budesonide-formoterol in adults with mild to moderate asthma, Hardy et al, Lancet September 2019 

Bottom line: Yes, probably. In this study of ~900 patients with mild asthma, the combination of inhaled corticosteroids (ICS) and beta agonist (SABA) (Symbicort Turbohaler) used PRN led to reduced incidence of both moderate and severe asthma exacerbations. Europe changed their guidelines in 2019 and now recommend ICS-SABA prn as first line in mild asthma. In the US, we don’t have access to the Turbohaler, and the ICS-SABA is much more expensive than albuterol MDI. For very low risk patients, you can probably continue albuterol only, but for anyone with any more risk, consider Symbicort MDI (budesonide-formoterol). 

The question: When should we stop and resume DOACs for patients with atrial fibrillation who are going for surgery?

The paper: Perioperative Management of Patients with Atrial Fibrillation Receiving a Direct Oral Anticoagulant, Douketis et al, JAMA Internal Medicine, August 2019

Bottom line: For patients who are on dabigatran, rivaroxaban, or apixaban for atrial fibrillation undergoing LOW bleeding risk surgeries/procedures (e.g. colonoscopy, dental extraction, pacemaker), stop DOAC 1 day before surgery, restart POD#1. For HIGH bleeding risk surgeries (most surgeries), stop DOAC 2 days before, restart 2-3 days after. Using this standardized perioperative management strategy, there are acceptable rates of bleeding and of arterial thromboembolism, but that number is not 0.

The question: What is new in the 2019 IDSA Pneumonia Guidelines?

The paper: Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America, American Journal of Respiratory and Critical Care Medicine,, October 2019

Bottom line: These guidelines, available here: (https://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST) are 23 pages long. Please feel free to read the entire thing. Here are my personal favorite practice changers: 1) Health care associated pneumonia (HCAP) is gone! RIP. 2) You only need blood and respiratory cultures in patients with pneumonia for whom you are treating empirically for either MRSA or pseudomonas 3) No steroids for non-severe CAP 4) Only cover anaerobes in presumed aspiration pneumonia if confirmed empyema or lung abscess (no more flagyl!) 4) Amoxicillin is now FIRST line treatment for uncomplicated outpatient CAP. 5) No routine CXR after pneumonia.