COVID-19 Update (Green, 9/23/2020)

Great thanks to our local expert for an excellent, power packed update this week on COVID-19. As I mentioned in my introduction to Grand Rounds on Wednesday, Dr. Green has been a tremendous resource to our hospital, our residency, and our community from the very start of this pandemic. Just six months ago, with our first two cases of COVID-19 having walked through our doors, he gave a great presentation. And how much we have learned in 6 months time!?!

Gary talks fast, changes slides even quicker than he talks, and packs his presentations from virology to epidemiology to pathophysiology, but here are my key takeaways for COVID-19, 6 months in.

Epidemiology:

As of this week, the US has recorded almost 7 million cases of COVID-19 and over 203,00 fatalities. California has 793,000 cases and 15,000 fatalities. Sonoma County has had 7225 cases and 120 deaths. 

Dr. Green said he believes that Sonoma County's peak of Phase 1 of this pandemic was mid to late August, putting us slightly behind the rest of the Bay Area (which is why we also are "behind" in reopening). He credits this later peak to the work Dr. Mase and our Public Health Department has done in public health prevention methods.

Whereas hospitalization rates in some cities have been much higher (25% in NYC) local data shows in Sonoma County that 5% of those testing positive have been hospitalized (49% male, 51% female).

Virology:

Dr. Green reminded us that the Coronavirus is a single-stranded RNA virus, which is important because RNA viruses (e.g. seasonal influenza) replicate with continuous random mutations. Whereas DNA viruses are more stable and tend to remain conserved, ssRNA viruses are frequently changing. COVID-19 is no exception.

There are currently 6 major clades of COVID-19 (D614G, L845, L3606F, D448del and G392D) and 14 subclades circulating. The virus that seems to be dominating worldwide is now the D614G clade (color blue in images below), which does seem to be slightly more infectious than the original virus but does not appear to be more severe. 

https://www.cell.com/cell/pdf/S0092-8674(20)30820-5.pdf

Is COVID-19 Droplet or Airborne?

There has been much discussion in the medical literature and lay press about whether or not COVID-19 is primarily spread through large respiratory droplets OR by smaller suspended particles that can travel farther. Dr. Green's answer is that COVID-19 is mostly droplet tranmission, but also probably a little bit airborne (e.g. more like influenza, which has features of both than measles or TB, which are primarily airborne). 

This week, after the CDC revoked a statement warning about airborne COVID-19 transmission, the California Department of Public Health (CDPH) released a statement saying that "long range (>6ft) aerosol transmission such as with airborne transmitted viruses such as measles, is the area of controversy. CDC did signal that the updated guidelines would acknowledge opportunistic airborne SARS-COV 2 transmission in settings with poor ventilation." Key in this statement is that airborne is likely the exception (not the rule) and requires poor ventilation to be spread in this manner.

What does airline travel have to do with this?

Dr. Green cited a study from a spring evacuation flight from Milan, Italy to South Korea (11 hour flight), in which flight was conducted with strict infection control procedures by the Korean CDC and WHO. There were 299 asymptomatic passengers on board; several others were refused passage due to symptoms. After arrival in Korea passengers were quarantined for 2 weeks at a government facility. Ultimately from that flight, there were 6 asymptomatic + Covid patients and 1 who developed symptoms and tested positive on D14. A study of the airplane location and transmission patterns surmised that there was unlikely to have been airborne transmission, more likely transmission occured through contaminated high touch areas (e.g. that dang bathroom). The CDC link for more information is here. 

https://wwwnc.cdc.gov/eid/article/26/11/20-3353-f1

When and how to test for COVID-19?

Dr. Green shared a virologic study testing for COVID-19 in different respiratory sites from July 2020 (link to that Lancet article here), which found viral load in oropharynx, nasopharynx and sputum at much higher levels in the first 0-7 days. Viral levels were detectable but decreasing markedly in the oropharynx by day 8, and decreasing in nasopharynx and sputum to a lesser extent, though lower load by over day 14. This study underscoring the need for earlier testing for better viral detection (no matter which site). Bottom line: earlier testing is likely more accurate.

What about blood type and COVID risk?

There were reports early in the pandemic about certain blood types being associated with increased risk of testing positive for COVID and/or possibly worse outcomes. That literature is still evolving (and is frankly a little messy). A very early study from Wuhan, China (available here) proposed a link between Blood type A and higher risk of acquiring COVID-19. A later study (available here) found no relationship to Blood type A but rather that Blood types B, AB and RH+ were all associated with higher odds of severe disease; in that study Blood type O seemed to have lower risk of testing positive for COVID. A more recently released genomic study from NEJM (found here) found a possible a genetic susceptibility locus in patients with COVID-19 with respiratory failure and a potential involvement of the ABO blood group system. Bottom line: for now, there is no clinical reason to risk stratify using ABO. 

What about vitamins and minerals?

Jury is still out. Per Gary Green, there is no good evidence on Zinc as protective. Vitamin A is currently being studied at UCLA in children in COVID, Vitamin C is being studied in Richmond, VA. Vitamin D seems to have a correlation in several studies, but very unlikely causation. Dr. Green reminded us that some vitamin and supplements can be dangerous in high doses, namely Vitamins A, E, D, and K (fat soluble one) and a recent statement from BMJ states that "there is no strong scientific evidence that very high intakes (mega supplement) of vitamin D will be beneficial in preventing or treating COVID-19". Bottom line: stay tuned for forthcoming studies on vitamins.

Unique COVID-19 manifestations include:

• Late onset ARDS (~8 days) and multiorgan dysfunction (MODS)
• Thrombotic events, including VTE (25-31%) and arterial thrombosis (CVA, acute limb ischemia)
• Cardiac events (STEMI w/non occlusive coronaries, LV failure, myocarditis, kawasaki like illness)
• Neurologic events (acute CVA in young patients), Guillain-Barre syndrome, encephalitis/opathy and seizures
• Dermatologic events (pernio/Chilblains "covid toes")

What do we know about the cytokine storm? Should it be also called the bradykinin storm?

Here, Dr. Green expounded on a bunch of virology and biochemical mechanisms that are hard for me to capture in words (partly because I had a hard time keeping up!). The links to the papers are here and here, and the images from each of those studies are below. The top one discussing the immunologic response and the bottom the bradykinin storm. 

The gist of this part of the talk is that COVID-19 seems to elicit biphasic viral response that was also seen in virus causing the 2003 SARS virus outbreaks. In phase one (days 0-4), an acute infection stimulates an immune response. If that immune response is unsuccessful in clearing the virus, there is a second adaptive immunity response, which leads to a storm (see image below)

https://jvi.asm.org/content/jvi/84/3/1289.full.pdfAdd caption

This immunology and pathophysiology is actually very clinically important because it informs our current treatment approach for severe COVID-19 illness; that is, antivirals early, anti-inflammatories/immunologics (e.g. dexamethasone, tociluzimab) later when that inflammatory cascade is occuring. Here is my very favorite image from Dr. Green's talk:

I use this image ALL the time when talking with residents about this illness. It also helps me ground myself in where we are in an individual patient's course (e.g. symptom day 12 is very different than symptom day 4)

At SSRRH and around the country, we are tracking specific labs (procalcitonin, D Dimer, LDH, CRP, PMN/lymph, ferritin and sometimes baseline IL-6) to assess where a patient is in their disease course and how likely it is that they will develop severe illness. Several publications suggest that some or all of these values may have predictive value for severe disease.

This includes "Simple Rule of 6" (Ferritin>600, LDH>600, CRP>60) as well as other markers for severe disease: D Dimer >2-6, IL6 >163, and PMN/Lymph ratio >3.5

Why are we doing Convalescent Plasma?

Plasma is very safe and may improve outcomes in COVID-19. May is the key word here. Plasma was used in the influenza epidemic of 1918, also during outbreaks of polio, mumps and measles in the 1940s, in 2003 in the SARS Coronavirus in Hong Kong. Its use and study was largely abandoned after the discovery of penicillin and other antibiotics. It was tried (and failed) in 3003 (West Nile VIrus), 2012 (MERS) and 2014 (Ebola) outbreaks. 

SSRRH has been participating in a historic Extended Access Program via May Clinic, involving over 82,000 patients and 2700 sites. This is NOT an RCT. That program closed 8/31. Mayo is just beginning to study the potential benefit of convalescent plasma through this data set. It does appear in early papers that plasma given early that happened to contain high Antibody titers is associated with lower 30 day mortality. Preliminary results are available here. 

Figure below from that paper compares 30 day mortality in low, medium, and high titer plasma given early <3 days vs. late >4 administration of plasma. As we currently have no clinical way to measure antibody titers in plasma, Dr. Green is occasionally giving more than one unit in very sick people. This is experimental.

What about Remdesivir?

Here at SSRRH, thanks to Carolyn Dam (pharmacy) and Dr. Green, we were part of the earliest compassionate use of Remdesivir for our very first COVID-19 patients. Since then, data has begun to emerge on the utility of this antiviral designed originally for treatment of Ebola. Preliminary reports suggested benefit, particularly on duration of disease. 

The more recent ACTT-NIH study of 538 patients with severe disease found a reduce median recovery time (11 vs. 15 days for placebo, statistically significant) and a trend toward mortality benefit 7.1% vs. 11.9% (though not statistically significant). It appears that remdesivir is more effective the earlier it is administered (not unlike tamiflu) and most effective in patients who require oxygen but who are not ventilated. 

Where are we today, September 2020, 6 months into our own pandemic experience? 

In addition to working from home, wearing our masks, and helping our kids fumble through distance learning, our current standard of care at SSRRH for COVID-19 includes the following:

• Full PPE for clinical staff caring for suspected or confirmed cases of COVID-19 
• Swab testing for COVID-19 for all admitted patients and preoperative patients
• Daily labs for patients including IL-6 (baseline), CRP, didmer, ferritin, procalcitonin, CBC (leukopenia) and thrombocytopenia
• Treatment:
• Early convalescent plasma for all hospitalized pts (even asymptomatic ones)
• Proning (for anyone needing O2)
• High flow oxygen before mechanical ventilation
• Early IV Remdesivir for severe illness
• Anticoagulation for everyone, double for our sickest
• Steroids/dexamethasone (later-- if/when cytokine storm)
• Other immunosuppressants only with care (taciluzimab), watch for secondary bacterial infections
• Blood sugar control (diabetics)

Caring for Incarcerated Patients (Lozada, 9/15/2020)

I have deep gratitude for a powerful Grand Rounds this week by Dr. Christina Lozada, on Caring for Incarcerated Patients.

Dr. Lozada presented statistics on the state of mass incarceration in this country, reflected on her personal and professional experience of caring for incarcerated patients during her training, and encouraged us to do better in caring for incarcerated patients.

The US has the highest incarceration rate of any industrialized nation in the world.

• 4.4% of the world's population, 22% of the world's prisoners
• 2.3 million incarcerated people in the US, 4.5 million on parole, and 3 million ex-convicts
• ~870/100,000 US citizens 
• 57% in state prisons, 27% local jails/prison, 9% federal prisons

Who are our jail patients? 

Disproportionately young people of color, poor people, mentally ill people, poor people

• 34% non-Hispanic Black, 24% Hispanic
• Black and Hispanic men are incarcerated at 5.1 and 1.4 x rate of whites
• Mean age 32.1 (jail), 35.6 (prison)
• 10% are Veterans, 12-17% were homeless in the year prior to incarceration
• More than half have less than a high school diploma

Females are the fastest growing population in jails and prisons

• Compared to men, incarcerated women have higher rates of chronic disease, substance use disorder, and mental illness. 
• Elevated rates of depression, PTSD and antisocial personality disorder
• Most incarcerated women have experienced childhood physical and/or sexual abuse
• 6-10% incarcerated women are pregnant

Mental health issues are important

• 25% of all inmates have a mental health diagnosis (even higher for women 30-62%)
• 70-75% have taken a psychotropic medication
• Depression, PTSD and substance use disorder all very common. PTSD associated with higher rates of risky behavior including prostitution, IVDU, substance abuse

Dr. Lozada invoked The 8th Amendment of The Bill of Rights (1791) and Supreme Court Case Estelle vs. Gamble (1976) as the two main pillars of federal law that protect prisoners and should ensure them adequate access to high quality health care. She also called us to review our very own Hippocratic Oath.

The 8th Amendment guarantees freedom from cruel and unusual punishment. Estelle vs. Gamble ensures: access to care (including hospitals and specialists), ordered care (i.e. ordered by a physician), medical care without bias to the incarcerated status, proper medical records, confidentiality, autonomy (right to refuse care). 

While the law guarantees provision of care for prisoners, it frequently falls short of an acceptable standard of care. This is because standards are vague and/or undefined. There are differences in budgets and policies across federal, state and local jurisdictions.

Three important ethical issues to take into account in caring for incarcerated patients that may not be well-respected or well understood.

• Privacy: incarcerated patients have the same right to privacy as any other patients (including HIPAA protections, having officers in the room during interviews/examinations, etc)
• Autonomy: incarcerated patients have the right to make their own medical decisions and the right to refuse medial care as well
• Surrogate decision maker: incarcerated patients have the same right to designate a surrogate decision maker in case they are unable to make their own medical decisions (the warden is NOT the default surrogate)

Correctional Care Companies (private, for-profit corporations that are contracted to provide health care inside jails and prisons) have inverse incentives for care delivery

• These companies get paid per patient per day: while they provide direct medical care (e.g. urgent care, chronic disease management), any care that requires transfer to hospital or specialist care comes out their profits
• There have been hundreds of lawsuits against them, multi-million dollar settlements
• Investigative reporters have uncovered hundreds of preventable deaths: including ignoring visible and growing cancerous tumors, placental abruption and chorioamnionitis leading to fetal demise, untreated DKA, undiagnosed ruptured duodenal ulcers, and more.

What do we know about how shackles in the hospital impacts care?

• inability to break falls when ambulating
• difficulty positioning during seizure management
• reduced mobility increasing the risk of thrombosis
• impede physical exam maneuvers
• prevent development of physician-patient trust
• reinforce stigma and judgement of incarcerated patients

Of note, The British Medical Association advocates that patients should be examined and treated without restraints or prison officials unless there is a security or escape risk

Patients who are incarcerated often experience their hospitalization as a negative one. They feel judged and mistreated. They feel unlistened to and mistrusted. Medical providers often refer to them as "jail patients" and describe them as unreliable, social outcasts, deserving of their medical ailments. Many of us do not have formal training on caring for incarcerated patients nor are we aware of laws and policies in place to ensure they receive good medical care.

What can WE do as medical providers caring for incarcerated patients?

• Ask prison officers to remove shackles in order to fully assess patient
• Ask prison officers to remove themselves from the room or stand at the doorway for more privacy
• Use accurate and stigma-free language that prioritizes individuals over characteristics
• Avoid defining people by the crime for which that are accused or convicted
• Ask if the patient consents to discussing PHI in front of law enforcement officials or asking officers to move out of hearing range
• Try to make a patient that is incarcerated feel more comfortable disclosing potentially legally detrimental elements of the medical history
• Become familiar with hospital policies related to the care of incarcerated patients
• Incorporate education of these topics into credentialing or regular hospital-based education meetings
• Take a tour of nearby jail medical facilities and put together a list of resources and contacts
• Ensure careful discharge planning as times of transition

And finally, consider the following thoughts:

Resources:

• AMEND: UCSF center designed to improve health inside correctional care facilities https://amend.us/providing-acute-care-for-seriously-ill-incarcerated-patients-in-the-community/
• American College of Emergency Physicians: https://www.acep.org/administration/resources/recognizing-the-needs-of-incarcerated-patients-in-the-emergency-department/
• AAFP Davis DM, Bello JK, Rottnek F. Care of Incarcerated Patients. Am Fam Physician. 2018;98(10):577-583.
• https://www.prisonpolicy.org/

Single Payer Health Care (Duncan, 9/9/2020)

Great thanks to Dr. Parker Duncan who gave a passionate presentation on Single Payer Health Care on his very own birthday! Dr. Duncan started with three foundational premises (which he called his disclosures). The beliefs that:

1) Health care is a human right.

2) The barriers to achieving single payer health care in the US are rooted in struggles with racism and inequality (not simply the money).

3) Thus, before health care for all, first make sure Black Lives Matter.

Dr. Duncan also introduced us to the three phases of A Road Map to Golden State Care,  a comprehensive plan written by the California Physician's Alliance (CaPA), which lays out strategic steps to get California to universal coverage and an equitable health care system. 

Phase 1 involves a focus on cost control measures (making the state the sole prescription drug/DME purchaser as well as creating an all payer claims database), establishing something called the Golden State Care and Trust Fund (GSCTF), and improving Medi-Cal, which is already California's largest insurer.

Phase II creates a Medi-Cal buy-in via Covered California (a public option) as well as all-payer rate setting via Golden State Care.

and

Phase III involves transitioning to a true GSCTF which includes a 95/5% mandate (that is 5% cap on administrative spending) vs. non-profit insurance managers

An info-graphic of the strategic plan is seen below. The road map, published in 2019, can be found here in its entirety. 

Dr. Duncan shared some of the current bills that have passed and/or are moving through CA legislature-- essentially incrementally changing our system. These include SB-104 (signed into law 7/2019), which expanded Medi-Cal to undocumented adults ages 19-25 "who are otherwise eligible for these benefits but for their immigration status", expanded pregnancy Medi-Cal for maternal mental health conditions, and established the founding of a Health CA for all Coalition.

There are other bills making their way through the CA Legislature including cost containment bills and additional bills to expand Medi-Cal to undocumented seniors. For more information on legislative issues. Dr Duncan recommends you go to this resource: Health Access, California's Health Consumer Advocacy Coalition

Also, consider signing up for daily emails with health policy updates here: PNHP Qote of the Day, written by Dr. Don McCanne. 

Another excellent health policy resource that is politically neutral and very well researched and reported is the Kaiser Family Foundation. 

HIV Update for Primary Care (Toub 9/2/2020)

Dr. Danny Toub, our local HIV expert, gave an information-packed grand rounds presentation this week on HIV.  In the 1990s, HIV was the #1 cause of death among US persons ages 25-44. Great strides have been made over the last two decades. While HIV death rates continue to downtrend, there are still 1.17 million people living with HIV in the US. There are 149,500 people living with HIV in California and about 2,000 in Sonoma County. 

Unfortunately, rates of new infection are disproportionately highest in black and brown men who have sex with men (MSM). In fact, the lifetime risk of acquiring HIV for an African American MSM is 1 in 2!

The Basics:

CD4 counts are used to stage disease

• normal CD4 >500
• HIV (not AIDS) > 200
• AIDS: <200 or Opportunistic infection (OI)/Cancer

HIV Viral Load is used to monitor response to antiviral therapy 

• normal: undetectable
• goal: unmeasurable
• high: >200K

Take home point #1: Viral suppression is KEY KEY KEY in HIV management

• 2018 viral suppression rates now reach 81-90% in most populations (lower in youth and patients with unstable housing, but much better than a decade ago)
• The US Government has rolled out a program with the goal of reducing HIV new diagnoses by 75% in 5 years and 90% in 10 years using the FOUR Pillars of ending the HIV epidemic:
• Diagnose all people with HIV as early as possible
• Treat people with HIV rapidly and effectively to reach viral suppression
• Prevent new HIV transmission by using PrEP and syringe services
• Respond quickly to new HIV outbreaks
• 

Take home point #2: There are so many HIV Resources for you to rely on for help. Here are Dr. Toub's recommendations

• Team VIDA MD on call 707-583-8823 (24/7)
• National HIV curriculum: www.hiv.uw.edu
• CCC (Clinical Consultation Center): http://nccc.ucsf.edu
• Pacific AETC Quick Guide (26 page): http://paetc.org/
• Podcasts: https://thecurbsiders.com/tag/hiv
• Crushing and Liquid formulations of ART: https:/hivclinic.ca

Take home point #3: Antiviral Therapies (ART) are so much simpler than they used to be. Many regimens are just one pill once a day!

• Current ART Guidelines include an initial regimen of 2 NRTIs + INSTI (now available in combination forms)
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are in: abacavir, emtricitabine, lamivudine, and tenofovir (AF or DF)
• Integrase inhibitors (INSTI) are in: bictegravir, dolutegravir, raltegravir
• Protease inhibitors (PIs) are out
• Boosters are out

Take home point #4: Start ART in anyone diagnosed with HIV as soon as possible (within 2 weeks in anyone with OI), call team VIDA for any questions.

• HIV replication increases mortality
• Benefits of early treatment outweighs risk (ACTG A5164 Study)
• this is particularly true in PCP but also in cryptosporidiosis, microsporidiosis, PML, Kaposi's sarcoma and serious bacterial infections
• possible exceptions: cryptococcal meningitis, TB, CNS toxoplasmosi

Take home point Point #5: Ambulatory Care of stable patient with HIV is much like care of all our patients with any chronic disease:

• Chronic Disease 101 (a la Danny Toub)
• Is the medicine you are taking effective? (--> viral load)
• Are you able to take your medications? (access ($$, pharmacy issues), adherence, tolerance)
• Can we do better? (i.e. side effects, pill burden, etc)
• Routine labs (DHHS ART Guidelines table 3: www.aidsinfo.nih.gov/guidelines)
• HIV Viral load and CMP q 6 months
• HbA1C, lipids, urinalysis (if CKD), RPR, GC/CT (3 site),, +/- HCV, CBC (CD4)
• Health Care Maintenance: www.hiv.uw.edu/go/basic-primary care
• Vaccination
• Cancer Screening

Take home point #6: Treatment=Prevention

• "People who take ART daily as prescribed and achieve and maintain an undetectable viral load have effectively NO risk of sexually transmitting the virus to an HIV negative partner"
• Undetectable= Untransmittable (U=U)         

Take home point #7: Pre-exposure prophylaxis (PreP) is an amazing and underutilized HIV biomedical prevention tool. If you do reproductive services in your primary care practice (i.e. birth control and STD testing), you should also be doing PrEP

• PrEP is safe 
• PrEP is effective 
• if men take  >4x/week
• if women take 6-7 times per week
• PrEP is patient centered 
• PrEP is paid for! (as a Grade A USPSTF recommendation

• However, only 1% of African Americans and 3% of Latinos who would benefit are on PrEP
• We should be offering PrEP to ALL:
• Sexually active adults and adolescents who have had any anal or vaginal sex in the past 6 months AND 1) have an HIV+ sexual partner OR 2) Recent bacterial STI OR 3) Hx of inconsistent or no condom use with partners
• Person who injects drugs AND has a HIV+ injecting partner OR shares drug prep or injection equipment
• Just need negative HIV test before rx, no s/sx of acute infection, normal renal function, no contraindicated meds
• Rx TDF/FTC OR TAF/FTC once daily
• Monitoring visit q90 days: check HIV status, pregnancy test, renal function, STI screen, risk reduction counseling
• Online Prep learning opportunities:
• Quick HIV clinical guide
• National HIV curriculum
• HIV prevention Certified Provider Program

And finally, my own personal reflections from working with Danny and listening to him speak:

be strength based

be non-judgemental

be kind

be there for patients ALWAYS