Covid19 update 3/18/20

[Deacon]

ACC-CCA Webinar 3.18.20 (Epidemiology, CVD Treatment & Management)
Notes provided University of Pittsburgh Medical Center FITs: Agnes Koczo, MD, Ricardo Nieves, MD, Amr F. Barakat, MD

As China is getting close to declare victory over COVID-19 (only 10-20 new cases a day across the country), here are some important lessons learned from the Chinese experience:

**Chinese Guidelines for Diagnosis and Treatment of COVID-19 (7th Edition)**

Virology and Epidemiology

• SARS-CoV-2 à β genus, diameter 60-140 nm
• Shares 79% of nuclear identity of SARS-CoV-1 and 52% of that of MERS
• ACE-2 is the host cell receptor
• Affects alveolar type II cells primarily à lung pathology very similar to SARS and MERS (bilateral diffuse alveolar damage with cellular fibromyxoid exudates)
• Can also affect the heart, the liver, and the kidney
• Disinfection by Ethanol and UV light, not inactivated by Chlorhexidine
• Epidemic started in China, now Europe is the epicenter
• Mortality in China 2.3%, but ~5% in Italy
• Median incubation period 4 – 5.2 days (95% percentile is 12.5 days)
• Main source of infection is asymptomatic infected people
• Route of transmission is respiratory droplets, close contact with asymptomatic infected people, long-term environmental exposure to high viral aerosolized load, possibly fecal transmission too
• R0 2.2 – 2.95 (i.e. one infected person infects on average 2-3 healthy individuals)

Clinical Findings

· WHO diagnostic criteria (one epidemiological + 2 clinical findings OR 3 clinical findings)

o Epidemiological criteria:

§ H/o travel to (or residence in) high risk areas
§ H/o contact with a confirmed or suspected case
§ Attendance of events where clusters of cases were reported​

o Clinical criteria:

§ Fever
§ Respiratory symptoms (e.g. cough and dyspnea)
§ Leucopenia/ Lymphopenia (unclear etiology but very characteristic with COVID-19)​

· Frequency of symptoms and complications:

o Fever 98%
o Cough 76% (mostly dry)
o Lymphopenia 63% - lowest at day 7, prolonged lymphopenia poor prognostic sign
o Diarrhea 3%
o Complications: ARDS 29%, acute cardiac injury 12%, AKI 7%, septic shock 7%, secondary bacterial infection 10%​

· Average duration of dyspnea is 13 days, 45% of survivors still had cough on discharge
· Median duration of viral shedding is 20 days (up to 37 days)

COVID vs Influenza

o Similar constellation of symptoms – recommend evaluation with RVP
o Clinically, onset of COVID is slower than influenza which tends to be more abrupt
o Additionally there appears to be less sputum production in COVID as compared to influenza​

Diagnostic Tests

• RNA detection (RT-PCR) from nasopharyngeal swab, sputum, lower respiratory tract samples (best yield), blood and feces
• Serum antibody detection (IgM and IgG)
  • RNA testing alone has high false negative
  • When RNA testing + serum Ab testing à 98% sensitivity
  • Some cases tested positive for RNA again after discharge with negative test (unclear significance for now)
• Chest CT
  • Bilateral lung involvement
  • Peripheral distribution
  • Diffuse distribution
  • Ground glass opacities (can appear before the clinical onset of illness)
  • No septal thickening

Treatment

• Isolation
  • All confirmed and suspected cases (did not specify but seems that they used airborne given use of N95 and mention of negative pressure rooms)
  • PPE for healthcare workers à N95 when taking care of suspected or confirmed cases / Surgical masks everywhere else in the hospital (ALL THE TIME)
• Supportive therapy
  • Sufficient caloric intake (many patients had hypoproteinemia)
  • Water and electrolytes
• Antiviral therapy
  • So far, no specific antiviral for SARS-CoV-2
• Steroids
  • Controversial
  • For 3-5 days only

Discharge Criteria

• Normal temperature for >3 days
• Improvement of respiratory symptoms
• 2 consecutive negative respiratory specimens at least 24 hours apart

**COVID-19 and Cardiovascular Disease**
COVID-19 patients with underlying cardiovascular disease have the highest fatality rate (10.5%)

Mechanisms of Acute Cardiac Damage

· ACE-2-mediated direct cellular damage
· Hypoxia-induced myocardial damage
· Microvascular damage
· SIRS

Clinical Presentations and Complications

• Arrhythmias (17%)
• Acute cardiac injury (elevated high-sensitivity troponin) (12%)
• Elevated regular troponin or CK-MB (7.2%) à occurs in severe cases (mostly negative in mild and moderate cases) à mortality 49%
• Fulminant myocarditis can occur (they presented a case with regional STE [inferior leads], negative coronary angiogram, initial drop in EF to 27%, and complete recovery with supportive therapy)
• STEMI can also occur as a complication
• Important observations:
  • ↓ pericardial adipose tissue correlates with COVID-19 severity
  • There may be evidence of chronic cardiovascular damage following COVID-19

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Important Final Remarks

• The most dangerous thing about this epidemic from the Chinese perspective is the transmission by asymptomatic or mildly symptomatic infected individuals.
• We learned from Wuhan and Italy that young healthy people can also get severe disease and die
• Many infections in healthcare professionals (in China à 3.8% of the cases are HC workers, of those, 15% were severe/critically ill, 5 deaths)
• Observation from Wuhan is that the rate of co-infection with other respiratory viruses especially influenza is high. Dr Bin Cao said “As if they always came together” when referring to influenza pneumonia and COVID-19. This has huge implications since many US hospital protocols now say that if RVP is +ve then no need to test for SARS-CoV-2.
• Best way to prepare from a hospital perspective is DIAGNOSIS(you need to know who’s infected and who’s not once they present to clinic or ED à RNA testing IMMEDIATELY) – to ensure proper isolation and admission to appropriate wards/ICU.
• Changes to hospitals workflow in Wuhan:
  • All outpatient clinics were closed during the epidemic surge
  • All outpatient visits were performed virtually or by telephone (if medical attention is needed à ED)
  • Marked increase in the use of thrombolysis (vs primary PCI) for STEMI
• Social isolation/ distancing is EFFECTIVE à needs to be done for at least 2-4 weeks
• Best way to think about the situation now is: No more normal life, it’s COVID-19 pandemic life (things that are not normally acceptable or feasible should be now, to face the pandemic)

 

[JonC]

Thank you for the information. It is good info.

I'd give you a big hug and a kiss if you were here.

 

[church mouse guy]

Which people are most vulnerable to COVID-19?
While researchers are still learning about how the new coronavirus affects people, it seems that older adults and those living with chronic health problems such as diabetes, heart disease, cancer or lung disease are more likely to become seriously ill with COVID-19 than younger people with good overall health.

Coronavirus (COVID-19): Frequently Asked Questions

 

[Deacon]

Thank you for the information. It is good info.

I'd give you a big hug and a kiss if you were here.

Keep you distance Jon! ...and wear a mask. LOL

Greet those among you with a hearty elbow bump.

Rob

 

[Benjamin]

Good information.

Something I don't understand is the claim it is highly asymptomatic, yet I'm hearing from 88% to 98% have a fever? Also a high percentage have a cough. Those sound like symptoms to me?

 

[Gold Dragon]

Good information.

Something I don't understand is the claim it is highly asymptomatic, yet I'm hearing from 88% to 98% have a fever? Also a high percentage have a cough. Those sound like symptoms to me?

Those percentages are of the symptomatic patients.

Also a large proportion of transmission is from people who are asymptomatic at the time of transmission but eventually become symptomatic.

 

[Benjamin]

...from people who are asymptomatic at the time of transmission but eventually become symptomatic.

Makes sense. But, that clarification of eventually becoming symptomatic would seem to put the claims of this disease being highly asymptomatic into a different perspective. Many are going on the assumption of like 80% are asymptomatic but if that reference is in regards to at the time of transmission and not as an end result then it is misleading.

 

[Gold Dragon]

Makes sense. But, that clarification of eventually becoming symptomatic would seem to put the claims of this disease being highly asymptomatic into a different perspective. Many are going on the assumption of like 80% are asymptomatic but if that reference is in regards to at the time of transmission and not as an end result then it is misleading.

The problem is we are not testing asymptomatic people so it is hard to get an accurate idea of how many folks are completely asymptomatic carriers. Our best data on that is probably from S. Korea where they just bombarded the country with testing even for asymptomatic patients. I haven’t looked at those numbers recently. A lot of this kind of data we will not know until after the fact when it is reviewed in hindsight and proper modeling is done.

 

[Benjamin]

The problem is we are not testing asymptomatic people so it is hard to get an accurate idea of how many folks are completely asymptomatic carriers. Our best data on that is probably from S. Korea where they just bombarded the country with testing even for asymptomatic patients. I haven’t looked at those numbers recently. A lot of this kind of data we will not know until after the fact when it is reviewed in hindsight and proper modeling is done.

Yes, personally I like the sound of the odds that 80% are asymptomatic but I'm hearing very little from those who have shown very little symptoms and I'm doubting that % as representative of what one can expect if they are infected. I also believe since the numbers aren't in yet that leading people to think they have those kinds of odds unfortunately lessons the urgency to be diligent especially in the young who would think they are most likely to fall into the "asymptomatic category" which is not even supported by good data. .

 

[Deacon]

Makes sense. But, that clarification of eventually becoming symptomatic would seem to put the claims of this disease being highly asymptomatic into a different perspective. Many are going on the assumption of like 80% are asymptomatic but if that reference is in regards to at the time of transmission and not as an end result then it is misleading.

Nowhere in the outline is the phrase “highly asymptomatic” used.
In fact the diagnostic criteria are chiefly measured by presenting symptoms.

Clinical Findings
· WHO (World Health Organization) diagnostic criteria (one epidemiological (distribution and incidence) + 2 clinical findings OR 3 clinical findings)

o Clinical criteria:

§ Fever
§ Respiratory symptoms (e.g. cough and dyspnea)
§ Leucopenia/ Lymphopenia (unclear etiology but very characteristic with COVID-19)​

· Frequency of symptoms and complications:

o Fever 98%
o Cough 76% (mostly dry)
o Lymphopenia 63% - lowest at day 7, prolonged lymphopenia poor prognostic sign (low levels of white blood cells)
o Diarrhea 3%
o Complications: ARDS (acute respiratory distress syndrome) 29%, acute cardiac injury 12%, AKI 7%, (acute kidney injury) septic shock 7%, secondary bacterial infection 10% (there is some pretty bad stuff here)​

· Average duration of dyspnea is 13 days, 45% of survivors still had cough on discharge
· Median duration of viral shedding is 20 days (up to 37 days) (that means contagious for more than a month!)

Rob

 

[church mouse guy]

Can you have COVID-19 without symptoms?
Yes. Symptoms of COVID-19 usually show up from two to 14 days after exposure, but some people who are infected do not develop symptoms and do not feel ill.

Coronavirus (COVID-19): Frequently Asked Questions

 

[Deacon]

My employer closed our cardiology office last week and we will remain closed for at least 2 weeks, til early April... but things are changing daily.
We’ve been running telephone appt. with old patients and not accepting new patients (since there are few face-to-face appointments made.

The office was deep cleaned, no one was allowed in during the closure.
When I return to the office to perform stress tests (and other staff return to do other diagnostic testing) we will be masked and gowned and use high risk protocols between patients to insure we are not a vector of transmission.
Patients will probably be given a beeper and asked to wait in their car rather than congregate in a crowded waiting room.

The U.S. has entered the epidemic late, thanks in part to the actions of the government shutting down travel and encouraging isolation.

That won’t last forever.... U.S. virus statistics appear to be following the pattern seen in Italy.

This is not over yet!

Rob

 

[church mouse guy]

No this is not over yet. Mini AOC googled China and now her computer seems to have a virus.

 

[Benjamin]

Nowhere in the outline is the phrase “highly asymptomatic” used.
In fact the diagnostic criteria are chiefly measured by presenting symptoms.

Maybe the phrase "highly asymptomatic" is not applicable according to your "diagnostic criteria are chiefly measured by presenting symptoms." but people are hearing that 80% are having no or mild symptoms and I see nothing excluding asymptomatic persons except maybe they wouldn't be in a clinical setting if not showing symptoms to begin with. It would seem that also "mild symptoms" would have to be excluded from your "diagnostic" criteria.

I'm just curious as to the actual numbers that are asymptomatic and if that number (80%) is exaggerated or not.

 

[Gold Dragon]

Maybe the phrase "highly asymptomatic" is not applicable according to your "diagnostic criteria are chiefly measured by presenting symptoms." but people are hearing that 80% are having no or mild symptoms and I see nothing excluding asymptomatic persons except maybe they wouldn't be in a clinical setting if not showing symptoms to begin with. It would seem that also "mild symptoms" would have to be excluded from your "diagnostic" criteria.

I'm just curious as to the actual numbers that are asymptomatic and if that number (80%) is exaggerated or not.

I’ve never heard of that 80% number in my readings. Any number at this point of asymptomatic carriers would be a guess based on very little unreliable data with a lot of bias (that is a statistics term for factors that influence the data away from the true value you are looking for).

Asymptomatic Carriers of COVID-19 Make It Tough to Target

These guys report a very wide range of findings for this number, but none as high bas 80%. If you look at the upper range of the error in the tianjin numbers you get a number near 80%. I would have to look at each of those studies to see which ones have more reliable data. Too much work.

The findings mirror those in 2 other recent studies by Dutch and Japanese investigators that also point to the problem of asymptomatic carriers of COVID-19. Japanese researchers looked at the 634 passengers who tested positive for COVID-19 on the Diamond Princess cruise ship. They found that 17.9% of these passengers were asymptomatic. Dutch researchers estimate that the “the proportion of pre-symptomatic transmission was 48% (95%CI 32-67%) for Singapore and 62% (95%CI 50-76%) for Tianjin, China.”

 

[Benjamin]

I’ve never heard of that 80% number in my readings.

"COVID-19 Coronavirus Facts

• COVID-19 causes a wide range of symptoms including fever, cough, and difficulty breathing.
• Most people (about 80%) develop only mild symptoms, particularly children."

Coronavirus: Many Questions, Common Sense Answers

I have heard this 80% having no or mild symptoms several times and seen a couple pie graphs showing the same. I believe one was in a press conference but can't find it off hand.

Any number at this point of asymptomatic carriers would be a guess based on very little unreliable data...

That's what I'm getting at we have people claiming a % of asymptomatic cases on one hand and on the other hand people claiming a % of the type and number of symptoms on an undetermined number of cases, so both seem to be unreliable or to lack clarification either way.

I scrutinize everything I read about this disease. Me thinks the “diagnostic” model above is a little screwed up. My beef is with the lack of clarification when claiming a % of symptoms without reference to a certain class of cases being that the “high” amount of presumed asymptomatic cases which would seem to also be in consideration are presumed to be diagnosed as well, when in reality this is a lot of hypothesis on a limited amount of data.

 

[Gold Dragon]

"COVID-19 Coronavirus Facts

• COVID-19 causes a wide range of symptoms including fever, cough, and difficulty breathing.
• Most people (about 80%) develop only mild symptoms, particularly children."

Coronavirus: Many Questions, Common Sense Answers

I have heard this 80% having no or mild symptoms several times and seen a couple pie graphs showing the same. I believe one was in a press conference but can't find it off hand.

Oh that 80%. That is just saying that 80% of cases are mild and don’t need hospital. So they have a cough, fever stay at home for a few days and recover.

However around 20% need hospitalization, 5% need ICU and 1% end up dying. These are all rough “back of the napkin” type numbers for what we think happens in a “normal” country that is prepared for covid19. The actual numbers will be different and are constantly changing and depends on how prepared that country or region is in responding to covid19.

The numbers presented in the OP are actual case numbers and look pretty consistent with others I have seen.

 

[church mouse guy]

My employer closed our cardiology office last week and we will remain closed for at least 2 weeks, til early April... but things are changing daily.
We’ve been running telephone appt. with old patients and not accepting new patients (since there are few face-to-face appointments made.

The office was deep cleaned, no one was allowed in during the closure.
When I return to the office to perform stress tests (and other staff return to do other diagnostic testing) we will be masked and gowned and use high risk protocols between patients to insure we are not a vector of transmission.
Patients will probably be given a beeper and asked to wait in their car rather than congregate in a crowded waiting room.

The U.S. has entered the epidemic late, thanks in part to the actions of the government shutting down travel and encouraging isolation.

That won’t last forever.... U.S. virus statistics appear to be following the pattern seen in Italy.

This is not over yet!

Rob

"Coronavirus, of course, is wreaking havoc in Italy. There are factors in Italy that don’t exist in America: Hundreds of thousands of Chinese workers traveling back and forth between Italy and China, an aged population, heavy smoking, and terrible air pollution."

https://www.americanthinker.com/blo...ted_events_moved_with_startling_rapidity.html

 

[Scott Downey]

"Coronavirus, of course, is wreaking havoc in Italy. There are factors in Italy that don’t exist in America: Hundreds of thousands of Chinese workers traveling back and forth between Italy and China, an aged population, heavy smoking, and terrible air pollution."

https://www.americanthinker.com/blo...ted_events_moved_with_startling_rapidity.html

Another factor, italy has 60 million people crammed into a small country. That concentrates everything together more tightly than the US.

 

[Scott Downey]

Baxtor donates millions of chloroquine tablets for covid-19 use.

Bayer donates millions of tablets of chloroquine to help in COVID-19 fight