Please see updated protocol at EVMS website: 

_https://www.evms.edu/covid-19/medical_information_resources/#d.en.140202




COVID Protocol (updated March 24, 2020)

Paul E. Marik MD, FCCP, FCCM

Eastern Virginia Medical School

Department of Internal Medicine

Chief, Pulmonary and Critical Care Medicine

825 Fairfax Ave, Rm 575, Norfolk, VA 23507

( 757.446.8910 7 757.446.5242

marikpe@evms.edu : www.evms.edu

URGENT! Please circulate as widely as possible. It is crucial that every pulmonologist, every critical care doctor and nurse, every hospital administrator, every public health official receive this information immediately.

Folks: I have updated our approach to COVID‐19 based on the best (and most recent) available literature and the Shanghai Management Guideline for COVID. We should not re‐invent the wheel, but learn from others experience.

A few General thoughts:

1. It is likely that 40‐80% of the population across the world will become infected with this virus. It is therefore unrealistic for us to expect this is will just go away. Our goal should therefore to reduce the mortality in those who are at greatest risk of dying. This requires that those at risk “socially” isolate themselves and then once they become infected we should treat aggressively to prevent disease progression.

2. The course of the disease is quite predictable. Acute respiratory failure occurs on day 6‐8 (due to cytokine storm) . In those patients requiring supplemental oxygen we need to be very aggressive to prevent progression to ARDS. Once ARDS develops the mortality is high.

3. It is likely that there will not be a single “magic bullet” to cure COVID‐19. Rather we should be using multiple drugs that have synergistic and overlapping biological effects, that are, safe, cheap and could be made readily available. The impact on middle and low income countries will be enormous; these countries will not be able to afford expensive designer molecules.

4. Chloroquine and hydroxychloroquine significantly decrease the duration of viral shedding. These agents (if available) could be used to mitigate/curtail the spread of this virus They may be used in elderly patients with comorbidities at risk of progression and death.

5. Zn inhibits viral RNA dependent RNA polymerase (replicase) . Chloroquine and hydroxychloroquine are potent Zn ionophores that increase intracellular Zn concentrations.

6. Quercetin is a plant phytochemical. Experimental and early clinical data (published in high impact journals) suggests that this compound has broad antiviral properties (including against coronavirus) and acting at various steps in the viral life cycle. It also appears to be a potent inhibitor of heat shock proteins (HSP 40 and 70) which are required for viral assembly.

7. It is not clear if the dose of Vitamin C should be reduced to 6 g/day in patients with very high ferritin levels. In patients with high ferritin free iron is released form ferritin under hypoxic condition, and this may have a prooxidant effect in combination with Vitamin C. Monitor ferritin and CRP; if both going up consider reducing dose to 6g/day (see below).

8. We are all inhabitants of the same planet, we are in this together and we need to act decisively, and right now.

Prophylaxis

While there is limited data , Vitamin C (500 BID), Zn (75‐100mg/day) and Quercetin (500‐1000 mg/day) may have a role in high risk populations (i.e. all of those on this planet).

Mildly symptomatic patients (on floor):

*Vitamin C (500 BID/ TID) and Zn (75‐100mg/day) and Quercetin (500‐1000 mg/day).

* Observe closely

* N/C 2L /min if required

* Avoid Nebulization and Respiratory treatments. Use MDI if required

* NO Bagging

* NO NIV CPAP BiPAP or Hi‐flow

• T/f to ICU for increasing respiratory signs/symptoms

Respiratory symptoms (SOB; hypoxia: admit to ICU):

1. Chloroquine 500mg PO BID for 7‐10 days or hydroxychloroquine 400mg BID day 1 followed by

200mg BID for 4 days.

2. Vitamin C 3g IV q 6 hourly until extubated and for at least 4 days up to 10 days (see dosage adjustment below).

3. Thiamine 200mg q 12 (PO or IV)

4. Azithromycin 500mg day 1 then 250mg for 4 days

5. Melatonin 6mg at night

6. Zn 75‐100mg/day

7. Broad spectrum antibiotics only if superadded bacterial pneumonia is suspected based on procalcitonin levels and resp. culture (no bronchoscopy) Co‐infection with other viruses appears to be uncommon, however a full respiratory viral panel is still recommended; superadded bacterial infection is uncommon on presentation (may develop with prolonged ventilation).Magnesium: 2 g stat IV. Keep Mg between 2.0 and 2.4 mmol/l. Prevent hypomagnesemia (increases the cytokine storm and prolongs Qtc)

9. While Angiotensin II (Giapreza) has no role in the treatment of septic shock, it is of theoretical benefit in COVID‐19 shock as Ang II downregulates the ACE‐2 receptor.

10. Optional: Tocilizumab (if available) may have a role in cytokine storm (specific !L‐6 inhibitor)

11. Optional: Atorvastatin 40‐80 mg/day. Of theoretical but unproven benefit.. may have a role in the hyper‐inflammatory ARDS phenotype (typical of COVID‐19)

12. Escalation of respiratory support (steps)

a. N/C 1‐6 l/min

b. High Flow up to 30 L/min

c. Intubation … By Expert intubator; Rapid sequence. No Bagging; Full PPE,

d. Volume protective ventilation following ARDSnet table

e. APRV

f. Prone positioning

g. ??? ECMO < 60yrs and no severe commodities/organ failure. Plasma exchange should be considered before ECMO; see below.

There is widespread concern that using HFNC could increase the risk of viral transmission. There is however there is no solid evidence to support this fear.

13. Consider plasma exchange for cytokine storm/HLH picture (see steroids below)

The use of CVVH filters that absorb cytokines (Cytosorb) should also be considered.

14. Steroids:

This topic is controversial. However, the only study on steroids and COVID (from Wuhan) demonstrates a marked mortality reduction with methylprednisolone (60mg daily)

* During the early viral replicative stage; probably best to avoid.

* During the hyperimmune phase (day 6‐8 onward)…. Hydrocortisone 50mg q 6 for 4 days may be given on a case by case basis.. based on features of ARDS and high CRP

• Pts may evolve into an HLH/cytokine vortex phase, marked by increasing ferrin, IL‐6 and worsening oxygenation. These patients may benefit from high dose methylprednisolone. (dose ?? 100mg q 6))

15. Monitoring

* Daily: PCT, CRP, BNP, Troponins, Ferritin, Neutrophil‐Lymphocyte ratio, D‐dimer.

*Seems like CRP and Ferritin are good biomarkers and tracks disease severity

* Il‐6 at baseline and ? every 3‐4 days

* Monitor QTc interval if using chloroquine/hydrochloroquine and azithromycin and monitorMg++

* No routine CT scans, follow CXR and chest ultrasound;

* Follow ECHO closely; Pts develop a severe cardiomyopathy.