Today we discussed a variety of topics, and most excitingly, revealed that our inpatient anti-infective therapy guideline is now published on HHSConnect on the ASP page.

Same disclaimer applies: we have no direct clinical experience dealing with COVID+ patients and information has been taken from a variety of excellent resources as listed in the prior post. We make no claims for originality!

Pathophysiology and Stages of COVID

This is key folks. There seems to be a early viral replication phase, followed by a later dysregulated inflammatory response phase marked by ARDS and a cytokine storm. In the early phase, antiviral therapy may be much more helpful than delayed initiation. Once the late phase has arrived the mainstay of treatment will likely be immune-modulating agents (anti-IL6 agents and steroids..more on this later.

Modes of Transmission of COVID

• Droplet (main)
• Airborne
• Contact

Yes, you read that correctly. There is evidence that aerosolization does occur and therefore in our hospital, we use a N95/face shield for all PUIs and confirmed patients – a move we strongly believe will improve the safety of our healthcare workers (HCWs)

https://www.nejm.org/doi/full/10.1056/NEJMc2004973

• Air – 3 hours
• Copper – 4 hours
• Cardboard 24 hours
• Stainless steel – 2-3 days
• Plastic – 3 days [we should all be cleaning our work surfaces as frequently as possible]

Airway Management Prior to Intubation

• Goal SpO2 92-96% when on supplemental O2
• In our institution, O2 may be escalated to NRB at 6LPM, after which ICU should be consulted for ‘refractory’ hypoxia when the SpO2 <92%
• Our hospital discourages HFNC/NIPPV due to aerosolization risk and encourages early intubation, a position consistent with many other organizations, including MGH
• We discussed the data from SARS however that there is no definitive evidence that HFNC places HCWs at increased risk, and in fact, the act of intubation is linked with increased risk of HCWs.
• The six risk factors that placed HCW at highest risk for contracting SARS were:
  • minimum distance between beds of 1 m
  • availability of washing or changing facilities for staff
  • whether resuscitation was ever performed in the ward
  • whether staff members worked while experiencing symptoms
  • whether any host patients required oxygen therapy [of any kind]
  • whether any host patients required bi-level positive airway pressure ventilation
• SCCM position – “For adults with COVID-19 and acute hypoxemic respiratory failure despite conventional oxygen therapy, we suggest using HFNC over conventional oxygen therapy”
• ANZICS position –“High flow nasal oxygen (HFNO) therapy (in ICU): HFNO is a recommended therapy for hypoxia associated with COVID-19 disease, as long as staff are wearing optimal airborne PPE. The risk of airborne transmission to staff is low with well fitted newer HFNO systems when optimal PPE and other infection control precautions are being used. Negative pressure rooms are preferable for patients receiving HFNO therapy.”
• In summary, while early intubation is the official policy of our institution, I would not be surprised if during a surge, HFNC may be used to prevent intubation and protect a scarce resource for those who need it the most
• Once your O2 <92% on 6L O2 – for now, call your consultant for likely early intubation

Sources:

a. ‘Why Did Outbreaks of Severe Acute Respiratory Syndrome Occur in Some hospital Wards But Not in Others – Yu et al in Clinical Infectious Diseases 2007

b. Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada – PLOS1 2010

Pharmacological Therapies

• Hydroxychloroquine + Azithromycin – Marseille Study – Gautret et al
  • Tiny study of 20 patients in France found that on Day 6, Tx group individuals showed a much lower than average PCR positive compared to untreated controls
  • This effect was magnified by the addition of Azithromycin
  • Reasonable dosing is currently HCQ 400 BID x 1 day, followed by 200mg q12rs x 5 – 10 days. Azithromycin is 500mg x 1d followed by 250mg daily
  • There is a long list of contraindications, including QT prolongation to be aware of and G6PD deficiency for HCQ
  • https://www.mediterranee-infection.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA.pdf
  • Who Should Get It?
    • Our ASP guideline states those with moderate-severe COVID SHOULD receive it while PUIs who are deteriorating quickly should also receive it
• Remdesivir
  • antiviral drug developed as a treatment for Ebola and Warburg virus
  • Gilead suspended compassionate use and restricted it to clinical trial use only so we will withhold discussing this for now
• Lopinavir+Ritonavir
  • NEJM study of 199 patients with laboratory confirmed SARS-CoV-2 infection underwent randomization and no difference in clinical improvement and mortality for the 28 days that patients were tracked
  • https://www.nejm.org/doi/pdf/10.1056/NEJMoa2001282?articleTools=true
• Anti-IL6 Therapy – Tocilizumab
  • During a potential cytokine storm, this medication may be crucial, but studies are underway
• Steroids – Consider Giving During Dysregulated Immune/ARDS Phase
  • Controversial, as early use thought to increase viral shedding – but my personal opinion is consistent with one of our ICU doctors,  that there is evidence for its use in critically ill patients [i.e in the later phase once ARDS develops
  • Other guidelines state to withhold unless other indication for steroid develops but this is not consistent with strong evidence from the following study that showed a significant survival benefit to acutely ill patients who did receive methylprednisolone
  • https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2763184
• ACEi/ARBs – Continue!
  • There is concern that ACEi/ARB use association with increase in expression of ACE2, which is the binding site of the virus BUT it is unknown what exactly that finding means and the European Society of Cardiology issues an extremely strongly worded statement that in the absence of any evidence that it actually leads to acquisition/transmission of the virus, that patients should continue their RAAS inhibition
  • In fact, some have even postulated an anti-inflammatory benefit
  • Bottom lines – insufficient evidence and no one knows
• NSAIDs – No conclusive evidence
  • A variety of mechanisms have been postulated, WHO states insufficient evidence to recommend discontinuation
• Fluids – AVOID excessive administration

That’s all for now, much of what was said will likely change. Thank you all for your incredible dedication to each other and to our patients. You all are heroes and I am so proud of you.