SCCM Guidelines on COVID-19 Management – summarized

SCCM released a guideline on the management of COVID-19.  For those pressed for time, I’ve condensed the guidelines into a 13-page Q&A format.  The questions are formulated by me based on the guideline content and the answers are lifted from the SCCM guidelines, some of which I have reformatted from passive to active voice for easier reading.  Please reference the original guideline text, or message me if there are any errors.

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(download PDF file here)

REFERENCE:

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Waleed Alhazzani, Morten Hylander Møller, Yaseen M. Arabi , Mark Loeb, Michelle Ng Gong, Eddy Fan, Simon Oczkowski, Mitchell M. Levy, Lennie Derde, Amy Dzierba, Bin Du, Michael Aboodi, Hannah Wunsch, Maurizio Cecconi, Younsuck Koh, Daniel S. Chertow, Kathryn Maitland, Fayez Alshamsi, Emilie Belley-Cote, Massimiliano Greco, Matthew Laundy, Jill S. Morgan, Jozef Kesecioglu , Allison McGeer, Leonard Mermel, Manoj J. Mammen, Paul E. Alexander, Amy Arrington, John Centofanti, Giuseppe Citerio, Bandar Baw, Ziad A. Memish, Naomi Hammond, Frederick G. Hayden, Laura Evans, Andrew Rhodes

Hydroxychloroquine and Azithromycin for COVID-19

The group of Philippe Gautret (IHU-Méditerranée Infection, Marseille, France) presented their results on a non-randomized clinical trial using two antibacterial agents – hydroxychloroquine and azithromycin – for the treatment of COVID-19.

The results are promising, but the number of patients enrolled is small, and the study is not a randomized clinical trial.  Also, 6 of 26 patients in the treatment group were lost to follow-up, and no intention treat analysis has been included yet in the initial report.

The idea to use hydroxychloroquine, was based on a trial conducted in Chinese patients with COVID19 which showed a significant effect of chloroquine (an old antimalarial drug) on viral clearance as well as clinical outcome.  The dosing regimen for chloroquine was 500mg twice a day for ten days.

Hydroxychloroquine, which is an analogue of chloroquine, has been demonstrated to have anti-SARS-CoV activity in vitro, and has a better safety profile than chloroquine.

Azithromycin has been showed to be active in vitro against Zika and Ebola viruses, and prevent severe respiratory tract infections when given to patients with viral infection.

This study enrolled hospitalized patients older than 12 years old with documented SARS-CoV-2 carriage in nasopharyngeal sample on admission.  Patients with allergy or known contraindications to the drug (s.a. retinopathy, G6PD deficiency, QT prolongation) were excluded, as well as pregnant or breastfeeding patients.

The primary endpoint was virological clearance on day 6.

The treatment regimen is hydroxychloroquine sulfate PO 200 mg TID x 10 days.  The patients who refused treatment or were excluded based on criteria served as controls to the treatment group. Azithromycin was given to 6 patients (not part of the protocol) to prevent bacterial infection, at  a dose of 500mg PO x 1 then 250mg/day x 4 days.

Results of preliminary data showed that 70% of treatment group were virologicaly cured at day 6, compared with 12.5% in the control group (p = 0.001).  Subgroup analysis of patients who received both hydroxychloroquine and azithromycin showed that 100% of patients treated with both antibiotics were virologicaly cured, compared to 57.1% of patients treated with only hydroxychloroquine and 12.5% in the control group (p<0.001).

The study proposes that nasopharyngeal carriage of SARS-CoV2 can be cleared in 3-6 days in most patients.  Of note, mean duration of viral shedding (based on data from COVID cases in China) was 20 days (and up to 37 days).

Figure below:  percentage of patients with (+) nasopharyngeal samples through day 6.

Figure below:  percentage of patients with (+) nasopharyngeal samples through day 6.  Treatment group divided into 2 subgroups – hydroxychloroquine +/- azithromycin.

 

Raw data provided in the supplemental tables.  I colorized the table to show clearly why the data seems promising, with the limitations as discussed above.

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REFERENCE:

Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of
COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of
Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

COVID-19 PAGE

<Under construction>

Timeline:

  • December, 2019 – series of unexplained cases of PNA reported in Wuhan, China
  • January 12, 2020 – WHO tentatively named new virus as 2019-nCoV (2019 novel coronavirus)
  • January 22, 2020 – China National Health Commission reported details of first 17 deaths due to the new virus (see figure below for reported incidence and mortality reported by China)
  • January 30, 2020 – WHO announced 2019-nCoV epidemic, public health emergency of international concern
  • February 11, 2020
    • WHO formally named disease as COVID-19 (coronavirus disease 2019)
    • International Committee on Taxonomy of Viruses named the virus as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)

SARS-CoV-2 Details:

  • WHO classified COVID-19 as a βCoV of group 2B
  • Genomic sequence >80% identical to SARS-CoV and 50% to MERS-CoV
  • Classified under orthocoronavirinae subfamily

Taxonomy of Coronavirus:

Chronological Incidence and Mortality from COVID 19. (China Data)

Incidence of COVID in Italy.

Figure above:  measured and predicted number of patients infected in Italy

Figure above: measured and predicted number of patients in ICU in Italy.

 

Course of Disease

  • Incubation period (5.2 days)
  • Period from symptoms to death (14 days median, range 6-41 days)

Symptoms of COVID:

  • Most common symptoms = fever, cough, fatigue
  • Other symptoms: sputum production, headache, hemoptisis, diarrhea, dyspnea

Disorders Caused by SARS-COV2

TRANSMISSION:

  • Person-to-person transmission via direct contact or through droplets spread by coughing or sneezing
  • No evidence of transmission from mother to child (based on small study on women in third trimester confirmed to be infected with coronavirus – all underwent Caesarean section)
  • Cleaning Agents
    • studies on SARS, MERS, or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic x 9 days
    • coronavirus can remain infectious for from 2 hours up to 9 days
    • higher temperature (30-40C reduced duration of persistence of highly pathogenic MERS-CoV
    • at 4C, persistence of TGEV / MHV can be increased to >=28d
    • Persistence longer with hgiiher inocula
    • at room temperature HCoV-229E persists better at 50% compared to 30% relative humidity
    • can be inactivated by surface disinfection procedures
      • 62-71% ethanol, 0.5% hydrogen peroxide, 0.1%                within 1 minute
      • 0.05-0.2% benzalkonium chloride or 0.02 chlorhexidine digluconate are less effective
  • Other notes:
    • observational study:  students touch face with own hands 23x/hr, contacting mostly skin (56%), followed by mouth (36%), nose (31% and eyes (31%)
    • typical use of bleach is at a dilution of 1:100 of 5% sodium hypochlorite resulting in a final concentration of 0.05%.  Data suggests concentration of 0.1% applied x 1 minute is effective, recommend dilution of 1:50 of standard bleach
    • disinfection of smaller surfaces with 62-71% ethanol revealed similar efficacy
    • no in vitro data for hand washing against coronavirus contamination on hands, but in Taiwan, it was described that installing hand wash stations in ED was the only infection control measure which was significantly associated with protection for healthcare workers acquiring SARS-CoV.

PATHOPHYSIOLOGY

  • Virus targets the lung epithelial cells
    • Receptor-binding domain of virus spikes binds to angiotensin-converting enzyme 2 receptor of lung cells
  • Fusion with cell membrane

TREATMENT:

    • No specific antiviral drugs or vaccine currently
    • Broad-spectrum antiviral drugs
      • Nucleoside analogues
      • HIV-protease inhibitors

A course of treatment x 3-14 days

      • Oseltamivir 75mg PO BID
      • Lopinavir 500mg PO BID
      • Rito a ir 500mg PO BID
      • Ganciclovir 0.25 G IV BID
  • Remdesivir and chloroquine highly effective in control of 2019-nCoV infection IN VITRO

Other compounds in development

  • EIDD-2801 compound – shown high therapeutic potential for seasonal and pandemic influenza virus infections

 

 

Reference:

Sun, P., Lu, X., Xu, C., Sun, W. and Pan, B., 2020. Understanding of COVID‐19 based on current evidence. Journal of Medical Virology,.

En.m.wikipedia.org. 2020. Coronavirus. [online] Available at: <https://en.m.wikipedia.org/wiki/Coronavirus&gt; [Accessed 20 March 2020].

Rothan, H. and Byrareddy, S., 2020. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, p.102433.

Wu, Z. and McGoogan, J., 2020. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA,.

Remuzzi, A., & Remuzzi, G. (2020). COVID-19 and Italy: what next?. The Lancet. doi: 10.1016/s0140-6736(20)30627-9