Weekly Update, April 26th - May 9th

A summary of the most important changes in the literature in the past week.

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Six developments of note during the past week.

1) COVID-19 Disease and Kawasaki disease
Over the past week there have been several cases Kawasaki disease/an overlap syndrome of toxic shock and Kawasaki syndrome in children with COVID-19.  Reports note fever, conjunctivitis, a polymorphous, blanching rash, tongue involvement and swelling of hands and feet.

The Pediatric Intensive Care Society from Britain has alerted providers to be vigilant in identifying these patients and note that they often have GI symptoms, abdominal pain, myocarditis and coronary artery findings consistent with Kawasaki Disease. Lab abnormalities include an elevated troponin, and elevated CRP and sedimentation rate.  Of note, some of these patients have been COVID-19 negative.

Comment:  The classic constellation of symptoms for Kawasaki disease include: Fever for at least 5 days, Mucositis, Conjunctivitis, Polymorphous rash, Distal extremity edema, and Lymphadenopathy (which is commonly absent).  An incomplete syndrome is common.  There may be accompanying carditis.  The take home message for clinicians is to realize this association with COVID-19 likely exists and to have a low threshold for referral for a higher level of care.  

Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020; doi: 10.1542/hpeds.2020-0123


2) Self-Proning in the ED Improves Patients’ Oxygenation
A small, observational study of 50 patients with a median initial oxygen saturation of 80% found that adding oxygen by nasal canula or non-rebreather mask increased oxygen saturations to a median of 84%. Oxygen with self-proning increased oxygen saturations to a median of 94%. Ultimately, 24% went on to get intubated within the first 24 hours and 36% overall required intubation.

Comment:  Awake proning is being used in the acute care wards and now in the ED to improve oxygenation.  This observation study shows improvements in oxygenation, though long-term outcomes are unclear.  Whether this technique reduces intubations is unknow; it is also unknown how much it reduces intubations in the ED. 

These practices further support the more tranditional practices of paralysis and proning of patients with moderate/severe ARDS in the ICU with COVID.

Caputo ND, et al. Early Self‐Proning in Awake, Non‐intubated Patients in the Emergency Department: A Single ED’s Experience during the COVID‐19 Pandemic Academic Emergency Medicine 22 April 2020 https://doi.org/10.1111/acem.13994

3) Yet more good news about ACEI and ARBs in COVID-19 (but not so good about smoking, CAD, COPD)
An observational database study done at 169 hospitals in Europe, Asia and North American of 8910 patients with COVID-19 found that ACEI Sand ARBS did not worsen mortality and that ACEI seem to be protective (death in those on ACE inhibitors versus placebo (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54)). ARBs seemed to be neutral in terms of death.  ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).

CAD, age of 65 years of age, heart failure, a history of cardiac arrhythmias, COPD and current smoking all were associated with an increase in mortality.

Comment:  This is the largest study to date and confirms prior data:  ACEI and ARBs are at worst neutral and, in the case of ACEI may be protective in those with COVID-19.  Underlying illness including COPD and current smoking are risk factors for death from COVID-19.  This is not a randomized, controlled trial but is the largest data set we have to date.

Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 May 1, 2020 DOI: 10.1056/NEJMoa2007621

4) New Guidelines on Breast Feeding
The CDC has issued new guidelines which can be found here: https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html

  • Breast feeding is generally the best nutrition for an infant and COVID-19 does not SEEM to be a source of transmission of COVID-19 (though it can’t be entirely excluded yet).
  • Whether to breast feed or not should be a shared decision between the mother/parents and provider.
  • Hand washing and wearing a cloth facemask are critical. Note that the guideline makes no mention of N95 or surgical masks.
  • Assume that the infant of a COVID-19 positive mother who is breast feeding is itself COVID-19 positive for purposes of isolation.
  • Newborn and young child wellness visits (through 24 months) and vaccination should be prioritized.
  • Telemedicine can provide lactation support for mothers breast feeding.

Comment:  These are simplified but essentially the same as the prior breast-feeding guidelines for COVID-19 positive mothers.

5) Some good news: Remdesivir is given emergency approval by the FDA for use in COVID-19
An unpublished study showed a benefit of Remdesivir in COVID-19 positive patients requiring oxygen or intubation an showed that the average time to recovery (discharge or no need for supplemental oxygen) was 11 days with Remdesivir than with placebo (15 days).  There was a trend towards a mortality benefit but it did not meet statistical significance.  Five day of drug seemed to be as effective as 10 days of drug.

NIH release is here: https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

Comment:  This study continues since the requisite number of patients have not yet been recruited to assess all endpoints.  We are still awaiting peer review.

6) New COVID-19 symptoms recognized by the CDC.
These can be found here https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html and include: Repeated shaking chills, muscle pain, headaches sore throat and loss of taste.   The “classic” symptoms include fever, dyspnea, and cough.

There are reports of “frostbite-like” erythema and peeling of toes, especially in young patients though it is as of yet not categorized in terms of frequency. There are several possible mechanisms include microthrombi from hypercoagulability and vasospasm. There are no reviewed/published articles in the scientific literature as of yet.

A dermatology registry about COVID-19 skin manifestations is being compiled and can be found here: https://www.jaad.org/article/S0190-9622(20)30658-7/pdf

Finally, stroke and encephalopathy are being noted with increased frequency.  Stroke seems more likely in the young while encephalopathy are being noted in those who are older.

Cureus. 2020 Mar; 12(3): e7352. Published online 2020 Mar 21. doi: 10.7759/cureus.7352 

Rev Neurol. 2020 May 1;70(9):311-322. doi: 10.33588/rn.7009.2020179.




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