Day 72: Coronascience

The numbers accelerate apace; most notably the UK has risen above the China mark to 84,000 cases and well over 10,000 deaths. (On the bright side, Boris Johnson is out of hospital.) In Massachusetts, we're up 2,615 cases (11%) to 25,475, with 70 new deaths. One notable death was of a whistleblower nurse at the Life Care Center of Nashoba Valley in Littleton, where ten residents have died and 67 have tested positive. (The surviving staff are still being tested.)

Non-pneumonia symptoms have been getting more attention lately. A 400% jump in at-home cardiac arrest deaths in New York City has been attributed to viral myocarditis or some other mechanism by which the virus is damaging the heart. JAMA Cardiology has a detailed case study of a healthy patient with cardiac complications. An autopsy study in New Orleans found cardiomegaly, right ventricular dilatation, and "scattered individual cell myocyte necrosis" in the heart muscle. (There's an interesting discussion of the autopsy results on reddit.)

Another non-pneumonia symptom that, like sudden cardiac arrest, may explain early rumors of people dropping dead in the streets is stroke. JAMA Neurology published a paper yesterday about neurological manifestations of coronavirus in patients in Wuhan. They noted that "[s]ome patients without typical symptoms (fever, cough, anorexia, and diarrhea) of COVID-19 came to the hospital with only neurologic manifestation as their presenting symptoms."

Seventy-eight patients (36.4% [of 214]) had nervous system manifestations: CNS (53 [24.8%]), PNS (19 [8.9%]), and skeletal muscle injury (23 [10.7%]). In patients with CNS manifestations, the most common reported symptoms were dizziness (36 [16.8%]) and headache (28 [13.1%]). In patients with PNS symptoms, the most common reported symptoms were taste impairment (12 [5.6%]) and smell impairment (11 [5.1%]).

Another new category of symptom to pop up is dermatological: a French medical society has published a press release claiming that rash unaccompanied by pulmonary symptoms may indicate asymptomatic COVID-19 infection.

On the reproduction front is a preprint out of England about anosmia as a predictor of infection. They used app data from Britain to "find that loss of smell and taste were present in 59% of COVID-19 positive individuals compared to 18% of those negative to the test [...] We also find that a combination of loss of smell and taste, fever, persistent cough, fatigue, diarrhoea, abdominal pain and loss of appetite is predictive of COVID-19 positive test with sensitivity 0.54, specificity 0.86".

On a different sort of reproduction front, South Korea reported a total of 91 relapses on Friday, up from 51 total on Monday. For some unknown reason, officials believe these cases are "reactivations" rather than reinfections, even though Korean patients must test negative twice before being counted as recovered.

There has been some progress combatting the cytokine storm with the CCR5 antagonist leronlimab. An Israeli treatment involving placental cell therapy and a stem cell therapy from Australia have also shown promise.

A drug target of interest is the bradykinin receptor type 1 (B1), according to a theory in preprint:

We propose it all starts with ACE2 and its role in the kallikrein-kinin system, which to date has not investigated in the pathogenesis of SARS or COVID-19. The kinin-kallikrein system is a zymogen system that after activation leads to the release of the nona-petide bradykin that after binding to the B2-receptor on endothelial cells leads to capillary leakage and thus angio-edema. The prototype diseases of local peripheral transient increased bradykinin release are hereditary or acquired angio-edema. The clinical picture of COVID-19 is in line with a single-organ failure of the lung that is due to edema at the site of inflammation.

In shorter words, the virus' use of ACE2 receptors on lung cells uses them up, causing them to fail at one of their important jobs: keeping fluid from leaking into the lungs.

P.S. PlagueBlog forgot to mention that John Conway died yesterday of coronavirus. He was 82 years old.

P.P.S. Another approach to the cytokine storm is cytokine blockers, as recently discussed in The Lancet.