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ARDS diagram

May 6, 2020 - Dr. Archer's Update on COVID-19 response from the DOM and Medicine Program

COVID-19 Update:  There are no new cases of COVID-19 in our region today. The running total for the epidemic thus remains 61 cases in the KFL&A region and 57 people have already recovered. The SARS-CoV2 positive test prevalence is 1.2%. This contrasts with a 5.3% rate of test positivity for the province as a whole, a reminder of our low local incidence. Thus, the prevalence and incidence of the disease remains low in KFL&A. There are no COVID-19 patients in KGH today. Because of the absence of inpatient COVID-19 patients locally we have temporarily repurposed Connell 3 and will re-designate Kidd 10 as our COVID-19 ward. We did 371 COVID-19 tests from Friday to Sunday. There were 10 positive tests, with 5 of these being from Perth-Smith Falls and 5 from Lindsay/Peterborough. All tests from KFL&A were negative.

The epidemic continues to vary greatly by region within Ontario. COVID-19 incidence remains high in Toronto and Ottawa. However, the highest rate of disease in Ontario is nearby, in Leeds/Grenville/Lanark with Windsor being second in disease incidence.

PPE supply is stable with >3 weeks reserve at current level of activity. We are still committed to reprocess 

There is something strange about COVID-19 pneumonia and it’s called happy hypoxemia. COVID-19 is an acute respiratory illness caused by a droplet-borne coronavirus, SARS-CoV-2. By May1st 2020 the pandemic had resulted in ~3.3 million infections, over 235,000 deaths and global disruption of trade. While 80% of people with COVID-19 suffer a minor, acute respiratory infection, the mortality ranges from 2-7%. Some people with COVID-19 pneumonia get seriously ill and their blood oxygen drops to very low levels (this is called hypoxemic respiratory failure and it may land them on a ventilator). Autopsy data show these people have lung inflammation, diffuse alveolar damage (DAD), alveolar fluid accumulation, and occasional hyaline membranes, consistent with a well-known problem called acute respiratory distress syndrome (ARDS). Understanding the causes of low oxygen in COVID-19 is complicated by a paucity of hemodynamic and autopsy data. 

However, the presentation of COVID-19 patients differs from patients with ARDS, who are usually profound short of breath. While people with COVID-19 pneumonia have severe hypoxemia (low oxygen) they often don’t note any sense of being short of breath. This has led doctors to call their condition “happy hypoxemia”. While the patient may be happy the condition is both dangerous and poorly understood. My research lab (see below) is working on the problem, as are many others.

screen shot of zoom meeting with Archer lab members

Some members of my talented lab-seen during one of our ZOOM lab meetings. They are now back at the bench searching for COVID-19 treatments.

We believe happy hypoxemia represents (in part) a failure of a fundamental system in all our bodies (one which I bet you didn’t know you had). The system in question is called the homeostatic O2-sensing system (HOSS). It serves to optimize uptake and distribution of vital oxygen in our bodies. Its components include the lung arteries, the carotid body, adrenomedullary cells, and neuroepithelial bodies. If you have heard of none of these structures that’s OK (that’s why you need we science and medical geeks). Just know that the HOSS is a system in your body (like the central nervous system or the cardiovascular system). The HOSS optimizes oxygen uptake and oxygen delivery to the entire body through a mechanism called hypoxic pulmonary vasoconstriction (HPV). HPV is the pulmonary circulation’s homeostatic response to airway hypoxia, such as pneumonia. HPV constricts the blood vessels in the lung that serve lung segments with low oxygen (e.g. because of pneumonia). This redirects blood to better-ventilated alveoli, optimizing ventilation/perfusion (V/Q) matching. Meanwhile, the carotid body senses low blood oxygen (hypoxemia), causing the person to increase their rate and depth of breathing and this may also make them feel short of breath. Together these mechanism fight low oxygen and keep us stable during pneumonia.

COVID-19’s happy hypoxemia has variably been attributed to ARDS, impaired HPV and a high altitude pulmonary edema (HAPE), a form of lung edema that occurs at altitude and is cause by excessive HPV (Figure 1). Our prior research has shown that oxygen sensing in the HOSS is normally mediated by mitochondria in these specialized tissues. This makes sense because, as every school kid knows, mitochondria are the powerhouse of the cell and they use oxygen to generate energy (ATP). So of course mitochondria have sensors to ensure supply of what they require-oxygen! It turns out that the SARS-CoV-2 virus targets lung (and other) mitochondria. We suspect (but have not proved) that SARS-CoV-2 may interfere with mitochondrial O2-sensing (accounting for happy hypoxemia) and simultaneously cause mitochondrial-induced lung cell injury by triggering programmed cell death (leading to lung damage). Here is some lovely artwork illustrating our theory drawn by Ms. Julia Herr, showing the differences between COVID-19 pneumonia, HAPE and classical ARDS.

ARDS diagram

If you are interested in learning more, click here to see our paper which came out yesterday in the journal Circulation.

Care for the 99%: KFL&A is better positioned than the rest of the province to ramp care back up once given permission by Ontario Health. This announcement was expected to come today but apparently is delayed for 1-2 days. Stay tuned for a date to commence a ramp up that is customized to our regions local epidemiology, the status of COVID-19 in local LTC facilities and a hospital’s local supply chain. Once given the green light KHSC will implement its preparedness plan for the anticipated and necessary return to increased service for all patients, the 99% who do not have COVID-19 disease.

alarm clock with smiley face

A daily reminder for people in the community re COVID-19 testing and seeking health care in our hospitals: People in the community can self-refer for assessment and possible and testing. We are still focusing on testing symptomatic people (since the test for COVID-19 is likely not as specific in asymptomatic people) or people with confirmed COVID-19 contacts. There will soon be increased testing of certain vulnerable populations, stay tuned. If you are symptomatic with a new cough, fever, sore throat etc. please self-quarantine and seek out testing at Memorial Centre in Kingston, (see instructions below). Our hospitals and clinics are safe places to receive care (in part because everyone including staff is screened prior to entry and in part because the local incidence of COVID-19 remains low). You should not delay accessing care that you or your doctor deem to be urgent.

community instructions for testing

How’s the epidemic going? The COVID-19 epidemic is beginning to relent in Ontario. Although the COVID-19 curve has flattened, with a decline in daily cases numbers, there are at least two important caveats. First, COVID-19 remains a huge problem in long term care facilities (LTC) and second, the distribution of the disease varies markedly by region. 

To date there have been 62,458 cases of COVID-19 and 4111 deaths in Canada (see below). Once again these numbers are heavily influenced by the epidemic in Quebec and by the mortality in nursing homes across the country. (click link for daily update). Aggregate data (below) from ministries of health, show the ongoing impact of COVID-19, with 30,898 active cases and 3271 hospitalized people, although the percent of patients in ICUs is down to 15.1%. Also note the flattening of the curve (descending active cases in orange bar graph below. This is evidence of the flattening of the curve that we collectively have been working hard to achieve through physical distancing, testing and closing of schools, daycares and non-essential businesses. Canada is heading in the right direction, although there are still major areas of concern and nursing homes are an epidemic within an epidemic.

COVID-19 Canadian outbreak tracker

The graph below shows Ontario data. New case accrual continues to be decreased compared with last week. The rate of COVID-19 testing dipped from 17,000 tests/day last week to 10,564 tests on May 5th. Ontario has tested 2.53% of the entire population. This drop in testing rate led to an angry outburst by the premier. There is both irony and unfairness in criticizing Ontario’s underfunded public health system (because the underfunding was a decision made by the current government-last year). Moreover, it is rarely wise to flog the horse you’re riding.. Locally our public health teams and IPAC AT KHSC have been exemplary in testing, advising and implementing rational policies. That said, we likely need to prepare for a future in which testing is recurrent and occurs in the entire population. If this is correct we will need to do 10-times more tests/day than we have ever achieved to date.

Numbers pic showing Ontario COVID-19 data

The Ontario epidemic remain dire in LTC facilities as discussed yesterday

To see where Canada stands amongst nations in the COVID-19 pandemic, click here. To date there have been over 3.75 million cases and over 259,583 deaths globally. There is however continuing evidence that the global incidence of COVID-19 is flattening (blue and gold graphs at bottom of Figure).

Graph and stats showing current global COVID-19 cases/deaths/recovered

Capacity in KGH: KGH continues to have good surge capacity (below). Note that we still have plenty of ventilators and beds available. The dashboard shows testing results are pending for 3-4 patients in our hospital.

KGH Bed capacity

News from away: I talked to friends at Cleveland Clinic today. Their clinical research enterprise is essentially closed. In person outpatient clinic visits are down to <5% of pre-epidemic numbers. In contrast 75% + of their outpatient visits are now video visits. The incidence of COVID-19 positive tests is lower amongst Cleveland Clinic staff (~5%) than in the general population of Cleveland (~10%), reminding us that hospitals are rarely going to be the source of COVID-19 infection for patients or healthcare workers (which is also true in Canada).

Stay well!

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