COVID-19 Pathogenesis and Risk Factors

00:01 COVID-19 complications.

00:04 The December 2019 Wuhan, China experienced with SARS coronavirus 2 causing coronavirus infectious disease 2019 or COVID-19 has been instrumental in broadening the understanding of the world of a severe respiratory illness with great potential for complications.

00:25 In March 2020, the World Health Organization announced that COVID-19 qualified as a pandemic worldwide.

00:34 What has been important about this outbreak has been not just the fact that it causes mostly mild upper respiratory tract disease, but that it indeed also causes severe lower respiratory tract disease in a subset of the population who do very poorly with it.

00:51 Epidemiologically, 80% of infected patients that we know about have mild disease presenting with fevers, dry cough, fatigue, anorexia.

01:02 However, the remaining 20% develop severe to critical disease.

01:07 15% with severe illness which requires hospitalization or at the very least, medical attention.

01:12 And 5% critical disease requiring transfer to the intensive care unit.

01:18 Overall, the mortality estimates although still preliminary are a mortality or death rate of 4.2%.

01:29 So significantly higher than experienced with the very typical annual epidemic with influenza A and B.

01:37 However, there are some patients who do far less well with severe or critical COVID-19 infection.

01:43 And those would be patients who are older than 80 years old with a mortality estimate at least of 14%.

01:50 Those with pre-existing cardiovascular disease, mortality rate of 10%.

01:54 And those who have diabetes mellitus or a mortality rate of 7%.

01:59 It does appear that there are some emerging risk factors for patients who will do -- rest well or develop more severe disease after developing COVID-19 infection.

02:11 The initial experience comes out of, again those physicians and researchers in Wuhan, China, who in three separate studies have shared the following comorbidities.

02:22 Patients who have pre-existing hypertension, controlled or not controlled have a 24 to 30% risk of developing severe or fatal disease.

02:32 Those with pre-existing diabetes mellitus, both type I and type II have a 12 to 22% risk of developing fatal disease. Pre-existing coronary heart disease, 6%.

02:44 And those with pre-existing cerebrovascular disease, so cerebrovascular accidents or strokes, including transient ischemic events, anywhere from 2% up to 22% developing progression to a severe or fatal disease.

02:59 Why might this be so? Well, to understand that, we can take a step back and look at the pathogenesis of the SARS coronavirus 2 and how it attacks its target cells.

03:10 It binds to Angiotensin-converting enzyme 2 or ACE-2 as a receptor.

03:16 And there are epithelial cells which express this particular enzyme at their epithelial cell surface, specifically cells within the lung, intestines, kidneys and blood vessels, so endothelial cells.

03:30 It makes sense then that any individual who is on perhaps an Angiotensin-converting enzyme inhibitor or is on Angiotensin 2 receptor blocker might have an up regulation or higher expression of Angiotensin-converting enzyme 2 therefore providing more binding sites or a higher potential for binding of SARS coronavirus 2 and therefore much higher risk of developing not just COVID-19, but severe to fatal COVID-19.

04:01 So, there is a medical explanation potentially for those patients experiencing worse outcomes.

04:08 There also however, may be genetic polymorphisms within Angiotensin-converting enzyme 2 expression.

04:14 These event so far demonstrated especially in those of Asian ethnicity who also have diabetes, hypertension or a history of coronary heart disease or cerebrovascular disease.

04:27 So, these patients themselves might also experience worse outcomes because they genetically already hyper express ACE-2 as a binding site for SARS coronavirus 2.

04:39 What are then the risk factors for developing critical or potentially fatal COVID-19 infection? Remembering again that 5% of all patients so far in the literature we have available demonstrate this progression.

04:53 Those patients developing critical COVID-19 disease do so by developing acute respiratory distress syndrome, ARDS; hypotensive shock and multi-organ dysfunction.

05:07 So, just like you might anticipate for other severely progressive infections, not just respiratory infections, but infections which have systemic effects, so too with COVID-19 which progresses.

05:19 Specific risks for those entering into critical COVID-19 territory are those who are with older age.

05:27 And in fact looking at all patients who had critical disease with SARS coronavirus 2, the median age of these individuals was 60 years of age.

05:36 40% of them also had comorbid conditions and those again, diabetes, type I and II, cardiovascular disease and pre-existing hypertension.

05:47 There is one researcher or one excuse me, research group that has identified refractory case risks.

05:54 So those patients developing not just COVID-19 infection, but progressing to severe refractory disease.

06:01 And those are individuals who are more likely than not male, older, presents with anorexia and present without the typical fevers that have been characterized in other patients with typical or mild or COVID-19 infection.

06:17 Very recently, a data has suggested that those patients who present with peripheral oxygen saturation as marked by SpO2 of less than 90%, those are patients almost all of whom in an ICU setting have that as a presenting risk factor.

06:35 Median time to onset. So after initial presentation of the upper respiratory fevers, dry cough, fatigue, etc.

06:44 progressing to incentive care unit transfer or onset of critical care support that has been taking around 9 to 10 days.

06:54 This is not an acute present and then rapidly becomes worse.

06:57 This is a gradual onset, gradual progression, gradual deterioration which largely supports an immunologic mechanism for critical disease related to SARS coronavirus 2 and COVID-19 infection.

07:12 Those patients who do get transferred to the intensive care unit are doing so in large part because they need further respiratory support, whether that's positive pressure ventilation, oxygen delivery, etc., and so forth.

07:24 Cause of death so far is not 100% confirmed.

07:29 But it is suggested to be from progressive hypoxia which has been refractory to treatment or/and possible development of multi-organ failure requiring support which may or may not be successfully administered.

07:42 And anecdotally, many patients are expiring with uncontrollable or uncorrectable hypotensive shock.