Hi, I'm Kelly Pennington, and I'm a current Lung Transplant Fellow at the University of Toronto, and a former Pulmonary Critical Care Fellow at Mayo Clinic. Today, I'm going to be talking about not another respiratory virus. I have no relevant financial disclosures for this talk today. Today, I have the honor to provide the lead-in for this session and introduce our two fabulous speakers, Dr. Richard Wunderink and Dr. Francisco Sanz-Herrero. For our session today, I'm going to start by just giving an opening into the COVID-19 presentation, and we're going to talk about coronavirus and discuss the clinical syndrome. This is really to set you up so that you can listen to the lectures provided by Dr. Wunderink on the diagnosis of viral respiratory infections, and Dr. Francisco Sanz-Herrero, who's going to talk about novel respiratory viral therapies. To provide just a little bit of background, which I'm sure most of you are probably at this point very tired of hearing about coronavirus, but we're going to talk a little bit about the virology so that the subsequent two lectures make a little more sense. So, coronaviruses are enveloped RNA viruses that affect humans, mammals, birds, but bats are infected by a huge number of coronaviruses. More than 5,000 variants of coronaviruses are known to affect bats. There are two genres of coronaviruses that affect humans, both the alpha and beta genre. Like all viruses, the genome of the coronavirus only codes about four or five proteins. And probably the most important protein or the protein that's gotten the most press during this pandemic is the spike protein that gives the coronavirus this corona or crown-like shape. The role of the spike protein is that it mediates binding from the receptor infusion into the host cell. The spike protein will likely be the target of vaccinations that are developed during this pandemic. The coronaviruses that are responsible for SARS and COVID-19 use the particular receptor angiotensin converting enzyme 2 to gain entrance into the cells. I highlight this because it may partially explain why there's a pulmonary predilection for the virus and may partially explain why certain people are more affected by the virus than others if they have upregulation of ACE2 binding receptor sites. This is particularly known in patients with heart disease, hypertension, diabetes, and cigarette smoking. But how do we end up with a new virus like this? 70% of newly emerging infections are derived actually from wildlife and a proportionally large number of these infections are RNA viruses like coronavirus. It's because these types of viruses are very good at mutating to adapt to new hosts or environments. In most instances, a zoonotic disease will just spill over from a reservoir into a human population. It may infect one or two people, but then if it's unable to transmit from person to person, it really never comes to attention and just fades out. But if the infection is able to infect, multiply, and then transmit from person to person, the host pathogen is then able to form a pandemic or an epidemic like SARS-CoV-2. SARS-CoV-2 has been very effective at transmitting from one host to another host. SARS-CoV-2 is the result of spillover across species transmission, as we've discussed. And the viruses responsible for MERS and SARS started out with a similar mechanism. SARS was transmitted to humans from a civet cat. Although the original reservoir is unknown, it's largely believed to be secondary to bats. And MERS was transmitted to humans from camels. The reservoir for the virus causing COVID-19 is unknown, but the viral strains are very similar to bats. We think that the intermediary was probably this animal here called a pangolin. So for our case presentation, I'm going to present a patient that was one of our very first patients that we saw with COVID-19. And that was a 29-year-old woman who came in with hypoxemic respiratory failure four days prior to presentation. She developed fever, fatigue, and myalgias. Three days prior to presentation, she started to develop diarrhea and nausea, had a little bit of shortness of breath, and a dry cough. The progressive shortness of breath, however, is what prompted her to present to the ED on illness day four. She had a past medical history that was really only significant for obesity. Her BMI was around 44. She was a lifelong never smoker, worked as a preschool teacher, and lived with her sister who was actually diagnosed with COVID about two weeks prior to this patient. On initial presentation, she was saturating well on room air and really appeared non-toxic. Her basic laboratory evaluation was non-revealing. She did not have lymphopenia, as is often seen in patients with SARS-CoV-2. Her initial blood gas was satisfactory on just two liters nasal cannula. The only thing that seemed to be abnormal on her labs were elevations in inflammatory markers, including D-dimer, CRP, and IL-6. Her nasal PCR swab was positive for SARS-CoV-2. Her initial CT scan, as I'm going to highlight here, showed patchy ground glass opacities with areas of consolidation. There did seem to be more of a peripheral predilection, although the CT scan was actually pretty diffuse. This patient had a fairly typical clinical syndrome of SARS-CoV-2 or COVID-19. While as often being reported is that patients have fever and dry cough, we've come to subsequently know that another presenting symptom can be anosmia, as is with other upper respiratory viral infections. It's usually patients are infected, we believe, about one week prior to presentation, and the illness usually lasts for one to 14 days. Certain patients become very critically ill with SARS-CoV-2, and what's been reported as part of the critical illness is primarily ARDS. Although a significant proportion of the patients do develop kidney injury, and some actually even require pressures or develop shock, although single organ failure with ARDS still tends to be the most common presentation. Most patients will have mild to moderate disease. We still believe that to be true even at this point within the viral pandemic. Approximately 80% of laboratory-confirmed cases usually just have mild to moderate symptoms and do not require hospitalization. The proportion of truly asymptomatic individuals is still unclear, but hopefully we'll have more light on that as we're starting to test larger swaths of people. But it appears 13.8% or about 15% of patients, depending on the cohort that you're looking at or the country that you're evaluating, appears to develop severe disease with dyspnea and hypoxemic respiratory failure and lung infiltrates. A subset of severe cases go on to develop critical illness, and about 6% of cases or so actually develop shock, require multiple pressures, or develop multi-organ failure. Individuals at highest risk for severe disease appear to be those older than 60. Obesity seems to be a major risk factor, hypertension, diabetes, cardiac disease, and respiratory disease. Using available data, the median time from onset to clinical recovery from mild cases appears to be about two weeks. For patients with severe disease to require ICU admission, it tends to be about three to six weeks, depending on the impact of the disease, although there are reports of patients, and we have seen patients that have required prolonged intubation. The time of delay from presentation with mild to moderate disease to the development of severe disease appears to be about one week, as you're going to see with our patients. So on illness day five, she was admitted to the hospital, treated for community-acquired pneumonia. At this point in time, we were still giving antibiotics to folks to treat them, even in the case of known COVID infection. That has since changed. She was enrolled in a trial for convalescent plasma and received convalescent plasma. Unfortunately, her oxygen requirements gradually increased throughout the day, and she was actually transferred to the intensive care unit on hospital day five, the same day as admission, requiring high-flow nasal cannula oxygen, 50 to 70 percent, and was actually asked to try self-proning, although the patient found this to be very uncomfortable. On illness day six, her oxygen saturations were only able to maintain about 88 to 90 percent on 100 percent FiO2. She was becoming progressively tachypneic with respiratory rates of 50. She was ultimately intubated. Her initial PF ratio was around 75. We were unable to appropriately oxygenate her on 100 percent FiO2. She was subsequently paralyzed and proned, with improvement of her PF ratio and oxygenation. On illness day 10, she was placed in a supine position. Paralysis was definitively placed in a supine position. Paralysis was able to be lifted and sedation lightened. On illness day 12, she was able to be extubated to high-flow nasal cannula, and fortunately, on illness day 20, this patient was able to be discharged home with her sister. Some notable points from this patient's hospitalization that we've seen with other patients is that her sedation with propofol and even initially her triglycerides were elevated, and those did increase throughout her ICU stay. Her CK also increased and required us to find alternative sedation rather than propofol. This patient had minimal vasopressor support and really only had single organ failure with ARDS. Some notable take-home points from what we've learned so far with this pandemic and treating patients with novel coronavirus is that coronavirus is an RNA virus that is able to really adapt and mutate. This is not the first coronavirus that has caused epidemics or pandemics and likely won't be the last. COVID is a result of cross-species jump or spillover from animal reservoirs. That's where likely the origination of the virus. We're still learning about the syndrome of coronavirus and the best methods for treatment. So, I now have the pleasure of introducing Dr. Richard Wondering, who is going to be talking to you guys about diagnosing viral respiratory infections, so COVID-19 as well as other viral respiratory infections. And then Dr. Francisco Sanz-Herrera will be talking about viral respiratory therapies. And with that, we will end our presentation this morning. Thank you and have a good day.

COVID-19

coronaviruses

lung transplant

zoonotic origins

respiratory infections