So over the next few minutes, I'm just going to briefly outline some of the clinical features of SARS-CoV-2 infection. We know for many patients that the period between being exposed to the virus and developing symptoms is between five and six days, what we call the incubation period. This can be as long as 14 days, but importantly for this virus, before people are symptomatic, many of them can have virus detected beforehand in what we call the pre-symptomatic period. So this figure illustrates how it's possible to identify virus particularly in the upper respiratory tract, the nasopharynx, but also, potentially, stool samples before symptoms develop. We know also that before symptoms develop, people can transmit the virus, and one of the reasons this virus is so hard to control. If we ask what those symptoms are at onset, many people have mild symptoms. In a big study in UK, the most common symptom identified was anosmia, the loss of smell associated with a loss of taste. You can see other common symptoms include the skipped meals, a loss of appetite, fatigue, and then the more, classically, associated symptoms of fever, cough, and to some extent, diarrhea and delirium, confusion. So for most patients, the disease is mild and with or without any intervention. If we look at specimens taken from [inaudible] patients, then we can see over the days after symptoms, we can find virus where it says negative culture. It's possible to detect virus with sensitive techniques like PCR for several days, but this doesn't necessarily mean that the virus is viable. If we look at the top where it's possible to culture the virus and grow it, specimens are only positive for eight days in this study, and this is borne out in other studies. So if we look at people after the onset of symptoms, most patients can have virus cultured from the respiratory tract after eight days and it falls quite quickly. For most patients, this is a mild result. But of course, the reason this is such a devastating illness for the population is that a proportion of patients go on to get moderate or severe disease for reasons that we don't fully yet understand. Typically, it's around day seven after symptoms onset that people tend to deteriorate. If we look from this large UK study, the symptoms of people admitted to hospital, they differ from the community study. This is obviously, because patients have progressed and got complications. The most common complications would be in the lung. The most common symptoms reflecting that would be cough, fever, shortness of breath. We know from patients hospitalized that this is a disease that is more heavily affects those of older age, men, but of course, effecting all ages and both genders, but mortality higher in the older age groups. The P presentation in most patients to hospitals is with lung disease, this slide shows nine different patients x-rays on the left-hand column. For those who are less familiar with these, the black area of the lungs is normal lung and you can see on the left quite a lot of black area with relatively [inaudible] white area in it. On the left you can see some white at the base of the lungs here, on both sides, but on the right-hand side with more severe disease, you can see that the lungs are filled with much more of this white pattern which represents inflammation in the lungs. This represents the spectrum of lung disease. If we look at a CT scan, this is a cross-section, across someone's chest. At the top here, this is the front of the chest, this is the back of the spine, and this white area is the abnormal infection which you can see affecting the back of your lungs in particular, in the lower lungs. This is quite typical for COVID-19 disease caused by SARS-CoV-2. So some of the striking features clinically, although patients might have very low oxygen levels in their blood, they don't often necessarily feel that breathless and they can deteriorate very rapidly requiring support and intubation potentially going into intensive care. It's been recognized that actually by turning patients on their frontal proning, this can lead to some improvements in oxygenation and that's reflecting this distribution of disease. In those, unfortunate enough to die, we can look at the postmortem specimens. These are from two separate patients. For those less familiar, again, on the left, we have lat view of both lung tissues. The white area here is airway, and you can see these membranes or hyaline membranes which are results of inflammation in the airways. If we look in the lungs of patients with advanced SARS-CoV-2 or COVID, this is a very extensive inflammation. I think people who look at lung disease in general, recognize this is similar to many other diseases, but more severe and more extensive in its nature. As it progresses, you can see on the right here that there isn't very much airway space where this white area has gone and filled by cellular infiltrates, and this reflects the ongoing inflammatory process that as a result of infection, and makes oxygenation so difficult for patients admitted to intensive care unit. So although the key challenge of SARS-CoV-2 infection and COVID-19, is lung disease, we now recognize a number of other systems in the body which are infected. So the brain in particular, we often see patients with confusion and delirium, although many of these patients are relatively elderly and that can be a common presentation of many things. Stroke, or these, they're commonly associated and there is a syndrome similar to a condition called Guillain Barre syndrome which is inflammatory neuropathy which is recognized. We see involvement of the gastrointestinal tract with diarrhea and pancreatitis, and also the kidneys. We've seen evidence of coronary thrombosis, myocarditis. One of the most striking features of this particular illness is its association with clotting and procoagulation, so an increased tendency to clotting with thrombosis and embolism. This manifests itself in a number of different ways in patients which are important clinically. We are recently recognizing a rarer but significant clinical condition, a bit similar to a condition called Kawasaki syndrome in children which presents latest. We think of consequence of inflammatory response to this virus. So when we're trying to make a diagnosis for any disease, we have our clinical picture, which we describe and then we try and understand what the cause of that is. In the setting of a classic infection with SARS-CoV-2 and COVID-19, the pulmonary manifestations of disease often very characteristic. In a non-pulmonary disease, other tests are often required and the mainstay of diagnosis remains PCR for detection of the virus. This blue line in nasopharyngeal swabs or in the lung itself. As you can see, you can often find that virus for sometime after symptoms stop, but as we discussed earlier, not necessarily reflecting live virus. Then what can happen in the days after infection is that we start to develop antibody responses. So at this time, we don't yet use antibody responses routinely, although that is likely to become more common. There are two main antibody responses we focus on, IgM and IgG in the blood. IgM tends to rise quicker, the purple on here, but then fall away. IgG, we think, would be sustained for longer term based on our experience with other coronaviruses and early experience with SARS-CoV-2. It's IgG antibody that's likely to be the one that could protect us from reinfection with SARS-CoV-2. So what I've done is just summarize very briefly the main clinical manifestations of SARS-CoV-2 in disease COVID-19.
