In this third and final video, we will be reviewing the laboratory tests that are most helpful for monitoring the severity and progression disease, as well as helpful imaging studies. Finally, we will review the different stages of COVID-19 and factors that are associated with a poor prognosis or outcome. Laboratory findings are non-specific. However, I have found three values to be particularly helpful in assessing the severity and prognosis of COVID-19. C-reactive protein, abbreviated CRP, is a measure of the degree of inflammation and is elevated in the majority of cases. A normal value is 0-5. More severe cases of COVID-19 have levels of 100-400 and the higher the CRP, the higher the likelihood of severe disease. D-dimer is a reflection of abnormal clotting and is elevated in severe cases. A normal value is less than 0.5. A value of 1-2.5 is associated with approximately a threefold increase in clot formation in the veins or arteries. A value of greater than 2.5 is associated with a 6-7 fold increased risk of abnormal clotting. The lymphocyte count has been shown to be an important prognostic factor when it is under 800 or 0.8 thousand, the risk of poor outcome increases. Here are the values for the patient I presented. Note the marked elevation of CRP D-dimer, and the decrease in lymphocyte count. On day 3, an IL6 level was found to be markedly elevated at 48. Normal being less than 0.9 pictograms per ML. On day 6, we administered the IL6 inhibitor Tocilizumab. Note the improvement of these parameters following Tocilizumab administration. Here are two of our patients X-rays on day 1 and day 2. You can see the marked increase in lung opacification or whiteout consistent with the development of acute respiratory distress syndrome or ARDS. Chest X-ray is abnormal in 60 percent of patients. Chest CT is a more sensitive identifying abnormalities in 84 percent of cases. It should be emphasized the CT scan may identify abnormalities even in mild cases. In severe disease, 96 percent of the time abnormalities are identified. Here are two examples of a ground-glass appearance on the left is in one lung field, the arrow. On the right is bilateral ground-glass appearance. This figure is from the WHO and chose the various levels of the illness severity and potential outcome. Mild and moderate cases make up 80 percent of all cases and mild cases rarely progress to death. Moderate disease and severe disease more commonly progress and patients who are critical, like our patient, have a high chance of dying, 45-84 percent. Critically ill patients may develop septic shock with organ failure. This strange syndrome may be associated with high levels of cytokine, including interleukin-6 as seen in the case I presented. The average duration of hospitalization, in the WHO experience was 12 days, 11 days for non-severe cases, and 13 days for severe cases. Mechanical ventilation was required in 38 percent of severe cases. To assess what stage each patient is in and to detect whether or not the patient will worsen, it is important to understand the timing of the different stages of the disease. Whenever possible, it is important to estimate the time of exposure and know what day symptoms began. The usual incubation period after exposure is 4-5 days. During this period the patient has no symptoms. Onset of symptoms can take up to 14 days. Early on the symptoms tend to be mild and 40 percent do not progress. 5-8 days after the onset of symptoms, 40 percent of patients experience shortness of breath, indicating moderate disease. At 8-12 days, 15 percent of cases progress to severe disease. These patients experience a decrease in oxygen saturation below 93 percent and will require oxygen administration. At 12-14 days, five percent become critically ill, and require managing in the IMICU and often require mechanical ventilation as described in our case. Patients requiring mechanical ventilation who are less than 40 years old progress to death approximately 45 percent of the time, while those over 80 years of age have an 84 percent mortality. As shown in this image, the time course of progression tends to be faster for the Delta variant. The incubation period is 2-3 days rather than 4-5 days. Progression from mild to moderate disease may occur in 2-3 days after the onset of symptoms and progress to severe disease by day 4-5, and to critical disease by day seven. The case fatality ratio varies from country to country, ranging from a low of 0.9 percent in Turkey to a high of 7.6 percent in Mexico. In the US, the case fatality rate is 1.6 percent, United Kingdom, 1.8 percent, and Brazil 2.8 percent. Case fatality or CF, is defined as the number of deaths per total number of patients with disease. These percentages may be overestimates because mild disease is not always recognized, lowering the denominator. The case fatality rate will also be higher where care is limited, as exemplified by Mexico as well as Indonesia and South Africa. To put these values in perspective, influenzas case fatality rate is 0.1 percent. Therefore, the case fatality rate of COVID-19 is 9-76 times higher than seasonal influenza. Mortality is related to sex. Men having a higher mortality than women, as do patients with chronic illnesses, specifically, hypertension, diabetes, cardiovascular disease, lung disease, and cancer as shown in this table. Also, patients with obesity and sickle cell disease have worse outcomes. Mortality is also affected by age. Death is exceedingly rare below the age of 30 and begins to climb in those over the age of 60 being four percent, for ages 60-70, eight percent for ages 70-80 and 15-25 percent for those 80 and over. This series from New York City demonstrated even worse outcomes related to age with a very steep slope relating age to mortality beginning at age 50. Note that patients over 80 had a 60 percent mortality in this series. In summary, lab findings this disease are non-specific. CRP and D-dimer are helpful for assessing severity of the disease, and a low lymphocyte count is associated with a poor outcome. Chest X-ray has a low sensitivity. Chest CT scan being more sensitive and often showing ground-glass opacifications. Eighty percent of the time, disease is mild to moderate in severity. But the disease can progress to irreversible hypoxia, and death. Disease progression is more rapid for those infected with the Delta variant. A higher mortality is seen in men, those 60 years of age and older, and those with underlying diseases. Case fatality rates vary from country to country, ranging from 0.9-7.6. COVID-19 is 9-76 times more deadly than influenza.