Case fatality rate
The overall global case fatality rate is approximately 4.5% based on World Health Organization data as of 29 March 2020. Current case fatality rates vary between countries, for example:
Italy - 11%
Iran - 7%
Spain - 8%
UK - 6%
US - 1.5%
Australia - 0.4%.
The overall case fatality rate in China has been estimated to be 2.3% (0.9% in patients without comorbidities) based on a large case series of 72,314 reported cases from 31 December 2019 to 11 February 2020 (mainly among hospitalised patients).
Estimates that take into account asymptomatic patients and mild cases who have not been tested put the case fatality rate in the total population at around 0.125%; however, this estimate does not take into account exceptional cases (e.g., the current situation in Italy). The case fatality rate among people on board the Diamond Princess cruise ship, a unique situation where a more accurate assessment of the case fatality rate in a quarantined population can be made, was 0.99%. However, it should be noted that the rate in a younger, healthier population could be lower.
It is important to note that estimated case fatality rates should be treated with extreme caution as the situation is evolving rapidly, and case fatality rates are often overestimated at the onset of outbreaks owing to increased case detection of patients with severe disease. For example, at the start of the 2009 H1N1 influenza pandemic the case fatality rate varied from 0.1% to 5.1% depending on the country, but ended up being around 0.02%. Other factors that can affect case fatality rates include testing rates in each country, delays between symptom onset and death, and local factors (e.g., patient demographics, availability and quality of health care, other endemic diseases). For example, the case fatality rate in Italy may be higher than in other countries because Italy has the second oldest population in the world, the highest rates of antibiotic resistance deaths in Europe, and a higher incidence of smoking. The way COVID-19 related deaths are identified and reported in Italy may have also resulted in an overestimation of cases.
The overall case fatality rate appears to be less than that reported for severe acute respiratory syndrome coronavirus (SARS) (10%) and Middle East respiratory syndrome (MERS) (37%). Despite the lower case fatality rate, COVID-19 has so far resulted in more deaths than both SARS and MERS combined.
Case fatality rate according to age and presence of comorbidities
The majority of deaths in China have been in patients aged 60 years and older and/or those who have pre-existing underlying health conditions (e.g., hypertension, diabetes, cardiovascular disease). The case fatality rate was highest among critical cases (49%). It was also higher in patients aged 80 years and older (15%), males (2.8% versus 1.7% for females), and patients with comorbidities (10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6% for hypertension, and 5.6% for cancer).
In the US, the case fatality rate was highest among patients aged ≥85 years (10% to 27%), followed by those aged 65 to 84 years (3% to 11%), 55 to 64 years (1% to 3%), 20 to 54 years (<1%), and ≤19 years (no deaths). Patients aged ≥65 years accounted for 80% of deaths. The case fatality rate among critically ill patients admitted to the intensive care unit reached 67% in one hospital in Washington state. Most of these patients had underlying health conditions, with congestive heart failure and chronic kidney disease being the most common.
The presence of comorbidities is associated with greater disease severity and poor clinical outcomes, and the risk increases with the number of comorbidities a patient has.
Children have a better prognosis than adults, and deaths have been extremely rare (2 deaths have been identified in children up until 18 March 2020).
Causes of death
The leading cause of death in patients with COVID-19 is respiratory failure from acute respiratory distress syndrome.
In one retrospective study of 113 deceased patients, older age, male sex, presence of chronic hypertension or other cardiovascular comorbidites (as well as indicators of cardiac injury), symptoms related to hypoxaemia, and multi-organ dysfunction were more frequent in deceased patients compared with those who recovered. Other characteristics found to be more frequent in deceased patients include leukocytosis, lymphopenia, and elevated C-reactive protein level, and presence of complications.
In one retrospective study of 52 critically ill patients in Wuhan City, 61.5% of patients died by 28 days, and the median time from admission to the intensive care unit to death was 7 days for patients who didn’t survive. Non-survivors were more likely to develop acute respiratory distress syndrome and require mechanical ventilation. Non-survivors were older (>65 years of age) and more likely to have chronic medical illnesses.
Factors associated with disease progression and a poorer prognosis in one retrospective analysis of 78 patients in Wuhan City include older age, history of smoking, maximum body temperature on admission, respiratory failure, significantly decreased serum albumin level, and significantly elevated C-reactive protein.
Thrombocytopenia has been associated with increased risk of severe disease and mortality and may be useful as a clinical indicator for monitoring disease progression.
Other factors associated with a poor prognosis include higher Sequential Organ Failure Assessment (SOFA) score and a D-dimer level >1 microgram/L. Viral shedding continued until death in non-survivors.
Refractory disease (patients who do not reach obvious clinical and radiological remission within 10 days after hospitalisation) has been reported in nearly 50% of hospitalised patients in one retrospective single-centre study of 155 patients in China. Risk factors for refractory disease include older age, male sex, and the presence of comorbidities. These patients generally require longer hospital stays as their recovery is slower.
Infectivity of recovered cases
Potential infectivity of recovered cases is still unclear. There have been case reports of patients testing positive again after being discharged (i.e., after symptom resolution and two consecutive negative test results two days apart). This suggests that some patients in convalescence may still be contagious.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation has been reported in patients after hospital discharge. In a retrospective review of 55 patients in China, 9% of patients presented with SARS-CoV-2 reactivation. The clinical characteristics were similar to those of non-reactivated patients. Further research is required on these patients.
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