Prognosis

Case fatality rate

The overall global case fatality rate is currently approximately 5.7% based on World Health Organization data as of 7 April 2020. The case fatality rate varies between countries; for example, it is currently higher in countries such as Italy and Spain, and lower in countries such as Germany and Australia.[330]

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 hospitalized patients).[6] However, another study estimates the case fatality rate in China to be lower at 1.38% (after adjusting the crude estimate for censoring, demography, and under-ascertainment).[331]

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.[332] 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. Patients who die "with" COVID-19 and patients who die "from" COVID-19 are both counted towards the death toll.[333][334]

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).[333] 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.[335]

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%).[18] Despite the lower case fatality rate, COVID-19 has so far resulted in more deaths than both SARS and MERS combined.[336]

Case fatality rate according to age and presence of comorbidities

The case fatality rate increases with age.[331] 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.[337]

The majority of deaths in China have been in patients ages 60 years and older and/or those who have preexisting 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 ages 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).[6] Another study found the case fatality rate in China to be 6.4% in patients ages ≥60 years versus 0.32% in patients ages <60 years, and 13.4% in patients ages ≥80 years.[331]

In Italy, the case fatality rate was 8.5% in patients ages 60 to 69 years, 35.5% in patients ages 70 to 79 years, and 52.5% in patients ages ≥80 years.[87] In a case series of 1591 critically ill patients in Lombardy, the majority of patients were older men, a large proportion required mechanical ventilation and high levels of positive end-expiratory pressure, and the mortality rate in the intensive care unit was 26%.[338]

In the US, the case fatality rate was highest among patients ages ≥85 years (10% to 27%), followed by those ages 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 ages ≥65 years accounted for 80% of deaths.[7] 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.[339] The case fatality rate in residents in a long-term care facility in Washington was reported to be 34%.[340]

Children have a better prognosis than adults, and deaths have been extremely rare.[8] Three deaths have been reported in children in the US.[9]

Causes of death

The leading cause of death in patients with COVID-19 is respiratory failure from acute respiratory distress syndrome.[341]

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 hypoxemia, and multi-organ dysfunction were more frequent in deceased patients compared with those who recovered.[342] Other characteristics found to be more frequent in deceased patients include leukocytosis, lymphopenia, and elevated C-reactive protein level, and presence of complications.[343]

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. Nonsurvivors were more likely to develop acute respiratory distress syndrome and require mechanical ventilation. Nonsurvivors were older (>65 years of age) and more likely to have chronic medical illnesses.[344]

Prognostic factors

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.[90]

Thrombocytopenia has been associated with increased risk of severe disease and mortality and may be useful as a clinical indicator for monitoring disease progression.[171]

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 nonsurvivors.[79]

Refractory disease

Refractory disease (patients who do not reach obvious clinical and radiologic remission within 10 days after hospitalization) has been reported in nearly 50% of hospitalized patients in one retrospective single-center 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.[345]

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, although this is yet to be confirmed.[346][347]

Disease reactivation

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 nonreactivated patients. It is unclear whether these were true reinfections, or if the test result was a false-negative at the time of discharge. Further research is required.[348]

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