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]World Health Organization. Coronavirus disease (COVID-2019) situation reports. 2020 [internet publication].
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/
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]Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-51.
http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
http://www.ncbi.nlm.nih.gov/pubmed/32064853?tool=bestpractice.com
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]Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Mar 30 [Epub ahead of print].
https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30243-7.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32240634?tool=bestpractice.com
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]Wu P, Hao X, Lau EHY, et al. Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveill. 2020 Jan;25(3).
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.3.2000044
http://www.ncbi.nlm.nih.gov/pubmed/31992388?tool=bestpractice.com
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]Centre for Evidence-Based Medicine; Oke J, Heneghan C. Global COVID-19 case fatality rates. 2020 [internet publication].
https://www.cebm.net/global-covid-19-case-fatality-rates/
[334]Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 Mar 23 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2763667
http://www.ncbi.nlm.nih.gov/pubmed/32203977?tool=bestpractice.com
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]Centre for Evidence-Based Medicine; Oke J, Heneghan C. Global COVID-19 case fatality rates. 2020 [internet publication].
https://www.cebm.net/global-covid-19-case-fatality-rates/
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]Rajgor DD, Lee MH, Archuleta S, et al. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. 2020 Mar 27 [Epub ahead of print].
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30244-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32224313?tool=bestpractice.com
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]Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31986264?tool=bestpractice.com
Despite the lower case fatality rate, COVID-19 has so far resulted in more deaths than both SARS and MERS combined.[336]Mahase E. Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate. BMJ. 2020 Feb 18;368:m641.
https://www.bmj.com/content/368/bmj.m641.long
http://www.ncbi.nlm.nih.gov/pubmed/32071063?tool=bestpractice.com
Case fatality rate according to age and presence of comorbidities
The case fatality rate increases with age.[331]Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Mar 30 [Epub ahead of print].
https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30243-7.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32240634?tool=bestpractice.com
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]Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: a nationwide analysis. Eur Respir J. 2020 Mar 26 [Epub ahead of print].
https://erj.ersjournals.com/content/early/2020/03/17/13993003.00547-2020
http://www.ncbi.nlm.nih.gov/pubmed/32217650?tool=bestpractice.com
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]Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 17;41(2):145-51.
http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51
http://www.ncbi.nlm.nih.gov/pubmed/32064853?tool=bestpractice.com
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]Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Mar 30 [Epub ahead of print].
https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30243-7.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32240634?tool=bestpractice.com
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]Sorbello M, El-Boghdadly K, Di Giacinto I, et al. The Italian COVID-19 outbreak: experiences and recommendations from clinical practice. Anaesthesia. 2020 Mar 27 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/full/10.1111/anae.15049
http://www.ncbi.nlm.nih.gov/pubmed/32221973?tool=bestpractice.com
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]Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2764365
http://www.ncbi.nlm.nih.gov/pubmed/32250385?tool=bestpractice.com
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]CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19): United States, February 12 - March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-6.
https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm?s_cid=mm6912e2_w
http://www.ncbi.nlm.nih.gov/pubmed/32214079?tool=bestpractice.com
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]Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020 Mar 19 [Epub ahead of print].
https://jamanetwork.com/journals/jama/fullarticle/2763485
http://www.ncbi.nlm.nih.gov/pubmed/32191259?tool=bestpractice.com
The case fatality rate in residents in a long-term care facility in Washington was reported to be 34%.[340]McMichael TM, Currie DW, Clark S, et al. Epidemiology of Covid-19 in a long-term care facility in King County, Washington. N Engl J Med. 2020 Mar 27 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMoa2005412
http://www.ncbi.nlm.nih.gov/pubmed/32220208?tool=bestpractice.com
Children have a better prognosis than adults, and deaths have been extremely rare.[8]Ludvigsson JF. Systematic review of COVID-19 in children show milder cases and a better prognosis than adults. Acta Paediatr. 2020 Mar 23 [Epub ahead of print].
https://onlinelibrary.wiley.com/doi/pdf/10.1111/apa.15270
http://www.ncbi.nlm.nih.gov/pubmed/32202343?tool=bestpractice.com
Three deaths have been reported in children in the US.[9]CDC COVID-19 Response Team. Coronavirus disease 2019 in children: United States, February 12 – April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 6 [Epub ahead of print].
https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm
Causes of death
The leading cause of death in patients with COVID-19 is respiratory failure from acute respiratory distress syndrome.[341]Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3 [Epub ahead of print].
https://link.springer.com/article/10.1007%2Fs00134-020-05991-x
http://www.ncbi.nlm.nih.gov/pubmed/32125452?tool=bestpractice.com
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]Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091.
https://www.bmj.com/content/368/bmj.m1091.long
http://www.ncbi.nlm.nih.gov/pubmed/32217556?tool=bestpractice.com
Other characteristics found to be more frequent in deceased patients include leukocytosis, lymphopenia, and elevated C-reactive protein level, and presence of complications.[343]Deng Y, Liu W, Liu K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020 Mar 20 [Epub ahead of print].
https://journals.lww.com/cmj/Abstract/publishahead/Clinical_characteristics_of_fatal_and_recovered.99319.aspx
http://www.ncbi.nlm.nih.gov/pubmed/32209890?tool=bestpractice.com
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]Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 Feb 24 [Epub ahead of print].
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30079-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32105632?tool=bestpractice.com
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]Liu W, Tao ZW, Lei W, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J (Engl). 2020 Feb 28 [Epub ahead of print].
https://journals.lww.com/cmj/Abstract/publishahead/Analysis_of_factors_associated_with_disease.99363.aspx
http://www.ncbi.nlm.nih.gov/pubmed/32118640?tool=bestpractice.com
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]Lippi G, Plebani M, Michael Henry B. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020 Mar 13;506:145-8.
https://www.sciencedirect.com/science/article/pii/S0009898120301248?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/32178975?tool=bestpractice.com
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]Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
https://www.thelancet.com/pb-assets/Lancet/pdfs/S014067362305663.pdf
http://www.ncbi.nlm.nih.gov/pubmed/32171076?tool=bestpractice.com
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]Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020 Mar 16 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa270/5805508
http://www.ncbi.nlm.nih.gov/pubmed/32173725?tool=bestpractice.com
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]Chen D, Xu W, Lei Z, et al. Recurrence of positive SARS-CoV-2 RNA in COVID-19: a case report. Int J Infect Dis. 2020 Mar 5 [Epub ahead of print].
https://www.ijidonline.com/article/S1201-9712(20)30122-3/pdf
http://www.ncbi.nlm.nih.gov/pubmed/32147538?tool=bestpractice.com
[347]Xing Y, Mo P, Xiao Y, et al. Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020. Euro Surveill. 2020 Mar;25(10).
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000191
http://www.ncbi.nlm.nih.gov/pubmed/32183934?tool=bestpractice.com
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]Ye G, Pan Z, Pan Y, et al. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect. 2020 Mar 11 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/32171867?tool=bestpractice.com