Article Information

Corresponding author: Paul E. Marik, MD, FCCM, FCCP

Article Type : Research Article

Volume : 2

Issue : 4

Received Date : 16 Jun ,2021


Accepted Date : 24 Jun ,2021

Published Date : 28 Jun ,2021


DOI : https://doi.org/10.38207/jcmphr20210073

Citation: Marik PE, Iglesias J, Varon J, Kory P. COVID-19 in-hospital Mortality: A Concise Worldwide Review. J Comm Med and Pub Health Rep 2(4): https://doi.org/10.38207/jcmphr20210073

Copyright: © © 2021 Paul E. Marik. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite
  COVID-19 in-hospital Mortality: A Concise Worldwide Review

Paul E. Marik, MD, FCCM, FCCP1, *, Jose Iglesias, DO2, Joseph Varon, MD, FCCM, FCCP3, Pierre Kory, MD4

1Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
2Department of Nephrology, Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA
3Department of Critical Care Medicine, United Memorial, Medical Center, Houston, TX, USA
4Front Line Covid-19 Critical Care Alliance

*Corresponding Author: Paul E. Marik, MD, FCCM, FCCP, Professor of Medicine, Chief, Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, 825 Fairfax Ave, Suite 410, Norfolk, VA 23507, USA

Abstract
Background:
The global burden of death due to Coronavirus-19 (COVID-19) is considerable. The average mortality for patients hospitalized with COVID-19 has not been reported. This data is important to serve as a benchmark to compare the outcomes of studies across the globe.

Methods: We performed a scoping review of studies across the globe that reported 28-day/hospital mortality. We include studies that enrolled consecutive, unselective patients with COVID-19 and excluded studies with less than 200 participants. Studies were grouped by geographic location, namely Asia, Europe, the USA, and South America. The primary endpoint was the 28-day/ hospital mortality. Comparison across geographic areas and pairwise analysis between groups were performed employing Kruskal-Wallis one-way analysis of variance.

Results: Fifty-three studies met our inclusion criteria, enrolling a total of 767 761 patients. There were 12 studies from Asia with a median mortality of 13 %, 21 studies from Europe with a median mortality of 23 %, 18 studies from the USA with a median mortality of 20 %, and 2studies from South America with a median mortality of 30.0 %. The overall median hospital mortality of all 53 studies was 21 %. The mortality differed significantly between regions (p < 0.001). Twenty-four studies reported the percentage of patients remaining in the hospital after 28 days; this averaged 18.5 ± 17.3 percent. The median age was 64 years (IQR 61, 67), with age differing significantly between regions (p < 0.001). There was a good correlation between the mean age of the subjects in each study and the hospital mortality (correlation coefficient 0.575, p=0.000).  Overall, 57 % of patients were male and 21 % of patients were admitted to the ICU.

Conclusion: The median hospital mortality was 21% and this varied significantly across geographic regions. Due to the large percentage of patients still hospitalized at day 28, the real hospital mortality from COVID-19 is likely much higher, reflecting the high death toll of this disease. Coronavirus-19 disease (COVID-19) emerged from China toward the end of 2019 spreading rapidly to reach every nation across the globe. Approximately 20% of patients infected with SARS-CoV-2 require hospitalization with the disease-carrying a high hospital mortality. [1,2] The average mortality burden of hospitalized patients with COVID-19 has not been reported, nor has the variation across geographic areas been studied. This data is important in order to benchmark the outcomes of studies evaluating the hospital mortality of patients with COVID-19 as well as to understand geographic variations in reported hospital mortality.

Keywords: COVID-19; in-hospital mortality, review, age, world.

Introduction
Coronavirus-19 disease (COVID-19) emerged from China toward the end of 2019 spreading rapidly to reach every nation across the globe. Approximately 20 % of patients infected with SARS-CoV-2 require hospitalization with the disease carrying a high hospital mortality. [1,2]

The average mortality burden of hospitalized patients with COVID-19 has not been reported, nor has the variation across geographic areas been studied. This data is important in order to benchmark the outcomes of studies evaluating the hospital mortality of patients with COVID-19 as well as to understand geographic variations in reported hospital mortality.

Methods
We performed a comprehensive search of PubMed, Scopus, and Google Scholar for studies published between December 1, 2019, and December 1, 2020, reported in-hospital mortality for patients admitted to hospital with coronavirus-19 (COVID-19) disease. The following keywords were used for the search: ‘‘Coronavirus 2019’’, ‘‘COVID-19’’, ‘‘SARSCoV2’’, “hospital mortality”, “in-hospital mortality”, ‘‘mortality’’ and ‘‘all-cause mortality’’. We included only those studies that enrolled consecutive, non-selective patients admitted to the hospital with COVID-19 that reported 28-day or hospital mortality. We excluded studies that enrolled less than 200 patients and those limited to critically ill patients or any other specific demographic group. The studies were screened to avoid an overlap in patient populations. The following variables were recorded for each study; first author, country, sample size, number of hospitals providing data, date of the first day of enrollment, date of last day of enrollment, mean age, percentage of male patients, percentage of patients admitted to ICU, 28-day/hospital mortality, and percentage of patients still hospitalized at day 28. The countries were grouped as
follows: Asia (including India and Iran), Europe, United States of America (USA) and South America.
The primary goal of the study was to compare the 28-day mortality across the four geographic areas; we calculated the median (IQR) 28-day/hospital mortality for each geographic group and for all studies combined. Further, we explored the differences among geographic groups in age, sex, percent of patients in the ICU, percent patients requiring mechanical ventilation (MV), percent of patients in the ICU, percent mortality on MV, percent ICU mortality, and percent of patients remaining in the hospital after 28 days. As most of the variables were not normally distributed, they are reported as the median and inter-quartile range (IQR). Comparison across geographic areas and pairwise analysis between groups were performed employing Kruskal-Wallis one-way analysis of variance. Pearson’s Bivariate analysis was employed to ascertain the possible relationship between 28-day mortality and age, male sex, percent of patients in the ICU, percent patients requiring mechanical ventilation (MV). Statistical analysis was performed using NCSS 2021 (Kaysville, Utah).

Results
After screening 1087 published reports, 53 studies from 11 countries met our inclusion criteria. [3-55] [3-52] [53-55] The studies listed by date of enrollment are provided in Table 1. Overall, 676 761 patients were enrolled in these studies. A large national database from Brazil contributed 38 % of patients (254 288 patients).[17] The hospital mortality and characteristics of the studies grouped by geographic region are provided in Table 2. While the hospital mortality varied from 3.1 % (China) to 43 % (Italy), the median mortality was 13 % for Asia, 23 % for Europe, 20 % for the USA, and 30 % for South America. The overall median hospital mortality of all 53 studies were 21 %. Twenty-four studies reported the percentage of patients remaining in the hospital after 28 days; this averaged 18 %. The median age was 64 years (IQR 61, 67). Overall, 57 % of patients were male and 21 % of patients were admitted to the ICU. There was a statistically significant difference across geographic groups in 28-day mortality, median age, gender, percentage of patients in the ICU, and percentage of patients receiving mechanical ventilation (Table 2). Pairwise analysis of geographic areas demonstrated significant differences in 28-day mortality differing between USA-Europe, USA-Asia, Europe-Asia, and Asia-South America (Table 2). Similarly, the pairwise analysis demonstrated significant differences in age between USA-Europe, USA-Asia, Europe-Asia, and Europe-South America. The utilization of ICU resources and the use of mechanical ventilation differed among geographic areas. Particularly striking is the difference in the use of MV between the USA and Asia. There was a good correlation between the mean age of the subjects in each study and the hospital mortality (correlation coefficient 0.575, p = 0.000; see Figure 1). The percentage of males in each study correlated poorly with hospital mortality (r = 0.25, p = 0.06).

Table 1. The studies listed by date of enrollment are:

Author

Country

n

n-hospitals

Date started

Duration Days

Age (yrs.)

Male (%)

ICU (%) Mortality (%)

Guan [3]

China

1 590

575

12/11/2019

51

48.0

57.2

6.2

3.1

Wu [4]

China

201

1

12/25/2019

32

51.0

63

26.4

21.9

Zhang [5]

China

663

1

1/1/2020

36

55.0

48.0

-

3.8

Liu [6]

China

245

1

1/1/2020

59

53.9

46.5

-

13.8

Liu [7]

China

383

1

1/2/2020

59

46.0

42.3

-

12.9

Luo [8]

China

1 018

2

1/9/2020

82

61.0

51.2

17.0

19.7

Shi [9]

China

416

1

1/20/2020

21

64.0

49.3

-

13.7

Li [10]

China

548

1

1/26/2020

10

60.0

31.0

-

16.5

Cheng [11]

China

701

4

1/28/2020

14

63.0

52.0

10.4

16.1

Sbidian [12]

France

4 642

39

2/1/2020

65

66.1

59.0

2.6

22.5

Knight [13]

UK

35 463

260

2/6/2020

104

73.0

58.3

-

32.2

Docherty [14]

UK

20 133

208

2/6/2020

73

73.0

59.9

17.0

26.0

Lodigiani [15]

Italy

388

1

2/13/2020

57

66.0

68.0

16.0

26.0

Fried [16]

USA

11 721

208

2/15/2020

65

63.8

53.0

20.0

21.4

Ranzani [17]

Brazil

254 288

-

2/16/2020

181

60.0

56.0

39.0

38.0

Nikpouraghdam [18]

Iran

2 968

1

2/19/2020

56

55.0

66.0

-

8.0

Castelnuovo [19]

Italy

3 894

30

2/19/2020

94

67.0

61.7

-

18.2

Yehia [20]

USA

7 139

92

2/19/2020

102

68.0

51.3

40.0

20.3

Jalili [21]

Iran

28 981

1034

2/20/2020

60

57.3

56.0

-

24.4

Fumagalli [22]

Italy

516

2

2/22/2020

48

67.0

66.9

-

23.2

Ciceri [23]

Italy

950

1

2/25/2020

78

65.0

68.0

14.0

17.0

Vena [24]

Italy

317

1

2/25/2020

29

71.0

67.0

20.5

43.0

Karagiannidis [25]

Germany

10 021

920

2/26/2020

53

68.3

51.9

-

22.2

Navaratnam [26]

UK

91 541

500

3/1/2020

91

-

55.3

-

30.8

Byttebier [27]

Belgium

959

4

3/1/2020

152

69.2

54.5

-

15.6

Ahschul [28]

USA

2 355

10

3/1/2020

46

65.3

46.7

-

26.4

Bahl [29]

USA

1 461

8

3/1/2020

30

62.0

53.0

-

22.3

Redd [30]

USA

202

9

3/1/2020

32

63.0

55.0

17.5

15.8

Richardson [31]

USA

5 700

12

3/1/2020

31

63.0

60.3

14.2

21.0

Myers [32]

USA

377

21

3/1/2020

30

61.0

56.0

29.9

15.6

Petrilli [33]

USA

1999

4

3/1/2020

32

62.0

62.0

32.5

14.1

Kim [34]

USA

2491

154

3/1/2020

62

62.0

53.0

32.0

17.0

Nadkarni [35]

USA

4389

9

3/1/2020

60

65.0

56.0

-

24.0

Piroth [36]

France

89 530

-

3/1/2020

60

65.0

53.0

16.3

16.9

Marcolino [37]

Brazil

2054

25

3/1/2020

202

59.0

52.6

41.4

22.0

Ayerbe [38]

Spain

2075

17

3/1/2020

50

67.5

60.0

-

14.5

Goyal [39]

USA

393

2

3/3/2020

28

62.0

60.6

-

10.2

Garibaldi [40]

USA

832

5

3/4/2020

51

63.0

53.0

-

16.0

Berenguer [41]

Spain

4035

127

3/6/2020

11

70.0

61.0

18.5

28.0

Santus [42]

Italy

412

3

3/7/2020

61

66.0

68.0

-

25.5

Palaiodimos [43]

USA

200

-

3/9/2020

13

64.0

49.0

16.0

24.0

Guisado-Vasco [44]

Spain

607

1

3/10/2020

36

69.0

65.0

8.7

23.2

Arshad [45]

USA

2541

6

3/10/2020

53

64.0

51.0

24.2

18.1

Goodall [46]

UK

981

1

3/12/2020

34

69.0

64.0

-

36.0

Mikami [47]

USA

3708

8

3/13/2020

35

66.0

57.0

-

21.7

Catteau [48]

Belgium

8910

109

3/14/2020

48

71.0

54.5

 

21.6

Rosenberg [49]

USA

1438

25

3/15/2020

40

63.0

59.7

22.8

20.3

Chopra [50]

USA

1648

39

3/16/2020

107

62.0

51.8

13.2

24.2

Horby [51]

UK

6425

176

3/19/2020

81

66.0

64.0

-

24.6

Vizcaychipi [52]

UK

923

2

3/20/2020

33

67.0

61.7

15.0

32.0

Sasas-Rojo [53]

Spain

15 111

150

3/24/2020

98

69.4

57.2

8.3

21.0

Budhiraja [54]

India

976

5

4/1/2020

60

47.5

67.1

29.0

10.5

Rosenthal [55]

USA

35302

592

4/1/2020

60

63.3

53.4

19.4

20.3

Table 2: Entire Cohort of studies : mortality and characteristics of hospitalized patients §

 

 

USA (n=87660)

Europe(n=294069)

Asia(n=38690)

South America

p

 

 

 

 

 

 

 

 

 

 

 

 

(Brazil) (n=256,312)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Age

63

(62,64) [18]

67

(66, 69) [21]

54

(48, 61) [12]

59

(44. 45) [2]

0.00001 ¶

 

% Male

51

(53, 58) [18]

61

(56,65) [21]

48

(58, 51) [12]

54

(39, 53) [2]

0.001

 

 

ICU (%)

20

(16, 32) [12]

16

(14,20) [10]

17

(8,28) [5]

40

(29, 31) [2]

0.043

 

MV (%)

18

(12, 22)

[15]

15

(10, 17)

[11]

8 (3,13) [7]

27

(17, 24) [2]

0.023

 

Hospital 28-day

20

(16, 23)

[18]

23

(20, 29)

[21]

13

(9, 17) [12]

30

(16, 29) [2]

0.00001 ¶

 

mortality (%)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ventilator Mortality

46

(36, 71)

[8]

40

(35, 59)

[5]

*

 

80

[1]

0.46

 

 

 

(MV) (%)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ICU Mortality (%)

64

(37, 68)

[2]

29

(20, 34)

[2]

*

 

53

(35, 44) [2]

0.19

 

 

 

% Patients

12

(6, 33) [8]

13

(9, 20) [12]

19

(6, 76) [3]

24

(9,38) [2]

0.22

 

 

 

remaining in

 

 

 

 

 

 

 

 

 

 

 

 

 

 

hospital

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Number of studies

18

 

 

21

 

 

12

 

2

 

 

 

 

  • Median (IQR) [number of studies reported] * No data reported

¶ Pairwise differences between groups (p= less than 0.05)

Age: USA-Europe, Europe-Asia, USA-Asia, Europe-South American.

Gender: Europe-Asia; USA-Europe.

  • In ICU: Europe-South America, Asia-South America.
  • on MV: USA-Asia, Europe- South America, Asia- South America.

28-day mortality: USA-Europe, USA-Asia, Europe-Asia, Asia-South America

Figure 1. Plot of Age versus Hospital mortality

 Discussion
The median in-hospital/28-day mortality for COVID-19 averaged 21 % across the globe. This mortality statistic is useful to compare studies that evaluate the outcomes of patients hospitalized with COVID-19. Due to the high percentage of patients remaining in hospital at day 28, the true hospital mortality is likely much higher and closer to 30%. Furthermore, we noted a marked variation in mortality between geographic regions across the globe. Strikingly, the average mortality was low in China (13 %) while it was high in South America-Brazil (30 %). The low mortality reported in the Chinese studies is likely related to the low median age of the patients (54 years; IQR 48-61) as well as hospital admission criteria (and hospital resources) which likely differed from other parts of the world. As has been demonstrated in previous studies, age is a major determinant of outcome in patients hospitalized with COVID-19. [56-58] Although the incidence of comorbidities increases with aging, this alone does not completely explain the effect of age on mortality. A large meta-analysis that evaluated comorbidities and disease severity across geographic areas demonstrated that the proportion of the three major comorbidities diabetes mellitus, hypertension, and cardiovascular disease was highest in the USA compared to Europe and Asia, with Asia demonstrating the lowest proportional burden of comorbidities.[59] Despite this Asia was noted to have a higher degree of severity of illness when compared with the burden of comorbidities. [59,60] One of the potential mechanisms to explain the increased mortality with aging is phenomenon is immunosenescence, whereby a failure to mount an effective adaptive immune response leads to the dysregulated release of cytokines. In addition, inflammation, a chronic low-grade inflammation that develops with advanced age may contribute to immune dysregulation and poorer outcome in elderly patients.[58] In the current study, it is noteworthy that the use of MV differed significantly between the USA and Asia. Multiple potential factors may account for this observation including the effect of age, more liberal admission criteria with lower severity of illness, and different approaches to the management of COVID-19 patients. The mortality of 38 % reported in the large national Brazilian study is noteworthy.[17] This is likely due to the large disease burden in this lower-middle-income country with regional disparities in the provision and accessibility of health care.

Conclusions
The median hospital mortality for COVID-19 averaged 21 %, however, this statistic varied widely by geographic area, being lowest in Asia and highest in South America. Furthermore, while patient’s age and comorbidities as well as admission criteria influence hospital mortality, the accessibility of health care and availability of medical resources likely have a major impact on patient outcomes.

Declarations

Ethics approval: Not relevant

Availability of data: Available on request

Competing interests: None of the authors has any competing interests in the manuscript.

Funding: This study was unfunded.

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