In December 2019, a series of viral infections, eventually named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in China and quickly spread across the world [1]. The United States (USA) has been profoundly affected, reporting the most confirmed cases of SARS-CoV-2 of any country. As of June 10, 2020, SARS-CoV-2 infection has been confirmed in more than 7.3 million individuals in 188 countries and regions, with an overall mortality rate of more than 5.7% [2]. The State of Michigan has been particularly devastated by this disease; it ranks 9th in the USA with 65,182 total confirmed cases of SARS-CoV-2 and 6th in the USA with 5955 total deaths [2]. While the clinical course of patients with SARS-CoV-2 infection can vary from completely asymptomatic to critically ill, an understanding of differing patient characteristics and outcomes of infected patients is critical for health and government officials engaged in planning efforts to address outbreaks. We sought to describe the demographics, baseline comorbidities, and outcomes in patients with SARS-CoV-2 who required mechanical ventilation from a single hospital system in the state of Michigan, USA.
This retrospective observational study was conducted at St. Joseph Mercy Oakland Hospital, and data were obtained from medical records from the 7 hospitals in the health system (1996 beds). The institutional review board approved the study as minimal-risk research using data collected for routine clinical practice and waived the requirement for informed consent. All consecutive patients from March 10, 2020 to April 15, 2020 who required hospital admission with confirmed SARS-CoV-2 infection by positive result on polymerase chain reaction (PCR) testing of a nasopharyngeal sample were included in this study. The focus of this study was SARS-CoV-2 patients who required mechanical ventilation in the Intensive Care Unit (ICU), and only patients who completed their hospital course within the health system at study end (discharged alive or dead) were included in the study.
During the study period a total of 901 adult patients with confirmed SARS-CoV-2 infection were admitted to the 7 hospitals within the health system. After initial chart review 152 patients requiring mechanical ventilation were included. Of the 152 mechanically ventilated patients with confirmed SARS-CoV-2 infection, 39% (60) survived until discharge and 61% (92) died. The median age of patients was 68 years old (IQR 58–75), and 62.5% (95) were male. Forty-eight percent of patients had three or more comorbidities, the most common being hypertension (73%), hypercholesterolemia (61%), and diabetes mellitus (45%). Increased age, pre-existing hypertension, pre-admission statin use, increased fluid administration, need for continuous renal replacement therapy (CRRT), and use of vasopressor/inotrope were associated with increased mortality. There was a decreased risk of mortality in patients treated with steroids and vitamin C, and in patients with greater urine output (Table 1 ).
Table 1.
Demographics, comorbidities, events, medications pre & after admission to hospital.
| Survivor (n = 60) | Non-survivor (n = 92) | Total (n = 152) | P value | Odds ratio |
|
|---|---|---|---|---|---|
| 95% C.I. | |||||
| Pre-hospital demographics | |||||
| Age (years) | |||||
| Mean ± St. Dev. | 59 ± 13 | 71 ± 10 | 66 ± 13 | 0.0000⁎ | 1.081 |
| Median [IQR] | 61 [50–71] | 72 [64–78] | 68 [58–75] | 0.0000⁎ | 1.047–1.116 |
| Sex | |||||
| Male | 36 (60%) | 59 (64%) | 95 (62.5%) | 0.6101 | |
| Female | 24 (40%) | 33 (36%) | 57 (37.5%) | ||
| Race | |||||
| Black | 33(55%) | 41(%) | 71(47%) | 0.2478 | |
| White | 23(38%) | 51(%) | 70(46%) | ||
| Other | 4(7%) | 8(%) | 11(7%) | ||
| Ethnicity | |||||
| Hispanic | 2 (3%) | 2 (2%) | 4 (3%) | 0.5168 | |
| Non-Hispanic | 58 (97%) | 90 (98%) | 148 (97%) | ||
| BMI (kg/m2) | |||||
| Mean ± StDv | 32 ± 7 | 31 ± 7 | 32 ± 7 | 0.228 | |
| Median [IQR] | 32 [27–36] | 29 [26–34] | 31[26–35] | 0.144 | |
| Pre-admission comorbidities | |||||
| HTN | 37(62%) | 74(84%) | 111(73%) | 0.0108⁎ | 2.556 1.229–5.315 |
| Coronary artery disease (CAD) | 6(10%) | 17(18%) | 23(15%) | 0.1542 | |
| Diabetes | 23(38%) | 43(47%) | 69(65%) | 0.1583 | |
| Hypercholesterolemia | 31(52%) | 61(66%) | 92(61%) | 0.0710 | |
| Asthma | 9(15%) | 16(17%) | 25(16%) | 0.6985 | |
| COPD | 6(10%) | 17(18%) | 23(15%) | 0.1463 | |
| Renal disease | 9(15%) | 13(14%) | 22(14%) | 0.9203 | |
| Cirrhosis | 1(2%) | 0(0%) | 1(1%) | 0.3947 | |
| Smoker | 0.8737 | ||||
| Current (or quit < 6 months) | 2(3%) | 3(3%) | 5(3%) | ||
| Former (quit > 6 months) | 16(27%) | 27(29%) | 43(28%) | ||
| Never | 27(45%) | 37(40%) | 64(42%) | ||
| Unknown | 15(25%) | 25(27%) | 40(26%) | ||
| Pre-admission medications | |||||
| ACE inhibitors | 12(20%) | 23(25%) | 35(23%) | 0.4751 | |
| ARBs | 6(10%) | 17(18%) | 23(15%) | 0.1542 | |
| Statin | 24(40%) | 57(62%) | 81(53%) | 0.0080⁎ | 2.443 1.225–4.756 |
| Oral steroids | 6(10%) | 10(11%) | 16(11%) | 0.8625 | |
| Antithrombotic | 19(32%) | 38(41%) | 57(38%) | 0.2301 | |
| Anticoagulant | 7(12%) | 15(16%) | 22(14%) | 0.4274 | |
| ICU stay information | |||||
| Length of hospital stay (days) | |||||
| Mean ± SEM | 13.1 ± 1.2 | 8.3 ± 0.7 | 10.2 ± 0.7 | 0.0003⁎ | 0.852 |
| Median [IQR] | 11 [8–17] | 7 [4–12] | 8 [4–14] | 0.0000⁎ | 0.804–0.903 |
| Length of ICU stay (days) | |||||
| Mean ± SEM | 21 ± 1.4 | 10.1 ± 0.7 | 14.4 ± 0.8 | 0.0000⁎ | 0.923 |
| Median [IQR] | 19 [14–23] | 9 [5–14] | 13 [7–20] | 0.0002⁎ | 0.882–0.968 |
| Intub. fluid admin. (ml/kg/h) | |||||
| Mean ± SEM | 0.56 ± 0.05 | 0.76 ± 0.05 | 0.68 ± 0.04 | 0.0057⁎ | 3.616 |
| Median [IQR] | 0.47 [0.4–0.7] | 0.64 [0.4–1.0] | 0.57[0.4–0.9] | 0.0043⁎ | 1.394–9.379 |
| Intub. urine output (ml/kg/h) | |||||
| Mean ± SEM | 0.75 ± 0.05 | 0.4 ± 0.03 | 0.54 ± 0.03 | 0.0000⁎ | 0.048 |
| Median [IQR] | 0.76 [0.5–1.0] | 0.34 [0.2–0.6] | 0.49[0.2–0.8] | 0.0000⁎ | 0.014–0.162 |
| ICU stay events | |||||
| Continuous renal replacement therapy (CRRT) | 5(8%) | 20(23%) | 26(17%) | 0.0189⁎ | 3.300 1.170–9.311 |
| Acute drop of hemoglobin | 8(13%) | 16(7%) | 24(16%) | 0.4839 | |
| Cerebral thromboembolism | 1(2%) | 2(2%) | 3(2%) | 1.000 | |
| Pulmonary embolism | 4(7%) | 5(5%) | 9(6%) | 1.000 | |
| Deep vein thrombosis | 6(10%) | 4(4%) | 10(7%) | 0.1922 | |
| Coronary artery thrombosis | 0(0%) | 3(3%) | 3(2%) | 0.2793 | |
| Acute heart failure (EF < 30%) | |||||
| No | 54(90%) | 81(88%) | 135(89%) | 0.6483 | |
| Yes | 3(5%) | 2(2%) | 5(3%) | ||
| N/A | 3(5%) | 9(10%) | 12(8%) | ||
| ICU stay medications | |||||
| Steroids | 46(77%) | 54(59%) | 100(66%) | 0.0225⁎ | 0.432 0.209–0.896 |
| Deep vein therapy (Prophylactic) | 58(97%) | 86(93%) | 144(95%) | 0.2473 | |
| Therapeutic anti-coagulation | 25(42%) | 41(45%) | 66(43%) | 0.7290 | |
| Hydroxychloroquine sulfate | 58(97%) | 86(93%) | 144(95%) | 0.4803 | |
| Azithromycin | 49(82%) | 66(72%) | 115(76%) | 0.1637 | |
| Tocilizumab | 5(8%) | 11(12%) | 16(11%) | 0.4624 | |
| Zinc | 27(45%) | 31(34%) | 58(38%) | 0.1371 | |
| Vitamin C | 39(65%) | 40(43%) | 79(52%) | 0.0066⁎ | 0.394 0.200–0.778 |
| Vitamin D | 8(13%) | 8(9%) | 16(11%) | 0.3428 | |
| Vasopressor/inotrope admin. | 33(55%) | 79(86%) | 112(74%) | <0.0001⁎ | 5.386 2.439–11.90 |
| ICU stay lab results | |||||
| Ferritin at discharge (ng/mL) | |||||
| Mean ± SEM | 663 ± 97 | 1952 ± 455 | 1812 ± 211 | 0.0251⁎ | 1.001 |
| Median [IQR] | 476 [359–881] | 1166[594–1500] | 849[462–1431] | 0.0001 | 1.00–1.002 |
| LDH at discharge (U/L) | |||||
| Mean ± SEM | 301 ± 22 | 947 ± 276 | 705 ± 177 | 0.07622 | 1.008 |
| Median [IQR] | 287 [230–347] | 461 [351–644] | 393[286–538] | 0.0001⁎ | 1.003–1.014 |
Data are Mean ± St. Dev., Median [IQR] or n (%). p values were calculated by t-test, Mann-Whitney U test, χ2 test, or Fisher's exact test, as appropriate. Univariate logistic regression odds ratio and 95% Confidence of intervals (C.I.) are given for the variables with significant difference (P < 0.05). *: indicates significant difference. ACE: angiotensin-converting enzyme. ARB: angiotensin receptor blockers, BMI: body mass index, care unit, COPD: chronic obstructive pulmonary disease, EF: ejection fraction, HTN: hypertension, ICU = intensive care unit, IQR = Inter quartile range, LDH: lactate dehydrogenase.
As this is a previously unknown virus, the mainstay of treatment for hospitalized patients has been isolation and supportive care including supplemental oxygen therapy, fluid resuscitation, administration of antimicrobials for treatment of secondary bacterial infections, and prevention of end-organ dysfunction [3]. Due to the constantly changing hypotheses on best management practices for SARS-CoV-2, treatment protocols vary widely between hospitals and mortality in patients with critical disease characteristics requiring ICU care have been reported to be as high as 78% [1,4,5].
SARS-CoV-2 has placed a tremendous strain on hospitals and hospital resources all over the world; this study can potentially help health officials identify patients who are at higher risk of death, guide planning efforts for management of this disease, as well as direct further prospective study looking at specific therapies in an effort to improve patient outcomes.
Disclosures
No grants, no sponsors, and no funding sources provided direct or indirect financial support to the research work contained in the manuscript. The authors have no conflict of interest to report.
CRediT authorship contribution statement
Sandeep Krishnan:Investigation, Methodology, Data curation, Writing - original draft, Writing - review & editing.Kinjal Patel:Investigation, Writing - original draft, Writing - review & editing.Ronak Desai:Investigation, Writing - original draft, Writing - review & editing.Anupam Sule:Investigation, Writing - original draft, Writing - review & editing.Peter Paik:Investigation, Writing - review & editing.Ashley Miller:Investigation, Writing - review & editing.Alicia Barclay:Investigation, Writing - review & editing.Adam Cassella:Investigation, Writing - review & editing.Jon Lucaj:Investigation, Writing - review & editing.Yvonne Royster:Investigation, Writing - review & editing.Joffer Hakim:Writing - review & editing.Zulfiqar Ahmed:Writing - review & editing.Farhad Ghoddoussi:Investigation, Formal analysis, Data curation, Methodology, Writing - original draft, Writing - review & editing.
References
- 1.Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Johns Hopkins University COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) 2020. https://coronavirus.jhu.edu/map.html
- 3.World Health Organization . World Health Organization; 2020. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: Interim guidance, 28January 2020.https://apps.who.int/iris/handle/10665/330893 [Google Scholar]
- 4.Richardson S., Hirsch J., Narasimhan M., et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052–2059. doi: 10.1001/jama.2020.6775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.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;395(10229):1054–1062. doi: 10.1016/S0140-6736(20)30566-3. [DOI] [PMC free article] [PubMed] [Google Scholar]