To the Editor: The coronavirus disease 2019 (COVID-19) pandemic has resulted in 38 394 169 cases and 1 089 047 deaths worldwide as of 15 October 2020, although to date, Australia has been relatively spared, with only 11 441 cases and 118 deaths.1 Globally, health care systems and intensive care units (ICUs) have been under immense pressure and wide regional variation in mortality has been observed, both between2, 3, 4, 5 and within countries.6 It has been suggested that a higher ICU case volume of COVID-19 may be associated with increased mortality, although this has not yet been systematically investigated. Intuitively, a negative volume–outcome association is plausible under pandemic conditions, as a stretched system running above maximal capacity may not be able to deliver its usual standard of care.
The SPRINT-SARI (Short Period Incidence Study of Severe Acute Respiratory Infection) Australia study aims to provide near real-time observational data on patients with COVID-19 admitted to participating ICUs. Herein, we report results of an interim analysis of the SPRINT-SARI database to determine whether a COVID-19 case volume–outcome association exists locally at participating sites.
Data pertaining to confirmed COVID-19 ICU admissions in the SPRINT-SARI database between 27 February and 30 June 2020 were extracted. The primary exposure variable was case volume. Sites were dichotomised into a low-volume group (LVG) and high-volume group (HVG) based on the median number of COVID-19 admissions to each institution. The primary outcome was hospital mortality. Patients still in hospital were excluded from the mortality analysis. Mixed effects logistic regression was performed using age, Acute Physiological and Chronic Health Evaluation (APACHE) II score, and receipt of mechanical ventilation as fixed effects and site as a random effect, with patients nested within sites. Odds ratio (OR) of death with 95% confidence interval (CI) and P values are reported.
We performed sensitivity analyses, defining low and high case volume on the basis of the median ICU-bed hours and an arbitrary cut-off of ten or more confirmed COVID-19 cases, and modelling volume as a continuous variable (separate models for number of cases and ICU-bed hours as the marker of volume). Moreover, all analyses were repeated with only patients who received mechanical ventilation.
There were 232 confirmed COVID-19 admissions in 47 ICUs, and of these, 196 (84%) were discharged from hospital. There were 102 (44%) admissions in the LVG (median site volume, 4; interquartile range [IQR], 2–5) and 130 (56%) in the HVG (median, 12; IQR, 10–37). Demographic characteristics and outcomes are described in Table 1. The mechanical ventilation rate was 61% in the LVG and 52% in the HVG. Crude mortality was 17/102 (17%) and 14/130 (11%) in the LVG and HVG respectively. After adjustment for age, APACHE II score and mechanical ventilation, there was no statistically significant difference in mortality in the HVG compared with LVG (OR, 0.96; 95% CI, 0.35–2.63; P = 0.93).
Table 1.
Patient characteristics and outcomes for confirmed coronavirus disease 2019 (COVID-19) intensive care unit (ICU) admissions
| Low-volume group | High-volume group | |
|---|---|---|
| Total number of patients | 102 | 130 |
| Demographic characteristics | ||
| Age (years), median (IQR) | 68 (57–72) | 62 (49–72) |
| Sex, female | 32 (31%) | 42 (33%) |
| Body mass index (kg/m2), median (IQR) | 30 (25–32) | 29 (24–32) |
| Smoking history | 18 (18%) | 17 (13%) |
| Comorbidities | ||
| Obesity | 23 (23%) | 32 (25%) |
| Diabetes | 26 (25%) | 38 (29%) |
| Asthma | 12 (12%) | 12 (9%) |
| ACEI/A2RB | 23 (23%) | 27 (21%) |
| Chronic cardiovascular disease | 24 (24%) | 17 (13%) |
| Day 1 APACHE II score, median (IQR) | 16 (12–19) | 13 (8–17) |
| Outcomes | ||
| Mortality | 17 (17%) | 14 (11%) |
| Still in ICU | 14 (14%) | 22 (17%) |
A2RB = angiotensin II receptor blocker; ACEI = angiotensin-converting enzyme inhibitor; APACHE = Acute Physiological and Chronic Health Evaluation; IQR = interquartile range.
All the sensitivity analyses (Table 2) also demonstrated that there were no significant differences in mortality based on case volume, regardless of whether all patients or only mechanically ventilated patients were analysed.
Table 2.
Adjusted hospital mortality and sensitivity analyses for confirmed coronavirus disease 2019 (COVID-19) admissions with completed outcome
| Low-volume group | High-volume group | Adjusted OR (95% CI) | P | |
|---|---|---|---|---|
| Primary outcome* | ||||
| Median split by site volume | 17/102 (17%) | 14/130 (11%) | 0.96 (0.35–2.63) | 0.93 |
| Sensitivity analyses* | ||||
| Median split by ICU-bed hours | 20/128 (16%) | 11/104 (11%) | 0.9 (0.32–2.54) | 0.85 |
| High-volume arbitrarily set to > 10 COVID-19 admissions | 22/134 (16%) | 9/98 (9%) | 1.41 (0.47–4.27) | 0.54 |
| Site volume as a continuous variable | na | na | 1.04 (0.98–1.1) | 0.17 |
| Site ICU-bed hours as a continuous variable (per 100 hours) | na | na | 1.02 (0.99–1.04) | 0.27 |
| With sample limited to mechanical ventilation patients only† | ||||
| Median split by site volume | 14/62 (23%) | 12/68 (18%) | 0.91 (0.29–2.82) | 0.87 |
| Median split by ICU-bed hours | 17/79 (22%) | 9/51 (18%) | 0.81 (0.25–2.62) | 0.73 |
| High-volume arbitrarily set to > 10 COVID-19 admissions | 19/90 (21%) | 7/40 (18%) | 1.3 (0.36–4.69) | 0.69 |
| Site volume as a continuous variable | na | na | 1.04 (0.95–1.13) | 0.43 |
| Site ICU-bed hours as a continuous variable (per 100 hours) | na | na | 1.01 (0.97–1.05) | 0.6 |
ICU =intensive care unit; na = not applicable; OR = odds ratio.
n = 196.
n = 130.
While the SPRINT-SARI database offers comprehensive data on critically ill patients with COVID-19 in Australia, there are some important limitations to acknowledge. The overall case numbers were small, limiting the number of covariates that could reasonably be adjusted for. The number of confirmed COVID-19 admissions at each individual site was very small. We also did not have data pertaining to overall ICU capacity at individual sites.
There are currently insufficient data to determine whether there is a case volume–outcome association for COVID-19 mortality in Australian ICUs. As the COVID-19 pandemic is still unfolding, such relationships may emerge, highlighting the necessity of ongoing monitoring via platforms such as SPRINT-SARI.
Competing interests
None declared.
Acknowledgements
SPRINT-SARI Australia Management Committee: Aidan Burrell, Allen Cheng, Andrew Udy, Annamaria Palermo, Benjamin Reddi, Claire Reynolds, Craig French, D James Cooper, Edward Litton, Husna Begum, Lewis Campbell, Mahesh Ramanan, Mark Plummer, Richard McAllister, Simon Erickson, Tessa Broadley, Tony Trapani and Winston Cheung.
SPRINT-SARI Australia Investigators: Adam Visser, Adrian Mattke, Adrian Regli, Alan Rashid, Alexis Tabah, Alison Walker, Allen Cheng, Amanda Corley, Andrew Udy, Anil Ramnani, Anthony Eidan, Bart DeKeulenaer, Benjamin Reddi, Brent Richards, Cameron Knott, Cara Moore, Carmel Delzoppo, Catherine Boschert, Catherine Tacon, Craig French, Danielle Austin, David Brewster, David Cooper, David Crosbie, David Hawkins, Edda Jessen, Eduardo Martinez, Edward Fysh, Edward Litton, Felix Oberender, Forbes McGain, Gavin Salt, Glenn Eastwood, Gopal Taori, Hayden White, Hergen Buscher, Ian Seppelt, Isabel Anne Leditschke, Janelle Young, Jayshree Lavana, Jeremy Cohen, Jessica Lugsdin, John Botha, John Santamaria, Jonathan Barrett, Kasha Singh, Kevin Laupland, Khaled El-Khawas, Kristine Estensen, Kush Deshpande, Kyle White, Leigh Fitzpatrick, Lewis Campbell, Mahesh Ramanan, Manoj Saxena, Marion Kainer, Mark Kol, Mark Page, Mark Plummer, Martin Sterba, Matthew Anstey, Matthew Brain, Matthew Maiden, Myrene Kilminster, Naomi Hammond, Neeraj Bhadange, Nicole Humphreys, Paras Jain, Paul Azzi, Paul Secombe, Paula Lister, Peter Chan, Peter McCanny, Phillip Britton, Pierre Janin, Ravi Krishnamurthy, Ravikiran Sonawane, Ravindranath Tiruvoipati, Richard Totaro, Rinaldo Bellomo, Ritesh Sanghavi, Samantha Bates, Sandra Peake, Shailesh Bihari, Shane George, Simon Erickson, Steve Webb, Subhash Arora, Subodh Ganu, Thomas Rozen, Toni McKenna, Umesh Kadam, Vineet Nayyar, Wei Han Choy and Wisam Albassam.
SPRINT-SARI Australia participating sites: Albury Wodonga Health, Alice Springs Hospital, Angliss Hospital, Austin Hospital, Ballarat Base Hospital, Bankstown-Lidcombe Hospital, Barwon Health, Bendigo Hospital, Box Hill Hospital, Bunbury Hospital, Bundaberg Hospital, Caboolture Hospital, Cabrini Hospital Malvern, Cairns Hospital, Calvary Mater Newcastle, Campbelltown Hospital, Canberra Hospital, Concord Hospital, Dandenong Hospital, Epworth Richmond, Fiona Stanley Hospital, Flinders Medical Centre, Footscray Hospital, Frankston Hospital, Gold Coast University Hospital, Hervey Bay Hospital, Ipswich Hospital, John Hunter Hospital, Joondalup Health Campus, Launceston General Hospital, Lismore Base Hospital, Liverpool Hospital, Logan Hospital, Lyell McEwan Hospital, Maroondah Hospital, Mater Hospital Brisbane, Mildura Base Hospital, Monash Children’s Hospital, Monash Medical Centre, Nepean Hospital, Northeast Health Wangaratta, Northern Hospital, Perth Children’s Hospital, Port Macquarie Base Hospital, Prince of Wales Hospital, Princess Alexandra Hospital, Queensland Children’s Hospital, Redcliffe Hospital, Rockingham Hospital, Royal Adelaide Hospital, Royal Brisbane and Women’s Hospital, Royal Children’s Hospital, Royal Darwin Hospital, Royal Hobart Hospital, Royal Melbourne Hospital, Royal North Shore Hospital, Royal Perth Hospital, Royal Prince Alfred Hospital, Sir Charles Gairdner Hospital, St George Hospital, St John of God Hospital Midland, St John of God Hospital Murdoch, St Vincent’s Hospital Melbourne, St. Vincent’s Hospital Sydney, Sunshine Coast University Hospital, Sunshine Hospital, Sydney Children’s Hospital Randwick, The Alfred Hospital, The Children’s Hospital at Westmead, The Prince Charles Hospital, The Queen Elizabeth Hospital, Toowoomba Hospital, Warrnambool Base Hospital, Werribee Mercy Hospital, Westmead Hospital, Wollongong Hospital and Women’s and Children’s Hospital Adelaide.
References
- 1.World Health Organization. Coronavirus disease (COVID-19) dashboard. https://covid19.who.int (viewed 15 Oct 2020)
- 2.Bhatraju P.K., Ghassemieh B.J., Nichols M., et al. COVID-19 in critically ill patients in the Seattle Region — case series. N Eng J Med. 2020;382:2012–2022. doi: 10.1056/NEJMoa2004500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.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;323:1574–1581. doi: 10.1001/jama.2020.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.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-center, retrospective, observational study. Lancet Respir Med. 2020;8:475–481. doi: 10.1016/S2213-2600(20)30079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Docherty A.B., Harrison E.M., Green C.A., et al. Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: Prospective observational cohort study. BMJ. 2020;369:1–12. doi: 10.1136/bmj.m1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Qian Z., Alaa A.M., van der Schaar M., et al. Between-centre differences for COVID-19 ICU mortality from early data in England. Intensive Care Med. 2020;46:1779–1780. doi: 10.1007/s00134-020-06150-y. [DOI] [PMC free article] [PubMed] [Google Scholar]