Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study

Terry Lee, Matthew P Cheng, Donald C Vinh, Todd C Lee, Karen C Tran, Brent W Winston, David Sweet, John H Boyd, Keith R Walley, Greg Haljan, Allison McGeer, François Lamontagne, Robert Fowler, David Maslove, Joel Singer, David M Patrick, John C Marshall, Kevin D Burns, Srinivas Murthy, Puneet K Mann, Geraldine Hernandez, Kathryn Donohoe, Genevieve Rocheleau, James A Russell, ARBs CORONA I study investigators, Terry Lee, Matthew P Cheng, Donald C Vinh, Todd C Lee, Karen C Tran, Brent W Winston, David Sweet, John H Boyd, Keith R Walley, Greg Haljan, Allison McGeer, François Lamontagne, Robert Fowler, David Maslove, Joel Singer, David M Patrick, John C Marshall, Kevin D Burns, Srinivas Murthy, Puneet K Mann, Geraldine Hernandez, Kathryn Donohoe, Genevieve Rocheleau, James A Russell, ARBs CORONA I study investigators

Abstract

Background: There have been multiple waves in the COVID-19 pandemic in many countries. We sought to compare mortality and respiratory, cardiovascular and renal dysfunction between waves in 3 Canadian provinces.

Methods: We conducted a substudy of the ARBs CORONA I study, a multicentre Canadian pragmatic observational cohort study that examined the association of pre-existing use of angiotensin receptor blockers with outcomes in adults admitted to hospital with acute COVID-19 up to April 2021 from 9 community and teaching hospitals in 3 Canadian provinces (British Columbia, Ontario and Quebec). We excluded emergency department admissions without hospital admission, readmissions and admissions for another reason. We used logistic and 0-1-inflated β regression models to compare 28-day and in-hospital mortality, and the use of invasive mechanical ventilation, vasopressors and renal replacement therapy (RRT) between the first 3 waves of the COVID-19 pandemic in these provinces.

Results: A total of 520, 572 and 245 patients in waves 1, 2 and 3, respectively, were included. Patients in wave 3 were on average younger and had fewer comorbidities than those in waves 1 and 2. The unadjusted 28-day mortality rate was significantly lower in wave 3 (7.8%) than in wave 1 (18.3%) (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.24-0.78) and wave 2 (16.3%) (OR 0.46, 95% CI 0.27-0.79). After adjustment for differences in baseline characteristics, the difference in 28-day mortality remained significant (adjusted OR wave 3 v. wave 1: 0.46, 95% CI 0.26-0.81; wave 3 v. wave 2: 0.52, 95% CI 0.29-0.91). In-hospital mortality findings were similar. Use of invasive mechanical ventilation or vasopressors was less common in waves 2 and 3 than in wave 1, and use of RRT was less common in wave 3 than in wave 1.

Interpretation: Severity of illness decreased (lower mortality and less use of organ support) across waves among patients admitted to hospital with acute COVID-19, possibly owing to changes in patient demographic characteristics and management, such as increased use of dexamethasone. Continued application of proven therapies may further improve outcomes.

Study registration: ClinicalTrials.gov, no. NCT04510623.

Conflict of interest statement

Competing interests: James Russell reports an investigator-initiated grant from Grifols that was provided to and administered by the University of British Columbia (UBC). He reports patents owned by UBC that are related to the use of PCSK9 inhibitor(s) in sepsis and the use of vasopressin in septic shock, and a patent owned by Ferring Pharmaceuticals for use of selepressin in septic shock. He is an inventor on these patents. He was a founder, director and shareholder in Cyon Therapeutics and is a shareholder in Molecular You. He reports consulting fees from SIB Therapeutics (developing a sepsis drug) and Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). He is no longer actively consulting for any industry. He was a nonfunded science advisor and member of the Government of Canada COVID-19 Therapeutics Task Force (June 2020–December 2021) and a nonfunded member of the data and safety monitoring board of a trial of plasma in COVID-19 (PassITON) (2020–2021) sponsored by the National Institutes of Health. No other competing interests were declared.

© 2022 CMA Impact Inc. or its licensors.

Figures

Figure 1:
Figure 1:
Flow diagram showing patient selection. Note: ED = emergency department, ICU = intensive care unit.
Figure 2:
Figure 2:
Number of patients with acute COVID-19 enrolled in each wave, by province.
Figure 3:
Figure 3:
Comorbidities of patients in waves 1, 2 and 3. p value based on χ2 test or Fisher exact test, as appropriate.
Figure 4:
Figure 4:
COVID-19 therapies administered during the hospital stay. p value based on χ2 test or Fisher exact test, as appropriate.
Figure 5:
Figure 5:
Comparison of outcomes between waves by regression analysis. The following factors were accounted for in the adjusted analysis: age, sex, chronic heart disease, hypertension, chronic kidney disease, diabetes, baseline systolic blood pressure, baseline heart rate, baseline oxygen saturation level, baseline creatinine level and site. *Adjusted regression analysis was not feasible numerically as too few patients received renal replacement therapy during the first 14 days. Note: CI = confidence interval, DAF = days alive and free, OR = odds ratio.

References

    1. Smart K. Tough choices needed to slow new wave of COVID-19 [news release] Ottawa: Canadian Medical Association; 2021. Dec 17, [accessed 2021 Dec. 21]. Available: .
    1. Soriano V, de Mendoza C, Gómez-Gallego F, et al. Third wave of COVID-19 in Madrid, Spain. Int J Infect Dis. 2021;107:212–4.
    1. Fan G, Yang Z, Lin Q, et al. Decreased case fatality rate of COVID-19 in the second wave: a study in 53 countries or regions. Transbound Emerg Dis. 2021;68:213–5.
    1. Domingo P, Pomar V, Mur I, et al. Not all COVID-19 pandemic waves are alike. Clin Microbiol Infect. 2021;27:1040.e7–10.
    1. Ioannidis JPA, Axfors C, Contopoulos-Ioannidis DG. Second versus first wave of COVID-19 deaths: shifts in age distribution and in nursing home fatalities. Environ Res. 2021;195:110856.
    1. Radovanovic D, Santus P, Coppola S, et al. Characteristics, outcomes and global trends of respiratory support in patients hospitalized with COVID-19 pneumonia: a scoping review. Minerva Anestesiol. 2021;87:915–26.
    1. Iftimie S, Lopez-Azcona AF, Vallverdu I, et al. First and second waves of coronavirus disease-19: a comparative study in hospitalized patients in Reus, Spain. PLoS One. 2021;16:e0248029.
    1. Salyer SJ, Maeda J, Sembuche S, et al. The first and second waves of the COVID-19 pandemic in Africa: a cross-sectional study. Lancet. 2021;397:1265–75.
    1. Seong H, Hyun HJ, Yun JG, et al. Comparison of the second and third waves of the COVID-19 pandemic in South Korea: importance of early public health intervention. Int J Infect Dis. 2021;104:742–5.
    1. Kawasuji H, Takegoshi Y, Kaneda M, et al. Transmissibility of COVID-19 depends on the viral load around onset in adult and symptomatic patients. PLoS One. 2020;15:e0243597.
    1. Avadhanula V, Nicholson EG, Ferlic-Stark L, et al. Viral load of severe acute respiratory syndrome coronavirus 2 in adults during the first and second wave of coronavirus disease 2019 pandemic in Houston, Texas: the potential of the superspreader. J Infect Dis. 2021;223:1528–37.
    1. Somerville M, Curran JA, Dol J, et al. Public health implications of SARS-CoV-2 variants of concern: a rapid scoping review. BMJ Open. 2021;11:e055781.
    1. Garcia-Beltran WF, Lam EC, Astudillo MG, et al. COVID-19-neutralizing antibodies predict disease severity and survival. Cell. 2021;184:476–88e11.
    1. Pairo-Castineira E, Clohisey S, Klaric L, et al. Genetic mechanisms of critical illness in COVID-19. Nature. 2021;591:92–8.
    1. Goldberg Y, Mandel M, Bar-On YM, et al. Waning immunity after the BNT162b2 vaccine in Israel. N Engl J Med. 2021;385:e85.
    1. Mishra S, Wang L, Ma H, et al. Estimated surge in hospital and intensive care admission because of the coronavirus disease 2019 pandemic in the Greater Toronto Area, Canada: a mathematical modelling study. CMAJ Open. 2020;8:E593–604.
    1. Palamim CVC, Marson FAL. COVID-19: the availability of ICU beds in Brazil during the onset of pandemic. Ann Glob Health. 2020;86:100.
    1. Shoukat A, Wells CR, Langley JM, et al. Projecting demand for critical care beds during COVID-19 outbreaks in Canada. CMAJ. 2020;192:E489–96.
    1. RECOVERY Collaborative Group. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693–704.
    1. Tomazini BM, Maia IS, Cavalcanti AB, et al. COALITION COVID-19 Brazil III Investigators. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324:1307–16.
    1. Russell JA, Marshall JC, Slutsky A, et al. Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection. BMJ Open. 2020;10:e040768.
    1. von Elm E, Altman DG, Egger M, et al. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.
    1. COVID-19 daily epidemiology update. Ottawa: Government of Canada; [accessed 2021 June 1]. Available: .
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Murthy S, Archambault PM, Atique A, et al. SPRINT-SARI Canada Investigators and the Canadian Critical Care Trials Group. Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study. CMAJ Open. 2021;9:E181–8.
    1. Piroth L, Cottenet J, Mariet AS, et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Respir Med. 2021;9:251–9.
    1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–9.
    1. 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;395:1054–62.
    1. RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022;399:143–51.
    1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13.
    1. Ovadya D, Bachar K, Peled M, et al. Weaning of severe COVID-19 mechanically ventilated patients: experience within a dedicated unit in Israel. Isr Med Assoc J. 2020;22:733–5.
    1. Bordon J, Akca O, Furmanek S, et al. Acute respiratory distress syndrome and time to weaning off the invasive mechanical ventilator among patients with COVID-19 pneumonia. J Clin Med. 2021;10:2935.
    1. Curci C, Negrini F, Ferrillo M, et al. Functional outcome after inpatient rehabilitation in postintensive care unit COVID-19 patients: findings and clinical implications from a real-practice retrospective study. Eur J Phys Rehabil Med. 2021;57:443–50.
    1. Johnson JK, Lapin B, Green K, et al. Frequency of physical therapist intervention is associated with mobility status and disposition at hospital discharge for patients with COVID-19. Phys Ther. 2021;101:pzaa181.
    1. Nasa P, Azoulay E, Khanna AK, et al. Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method. Crit Care. 2021;25:106.
    1. Nguyen LH, Drew DA, Graham MS, et al. COronavirus Pandemic Epidemiology Consortium. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health. 2020;5:e475–83.
    1. Frost DW, Shah R, Melvin L, et al. Principles for clinical care of patients with COVID-19 on medical units. CMAJ. 2020;192:E720–6.
    1. Coccia M. The impact of first and second wave of the COVID-19 pandemic in society: comparative analysis to support control measures to cope with negative effects of future infectious diseases. Environ Res. 2021;197:111099.
    1. Ko K, Nagashima SEB, Ouoba S, et al. Molecular characterization and the mutation pattern of SARS-CoV-2 during first and second wave outbreaks in Hiroshima, Japan. PLoS One. 2021;16:e0246383.
    1. Chan WM, Ip JD, Chu AWH, et al. Phylogenomic analysis of COVID-19 summer and winter outbreaks in Hong Kong: an observational study. Lancet Reg Health West Pac. 2021;10:100130.
    1. Barallat J, Fernández-Rivas G, Quirant-Sánchez B, et al. Seroprevalence of SARS-CoV-2 IgG specific antibodies among healthcare workers in the Northern Metropolitan Area of Barcelona, Spain, after the first pandemic wave. PLoS One. 2020;15:e0244348.
    1. Utrero-Rico A, Ruiz-Hornillos J, González-Cuadrado C, et al. IL-6-based mortality prediction model for COVID-19: validation and update in multicenter and second wave cohorts. J Allergy Clin Immunol. 2021;147:1652–61e1.

Source: PubMed

3
Sottoscrivi