Comparison of COVID-19 with influenza A in the ICU: a territory-wide, retrospective, propensity matched cohort on mortality and length of stay.

OBJECTIVES: Direct comparisons between COVID-19 and influenza A in the critical care setting are limited. The objective of this study was to compare their outcomes and identify risk factors for hospital mortality. DESIGN AND SETTING: This was a territory-wide, retrospective study on all adult (≥18 years old) patients admitted to public hospital intensive care units in Hong Kong. We compared COVID-19 patients admitted between 27 January 2020 and 26 January 2021 with a propensity-matched historical cohort of influenza A patients admitted between 27 January 2015 and 26 January 2020. We reported outcomes of hospital mortality and time to death or discharge. Multivariate analysis using Poisson regression and relative risk (RR) was used to identify risk factors for hospital mortality. RESULTS: After propensity matching, 373 COVID-19 and 373 influenza A patients were evenly matched for baseline characteristics. COVID-19 patients had higher unadjusted hospital mortality than influenza A patients (17.5% vs 7.5%, p<0.001). The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) adjusted standardised mortality ratio was also higher for COVID-19 than influenza A patients ((0.79 (95% CI 0.61 to 1.00) vs 0.42 (95% CI 0.28 to 0.60)), p<0.001). Adjusting for age, PaO2/FiO2, Charlson Comorbidity Index and APACHE IV, COVID-19 (adjusted RR 2.26 (95% CI 1.52 to 3.36)) and early bacterial-viral coinfection (adjusted RR 1.66 (95% CI 1.17 to 2.37)) were directly associated with hospital mortality. CONCLUSIONS: Critically ill patients with COVID-19 had substantially higher hospital mortality when compared with propensity-matched patients with influenza A.

Population study on diagnosis, treatment and outcomes of critically ill patients with tuberculosis (2008-2018).

BACKGROUND: Tuberculosis (TB) is a preventable and curable disease, but mortality remains high among those who develop sepsis and critical illness from TB. METHODS: This was a population-based, multicentre retrospective cohort study of patients admitted to all 15 publicly funded Hong Kong adult intensive care units (ICUs) between 1 April 2008 and 31 March 2019. 940 adult critically ill patients with at least one positive Mycobacterium tuberculosis (MTB) culture were identified out of 133 858 ICU admissions. Generalised linear modelling was used to determine the impact of delay in TB treatment on hospital mortality. Trend of annual Acute Physiology and Chronic Health Evaluation (APACHE) IV-adjusted standardised mortality ratio (SMR) over the 11-year period was analysed by Mann-Kendall's trend test. RESULTS: ICU and hospital mortality were 24.7% (232/940) and 41.1% (386/940), respectively. Of those who died in the ICU, 22.8% (53/232) never received antituberculosis drugs. SMR for ICU patients with TB remained unchanged over the study period (Kendall's τb=0.37, p=0.876). After adjustment for age, Charlson comorbidity index, APACHE IV, albumin, vasopressors, mechanical ventilation and renal replacement therapy, delayed TB treatment was directly associated with hospital mortality. In 302/940 (32.1%) of patients, TB could only be established from MTB cultures alone as Ziehl-Neelsen staining or PCR was either not performed or negative. Among this group, only 31.1% (94/302) had concurrent MTB PCR performed. CONCLUSIONS: Survival of ICU patients with TB has not improved over the last decade and mortality remains high. Delay in TB treatment was associated with higher hospital mortality. Use of MTB PCR may improve diagnostic yield and facilitate early treatment.

Characteristics and outcomes of patients admitted to adult intensive care units in Hong Kong: a population retrospective cohort study from 2008 to 2018.

BACKGROUND: Globally, mortality rates of patients admitted to the intensive care unit (ICU) have decreased over the last two decades. However, evaluations of the temporal trends in the characteristics and outcomes of ICU patients in Asia are limited. The objective of this study was to describe the characteristics and risk adjusted outcomes of all patients admitted to publicly funded ICUs in Hong Kong over a 11-year period. The secondary objective was to validate the predictive performance of Acute Physiology And Chronic Health Evaluation (APACHE) IV for ICU patients in Hong Kong. METHODS: This was an 11-year population-based retrospective study of all patients admitted to adult general (mixed medical-surgical) intensive care units in Hong Kong public hospitals. ICU patients were identified from a population electronic health record database. Prospectively collected APACHE IV data and clinical outcomes were analysed. RESULTS: From 1 April 2008 to 31 March 2019, there were a total of 133,858 adult ICU admissions in Hong Kong public hospitals. During this time, annual ICU admissions increased from 11,267 to 14,068, whilst hospital mortality decreased from 19.7 to 14.3%. The APACHE IV standard mortality ratio (SMR) decreased from 0.81 to 0.65 during the same period. Linear regression demonstrated that APACHE IV SMR changed by - 0.15 (95% CI - 0.18 to - 0.11) per year (Pearson's R = - 0.951, p < 0.001). Observed median ICU length of stay was shorter than that predicted by APACHE IV (1.98 vs. 4.77, p < 0.001). C-statistic for APACHE IV to predict hospital mortality was 0.889 (95% CI 0.887 to 0.891) whilst calibration was limited (Hosmer-Lemeshow test p < 0.001). CONCLUSIONS: Despite relatively modest per capita health expenditure, and a small number of ICU beds per population, Hong Kong consistently provides a high-quality and efficient ICU service. Number of adult ICU admissions has increased, whilst adjusted mortality has decreased over the last decade. Although APACHE IV had good discrimination for hospital mortality, it overestimated hospital mortality of critically ill patients in Hong Kong.

Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

BACKGROUND: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. METHODS: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. RESULTS: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). CONCLUSIONS: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.

BACKGROUND: Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. METHODS: During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥ 1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. RESULTS: Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. CONCLUSIONS: Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection.

BACKGROUND: Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. METHODS: We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. RESULTS: Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. CONCLUSIONS: The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.