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Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.ORCID iD: 0000-0001-8711-9044
Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Nyköping Hosp, Sweden.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Infectious Diseases.
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2024 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 68, no 2, p. 226-235Article in journal (Refereed) Published
Abstract [en]

Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.Conclusion: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.

Place, publisher, year, edition, pages
WILEY , 2024. Vol. 68, no 2, p. 226-235
Keywords [en]
acute respiratory distress syndrome (ARDS); COVID-19; intensive care; multicenter; SARS-CoV-2; Sweden; ventilator-associated lower respiratory tract infection (VA-LRTI); ventilator-associated pneumonia (VAP); ventilator-associated respiratory infection (VARI)
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:liu:diva-198359DOI: 10.1111/aas.14338ISI: 001071979900001PubMedID: 37751991Scopus ID: 2-s2.0-85172284133OAI: oai:DiVA.org:liu-198359DiVA, id: diva2:1803415
Note

Funding Agencies|Thanks to Michelle S Chew for contributing to the construction of our database as well as manuscript revisions. Thanks to Anzal Abdirashid, Henrik Brofeldt, and Robert Staroscinski, for contributing greatly to data collection. The authors declare no confli

Available from: 2023-10-09 Created: 2023-10-09 Last updated: 2026-03-05
In thesis
1. Intensive Care of COVID-19 patients: From Admission to Outcome
Open this publication in new window or tab >>Intensive Care of COVID-19 patients: From Admission to Outcome
2026 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of the present thesis is to deepen the knowledge of severe and critical COVID-19 infection - its management and outcomes among ICU patients in Sweden. This is achieved through retrospective studies of ICU patients with COVID-19 from several Swedish hospitals focusing on their management and outcomes (study I, III, IV). In addition, a prospective follow-up study was conducted on patients with post covid condition (PCC) (study II).

In the first paper (study I), all patients with respiratory failure due to COVID-19 who were admitted to an ICU in region Östergötland during the initial pandemic wave were included (n=100). The median age was 63 years, and the 60-day mortality rate was 22% across the entire pandemic wave. Divided into three consecutive tertiles, the 60-day mortality decreased from 33% in the first tertile to 15% and 18% in the subsequent two. Ninety-one percent had at least moderate acute respiratory distress syndrome (ARDS) and 88% required invasive mechanical ventilation (IMV). During the wave, the use of thromboprophylaxis increased, the steep rise in ICU admissions subsided, and ICU resources expanded. At four-month follow-up, 63% of survivors reported a decline in general health compared with their health status prior to SARS-CoV-2 infection.

In Study II, all patients with PCC at a clinical follow-up four months after hospital discharge in region Östergötland were included and interviewed two years after initial infection. Of 181 eligible patients, 165 participated in the study. The majority (84%) reported lingering problems affecting everyday life. Nevertheless, improvements were observed in both prevalence and severity of several symptoms and functional limitations compared with four months post-discharge. The most reported symptoms were cognitive, sensorimotor, and fatigue related. Comparison between ICU-treated and non-ICU-treated patients revealed no significant difference at 24-months.

In study III, factors associated with ventilator-associated lower respiratory tract infection (VA-LRTI) in COVID-19 were explored. All patients with respiratory failure requiring IMV who were admitted to an ICU in the southeast healthcare region of Sweden were included (n=536). Overall, 28.5% developed VA-LRTI, corresponding to an incidence rate of 20.8 first VA-LTRI episodes per 1000 IMV days. The incidence of VA-LRTI increased from 14.5 per 1000 days of IMV days during the first wave to 24.8 per 1000 IMV days during the subsequent two ways. Patients who developed VA-LRTI had fewer ventilator-free days, received corticosteroids more frequently, and were more often ventilated in prone position. Most detected pathogens were Enterobacteriaceae (38.9%) and Staphylococcus aureus (22.8%). Logistic regression analysis revealed significantly increased adjusted odds ratio (aOR) for first VA-LRTI for corticosteroid treatment (aOR 2.64 [95% confidence interval [CI]] [1.31–5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14–3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03–1.07]).

In the final paper (study IV), mortality disparities among patients with COVID-19 admitted to ICUs across seven Swedish hospitals were investigated using survival analysis. All patients admitted to one of the participating ICUs with respiratory failure due to COVID-19 were included (n=747). Across the cohort, 90-day mortality varied substantially between hospitals, ranging from 8.5% to 30%. In the final cox proportional hazards model adjusted for baseline covariates, pandemic wave and with random intercept for healthcare county, the adjusted hazard ratios (aHR) for 90‑day mortality by hospital spanned from: 2.38 to 5.06, using the hospital with the lowest mortality as reference. The results remained robust after sensitivity analysis, including complete case analysis, calculation of e-values, assessment of multicollinearity, and testing of the proportional hazards assumption.

In conclusion, initial high mortality of ICU-treated COVID-19 patients in region Östergötland, quickly declined during the first pandemic wave, paralleling increased ICU resources and expanded use of thromboprophylaxis. Moreover, many ICU survivors experienced reduced general health at four-month follow-up. Many survivors developed PCC and reported lingering symptoms affecting their everyday life two years after initial infection, but with significant improvement compared to the initial follow-up. Additionally, the VALRTI incidence in southeast healthcare region of Sweden was low compared with previously published data, although it increased across the pandemic waves - possibly related to expanded use of corticosteroid treatment. Finally, during the pandemic, the initial ICU to which a patient was admitted correlated with ICU mortality. These results contribute to the ongoing discussion regarding healthcare equity in Sweden, suggesting that geographical inequities were likely present at least during the pandemic.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2026. p. 113
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1993
Keywords
COVID-19, Post covid condition, Long Covid, ICU, VA-LRTI, VAP, ARDS, Sweden, Healthcare equity
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:liu:diva-221711 (URN)10.3384/9789181182118 (DOI)9789181182101 (ISBN)9789181182118 (ISBN)
Public defence
2026-04-10, Hugo Theorell, Building 440, Campus US, Linköping, 09:00 (Swedish)
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Note

Digital Appendices:

The digital appendices (Missing analysis, Secondary analysis, Survival analysis and e-values) refered to in the text were made available for download from this webpage 2026-03-11.

Available from: 2026-03-05 Created: 2026-03-05 Last updated: 2026-03-11Bibliographically approved

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