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      Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality

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          Abstract

          Purpose

          Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU).

          Methods

          Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models.

          Results

          CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010–1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993–0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223–5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852–8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757–1721, p = 0.528).

          Conclusion

          The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00134-022-06716-y.

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          Most cited references39

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          Acute respiratory distress syndrome: the Berlin Definition.

          V Ranieri, Gordon D Rubenfeld, B Taylor Thompson … (2013)
          The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning.
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            Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

            Philipp Koehler, Matteo Bassetti, Arunaloke Chakrabarti … (2020)
            Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
            Article 0 comments Cited 362 times – based on 0 reviews     Review now
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              International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).

              Antoni Torres, Michael Niederman, Jean Chastre … (2017)
              The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent.The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited.A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink).Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.
              Article 0 comments Cited 326 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Massimo Girardis:
                ORCID: http://orcid.org/0000-0002-2453-0829
                girardis.massimo@unimo.it
                Journal
                Journal ID (nlm-ta): Intensive Care Med
                Journal ID (iso-abbrev): Intensive Care Med
                Title: Intensive Care Medicine
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0342-4642
                ISSN (Electronic): 1432-1238
                Publication date (Electronic): 18 May 2022
                Pages: 1-8
                Affiliations
                [1 ]GRID grid.7548.e, ISNI 0000000121697570, Anesthesia and Intensive Care Medicine, , Policlinico di Modena, University of Modena and Reggio Emilia, ; Modena, Italy
                [2 ]GRID grid.7548.e, ISNI 0000000121697570, Infectious Diseases Unit, , Policlinico di Modena, University of Modena and Reggio Emilia, ; Modena, Italy
                [3 ]GRID grid.7548.e, ISNI 0000000121697570, Respiratory Diseases Unit, , Policlinico di Modena, University of Modena and Reggio Emilia, ; Modena, Italy
                [4 ]GRID grid.7548.e, ISNI 0000000121697570, Department of Medical and Surgical Sciences for Children and Adults, , University of Modena and Reggio Emilia, ; Modena, Italy
                [5 ]GRID grid.413363.0, ISNI 0000 0004 1769 5275, Microbiology and Virology Unit, , Azienda Ospedaliero-Universitaria Policlinico, ; 41124 Modena, Italy
                [6 ]GRID grid.7548.e, ISNI 0000000121697570, Virology and Molecular Microbiology Unit, , Policlinico di Modena, University of Modena and Reggio Emilia, ; Modena, Italy
                [7 ]GRID grid.413363.0, ISNI 0000 0004 1769 5275, Intensive Care Department, , University Hospital of Modena, ; L.go del Pozzo 71, 41125 Modena, Italy
                Author information
                http://orcid.org/0000-0002-2453-0829
                Article
                Publisher ID: 6716
                DOI: 10.1007/s00134-022-06716-y
                PMC ID: 9116062
                PubMed ID: 35583676
                SO-VID: 282727b0-556c-4822-a13d-c8ef366ada7a
                Copyright © © Springer-Verlag GmbH Germany, part of Springer Nature 2022
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 28 January 2022
                Date accepted : 22 April 2022
                Categories
                Subject: Original

                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: covid-19,cytomegalovirus reactivation,mechanical ventilation,sepsis
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: covid-19, cytomegalovirus reactivation, mechanical ventilation, sepsis

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