key: cord-0959459-r7gpwi10
authors: Suardi, Lorenzo Roberto; Pallotto, Carlo; Esperti, Sara; Tazzioli, Elisa; Baragli, Filippo; Salomoni, Elena; Botta, Annarita; Covani Frigieri, Francesca; Pazzi, Maddalena; Stera, Caterina; Carlucci, Martina; Papa, Raffaella; Meconi, Tommaso; Pavoni, Vittorio; Blanc, Pierluigi
title: Risk factors for non-invasive/invasive-ventilatory support in patients with COVID-19 pneumonia: a retrospective study within a multidisciplinary approach
date: 2020-09-11
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.09.012
sha: a3dcfa1bf1265acf11d5179b4ba98a4a8accc1e4
doc_id: 959459
cord_uid: r7gpwi10

Objectives To investigate risk factors for non-invasive/invasive-ventilatory support (NI/I-VS) in Coronavirus diseases 2019 (COVID-19) patients. Methods All consecutive patients admitted, from February 25 to April 25, 2020, to the Infectious Diseases Unit and Intensive Care Unit of Santa Maria Annunziata Hospital (Florence, Italy) with confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as need for continuous positive airway pressure (CPAP) or bilevel positive pressure non-invasive ventilation (BPAP) or mechanical ventilation (MV) than low-flow systems oxygen-therapy as Venturi Mask (VM) or nasal cannula. Results Ninety-seven patients were enrolled; 61,9% (60/97) were male, median age was 64 years; intra-hospital mortality was 9.3%. Thirty five out of 97 (36%) patients required ICU admission and 94.8% (92/97) were prescribed oxygen-therapy: 10.8% (10/92) with nasal cannula, 44.5% (41/92) with VM, 31.5% (29/92) with CPAP, 2.2% (2/92) with BPAP and 10.8% (10/92) underwent intubation for MV. Patients with body mass index >30, type II diabetes mellitus and presenting at the admission with dyspnoea, asthenia, SOFA score ≥2 points, PaO2/FiO2 < 300, temperature >38 °C, increased levels of lactate dehydrogenase (LDH), alanine aminotransferase, C-reactive protein and a d-dimer >1000 ng/ml underwent more frequently NI/I-VS at the univariate analysis. Multivariate logistic regression analysis confirmed temperature >38 °C (odds ratio [OR] 21.2, 95% confidential interval [95%CI] 3.5-124.5, p = 0.001), LDH > 250 U/L (OR 15.2, 95%CI 1.8-128.8, p = 0.012) and d-dimer >1000 ng/ml (OR 4.5, 95%CI 1.2-17.3, p = 0.027) as significantly associated with NI/I-VS requirement. A non-significant trend (p = 0.051) was described for PaO2/FiO2 < 300. Conclusions Temperature >38 °C, LDH > 250 U/L and d-dimer >1000 ng/ml resulted to be indipendent risk factors for NI/I-VS in COVID-19 patients. In order to quickly recognize patients likely at risk to develop a critical illness, inflammatory markers assessment should be warranted upon hospital admission.

Running title: risk factors for non-invasive/invasive-ventilatory support in patients with COVID-19 pneumonia * Correspondence should be sent to:

Lorenzo Roberto Suardi, MD Infectious Diseases Unit Santa Maria Annunziata Hospital Azienda USL Toscana Centro Bagno a Ripoli (Florence, Italy) E mail: lorenzoroberto.suardi@gmail.com Phone: +39 3405907701 ORCID ID:0000-0001-6753-4793 >1000 ng/ml (OR 4.5, 95%CI 1.2-17.3, p=0.027) as significantly associated with NI/I-VS requirement. A non-significant trend (p=0.051) was described for PaO2/FiO2 <300.

Temperature >38°C, LDH >250 U/L and d-dimer >1000 ng/ml resulted to be indipendent risk factors for NI/I-VS in COVID-19 patients. In order to quickly recognize patients likely at risk to develop a critical illness, inflammatory markers assessment should be warranted upon hospital admission. Facing a life-threatening infection, reliable risk factors recognition is warranted in order to guarantee a fast and appropriate medical response.

J o u r n a l P r e -p r o o f

The study was conducted at the Santa Maria Annunziata Hospital, a medium-size hospital with 300 beds in the southern area of Florence, Italy.

Retrospective, single-centre, observational cohort study. We included all consecutive adult patients presenting to the Emergency Department (ED) between February 25th to April 25th 2020 (60 days) and admitted to the Infectious Diseases Unit (IDU) or to the Intensive Care Unit (ICU) with confirmed diagnosis of COVID-19 according to a positive result on real-time reverse transcriptasepolymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasal and pharyngeal swab specimens.

Since the beginning of the study period, a multidisciplinary approach was carried out between the IDU and ICU specialists; 3 meetings per day were performed in order to share patients' management, especially supportive treatments, as ventilatory support, sperimental drugs, antiviral and antibiotic administration.

Treatmentsantivirals, antibiotics, immunomodulating agents (corticosteroids and tocilizumab) and ventilatory supportwere administered following local guidelines based on the best available evidence at that moment and consistently with the "Vademecum" realized by the Lombardia 

The primary aim was to investigate the risk factors for non-invasive/invasive-ventilatory support (NI/I-VS), meant as need for continuous positive airway pressure (CPAP) or bilevel positive pressure non-invasive ventilation (BPAP) or mechanical ventilation (MV), rather than low-flow oxygen support as Venturi Mask (VM) or nasal cannula.

Continuous variables were presented as median, interquantile range (IQR), maximum-minimum range and dichotomized where appropriate. Categorical variables were reported as percentages and compared using the Chi-squared test. Fisher's exact test was also used to estimate continuous variables if one set contained fewer than five expected subjects. Mann-Whitney U test was used for non-parametric continuous variables study (median). Logistic regression was performed to explore the risk factors associated with the primary outcome. All variables associated with the primary outcome in the univariate model, with at least a p <0.05, were entered into a backward-logistic multivariate regression model. Considering the total number of events (n=41) in our study and to avoid overfitting in the model, four variables were chosen for multivariable analysis on the basis of previous findings and clinical constraints. We tested in the model interactions that were significant on a stratified analysis odds ratio (OR) presented with 95% confidence intervals (95% CI). A value of p <0.05 was considered statistically significant. Statistical analysis was conducted using the SPSS software (version 23.0). An exposure history was reported for 11 (16.5%) patients coming from long-term care facilities, 3 (3.1%) patients with nosocomial transmission and 3 (3.1%) were health-care workers.

Comorbidities were present in nearly 60% of patients with hypertension being the most common one, followed by type II diabetes mellitus, cerebrovascular disease (including vascular dementia) and chronical obstructive pulmonary disease (COPD). In addition to this, 21 (21.6%) had a body mass index (BMI) higher than 30. The most common symptoms before admission were fever, cough, dyspnoea and asthenia. At the univariate analysis a BMI greater than 30, diabetes, history of dyspnoea or asthenia, SOFA score (at admission) ≥2 point, PaO2/FiO2 index (at admission) lower than 300, temperature (at admission) >38°C, increased lactate dehydrogenase, increased alanine aminotransferase, increased C-reactive protein and a D-dimer >1000 ng/ml were significantly associated with noninvasive/invasive-ventilatory support.

We included 75 patients with complete data for all variables in the multivariate backward-logistic regression model. At the multivariate analysis , temperature >38°C LDH >250 U/L and D-dimer >1000 ng/ml were significantly associated for non-invasive/invasive-ventilatory support requirement while a PaO2/FiO2 <300 resulted close to be significantly associated. (table 2) J o u r n a l P r e -p r o o f

In this cohort study, we analyzed the clinical characteristics of hospitalized COVID-19 patients in order to highlight possible risk factors associated with non-invasive/invasive-ventilatory support requirement. Baseline characteristics resulted to be similar to those reported in the largest Italian study available at this moment, by Grasselli et al (11) : prevalence of male sex, median age of 64 years and presenting as common comorbidities hypertension and diabetes. On the contrary, in our study, just 10% of patients suffered from cardiovascular disease. Similar baseline data have been previously reported by 2 studies from China (12, 13) and, more recently, by Richardson et al (14) from New York, United States.

On the other hand, older age, in our study, was not associated with a complicated course requiring intensive ventilatory support. As suggested by Grasselli et al (11) , the median age (63 years) of the hospitalized patient is comparable to the median age of the total Italian COVID-19 (4) cases. As a consequence, it could barely be associated with poorer outcome as a unique risk factor.

As reported in a case-series by Bhatraju et al (15) from the US and by Simmonet et al (16) , obesity seemed associated to severe COVID-19 illness. In our study population 15 (71.4%) out of 21 patients with a BMI greater than 30 received intensive ventilatory support (4 mechanical ventilation and 11 non-invasive ventilation). Nevertheless, obesity did not reach the significance threshold at the multivariate analysis in our study.

Moreover, focusing on patients' clinical features and laboratory findings at admission, fever, increased level of LDH and D-dimer resulted to be independently associated to higher intensity cure need; this findings are consistent with previously published studies by Zhou et al (17) and Wu et al (18) .

This report, to our knowledge, is one of the first case series from Italy describing a real-life experience from a joint IDU-ICU perspective. Our analysis confirmed the role as risk factors of J o u r n a l P r e -p r o o f Due to the observational and retrospective nature of the study, the need for a specific informed consent from individual patients was waived. An informed consent to treatment of personal data, an usual and mandatory practice upon on hospital admission, was acquired directly by the patients or the legal tutors. 

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SOFA: Sequential Organ Failure Assessment, PaO2/FiO2: ALT= alanine aminotransferase

We thank all our patients and their families, all the health-workers of the Infectious Diseases and Intensive Care Units of Santa Maria Annunziata Hospital (Florence, Italy).J o u r n a l P r e -p r o o f