2.1 Aim, design and setting
This is an observational study that analyzed and compared Delirium incidences in elderly patients with COVID-19 and sepsis for other etiologies from two cohorts which recruited patients in the emergency department at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, Brazil.
Our primary outcome was the incidence of delirium at admission in ED, which we defined using the Confusion Assessment Method (CAM). (12, 13) Secondary outcomes were ICU admission and in-hospital death.
Admissions to our ED are centrally managed by the Regulatory Central of the State of São Paulo, and severely ill patients are preferably referred to the hospital. During the COVID-19 pandemic, HCFMUSP became a major center for COVID-19 treatment in São Paulo, the epicenter of the pandemic in Brazil. In March 2020, the main hospital building was converted to a COVID-19–only facility, dedicating 1000 beds to the care of infected patients.
We adhered to the STROBE guidelines.
2.2 Selection of Participants
The first cohort study, conducted between September 30, 2019, and March 17, 2020, before the first COVID-19 case was diagnosed on our hospital, and analyzed the association between delirium and brain injury biomarkers in elderly septic patients admitted to the ED. Elderly patients (> 65 years) admitted less than 24 hours for sepsis were eligible to participate. Sepsis was defined as confirmed infection and an increase of 2 points or more in the Sequential Organ Failure Assessment (SOFA). (10) Patients in exclusive palliative care or previously hospitalization in the last 30 days were excluded. The protocol for this study was approved by the local Ethics Committee in Research (Protocol number 77169716.2.0000.0068), and informed consent by writing was obtained from all patients or legal guardians prior to inclusion.
The second cohort included all elderly patients admitted less than 24 hours for COVID-19 from April 8, 2021, to May 28, 2021. We excluded palliative care patients, previous hospitalization in the last 30 days, and the absence of SARS-CoV-2 confirmed infection. Confirmation of infection by SARS-CoV-2 was performed by real-time polymerase chain reaction (RT-PCR) in nasopharyngeal smear or tracheal aspirate. The study protocol was approved by the local Research Ethics Committee (protocol number 30417520.0.0000.0068). Written informed consent or verbal authorization from the patient or responsible family member was documented in the medical record to guarantee the patient's anonymity preservation.
We adhered to the principles expressed in the Declaration of Helsinki. All patient-identifiable information was stored in secure electronic servers, with access restricted to our researchers.
2.3 Measurements
Trained medical and nurses prospectively performed structured interviews with patients and their parents at admission, assessing all patients in the ED with age > 65 years who met the inclusion criteria for Delirium through the Confusion Assessment Method (CAM). Daily additional study information was collected by reviewing electronic medical records, nursing records, consulting notes, laboratory tests, and radiologic examinations from the complete hospitalizations. Completed standardized electronic case report forms using Research Electronic Data Capture resources. (11)
We collected data on demographics (age, sex, ethnicity, and literacy), clinical history (previous diagnoses and medications, physical examination, and supplemental oxygen), premorbid functional status (Katz Activities of Daily Living Scale), and laboratory tests routinely collected on admission (complete blood cell count, D-dimer, C-reactive protein, urea, creatinine, and albumin). We defined the first available results from within the first 24 hours of hospitalization as the admission results of laboratory tests.
2.4 Analysis
Considering that the incidence of delirium in elderly patients admitted to the ED for COVID-19 or other causes was 28 and 7%, respectively (2, 8), we calculated a sample of 100 patients to demonstrate that SARS-CoV-2 infection is four times more likely to develop Delirium than sepsis with 80% power. When we started the COVID-19 cohort study, we had already recruited 95 patients in the Sepsis cohort study.
We expected difficulties in recruiting patients for two reasons: 1. Our center is reference for severe cases of COVID-19, and most of the patients were admitted after 24 hours of admission in other hospitals; 2. Immunization against SARS-CoV-2 started in São Paulo in January 2021 and had already reduced the number of elderly patients hospitalized in our center.
We reported descriptive results for the total sample, comparing the variables of interest according to the overall incidence of delirium. We used the chi-square test to compare categorical variables, and we used the Student t-test (normal distribution) or the Wilcoxon rank-sum test (non-normal distribution) to compare numerical variables.
All statistical tests were two-tailed, and an α error of up to 5% was accepted to define the statistical significance of any results. Statistical analyses were performed using Stata MP 16.1 (StataCorp ®)