Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

Decreased Levels of SARS-CoV-2 Fusion-Inhibitory Antibodies in the Serum of Aged COVID-19 Patients.

BACKGROUND: The SARS-CoV-2 pandemic was particularly devastating for elderly people, and the underlying mechanisms of the disease are still poorly understood. In this study, we investigated fusion inhibitory antibodies (fiAbs) in elderly and younger COVID-19 patients and analyzed predictive factors for their occurrence. METHODS: Data and samples were collected in two cohorts of hospitalized patients. A fusion assay of SARS-CoV-2 spike-expressing cells with ACE2-expressing cells was used to quantify fiAbs in the serum of patients. RESULTS: A total of 108 patients (52 elderly (mean age 85 ± 7 years); 56 young (mean age 52 ± 10 years)) were studied. The concentrations of fiAbs were lower in geriatric patients, as evidenced at high serum dilutions (1/512). The association between fiAbs and anti-Spike Ig levels was weak (correlation coefficient < 0.3), but statistically significant. Variables associated with fusion were the delay between the onset of symptoms and testing (HR = -2.69; p < 0.001), clinical frailty scale (HR = 4.71; p = 0.035), and WHO severity score (HR = -6.01, p = 0.048). CONCLUSIONS: Elderly patients had lower fiAbs levels after COVID-19 infection. The decreased fiAbs levels were associated with frailty.

Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study.

Background: There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings. Methods: We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, to determine who infected whom. We evaluated general transmission patterns according to case type (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each case type across all posterior trees and comparing them to random expectations. Results: During the study period (1 March to 7 May 2020), we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10% to 19% for patients, and 21% for HCWs. We estimated that 16 importation events occurred with high confidence (4 patients, 12 HCWs) that jointly led to up to 41 secondary cases; in six additional cases (5 HCWs, 1 patient), importation was possible with a posterior probability between 10% and 50%. Most patient-to-patient transmission events involved patients having shared a ward (95.2%, 95% credible interval [CrI] 84.2%-100%), in contrast to those having shared a room (19.7%, 95% CrI 6.7%-33.3%). Transmission events tended to cluster by case type: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 2.16, 95% CrI 1.17-4.20, p=0.006); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.72, 95% CrI 0.87-9.00, p=0.06). The proportion of infectors being HCWcovid was as expected as random. We found a trend towards a greater proportion of high transmitters (≥2 secondary cases) among HCWoutbreak than patientnoso in the late phases (28.6% vs. 11.8%) of the outbreak, although this was not statistically significant. Conclusions: Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This finding highlights gaps in infection control and suggests the possible areas of improvements to limit the extent of nosocomial transmission. Funding: This study was supported by a grant from the Swiss National Science Foundation under the NRP78 funding scheme (Grant no. 4078P0_198363).

Fighting social isolation in times of pandemic COVID-19: the role of video calls for older hospitalized patients.

BACKGROUND: Loneliness and social isolation are associated with anxiety and psychological discomfort, especially amongst the oldest and fragile persons. AIMS: SILVER evaluates the acceptance of video calls by old hospitalized patients and their relatives during the ban on visits due to the COVID-19. Moreover, SILVER evaluates if the use of different communication technology is associated with different outcomes in terms of anxiety, fear of self and of others' death and mood. METHODS: SILVER is an observational multicentre study. Patients hospitalized in two geriatric units in Switzerland and in one orthogeriatric unit in Italy and their relatives were enrolled. Participants can freely choose to use phone or video calls and were evaluated over a week. We measured anxiety, fear of death and mood at baseline and at the end of the study with standard scales. The use of video or phone calls was associated to a change in these parameters by two-way ANOVA for repeated measures. RESULTS: Sixty-four patients and relatives were enrolled, 26.5% used phone calls and 73.5% video calls. The use of video calls was associated with a reduction in anxiety and fear of death in patients and relatives as compared to participants using phone calls. DISCUSSION: Old patients and their relatives accepted and appreciated the use of video calls during hospitalization; moreover, participant using video calls appears to be less anxious and less afraid of death. CONCLUSIONS: Video calls may be a useful communication tool for hospitalized older patients to keep social relationships with relatives and reduce their anxiety and fear of death. TRIAL REGISTRATION: Retrospectively registered on 1st September 2021 in ClinicalTrials.gov (NCT05000099).

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

Prognostic Role of Subcutaneous and Visceral Adiposity in Hospitalized Octogenarians with COVID-19.

BACKGROUND: We investigated the prognostic significance of visceral and subcutaneous adiposity in octogenarians with COVID-19. METHODS: This paper presents a monocentric retrospective study that was conducted in acute geriatric wards with 64 hospitalized patients aged 80+ who had a diagnosis of COVID-19 and who underwent a chest CT scan. A quantification of the subcutaneous, visceral, and total fat areas was performed after segmentations on the first abdominal slice caudal to the deepest pleural recess on a soft-tissue window setting. Logistic regression models were applied to investigate the association with in-hospital mortality and the extent of COVID-19 pneumonia. RESULTS: The patients had a mean age of 86.4 ± 6.0 years, and 46.9% were male, with a mean BMI of 24.1 ± 4.4Kg/m2 and mortality rate of 32.8%. A higher subcutaneous fat area had a protective effect against mortality (OR 0.416; 0.183-0.944 95% CI; p = 0.036), which remained significant after adjustments for age, sex, and BMI (OR 0.231; 0.071-0.751 95% CI; p = 0.015). Inversely, higher abdominal circumference, total fat area, subcutaneous fat area, and visceral fat were associated with worse COVID-19 pneumonia, with the latter presenting the strongest association after adjustments for age, sex, and BMI (OR 2.862; 1.523-5.379 95% CI; p = 0.001). CONCLUSION: Subcutaneous and visceral fat areas measured on chest CT scans were associated with prognosis in octogenarians with COVID-19.

Undetected Causes of Death in Hospitalized Elderly with COVID-19: Lessons from Autopsy.

BACKGROUND: Mechanisms and causes of death in older patients with SARS-CoV-2 infection are still poorly understood. METHODS: We conducted in a retrospective monocentric study, a clinical chart review and post-mortem examination of patients aged 75 years and older hospitalized in acute care and positive for SARS-CoV-2. Full body autopsy and correlation with clinical findings and suspected causes of death were done. RESULTS: Autopsies were performed in 12 patients (median age 85 years; median of 4 comorbidities, mainly hypertension and cardiovascular disease). All cases showed exudative or proliferative phases of alveolar damage and/or a pattern of organizing pneumonia. Causes of death were concordant in 6 cases (50%), and undetected diagnoses were found in 6. Five patients died from hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), five had another associated diagnosis and two died from alternative causes. Deaths that occurred in the second week were related to SARS-CoV-2 pneumonia whereas those occurring earlier were related mainly to heart failure and those occurring later to complications. CONCLUSIONS: Although COVID-19 hypoxemic respiratory failure was the most common cause of death, post-mortem pathological examination revealed that acute decompensation from chronic comorbidities during the first week of COVID-19 and complications in the third week contributed to mortality.

Nutritional risk at hospital admission is associated with prolonged length of hospital stay in old patients with COVID-19.

BACKGROUND & AIMS: To investigate the association of nutritional risk at admission with the length of hospital stay (LOS) and mortality in older patients with COVID-19. METHODS: Retrospective monocentric study in an acute geriatric hospital. Data were collected after an extensive review of medical records and the nutritional risk was assessed according to the Nutritional Risk Screening (NRS). Univariate and multivariate (adjusted for age, sex and comorbidity burden) Cox proportional-hazard and linear regression models were used to investigate the association with the above-mentioned outcomes. RESULTS: Of a total of 245 patients (86.1 ± 6.4 yrs), 50.6% had a severe nutritional risk with an NRS≥5/7 at admission. Lower BMI, cognitive impairment and swallowing disorders were more prevalent in the patients with a higher NRS. A NRS≥5 was not associated with mortality but prolonged by more than 3 days the LOS among the 173 survivors (ß 3.69; 0.71-6.67 95% CI; p = 0.016), with a discharge rate delayed by 1.8 times (HR 0.55; 0.37-0.83 95% CI; p = 0.101). CONCLUSION: Among the survivors of COVID-19 in an acute geriatric hospital, a NRS ≥5 at admission was associated with a longer LOS, but not with mortality.

Delirium in Older Patients With COVID-19: Prevalence, Risk Factors, and Clinical Relevance.

BACKGROUND: Delirium prevalence increases with age and is associated with poor outcomes. We aimed to investigate the prevalence and risk factors for delirium in older patients hospitalized with COVID-19, as well as its association with length of stay and mortality. METHOD: This was a retrospective study of patients aged 65 years and older hospitalized with COVID-19. Data were collected from computerized medical records and all patients had delirium assessment at admission. Risk factors for delirium as well as the outcomes mentioned above were studied by 2-group comparison, logistic regression, and Cox proportional hazard models. RESULTS: Of a total of 235 Caucasian patients, 48 (20.4%) presented with delirium, which was hypoactive in 41.6% of cases, and hyperactive and mixed in 35.4% and 23.0%, respectively. Patients with cognitive impairment had a nearly 4 times higher risk of developing delirium compared to patients who were cognitively normal before SARS-CoV-2 infection (odds ratio 3.7; 95% CI: 1.7-7.9, p = .001). The presence of delirium did not modify the time from symptoms' onset to hospitalization or the length of stay in acute care, but it was associated with an increased risk of dying (hazard ratio 2.1; 95% CI: 1.2-3.7, p = .0113). CONCLUSION: Delirium was a prevalent condition in older people admitted with COVID-19 and preexisting cognitive impairment was its main risk factor. Delirium was associated with higher in-hospital mortality. These results highlight the importance of early recognition of delirium especially when premorbid cognitive comorbidities are present.

Incidence, characteristics and clinical relevance of acute stroke in old patients hospitalized with COVID-19.

BACKGROUND: Stroke in the course of coronavirus disease (COVID-19) has been shown to be associated with more severe respiratory symptoms and higher mortality, but little knowledge in this regard exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke in geriatric patients hospitalized with COVID-19. METHODS: A monocentric cross-sectional retrospective study of 265 older patients hospitalized with COVID-19 on acute geriatric wards. 11/265 presented a stroke episode during hospitalization. Mortality rates and two-group comparisons (stroke vs non-stroke patients) were calculated and significant variables added in logistic regression models to investigate stroke risk factors. RESULTS: Combined ischemic and hemorrhagic stroke incidence was 4.15%. 72.7% of events occurred during acute care. Strokes presented with altered state of consciousness and/or delirium in 81.8%, followed by a focal neurological deficit in 45.5%. Ischemic stroke was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke increased by more than seven (OR 7.44; 95% CI 1.75-31.64; p = 0.007) and five times (OR 5.19; 95% CI 1.50-17.92; p = 0.009), respectively, the risk of stroke. Each additional point in body mass index (BMI) reduced the risk of stroke by 14% (OR 0.86; 95% CI 0.74-0.98; p = 0.03). In-hospital mortality (32.1% vs. 27.3%; p > 0.999) and institutionalization at discharge (36.4% vs. 21.1%; p = 0.258) were similar between patients with and without stroke. CONCLUSION: Incident stroke complicating COVID-19 in old patients was associated with active smoking, previous history of stroke, and low BMI. Acute stroke did not influence early mortality or institutionalization rate at discharge.

Predictors of In-Hospital Mortality in Older Patients With COVID-19: The COVIDAge Study.

OBJECTIVE: To determine predictors of in-hospital mortality related to COVID-19 in older patients. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients aged 65 years and older hospitalized for a diagnosis of COVID-19. METHODS: Data from hospital admission were collected from the electronic medical records. Logistic regression and Cox proportional hazard models were used to predict mortality, our primary outcome. Variables at hospital admission were categorized according to the following domains: demographics, clinical history, comorbidities, previous treatment, clinical status, vital signs, clinical scales and scores, routine laboratory analysis, and imaging results. RESULTS: Of a total of 235 Caucasian patients, 43% were male, with a mean age of 86 ± 6.5 years. Seventy-six patients (32%) died. Nonsurvivors had a shorter number of days from initial symptoms to hospitalization (P = .007) and the length of stay in acute wards than survivors (P < .001). Similarly, they had a higher prevalence of heart failure (P = .044), peripheral artery disease (P = .009), crackles at clinical status (P < .001), respiratory rate (P = .005), oxygen support needs (P < .001), C-reactive protein (P < .001), bilateral and peripheral infiltrates on chest radiographs (P = .001), and a lower prevalence of headache (P = .009). Furthermore, nonsurvivors were more often frail (P < .001), with worse functional status (P < .001), higher comorbidity burden (P < .001), and delirium at admission (P = .007). A multivariable Cox model showed that male sex (HR 4.00, 95% CI 2.08-7.71, P < .001), increased fraction of inspired oxygen (HR 1.06, 95% CI 1.03-1.09, P < .001), and crackles (HR 2.42, 95% CI 1.15-6.06, P = .019) were the best predictors of mortality, while better functional status was protective (HR 0.98, 95% CI 0.97-0.99, P = .001). CONCLUSIONS AND IMPLICATIONS: In older patients hospitalized for COVID-19, male sex, crackles, a higher fraction of inspired oxygen, and functionality were independent risk factors of mortality. These routine parameters, and not differences in age, should be used to evaluate prognosis in older patients.