Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

Qualitative Subgenomic RNA to Monitor the Response to Remdesivir in Hospitalized Patients with COVID-19: impact on the length of hospital stay and mortality.

BACKGROUND: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with COVID-19. We aim to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. METHODS: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for qRT-PCR was collected at baseline, and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main co-morbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. RESULTS: A total of 117 patients were included in the study, from which 24 had a negative sgRNA at baseline with a 62.5% (15/24) of early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 of them had a negative sgRNA at day 5 with 37/62 (59.6%) of early discharge and a mortality of 4.8% (3/62). In the 31 patients subgroup with positive sgRNA after 5 days of RDV, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In the multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3, and not needing treatment with corticosteroids or ICU admission. CONCLUSIONS: Qualitative sgRNA could help monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.

Hospital at home treatment with remdesivir for patients with COVID-19: real-life experience.

OBJECTIVES: Access and appropriateness of therapeutics for COVID-19 vary because of access or regulatory barriers, the severity of the disease, and for some therapies, the stage of the pandemic and circulating variants. Remdesivir has shown benefits in clinical recovery and is the treatment of choice for selected patients, both hospitalized and nonhospitalized, in main international guidelines. The use of remdesivir in alternatives to conventional hospitalization such as hospital at home (HaH) units remains incompletely explored. In this study, we aim to describe the real-life experience of outpatient remdesivir infusion for COVID-19 in a HaH unit. METHODS: We selected all the consecutive patients receiving remdesivir from a prospective cohort of 507 COVID-19 patients admitted at a HaH unit. Admission criteria included COVID-19 with a fraction of inspired oxygen requirement under 0.35 and respiratory rate under 22 rpm. Patients were daily assessed in person by a nurse and a physician. RESULTS: A total of 236 patients admitted at the HaH unit received remdesivir, 172 of whom were treated at home. Only 2% presented any adverse event related to the infusion, all of them mild. HaH saved 1416 day-beds, with only 5% of the patients requiring transfer back to the hospital. CONCLUSION: Remdesivir infusion in HaH units seems to be a safe and efficient alternative to conventional hospitalization for treating patients with nonsevere COVID-19.

Efficacy of early transfusion of convalescent plasma with high-titer SARS-CoV-2 neutralizing antibodies in hospitalized patients with COVID-19.

BACKGROUND: Despite most controlled trials have shown no measurable benefit of COVID-19 convalescent plasma (CCP) in patients with COVID-19, some studies suggest that early administration of CCP with high-titer anti-SARS-CoV-2 can be beneficial in selected patients. We investigated the efficacy of early administration of high-titer CCP to patients with COVID-19 who required hospitalization, STUDY DESIGN AND METHODS: Observational, propensity score (PS) matched case-control study of COVID-19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti-SARS-CoV-2 sample-to-cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high-standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis. RESULTS: A total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56-79), and 953 (60%) were men. Presenting factors independently associated with higher 30-day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d-dimer >700 ng/ml. After PS matching, transfusion of CCP was associated with a significant reduction in the 30-day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91-0.98; p = .001) that extended to the 60th day after COVID-19 diagnosis (OR: 0.95; 95% CI: 0.92-0.99; p = .01). CONCLUSION: Our results suggest that CCP can still be helpful in selected patients with COVID-19 and call for further studies before withdrawing CCP from the COVID-19 therapeutic armamentarium.

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19.

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.

Personalized Therapy Approach for Hospitalized Patients with Coronavirus Disease 2019.

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality.

Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host.

Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

Gustatory and olfactory dysfunctions in hospitalised patients with COVID-19 pneumonia: a prospective study.

IMPORTANCE: Identifying undetected clinical signs is imperative in the prevention of SARS-CoV-2. OBJECTIVE: To establish the prevalence of clinical gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. Clinical outcomes and recovery rates associated with gustatory and olfactory dysfunctions were also assessed. DESIGN: A prospective study was performed in 80 patients admitted to Hospital Clínic of Barcelona (Spain) for COVID-19 pneumonia. Patients were re-evaluated in the ward daily until discharge. Gustatory and olfactory dysfunction symptoms were retrospectively collected from emergency room (ER) charts after first assessments. Follow-up was performed in telemedicine consultation. SETTING: The single-centre study was performed in a hospitalisation ward at a university hospital. PARTICIPANTS: Consecutive patients meeting hospitalisation criteria for COVID-19 pneumonia were eligible. Study exclusion criteria were patients who could not speak, had previous gustatory and olfactory dysfunctions or whose PCR tests for SARS-CoV-19 were negative. INTERVENTIONS: Systematic assessment of gustatory and olfactory symptoms with standardised questions. OUTCOMES: Prevalence of gustatory and olfactory dysfunctions in patients with COVID-19 pneumonia. RESULTS: Of the 80 study subjects, 62.5% were male and the median age was 57 years. Half of the cohort (n=40) presented with comorbidities. The prevalence of chemosensitive disorder was 73.8% (n=59) (95% CI: 63.8 to 83.8), although self-reported symptoms were recorded in only 26.3% (n=21) of patients in the ER. Gustatory and olfactory dysfunctions were observed in 58.8% (n=47) and 55% (n=44) of cases, respectively. They were also the first symptoms in 25% (n=20) of patients. Anosmia was associated with ageusia, OR: 7, 95% CI: 2.3 to 21.8, p=0.001). No differences in clinical outcomes were observed when patients with and without gustatory and olfactory dysfunctions were compared. Recovery rates were 20% (n=10) and 85% (n=42) at days 7 and 45, respectively. CONCLUSION: The prevalence of gustatory and olfactory dysfunctions in COVID-19 pneumonia was much higher than in self-report. Presence of gustatory and olfactory dysfunctions was not a predictor of clinical outcomes.

Impact of Inflammatory Response Modifiers on the Incidence of Hospital-Acquired Infections in Patients with COVID-19.

INTRODUCTION: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19). METHODS: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case. RESULTS: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001). CONCLUSIONS: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk.

Trends in mortality of hospitalised COVID-19 patients: A single centre observational cohort study from Spain.

BACKGROUND: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time. METHODS: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020). FINDINGS: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend (p for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality. INTERPRETATION: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care. FUNDING: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII.

CONTEXTO: Nuestro objetivo es describir los cambios en las características y las estrategias de tratamiento de los pacientes hospitalizados por COVID-19, y detallar la tendencia de la mortalidad en el tiempo. MÉTODOS: Estudio observacional de cohortes de todos los pacientes consecutivos, ingresados por COVID-19 durante más de 48 horas, en el Hospital Clínic de Barcelona (del 1 de marzo al 30 de septiembre de 2020). RESULTADOS: Un total de 1645 pacientes consecutivos fueron evaluados durante un período de 7 meses. La mortalidad global (≤30 días) fue del 9.7% (159 pacientes): 7.7% en pacientes hospitalizados en salas convencionales, y 16.7% en pacientes que requirieron ingreso en UCI. La mortalidad global disminuyó del 11.6% en el primer mes al 1.4% en el último mes evaluado, reflejando una progresiva y significativa tendencia a la baja (p para la tendencia <0.001). La edad de los pacientes ha cambiado con el tiempo, habiendo alcanzado su pico en junio. La mayoría de cambios en el uso de antivirales y antiinflamatorios se han documentado. La edad (OR 1.1; CI 1.1­1.12), cardiopatía crónica (OR 1.7; CI 1.1­2.9), dímero-D>700 ng/mL (OR 2.3; CI 1.3­4.1), ferritina>489 ng/mL (OR 1.9; CI 1.5­3.2), PCR>7 mg/dL (OR 2.6; CI 1.5­4.6), y una menor duración desde el inicio de síntomas a la hospitalización (OR 1.11; CI 1.04­1.17) fueron factores asociados a la mortalidad intrahospitalaria a 30 días. Por el contrario, el ingreso hospitalario previo en los últimos meses (OR 0.80; CI 0.65­0.98) se asoció significativamente a una menor mortalidad. DISCUSIÓN: La mortalidad intrahospitalaria ha disminuido en los pacientes con COVID-19 durante los últimos meses, incluso siendo similares las características de los pacientes. Algunos cambios realizados en el manejo de estos pacientes podrían explicar esta tendencia decreciente. Nuestro estudio aporta datos actualizados en la mortalidad de los pacientes hospitalizados con COVID-19, que podrían ser útiles de cara a establecer unos cuidados estándar de calidad. FINANCIACIÓN: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme, EDRD. PPA [CM18/00132], NGP [FI19/00133] y CGV [FIS PI18/01061], han recibido becas del Ministerio de Sanidad y Consumo, ISCIII.