Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

Identifying Adverse Events in Patients Hospitalized in Isolation or Quarantine Due to COVID-19.

BACKGROUND: This study evaluated the adverse events of COVID-19 isolation or quarantine in patients with nosocomial SARS-CoV-2 infection admitted to the Hospital Universitario Insular de Gran Canaria. METHODS: This is a retrospective cohort study with 30-day follow-up of 126 patients diagnosed with nosocomial COVID-19 through polymerase chain reaction test, between May 1 and June 30, 2022, in a 500-bed university hospital in the island of Gran Canaria. RESULTS: Between May 1 and July 30, 2022, a total of 2250 patients were admitted to the Hospital Universitario Insular de Gran Canaria; 126 of them were diagnosed with nosocomial COVID-19 through a polymerase chain reaction test. The rate of nosocomial COVID-19 infection was 5.6%. From the 126 patients of the study population, 27 experienced an adverse event (21.4%) and 2 experienced 2 adverse events (1.6%) due to COVID-19 isolation or quarantine. Thus, a total of 31 adverse events occurred in 29 patients. These events included the following: delay in transfer to other centers of 11 patients who were pending of receiving a negative COVID-19 test result (35.5%), delay or cancellation of diagnostic tests in 9 patients (29%), delay or cancellation of doctor visit in 7 patients (22.6%), and delay or cancellation of surgical or other interventions in 4 patients (12.9%). CONCLUSIONS: Because of the adverse consequences of nosocomial COVID-19 infection in hospitalized patients, measures should be observed for the prevention and control of nosocomial infection transmission, and adverse events related to patient safety issues in health care in isolated or quarantined COVID-19 patients should be prevented.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Lifting COVID-19 mitigation measures in Spain (May–June 2020) La desescalada de las medidas de mitigación contra el COVID-19 en España (mayo–junio 2020)

Introduction The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly;positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

El impacto de la pandemia de COVID-19 sobre la salud. Informe SESPAS 2022 Health impact of COVID pandemic. SESPAS Report 2022

Objetivo Presentar, a los 22 meses de que la Organización Mundial de la Salud declarara como pandemia la infección global por SARS-CoV-2 el 11 de marzo de 2020, el impacto hasta el momento de la pandemia en términos de salud física y mental. Método Se han revisado resultados procedentes de metaanálisis y revisiones sistemáticas, citándose para algún aspecto específico de interés artículos individuales. La información nacional procede de la Red Nacional de Vigilancia Epidemiológica (RENAVE). Resultados Hasta finales de octubre se habían producido más de 250 millones de infecciones y 5 millones de muertes. En España se han notificado 4,7 millones de infecciones, aunque la cifra real es superior a los 7 millones. Se ha reducido la esperanza de vida, con efectos especialmente dramáticos en grupos de población con comorbilidad y de edad avanzada. Se constata un empeoramiento de la salud mental general. Es previsible que algunos colectivos, como los/las profesionales sanitarios/as, en su mayoría mujeres, y trabajadores/as de primera línea, tengan un mayor riesgo de desarrollar patologías de salud mental en el futuro. La pandemia y las medidas de control han tenido otras consecuencias indeseables, como la disminución de la actividad asistencial, el aumento del sedentarismo y el aumento de la violencia de género. Conclusiones Son necesarios estudios longitudinales para determinar la magnitud de las consecuencias de la propia infección y de las medidas de control y las actuaciones necesarias.

[Health impact of COVID pandemic. SESPAS Report 2022]. / El impacto de la pandemia de COVID-19 sobre la salud. Informe SESPAS 2022.

OBJECTIVE: The World Health Organization declared the global SARS-CoV-2 infection a pandemic on March 11, 2020. The objective of this paper is to present its impact in terms of physical and mental health 22 months later. METHOD: We have reviewed results from published meta-analysis and systematic reviews, and some individual articles on specific aspects of special interest. National information on infection comes for the Red Nacional de Vigilancia Epidemiológica (RENAVE). RESULTS: Up to the end of October, more than 250 million infections and 5 million deaths had been reported globally. In Spain, 4.7 million infections have been documented although the real figure might be above 7 million. The pandemic has reduced life expectancy, and its effects have been especially dramatic in people with comorbidities and the elderly. There is a worsening of mental health in the general population. It is foreseeable that some groups, such as health professionals, mostly women, and front-line workers, may have a greater risk of developing mental health pathologies. The pandemic and the control measures have had other undesirable consequences such as a decrease in healthcare utilization, an increase in sedentary lifestyle or an increase in gender violence. In addition to its immediate effect on morbidity and mortality, the control measures have damaged the overall health status of the global population. CONCLUSIONS: Longitudinal studies are necessary to determine the mid and long consequences of the pandemic and the control measures, and to identify and evaluate effective health interventions.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

A population-based controlled experiment assessing the epidemiological impact of digital contact tracing.

While Digital contact tracing (DCT) has been argued to be a valuable complement to manual tracing in the containment of COVID-19, no empirical evidence of its effectiveness is available to date. Here, we report the results of a 4-week population-based controlled experiment that took place in La Gomera (Canary Islands, Spain) between June and July 2020, where we assessed the epidemiological impact of the Spanish DCT app Radar Covid. After a substantial communication campaign, we estimate that at least 33% of the population adopted the technology and further showed relatively high adherence and compliance as well as a quick turnaround time. The app detects about 6.3 close-contacts per primary simulated infection, a significant percentage being contacts with strangers, although the spontaneous follow-up rate of these notified cases is low. Overall, these results provide experimental evidence of the potential usefulness of DCT during an epidemic outbreak in a real population.