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.

High Incidence of Asymptomatic Phase I IgG Seroconversion After an Acute Q Fever Episode: Implications for Chronic Q Fever Diagnosis.

BACKGROUND: The aim of this study was to describe the natural history of acute Q fever, including its clinical and serological evolution and progression to chronic Q fever. METHODS: Observational cohort study (January 2011-September 2020) performed at Valme University Hospital (Seville, Spain). Inclusion criteria: (1) patients aged ≥18 years; (2) acute Q fever diagnosis, defined as suggestive symptoms in the presence of phase II immunoglobulin G (IgG) titer >1:256; (3) at least 6 months' follow-up after the acute Q fever episode. The incidence of seroconversion to a chronic Q fever serological pattern, defined as phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis, was assessed. RESULTS: During the study period, 117 patients were included. Thirty-four (29%) patients showed phase I IgG titers ≥1:1024 6 months after acute Q fever diagnosis. All patients with classic serological criteria for chronic Q fever diagnosis remained asymptomatic despite no specific treatment, with a median (quartile 1-quartile 3 [Q1-Q3]) follow-up of 26.5 (14-44) months in this subgroup. No cases of Q fever endocarditis nor other persistent focalized infection forms were observed during the study period. CONCLUSIONS: A significant proportion of acute Q fever patients develop classic serological criteria for chronic Q fever diagnosis in the absence of additional data of chronic Q fever. Consequently, phase I IgG cutoff titers >1:800 should not be used as a criterion to consider such a diagnosis. The incidence of persistent focalized infection forms after acute Q fever is extremely low and does not justify the use of prophylaxis strategies.

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.).

[Rainfall and acute febrile syndrome in a dengue-endemic area]. / Pluviosidad como Predictor de Consulta por Síndrome Febril Agudo en un Area Endémica de Dengue.

OBJECTIVE: Describing patterns of acute febrile syndrome (AFS) consultation related to dengue and evaluating association with rainfall. METHODS: 318 undifferentiated AFS patients were detected in two clinics during a 7-month period (March to September) and then included in systematic clinical follow-up. 31 % of them (81/281) were IgM positive for dengue. Rainfall (litres/square meter-day) during the previous weeks was evaluated as a variable for predicting consultation patterns. RESULTS: June, July and September were the months in which the greatest number of AFS cases occurred. Cases of dengue were only significantly more frequent during July. When evaluating the previous weeks' rainfall patterns, consultation for AFS was seen to be associated with the average rainfall registered 5 weeks beforehand and such association was independent of the institution and/or month (incidence rate ratio IRR=1,04; 1-1.08 95 %CI, p=0.045). On the other hand, 5 consecutive weeks' average rainfall was an independent predictor of consultation for dengue 4 weeks later on (RTI=1 ,6 ; 1,15-2,22 95 %CI, p=0.006). A linear relationship was thus proposed (regarding these sentinel clinics) between consultation for dengue and rainfall: lt/mt-day (5 weeks' average rainfall) X 0 ,72 (0,60-0,84 95 %CI, p<0.001) = cases for each 100 000 habitants per week (4 weeks later). CONCLUSIONS: Studying rainfall could predict the pattern of consultation for dengue in endemic regions.

Pluviosidad como predictor de consulta por síndrome febril agudo en un área endémica de dengue / Rainfall and acute febrile syndrome in a dengue-endemic area

Objetivo Describir los patrones de consulta por SFA asociado al dengue y evaluar su asociación con la pluviosidad. Métodos En dos clínicas, durante un periodo de 7 meses (de marzo a septiembre) se identificaron 318 casos de SFA indiferenciado que se incluyeron en un seguimiento clínico sistemático. El 31 por ciento (81/281) fueron IgM positivos para dengue. Se evaluó la pluviosidad (litros/metro cuadrado por día) previa como variable explicatoria del patrón de consultas. Resultados Los meses con más casos de SFA fueron junio, julio y septiembre. Los casos de dengue sólo fueron significativamente más frecuentes en julio. Al evaluar los patrones de pluviosidad de las semanas anteriores, la consulta por SFA estuvo asociada con la pluviosidad promedio registrada 5 semanas antes y esta asociación fue independiente de la institución y del mes (Razón de tasas de incidencia ajustada: RTI=1,04; IC95 por ciento 1-1,08; p=0,045). Por otra parte, un promedio de la pluviosidad de 5 semanas consecutivas fue un predictor independiente de consulta por dengue, 4 semanas después (RTI=1,6; IC95 por ciento 1,15-2,22; p=0.006). Se evidenció una relación lineal entre la pluviosidad y las consultas por dengue: pluviosidad (promedio de 5 semanas) x 0,72 (IC95 por ciento 0,60-0,84; p<0,001)=casos por cada 100 000 habitantes en una semana (4 semanas después). Conclusiones La pluviosidad podría predecir el patrón de consulta por dengue en una región endémica.

Objective Describing patterns of acute febrile syndrome (AFS) consultation related to dengue and evaluating association with rainfall. Methods 318 undifferentiated AFS patients were detected in two clinics during a 7-month period (March to September) and then included in systematic clinical follow-up. 31 percent of them (81/281) were IgM positive for dengue. Rainfall (litres/square meter-day) during the previous weeks was evaluated as a variable for predicting consultation patterns. Results June, July and September were the months in which the greatest number of AFS cases occurred. Cases of dengue were only significantly more frequent during July. When evaluating the previous weeks' rainfall patterns, consultation for AFS was seen to be associated with the average rainfall registered 5 weeks beforehand and such association was independent of the institution and/or month (incidence rate ratio IRR=1,04; 1-1.08 95 percentCI, p=0.045). On the other hand, 5 consecutive weeks' average rainfall was an independent predictor of consultation for dengue 4 weeks later on (RTI=1 ,6 ; 1,15-2,22 95 percentCI, p=0.006). A linear relationship was thus proposed (regarding these sentinel clinics) between consultation for dengue and rainfall: lt/mt-day (5 weeks' average rainfall) X 0 ,72 (0,60-0,84 95 percentCI, p<0.001) = cases for each 100 000 habitants per week (4 weeks later). Conclusions: Studying rainfall could predict the pattern of consultation for dengue in endemic regions.