Excessive systemic inflammation and raised IL-6 levels resulting from dysregulated host immune responses^1-3 are associated with adverse clinical outcomes in patients hospitalized with COVID-19.⁴ This led to the design of several randomized clinical trials assessing the efficacy of IL-6 antagonists in patients with COVID-19. The IL-6 antagonists commonly investigated were monoclonal antibodies that bind either to membrane-bound and soluble IL-6 receptors (eg, tocilizumab and sarilumab) or directly to IL-6 (eg, siltuximab).⁵

Crimean–Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne disease. In Europe, cases have been reported only in the southeastern part of the continent. We report two autochthonous cases in Spain. The index patient acquired the disease through a tick bite in the province of Ávila — 300 km away from the province of Cáceres, where viral RNA from ticks was amplified in 2010. The second patient was a nurse who became infected while caring for the index patient. Both were infected with the African 3 lineage of this virus. (Funded by Red de Investigación Cooperativa en Enfermedades Tropicales [RICET] and Efficient Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level [EMERGE].)

Campylobacter is a very rare cause of bloodstream infection, although it has been found relatively frequently in patients infected with human immunodeficiency virus (HIV). The impact of highly active antiretroviral therapy (HAART) and new forms of immunosuppression on the incidence of Campylobacter bacteremia has not been sufficiently assessed. In this study we analyzed the incidence and microbiologic and clinical characteristics of Campylobacter bacteremia over 23 years. We reviewed the clinical records of all patients who had Campylobacter bacteremia from 1985 to 2007. Available strains were reidentified using universal polymerase chain reaction (PCR). During the study period, there were 71 episodes of Campylobacter bacteremia in 63 patients (0.24% of all bloodstream infections), and the incidence remained stable (mean, 0.06/1000 admissions per year and 0.47/100,000 inhabitants per year). Median age was 52 years (interquartile range, 31.25-72.5 yr), and 82% of patients were male. The underlying conditions included liver disease (21/64, 32.8%), HIV infection (15/64, 23.4%), malignancy (7/64, 10.9%), solid organ transplantation (2/64, 3%), hypogammaglobulinemia (10/64, 15.6%), and other (18/64, 31.2%). Twelve patients shared more than 1 underlying condition. Campylobacter bacteremia was community acquired in 81% of the episodes. The origin of the bloodstream infection was abdominal (43.5%), primary (26%), or extraintestinal (31%: respiratory 15%, cellulitis 4.8%, urinary 8%, other 3%). C jejuni was recovered in 66% of cases, C fetus in 19%, and C coli in 12%. Universal PCR was performed on 14 available strains. Molecular and conventional identification matched in 8 isolates. In contrast, molecular methods classified as C fetus (n = 2) and C jejuni (n = 1) 3 strains formerly identified only to genus level as Campylobacter species. In another 3 isolates, molecular identification was not consistent with the phenotypic identification (C fetus identified as C jejuni). Complications appeared in 23.9% of patients. Quinolone resistance was observed in 50% of the isolates. Only 37.8% of patients received appropriate empirical therapy. Mortality was 16.4%, although it was higher in HIV-infected patients than uninfected patients (33% vs. 10%; p = 0.04), in cases of hospital-acquired Campylobacter bacteremia compared with community-acquired cases (38.5% vs. 9.4%; p = 0.02), and in the presence of complications compared with patients without complications (100% vs. 0%; p < 0.001). The incidence of recurrence was 5% (3 patients with humoral immunodeficiency). There was a higher proportion of HIV-infected patients among patients with Campylobacter bacteremia in the pre-HAART era (1985-1996) than in the HAART era (1997-2007)-27.5% (11/40) vs. 14.3% (4/28)-although the difference was not statistically significant. Debilitating diseases such as chronic obstructive pulmonary disease emerged as predisposing conditions in the HAART era (0% before HAART era vs. 14.3% in HAART era; p = 0.032). Campylobacter bacteremia is no longer a significant disease of HIV-positive patients on HAART, but often affects other immunocompromised patients as well. Campylobacter bacteremia has an extraintestinal origin in as many as 31% of cases, and humoral immunodeficiency must be sought in patients with recurrent episodes. Quinolones should not be considered for empirical therapy.

BACKGROUND. Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive. METHODS. We conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population. RESULTS. Between April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5–7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19–1.14, log-rank P = 0.087). CONCLUSION. CP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant. TRIAL REGISTRATION. Clinicaltrials.gov, NCT04345523. FUNDING. Government of Spain, Instituto de Salud Carlos III.

Depending on the local prevalence of endocarditis, the NOVA prediction score (Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur) may safely obviate echocardiography in 14%–27% of patients with enterococcal bacteremia. Background. Frequency of enterococcal bloodstream infection (E-BSI) is increasing, and the number of episodes complicated by infective endocarditis (IE) varies. Performing transesophageal echocardiography (TEE) in all patients with E-BSI is costly and time-consuming. Our objectives were to identify patients with E-BSI who are at very low risk of enterococcal IE (and therefore do not require TEE) and to compare the outcome of E-BSI in patients with/without IE. Methods. Between September 2003 and October 2012, we performed a prospective cohort study (all patients with E-BSI) and a case-control study (patients with/without enterococcal IE) in our center. Results. We detected 1515 patients with E-BSI and 65 with enterococcal IE (4.29% of all episodes of E-BSI, 16.7% of patients with E-BSI who underwent transthoracic echocardiography, and 35.5% of all patients with E-BSI who underwent TEE). We developed a bedside predictive score for enterococcal IE—Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur (NOVA) score—based on the following variables: Number of positive blood cultures (3/3 blood cultures or the majority if more than 3), 5 points; unknown Origin of bacteremia, 4 points; prior heart Valve disease, 2 points; Auscultation of a heart murmur, 1 point (receiver operating characteristic = 0.83). The best cutoff corresponded to a score ≥4 (sensitivity, 100%; specificity, 29%). A score <4 points suggested a very low risk for enterococcal IE and that TEE could be obviated. Conclusions. Enterococcal IE may be more frequent than generally thought. Depending on local prevalence of endocarditis, application of the NOVA score may safely obviate echocardiography in 14%–27% of patients with E-BSI.