Not all COVID-19 pandemic waves are alike.

OBJECTIVE: We aimed to assess differences in patients' profiles in the first two surges of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Barcelona, Spain. METHODS: We prospectively collected data from all adult patients with SARS-CoV-2 infection diagnosed at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. All the patients were diagnosed through nasopharyngeal swab PCR. The first surge spanned from 1st March to 13th August 2020, while surge two spanned from 14th August to 8th December 2020. RESULTS: There were 2479 and 852 patients with microbiologically proven SARS-CoV-2 infection in surges one and two, respectively. Patients from surge two were significantly younger (median age 52 (IQR 35) versus 59 (40) years, respectively, p < 0.001), had fewer comorbidities (379/852, 44.5% versus 1237/2479, 49.9%, p 0.007), and there was a shorter interval between onset of symptoms and diagnosis (median 3 (5) versus 4 (5) days, p < 0.001). All-cause in-hospital mortality significantly decreased for both the whole population (24/852, 2.8% versus 218/2479, 8.8%, p < 0.001) and hospitalized patients (20/302, 6.6% versus 206/1570, 13.1%, p 0.012). At adjusted logistic regression analysis, predictors of in-hospital mortality were older age (per year, adjusted odds ratio (aOR) 1.079, 95%CI 1.063-1.094), male sex (aOR 1.476, 95%CI 1.079-2.018), having comorbidities (aOR 1.414, 95%CI 0.934-2.141), ICU admission (aOR 3.812, 95%CI 1.875-7.751), mechanical ventilation (aOR 2.076, 95%CI 0.968-4.454), and coronavirus disease 2019 (COVID-19) during surge one (with respect to surge two) (aOR 2.176, 95%CI 1.286-3.680). CONCLUSIONS: First-wave SARS-CoV-2-infected patients had a more than two-fold higher in-hospital mortality than second-wave patients. The causes are likely multifactorial.

Effectiveness and safety of intravenous tocilizumab to treat COVID-19-associated hyperinflammatory syndrome: Covizumab-6 observational cohort.

Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications.

The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19).

The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.

Characteristics and outcome of spontaneous bacterial meningitis in patients with diabetes mellitus.

BACKGROUND: Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM). METHODS: We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality. RESULTS: We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p <  0.001) and more often had a Charlson comorbidity score of ≥3 (40% vs 15%, p <  0.001). Neck stiffness (56% vs 75%, p <  0.001), headache (41% vs 78%) p <  0.001), nausea and/or vomiting (32% vs 56% p < 0.001), and rash (12% vs 26%, p = 0.007) were less frequent in diabetics, whereas altered mental status was more common. Streptococcus pneumoniae and Listeria meningitis were the most common etiologic agents (24 and 18%, respectively). Listeria was more frequent (18% vs. 10%, p = 0.033), whereas meningococcal meningitis was less frequent (10% vs 32%, p < 0.001). Overall mortality was higher in patients with diabetes (26% vs 16%, p = 0.025) concerning non-diabetics. CONCLUSIONS: Patients with bacterial meningitis and diabetes mellitus are older, have more comorbidities, and higher mortality. S. pneumoniae and L. monocytogenes are the predominant pathogens, Listeria being more common, whereas Neisseria meningitidis is significantly less frequent than in non-diabetics.

Recommendations of the Spanish Antibiogram Committee (COESANT) for selecting antimicrobial agents and concentrations for in vitro susceptibility studies using automated systems.

Automated antimicrobial susceptibility testing devices are widely implemented in clinical microbiology laboratories in Spain, mainly using EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints. In 2007, a group of experts published recommendations for including antimicrobial agents and selecting concentrations in these systems. Under the patronage of the Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) and the Study Group on Mechanisms of Action and Resistance to Antimicrobial Agents (GEMARA) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and aligned with the Spanish National Plan against Antimicrobial Resistance (PRAN), a group of experts have updated this document. The main modifications from the previous version comprise the inclusion of new antimicrobial agents, adaptation of the ranges of concentrations to cover the EUCAST breakpoints and epidemiological cut-off values (ECOFFs), and the inference of new resistance mechanisms. This proposal should be considered by different manufacturers and users when designing new panels or cards. In addition, recommendations for selective reporting are also included. With this approach, the implementation of EUCAST breakpoints will be easier, increasing the quality of antimicrobial susceptibility testing data and their microbiological interpretation. It will also benefit epidemiological surveillance studies as well as the clinical use of antimicrobials aligned with antimicrobial stewardship programs.

The spectrum of acute bacterial meningitis in elderly patients.

BACKGROUND: We conducted a prospective, observational study in Barcelona to determine the epidemiology, clinical features, and outcome of elderly patients with acute bacterial meningitis (ABM) compared with younger adults. METHODS: During 1982-2010, all patients with ABM were prospectively evaluated. There were two groups: I (15-64 years) and II (≥ 65 years). All patients underwent clinical examination on admission and at discharge following a predefined protocol. RESULTS: We evaluated 635 episodes of ABM. The incidence was 4.03/100,000 (Group I) and 7.40 /100,000 inhabitants/year (Group II) (RR = 1.84; 95%CI: 1.56-2.17, P < 0.0001). Elderly patients had co-morbid conditions more frequently (P < 0.0001) and more frequently lacked fever (P = 0.0625), neck stiffness (P < 0.0001) and skin rash (P < 0.0001), but had an altered level of consciousness more often (P < 0.0001). The interval admission-start of antibiotic therapy was longer for elderly patients (P < 0.0001). Meningococcal meningitis was less frequent in elderly patients (P < 0.0001), whereas listerial (P = 0.0196), gram-negative bacillary (P = 0.0065), and meningitis of unknown origin (P = 0.0076) were more frequent. Elderly patients had a higher number of neurologic (P = 0.0009) and extra-neurologic complications (P < 0.0001). The overall mortality ratio was higher in elderly patients (P < 0.0001). CONCLUSIONS: Elderly people are at higher risk of having ABM than younger adults. ABM in the elderly presents with co-morbid conditions, is clinically subtler, has a longer interval admission-antibiotic therapy, and has non-meningococcal etiology. It is associated with an earlier and higher mortality rate than in younger patients.