Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020.

Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies

Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery

Aims We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. Methods and results Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. Conclusion Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogen

The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses

The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 via induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. Here, we investigated the adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants and its effects on the responsiveness of immune cells upon stimulation with heterologous stimuli. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by inflammatory cytokine production after stimulation - higher IL-1/IL-6 release and decreased IFN-α production. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need for additional studies to elucidate their effects on both innate and adaptive immune responses.</p

IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections.

The host inflammatory response against infections is characterized by the release of pro-inflammatory cytokines and acute-phase proteins, driving both innate and adaptive arms of the immune response. Distinct patterns of circulating cytokines and acute-phase responses have proven indispensable for guiding the diagnosis and management of infectious diseases. This review discusses the profiles of acute-phase proteins and circulating cytokines encountered in viral and bacterial infections. We also propose a model in which the inflammatory response to viral (IL-18/ferritin) and bacterial (IL-6/CRP) infections presents with specific plasma patterns of immune biomarkers

Bacterial- and viral-induced inflammation are characterized by differential plasma levels of CRP and ferritin.

<p>(<b>A</b>) Mean or median concentrations of circulating CRP and ferritin in various viral and bacterial infections illustrate that viral infections are generally characterized by high plasma ferritin with concomitant low circulating CRP [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref018" target="_blank">18</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref045" target="_blank">45</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref047" target="_blank">47</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref054" target="_blank">54</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref057" target="_blank">57</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref091" target="_blank">91</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref094" target="_blank">94</a>], while bacterial infections are commonly characterized by high plasma CRP levels [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref095" target="_blank">95</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref100" target="_blank">100</a>]. (<b>B</b>) Proposed model in which the induction of IL-1β/IL-6 in response to bacterial infections contributes to elevated plasma levels of CRP, while viral infections are characterized by an IL-18 response, culminating in hyperferritinemia. Importantly, IL-1/IL-6/CRP and IL-18/ferritin do not fully reflect the bacterial-viral infection dichotomy, as various bacterial infections are known to elevate plasma IL-18 levels while some viral infections are known to raise plasma IL-1β levels [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref072" target="_blank">72</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005973#ppat.1005973.ref073" target="_blank">73</a>]. The direct correlation between circulating concentrations of IL-18 and ferritin has not yet been investigated and should be assessed in future studies. HCV: hepatitis C virus infection; EBV: Epstein-Barr virus infection; HIV: human immunodeficiency virus infection.</p

Data from: Topical vancomycin reduces the cerebrospinal fluid shunt infection rate: a retrospective cohort study

Object: Despite many efforts at reduction, cerebrospinal fluid (CSF) shunt infections are a major cause of morbidity in shunt surgery, occurring in 5-15% of cases. To attempt to reduce the shunt infection rate at our institution, we added topical vancomycin (intrashunt and perishunt) to our existing shunt infection prevention protocol in 2012. Methods: We performed a retrospective cohort study comparing all shunted patients in January 2010 to December 2011 without vancomycin (control group, 263 procedures) to all patients who underwent shunt surgery between April 2012 and December 2015 with vancomycin (intervention group, 499 procedures). Results: The overall shunt infection rate significantly decreased from 6.8% (control group) to 3.0% (intervention group) (p = 0.023, absolute risk reduction 3.8%, relative risk reduction 56%). Multivariate logistic regression analysis confirmed that the addition of topical vancomycin showed that cases treated under a protocol of topical vancomycin were associated with a decreased shunt infection rate (odds ratio [OR] 0.49 95% CI 0.25-0.998; p=0.049). Age < 1 year was associated with an increased risk of infection (OR) 4.41, 95% CI 2,10-9,26; p=0.001). Time from surgery to infection was significantly prolonged in the intervention group (p=0.001). Conclusion: Adding intraoperative vancomycin to a shunt infection prevention protocol significantly reduces CSF shunt infection rate

Changes in plasma cytokine concentrations during infections.

<p>Changes in plasma cytokine concentrations during infections.</p