Extraparenchymal neurocysticercosis in the United States: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neurocysticercosis is endemic in the developing world, but is becoming more common in the United States due to immigration.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man presented with headache, nausea and vomiting and was found to have hydrocephalus and meningitis. Brain imaging and immunological studies were suggestive of neurocysticercosis. Endoscopic removal of the cyst resulted in resolution of symptoms. This case represents a combination of two rare presentations of extraparenchymal neurocysticercosis; intraventricular neurocysticercosis and subarachnoid neurocysticercosis.</p> <p>Conclusion</p> <p>Although neurocysticercosis is pleomorphic in its presentation, extraparenchymal neurocysticercosis may be challenging to diagnose and treat. Clinicians should be aware of this condition given increasing incidence in the United States.</p

Discovery of a new generation of angiotensin receptor blocking drugs:Receptor mechanisms and in silico binding to enzymes relevant to SARS-CoV-2

The discovery and facile synthesis of a new class of sartan-like arterial antihypertensive drugs (angiotensin receptor blockers [ARBs]), subsequently referred to as “bisartans” is reported. In vivo results and complementary molecular modelling presented in this communication indicate bisartans may be beneficial for the treatment of not only heart disease, diabetes, renal dysfunction, and related illnesses, but possibly COVID-19. Bisartans are novel bis-alkylated imidazole sartan derivatives bearing dual symmetric anionic biphenyl tetrazole moieties. In silico docking and molecular dynamics studies revealed bisartans exhibited higher binding affinities for the ACE2/spike protein complex (PDB 6LZG) compared to all other known sartans. They also underwent stable docking to the Zn2+ domain of the ACE2 catalytic site as well as the critical interfacial region between ACE2 and the SARS-CoV-2 receptor binding domain. Additionally, semi-stable docking of bisartans at the arginine-rich furin-cleavage site of the SARS-CoV-2 spike protein (residues 681–686) required for virus entry into host cells, suggest bisartans may inhibit furin action thereby retarding viral entry into host cells. Bisartan tetrazole groups surpass nitrile, the pharmacophoric “warhead” of PF-07321332, in its ability to disrupt the cysteine charge relay system of 3CLpro. However, despite the apparent targeting of multifunctional sites, bisartans do not inhibit SARS-CoV-2 infection in bioassays as effectively as PF-07321332 (Paxlovid)

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir as treatments for COVID-19 in patients at high risk

Background Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable. Methods The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy. Results Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence. Conclusions Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations

Molecular epidemiology of SARS-CoV-2: the dominant role of arginine in mutations and infectivity

Background, Aims, Methods, Results, Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. The molecular biology of this virus has been extensively studied and computational methods applied are an example paradigm for novel antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis by proteases, such as furin, trypsin, and the Transmembrane Serine Protease 2 (TMPRSS2) that augment infection rates, while inhibition of the 3-chymotrypsin-like protease (3CLpro) can prevent the viral replication. Additionally, non-RBD and non-interfacial mutations may assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. This study aimed to report variant distribution of SARS-CoV-2 across European Union (EU)/European Economic Area (EEA) countries and relate mutations with the driving forces that trigger infections. Variants’ distribution data for SARS-CoV-2 across EU/EEA countries were mined from the European Centre for Disease Prevention and Control (ECDC) based on the sequence or genotyping data that are deposited in the Global Science Initiative for providing genomic data (GISAID) and The European Surveillance System (TESSy) databases. Docking studies performed with AutoDock VINA revealed stabilizing interactions of putative antiviral drugs, e.g., selected anionic imidazole biphenyl tetrazoles, with the ACE2 receptor in the RBD-ACE2 complex. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants, which stabilize the RBD-ACE2 complex, were investigated by computational approaches. Arginine is the critical amino acid in the polybasic furin cleavage sites S1/S2 (681-PRRARS-686) S2′ (814-KRS-816). Critical mutations into arginine residues that were found in the delta variant (L452R, P681R) and may be responsible for the increased transmissibility and morbidity are also present in two widely spreading omicron variants, named BA.4.6 and BQ.1, where mutation R346T in the S-protein potentially contributes to neutralization escape. Arginine binders, such as Angiotensin Receptor Blockers (ARBs), could be a class of novel drugs for treating COVID-19

Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that human endogenous retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. By comparing transcriptomes of bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy controls, and peripheral blood monocytes (PBMCs) from patients and controls, we have shown that HERVs are intensely dysregulated in BALF of COVID-19 patients compared to those in BALF of healthy control patients but not in PBMCs. In particular, upregulation in the expression of specific HERV families was detected in BALF samples of COVID-19 patients, with HERV-FRD being the most highly upregulated family among the families analyzed. In addition, we compared the expression of HERVs in human bronchial epithelial cells (HBECs) without and after senescence induction in an oncogene-induced senescence model in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the process of cellular senescence. This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in the involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to that in noninduced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations

Eosinophilic pneumonia associated with daptomycin: a case report and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Although several studies did not demonstrate that daptomycin may cause significantly higher rates of pulmonary adverse effects when compared with vancomycin or penicillinase-resistant penicillins, there have been a few case reports of severe pulmonary complications associated with daptomycin administration.</p> <p>Case presentation</p> <p>A rare case of eosinophilic pneumonia occurring 10 days after daptomycin administration in a 78-year-old Caucasian man with possible infectious endocarditis is described. He developed new onset fever, up to 38.5°C, with bilateral pulmonary crackles on physical examination and with no signs of severe respiratory failure. A chest computed tomography-scan showed bilateral nodular consolidations with air bronchograms and pleural effusions. Immediate discontinuation of daptomycin was followed by vigorous improvement of clinical signs and symptoms with progressive resolution of pulmonary consolidations a month later.</p> <p>Conclusion</p> <p>Physicians should be aware of this rare but serious complication during daptomycin treatment, and prompt discontinuation of the offending agent, with or without additional supportive treatment, must occur immediately.</p

The benefits, costs and feasibility of a low incidence COVID-19 strategy.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust

SARS-CoV-2 Molecular Transmission Clusters and Containment Measures in Ten European Regions during the First Pandemic Wave

International audienceBackground: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome SARS-CoV-2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation. Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super-spreading event found in Uusimaa-FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50–100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0–19 y.o. decreased only in those regions where schools’ closure was combined with a lockdown. Conclusions: The spatiotemporal profiling of the SARS-CoV-2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing

Towards a European strategy to address the COVID-19 pandemic.

Reduction of COVID-19 incidence across Europe in the early spring months of 2021 led to substantial relaxation of restrictions in summer, despite the emergence and spread of the more transmissible SARS-CoV-2 delta variant. As expected, this relaxation led to a renewed increase in incidence. How should Europe act, what strategies should it adopt, and what specific risks should it consider moving forward