On 30 January 2020, the World Health Organization (WHO) declared the current novel coronavirus disease 2019 (COVID-19) as a public health emergency of international concern and later characterized it ...as a pandemic. New data show that excess body mass and vitamin D deficiency might be related to the disease severity and mortality. The aim of this study was to evaluate whether latitude, as a proxy of sunlight exposure and Vitamin D synthesis, and prevalent obesity among European populations, is related to COVID-19 spread and severity. European COVID-19 data (incidence and fatality), including information on the prevalence of obesity, social distancing, and others were obtained by the "Our World in Data" website on 17 April 2021. Adjusted analysis showed that higher COVID-19 incidence and fatality were pictured in countries being in higher latitude, both during the whole period, as well as, during the time period 1 November 2020-31 March 2021. Higher incidence and fatality of COVID-19 were observed where the prevalence of overweight/obesity was higher during the whole time period, whereas during the time period 1 November 2020-31 March 2021, only COVID-19 incidence was higher but not a fatality. The present results provide insights for targeted interventions and preventive strategies against COVID-19.
Binding energies and dissociation constants of sartans bound to RBD/ACE2 complex.
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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).
Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) ...paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using ‘in-house’ methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of ‘non-responders’ a misnomer.
The importance of fluid resuscitation therapy during the early stages of sepsis management is a well-established principle. Current Surviving Sepsis Campaign (SSC) guidelines recommend the early ...administration of intravenous crystalloid fluids for sepsis-related hypotension or hyperlactatemia due to tissue hypoperfusion, within the first 3 h of resuscitation and suggest using balanced solutions (BSs) instead of normal saline (NS) for the management of patients with sepsis or septic shock. Studies comparing BS versus NS administration in septic patients have demonstrated that BSs are associated with better outcomes including decreased mortality. After initial resuscitation, fluid administration has to be judicious in order to avoid fluid overload, which has been associated with increased mortality, prolonged mechanical ventilation, and worsening of acute kidney injury. The "one size fits all" approach may be "convenient" but it should be avoided. Personalized fluid management, based on patient-specific hemodynamic indices, provides the foundations for better patient outcomes in the future. Although there is a consensus on the need for adequate fluid therapy in sepsis, the type, the amount of administered fluids, and the ideal fluid resuscitation strategy remain elusive. Well-designed large randomized controlled trials are certainly needed to compare fluid choices specifically in the septic patient, as there is currently limited evidence of low quality. This review aims to summarize the physiologic principles and current scientific evidence regarding fluid management in patients with sepsis, as well as to provide a comprehensive overview of the latest data on the optimal fluid administration strategy in sepsis.
We systematically reviewed the existing evidence to determine whether a relationship exists between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) and, if so, to define the ...strength of that relationship. The following terms were used in searches of the Entrez-PubMed database (1966-2009): human herpes virus 6, HHV 6, demyelination, multiple sclerosis, pathogenesis, diagnosis, serology, cerebrospinal fluid, IgG antibodies, IgM antibodies, PCR, and lymphoproliferative techniques . Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high A, intermediate B, and low C) as determined by the Moore and Wolfson criteria. Overall, 25 (41%) of 61 studies, 15 (60%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of quality II-1. Limitations of the available experimental techniques and perspectives for future research are discussed. The current review supports the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.
The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients ...presenting to the emergency department (ED) with septic shock.
Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined.
Sixty-one patients with septic shock 53% females, median age 83 years (IQR 71-88) were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0-2.9) mg/dL, 3.6 (2.1-6.8) mmol/L, 13.1 (10.0-21.4) ng/mL, 2.06 (0.84-3.49) ng/mL, and 205 (129-425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369,
= 0.004), LogCreatinine (rho = 0.537,
< 0.001), LogProcalcitonin (rho = 0.557,
< 0.001), and LogSuPAR (rho = 0.327,
= 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7-84.6,
= 0.013).
POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock.
Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARS-CoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and ...the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30-250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE.
Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs ...conducting a retrospective cohort study in two tertiary Academic Hospitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupation differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75-12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy.
Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID‐19). Plasma from patients that have overcome COVID‐19 infection, referred to ...as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID‐19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non‐randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion‐related acute lung injury and antibody‐dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.
Treatment options for multidrug resistant
strains (MDR-AB) are limited. Minocycline has been used alone or in combination in the treatment of infections associated with AB. A systematic review of the ...clinical use of minocycline in nosocomial infections associated with MDR-AB was performed according to the PRISMA-P guidelines. PubMed-Medline, Scopus and Web of Science
databases were searched from their inception until March 2019. Additional Google Scholar free searches were performed. Out of 2990 articles, 10 clinical studies (9 retrospective case series and 1 prospective single center trial) met the eligibility criteria. In total, 223 out of 268 (83.2%) evaluated patients received a minocycline-based regimen; and 200 out of 218 (91.7%) patients with available data received minocycline as part of a combination antimicrobial regimen (most frequently colistin or carbapenems). Pneumonia was the most common infection type in the 268 cases (80.6% with 50.4% ventilator-associated pneumonia). The clinical and microbiological success rates following minocycline treatment were 72.6% and 60.2%, respectively. Mortality was 20.9% among 167 patients with relevant data. In this systematic review, minocycline demonstrated promising activity against MDR-AB isolates. This review sets the ground for further studies exploring the role of minocycline in the treatment of MDR-AB associated infections.
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