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Introduction This study aimed to determine the prevalence of multidrug-resistant Gram-negative bacteria (GNB) from blood cultures in a tertiary-care hospital and the multiplex PCR assay's ability to detect resistance genes. Methods A total of 388 GNB isolates obtained from hospitalized patients between November 2019 and November 2021 were included in the study. Antimicrobial susceptibility testing was done by VITEK 2 system and broth microdilution method. Beta-lactamase-encoding genes were detected by multiplex PCR assays, BioFire-Blood Culture Identification 2 (BCID2) panel (bioMerieux, France). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically with VITEK AST-GN71 card (bioMerieux, France). The isolates of GNB were classified into multidrug-resistant, extensively-drug-resistant, and pandrug-resistant categories, and their prevalence and distribution in different wards, including coronavirus diseases 2019 (COVID-19) intensive care units (ICU), were calculated. Results Results revealed that all isolates of Acinetobacter baumannii and Pseudomonas aeruginosa were multidrug-resistant as well as 91.6% of Enterobacter cloacae, 80.6% of Proteus mirabilis, and 76.1% of Klebsiella pneumoniae, respectively. In fermentative bacteria, blaOXA-48-like (58.1%), blaNDM (16.1%), blaKPC (9.7%) and blaVIM (6.5%) genes were detected. More than half of Enterobacter cloacae (58.3%) and Klebsiella pneumoniae (53.7%) produced ESBLs. Among non-fermenters, the blaNDM gene was carried by 55% of Pseudomonas aeruginosa and 19.5% of Acinetobacter baumannii. In the COVID-19 ICU, Acinetobacter baumannii was the most common isolate (86.1%). Conclusions This study revealed high proportions of multidrug-resistant blood isolates and various underlying resistance genes in Gram-negative strains. The BCID2 panel seems to be helpful for the detection of the most prevalent resistance genes of fermentative bacteria.Copyright © GERMS 2022.
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Background: Patients with primary and secondary immunodeficiencies have shown an impaired humoral immune response to COVID-19 vaccination. It is therefore of paramount importance to investigate anti-SARS-CoV-2 antibody levels in plasma pools and in immunoglobulin (IgG) products used to treat these patients. AIM: To assess the evolution of anti-SARS-CoV-2 antibodies (S protein) in plasma pools and IgG products and its neutralizing activity to original-type virus (Wuhan) and the variants of concern (VOC), including Omicron. Method(s): Healthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020. Anti-SARS-CoV-2 S protein IgG titers were determined in plasma pools and in IgG batches by ELISA. Neutralization assays analyzed the capacity of IgG products to neutralize original-type virus and VOC (Alpha, Beta, Delta, Omicron BA.1 and BA.5), using pseudo viruses expressing S protein. Results were expressed as the dilution producing 50% neutralization (ID50). Result(s): In plasma pools, anti-SARS-CoV-2 S antibodies continuously increased throughout the study period regardless of the geographic origin. In the US, the first positive plasma pools were collected at the end of 2020. Since July 2021, an exponential increase over 30-fold of anti-SARS-CoV-2 S antibodies was reported. This trend continued increasing until the end of study period. Similarly, IgG products showed a similar evolution of anti-SARS-CoV-2 S antibodies. As expected, IgG batches released at the end of 2020 presented low SARS-CoV-2 neutralization activity. However, IgG products manufactured since August 2021 showed high neutralization activity against original-type virus and the rest of VOC. Regarding Omicron BA.5, a 5 to 10-fold increase was observed over time. Conclusion(s): This study reported the onset of elevated anti-SARS-CoV-2 antibody titers in plasma pools and IgG products since mid-2021, reflecting the evolution of the pandemic and vaccine campaigns. Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products.Copyright © 2023 Elsevier Inc.
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Introduction: Miliaria crystallina occurring during neonatal period is one of the differential diagnosis for vesiculopustular lesions in that age group. Congenital miliaria crystallina is a rare condition developing due to various causes. Case Report: An otherwise well, term female neonate born by caesarean section presented with generalised clear fluid filled vesicles over the trunk, upper limbs, face and scalp at birth. Mother was COVID-19 positive with fever and cough for 1 week. Otherwise she had an unremarkable antenatal, sexual history and examination. The vesicles were located on normal looking skin and ruptured easily on rubbing. Palms, soles and mucosae were normal. Tzanck smear from the vesicles showed a few deformed keratinocytes only. Venereal Disease Research Laboratory test in dilution for both mother and child was non-reactive. Baby's RT-PCR came negative. She fared well on follow up, the vesicles started to desquamate on the second day and completely disappeared on the third day. Mother's COVID-19 symptoms also subsided after child birth. A final diagnosis of congenital miliaria crystallina was made based on the characteristics of the vesicles. Discussion(s): Miliaria crystallina is triggered by environmental temperature and humidity. Congenital cases are associated with maternal febrile illnesses. However, there are reports of it occurring in newborns of mothers without fever in whom other factors are involved. This is the first report of congenital miliaria crystallina occurring in a neonate born to a COVID-19 positive mother. Conclusion(s): This case report highlights the importance of recognizing this benign self-limiting condition so as to avoid unnecessary investigations to find an alternative cause.
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Background: This study aimed to evaluate the outcomes of preclinical studies on the safety and immunogenicity of an inactivated COVID-19 vaccine candidate to warrant further clinical evaluation. Method(s): SARS-CoV-2 positive nasopharyngeal swab specimens were confirmed by real-time polymerase chain reaction and next-generation sequencing. The safety and immunogenicity tests of the COVID-19 vaccine were carried out in rats and Rhesus monkeys, and Balb/C mice and Rhesus monkeys, respectively. Result(s): The candidate vaccine was well tolerated and induced promising levels of SARS-CoV-2- specific IgG1, IgG2a, and Granzyme B in Balb/C mice, and anti-SARS-CoV-2 spike IgG and neutralizing antibodies in Rhesus monkeys. Based on cVNT results, the inactivated vaccine in 0.5 and 1 microg/100 microL doses was able to induce a neutralizing effect against the SARS-CoV-2 virus up to a dilution of 1:512 and 1:1000. The protective efficacy of the vaccine candidate was challenged with 2 x108 PFU of live viruses and confirmed by lung CT scan and histopathological evaluations compared to the control group. Repeated intramuscular injection of the candidate vaccine was generally well-tolerated in Rats and Rhesuses. No significant side effects were observed in rats injected with ten full human doses and in the Rhesus monkeys with three full human doses. Conclusion(s): Based on the findings presented in this study, it is recommended that this vaccine be moved into human testing commencing with a phase I clinical trial.Copyright © 2021 Muslim OT et al.
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Respiratory viral infections (RVI) such as influenza and COVID19 impact the host systemic immune system along with causing deleterious chronic inflammatory responses and respiratory distress. While the role of chronic inflammation in cancer is well-established, the role of RVI on tumorigenesis is poorly defined. To study the role of RVI on breast cancer, we first infected murine respiratory epithelial cells (mRES) with murine sendai virus (mSV), an analog for human parainfluenza virus. These infected mRES were co-cultured with 4T1 murine breast cancer cells in 1:1 dilution on a single 2D plate and also in trans-well format. Both in co-culture and transwell culture we saw a 40- 80% (p<0.05) increased proliferation of breast cancer cells. Similarly, when 4T1 cells were treated with the supernatant collected from infected mRES cells in 1:5 dilution, also demonstrated a 2.3 fold increased breast cancer cell proliferation. The cytokine analysis from the supernatant collected from infected mRES cells demonstrated a 17-23 fold enhanced secretion of alpha/beta-defensins. Direct treatment of alpha-defensin (cyptidin-4, 10 pg/mL) and beta-defensin-3 (mBD3, 20 pg/mL) on 4T1 cells demonstrated enhanced expression of chemokine metastatic receptor, CXCR4 (4.3 fold), angiogenic factor, VEGF (12.8 fold) and cell division favoring factor, CDK2 (8.1 fold). Further, analysis of infected mRES cells demonstrated upregulation of toll-like receptor 2 (TLR2) and NODlike receptor protein 3 (NLRP3) expression. Interesting, co-cultured of infected mRES with syngeneic murine CD4 T cells induced exhaustion phenotype (PD1+ and CTLA4+ ) differentiation of CD4 T cells. Taken together, these data suggest that respiratory viral infections through induction of cancer cell proliferation and inhibiting anti-tumor adaptive immune responses promote breast cancer proliferation.
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Short-range exposure to expired aerosols or droplet nuclei has been considered as the predominant route for SARS-CoV-2. The observed effect of mask wearing, and social distancing suggests the importance of expired jet in the spread of COVID-19. The well-known steady-state dilution model is no longer valid for the interrupted expiratory jet. We reanalysed the existing interrupted jet data and proposed a simple dilution model of expired jet using the two-stage jet model. The interrupted jet consists of two stages, i.e., the jet-like and puff-like stage. Results show dilution factor grows linearly with the distance at the jet-like stage but increases with the cubic of the increasing distance in the puff-like stage. Dilution factor at any distance for the puff-like stage decreases as the activity intensifies, which is still much larger than that estimated via the steady jet model. The findings can be further applied into the short-range airborne exposure assessment. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.
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Intro: Acinetobacter calcoaceticus - A.baumannii complex is an opportunistic pathogen that has emerged as one of the multidrug resistant organism frequently associated with nosocomial infections especially causing ventilator- associated pneumonia (VAP). Colistin and Polymyxin B are currently being used as salvage therapy for treating MDR Acinetobacter spp. However, the emergence of resistance of colistin has been reported and treatment is further complicated by poor lung tissue penetration. Thus, we implied to explore on the prevalence of its resistance in our own facility, being the national COVID-19 referral hospital. Method(s): This is a cross-sectional retrospective analysis of MDR Acinetobacter spp. done for isolates of 2019 and 2021. Only clinically significant isolates were sent to Institute of Medical Research (IMR) for colistin susceptibility testing by broth microdilution. The identification of the isolates was performed by Bruker MALDI-ToF. CLSI breakpoints were used to determine susceptibility, applying the change of breakpoints interpretation in year 2020. Finding(s): In 2021, out of 203 isolates, 195 (96%) were Acinetobacter baumannii. Other spp. isolated were A. nosocomialis (6, 3%) and A. proteolyticus (2, 1%). Out of that, 107 (52.7%) were resistant with MIC of >4 ug/ml and 96 (47.3 %) were intermediate with MIC of <2 ug/ml. Pre-pandemic, resistance rates were compared with 2019 and this showed 47% were resistant with MIC of >4 ug/ml and 52% were susceptible with MIC <2 ug/ml. Clinical characteristics of patients were analysed;previous use of carbapenem, ventilation history, length of stay, and outcome (alive or deceased). Most of patients were severely ill with majority of admissions due to Category 4-5 COVID-19 and required ventilation in critical care unit. Previous carbapenem exposure was not significantly associated with colistin resistance (p=0.936). Conclusion(s): Emergence of colistin resistant MDR Acinetobacter spp. is alarming. Infection control measures are crucial and other therapeutic options need to be explored to improve quality of care.Copyright © 2023
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Frequency of bacterial co-infections among patients with COVID-19 is not high, and over-prescribing of antibiotics may contribute the selection of resistant strains of enterobacteria and gram-negative non-fermenting bacteria. The aim of the study was to assess the local features of antibiotic resistance of K. pneumoniae and its genetic mechanisms against background of the COVID-19 infection pandemic. Material and methods. There was selected 37 carbapenem-resistant K. pneumoniae strains isolated in 2016, 2017 and 2020 from hospitalized patients, including 15 strains, isolated from patients with COVID-19 infection. Minimal inhibitory concentrations (MICs) of meropenem and colistin were determined by broth microdilution method. Determination of MICs of eravacycline, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam was performed using Sensititre diagnostic system on EUMDROXF plates. Susceptibility to 11 combinations of 2 antibiotics was detected by modified method of multiply combination bactericidal testing. For 4 K. pneumoniae strains high-throughput sequencing was performed, followed with the subsequent search for determinants of antibiotic resistance and virulence, assessment of plasmid profiles. Results. All strains were resistant to meropenem (MIC50 32 mg/l, MIC90 128 mg/l) and produced KPC and OXA-48 carbapenemases. Strains isolated in 2016-2017 were susceptible to colistin (MIC <=2 mg/l), in 2020 only 26.7% of the strains retained their susceptibility (MIC50 64 mg/l, MIC90 256 mg/l). Susceptibility to combinations of two antibiotics with colistin included reduced from 84.6-100% in 2016-2017 till 26.6-66.7% in 2020. The strains isolated in 2020 retained their susceptibility to ceftazidime/avibactam (MIC <=1 mg/l). 5 strains resistant to cefiderocol with a MIC 8 mg/l were identified. Strains 2564 and 3125 isolated in 2020 from sputum of patients with COVID-19 infection belonged to different sequence-types (ST12 and ST23) and contained the blaOXA-48 carbapenemase gene, additionally strain 2564 contained the blaKPC-27carbapenemase gene. Resistance to colistin was caused by inactivation of the mgrB genes due to insertion of IS1 and IS5-like transposons. Conclusion. The performed genetic studies demonstrate a diversity of mechanisms of antibiotic resistance in K. pneumoniae leading to the formation of resistance including to antibiotics that haven't been used in Belarus till now.Copyright © 2021 Geotar Media Publishing Group. All Rights Reserved.
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Background: Many mechanisms responsible for COVID-19 pathogenesis are well-known, but COVID-19 includes features with unclear pathogenesis, like autonomic dysregulation, coagulopathies, and high levels of inflammation. The SARS-CoV-2 spike protein receptor binding domain (RBD) receptor is angiotensin converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop immunoglobulins (Igs) that have negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity - ACE2-like 'abzymes'. Method(s): To explore this hypothesis, we studied 67 patients hospitalized with COVID-19 who had disodium ethylenediaminetetraacetate (EDTA) anticoagulated plasma samples available, obtained about 7 days after admission. We used commercially available fluorometric ACE2 assays (Abcam), and a SpectraMax M5 microplate reader (Molecular Devices), measuring Relative Fluorescent Unit (RFU, Ex/Em = 320/420 nm;RFU) in a kinetic mode every 20 min at 37C. ACE2 inhibitor provided in the assay kit was used for additional controls. In some control experiments, we added Zn2+ to plasma, or conducted serial dilutions to decrease Zn2+. To deplete Igs, we passed plasma samples through a 0.45 mum filter to remove large particles, then passed the material through 100kDa cut-off ultrafiltration membrane (PierceTM) columns, and finally used protein A/G Magnetic Beads (Life Technologies) to specifically deplete Ig, removing >99.99% of Ig as assessed with a human IgG ELISA Kit (Abcam). Result(s): ACE2 is a metalloprotease that requires Zn2+ for activity. However, we found that the plasma of 11 of the 67 patients could cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using EDTA anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn2+ was added, or the plasma was diluted to decrease EDTA concentration. After processing samples by size exclusion and protein A/G adsorption, the plasma samples did not cleave the ACE2 substrate peptide. Conclusion(s): The data suggest that some patients with COVID-19 develop Igs with activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure features of COVID-19 pathogenesis. (Figure Presented).
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Background: We evaluated SARS-CoV-2 antibody binding and neutralization responses at delivery among pregnant persons with prior SARS-CoV-2 infection by vaccine status. Method(s): We enrolled participants with evidence of prior SARS-CoV-2 infection detected in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) and followed them through delivery. Maternal delivery and cord blood samples were tested for SARS-CoV-2 binding antibodies to spike (anti-S) (from vaccination and/or infection) and anti-N (from infection only) IgG by Abbott Architect followed by neutralizing antibodies (classified as neutralizing if serum dilution inhibited infection by 50% [ND50 heat] >=20 and R2 >=0.9) if sample volume allowed. Positive IgG thresholds were Abbott index >=1.4 for anti-N and >=50 AU/mL for anti-S. Chi-squared test was used to compare differences in proportions between groups. Wilcoxon rank sum test was used to compare medians. Result(s): Among 71 participants with delivery and cord samples, median age was 33 years (interquartile range [IQR] 30-35) and median gestational age was 31.7 weeks (IQR 18.0-37.9) at enrollment in pregnancy. By delivery, 17 (24%) participants were unvaccinated, 21 (30%) were partially vaccinated or had completed a primary series, and 33 (46%) were boosted. Median time from infection (RT-PCR+ or antigen+ result) to delivery was 16.7 weeks (IQR 9.7- 24.3). At delivery, 33 (46%) of maternal (median 3.2 index) and 37 (52%) of cord samples (median 3.1 index) were anti-N IgG+. Participants with >=1 vaccine were more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,019 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 81%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Similarly, cord blood from participants with >=1 vaccine was more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,188 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 75%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Conclusion(s): Among pregnant people with prior SARS-CoV-2 infection detected during pregnancy, maternal and cord blood antibody binding and neutralization responses were higher among those receiving SARS-CoV-2 vaccination prior to delivery. (Table Presented).
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A Cryptococcus subspecies, neoformans, represents the most pathogenic infection for humans, particularly in immunocompromised hosts (e.g., cancer patients, drug users). In the present study, we described a 67-year old woman with non-Hodgkin lymphoma who developed an infectious disease sustained by Cryptococcus neoformans. Biochemical data documented a decrease in lymphocytes count while clinical evaluation was suggestive on meningeal infection. The microbiological analysis of the serum, using a dilution pattern through the CrAg lateral flow assay (Immy, Norman, OK 73069, USA) detected the antigen of Cryptococcus (dilution 1/1280), and a treatment with liposomal amphotericin B (3 mg/kg id) plus flucytosine (100 mg/kg per day orally in four divided doses) were started, showing an improvement of symptoms. This case report suggests that an antigen dilution can be used to perform a rapid diagnosis and to quickly start the pharmacological treatment.
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Background: In the last two years the pandemic Coronavirus Disease 19 (Covid19), caused by the virus SARS-CoV- 2, described for the first time in Wuhan (China) at the end of 2019, has caused over 359 million cases of infections and 5 million deaths worldwide. To fight this emergency, the pursuit of science has focused on vaccines development against SARS-CoV- 2, including the vaccine BNT162b2. This vaccine contains mRNA translating for SARS-CoV- 2 spike protein wrapped in lipid nanoparticles and its use was approved at the end of 2020. It has been proved that both the BNT162b2 vaccine and the SARS-CoV- 2 infection result in the production of neutralizing antibodies but remains to be clarified the duration of these responses, also versus variants of concern. Method(s): The present study aimed to prospectively analyse and correlate the antibody response and the neutralization capability induced by vaccination with BNT162b2 in a cohort of Sardinian subjects, including a group previously Cov2 infected. Each participant was evaluated for serum SARS-CoV2 Ab IgG RDB, 7 (T1) and 30 (T2) days after the second inoculum of BNT162b2, with chemiluminescent immunoassays (CLIA) and microneutralization assay (MNA) determining the highest serum dilution protecting 90 % of the infected wells. Result(s): All the participants, with or without previous infection, developed a positive antibody response (IgG anti-RBD > 1 AU/ml) within 7 and 30 days from the second vaccine dose and a strong correlation was found between IgG antibody levels and neutralizing activity. A strong difference was observed between the antibody levels of the naive subjects and the ones previously infected, specifically the antibody levels were higher (both at T1 and T2) in the latter group. No significant antibody differences were found for gender and age groups. In addition, there were no significant differences in antibody titre between healthy and immune-mediated subjects. Conclusion(s): In conclusion, this study confirms observed differences in vaccine responses between infection-naive and subjects with history of natural infection, with the presence in the second group of a significantly higher neutralizing and anti-RBD antibody titer. It also demonstrates the strong correlation between anti-RBD antibody titre and neutralizing activity, without significant differences between healthy subjects and subjects with immuno-mediated disease in the short-term. Further follow-up is ongoing in this cohort.
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The Air borne transmission is a very big concern for highly infectious diseases like Covid-19 and other airborne diseases. A micro droplet and aerosol can be carried out in the air and can remain flowing in air over a distance in a confined space, leading to affecting high number of people getting prone to infection and it is very dangerous in enclosed spaces or shared spaces. Public places, shared facilities are the areas, where infectious aerosol can be present in the air for a long duration. Ventilation of closed spaces, shared spaces is the need of hour to have analysed and deep study in context of infectious airborne diseases. Introduction of fresh air into the enclosed environment at regular interval of times may lead to fast dilution of air present in the enclosed space. The prominent building codes and HVAC guidelines allows as to calculate ACPH (Air changes per hour) in an enclosed space as per the occupancy and flow rate. The age of air is the criteria to define the amount of air residing in the enclosed space when it enters the space till its exhaust from that space. The more the age of air in the particular area the more can be the infection probability among the occupants. It is predominant to study the airflow pattern caused due to ventilation which can be collaborated with age of air to know about the infection probability. Typically, a classroom geometry is assumed with inlet outlet boundary conditions where exhaust fan is playing a major role of displacement ventilation. Study of air recirculation zones and dead zones is the point of interest of this study. Computational fluid dynamics is the most powerful tool in the present era to study the air flow pattern in enclosed and shared spaces.Copyright © 2022, Anka Publishers. All rights reserved.
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Case report Background: P olyethylene g lycol ( PEG) a llergy i s g enerally c onsidered a contraindication to COVID-19 mRNA vaccines as they are formulated in lipid nanoparticles that contain a PEGylated lipid. However, there is an uncertain risk of allergy to mRNA vaccines in PEG-allergic patients and sensitivity of skin testing in the diagnosis of PEG allergy is poor. Our patient presented to Allergy and Immunology Clinic with a history of systemic reaction to PEG (in bowel prep), now requiring a mRNA booster. The patient had tolerated two doses of the AstraZeneca vaccine prior but this vaccine was no longer available in our health region due to safety concerns. Method(s): The chart was reviewed, skin prick testing to polyethylene glycol (PEG) 3350 (Restoralax diluted in water) was negative. Intradermal testing to the Pfizer-BioNTech vaccine at a dilution of 1:100 was positive at 11mm. Histamine and saline controls were appropriate. Result(s): Graded administration of the Pfizer-BioNTech vaccine was offered and consent was obtained. The patient tolerated administration of the vaccine in four divided doses (0.03cc, 0.06cc, 0.09cc, and 0.12cc). The patient was observed for 20 minutes between doses and an hour after the last dose with no reaction. Conclusion(s): We found that skin test reactivity to the Pfizer-BioNTech COVID-19 vaccine, at a nonirritating concentration (1:100), does not reliably predict reactivity on vaccine inoculation. This case highlights that it is possible to safely administer COVID-19 mRNA vaccines to patients with positive intradermal testing to the vaccine and a high suspicion for PEG allergy.
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Background. The spread of extensive drug-resistance among gram-negative bacteria calls for the search for antimicrobics with new mechanisms of actions. The aim was to assess susceptibility of extensively drug-resistant K.pneumoniae strains to cefiderocol and other new inhibitor-protected beta-lactams, and to determine genetic mechanisms of antibiotic resistance. Methods. This study included 30 extensively drug-resistant K.pneumoniae strains collected in 2016-2021 from 4 regions of Belarus. Carbapenemase genes were detected by real-time PCR. Minimum inhibitory concentrations (MICs) for cefiderocol and other new antibiotics were assessed by microdilution method using the Sensititre system. Whole genome sequencing was performed for 2 resistant and 3 cefiderocol-susceptible strains. Genome assemblies and annotation were performed using UGENE v. 37.0 software. Nucleotide sequences were translated using CLC Sequence Viewer v. 8.0 (QIAGEN) package. The PROVEAN software was used to assess amino asides substitutions and their influence on the functional activity of proteins. Results. KPC carbapenemase-producers were 4 strains, OXA-48 - 17, KPC+OXA-48 - 1, NDM - 7, OXA-48 + NDM - 1. All KPC-producers were susceptible to imipenem/relebactam and meropenem/vaborbactam. Resistance to ceftazidime-avibactam was noted in all NDM producers and OXA-48+NDM co-producer. The study has identified 9 cefiderocol-resistant strains. These were NDM and OXA-48-producers isolated from hospitalized patients with COVID-19 infection from 3 regions of Belarus. Resistant strains had functionally significant nonsynonymous substitutions in the genes of TonB-dependent receptors for catecholate siderophores FepA (F472V, P64S) and Fiu (T92S). Conclusion. The study has shown high efficacy of new inhibitor-protected carbapenems and cephalosporins against certain types of carbapenemase-producers. Strains with mutational resistance to cefiderocol, an antibiotic not previously used in Belarus, have been identified.Copyright © Team of Authors, 2022.
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Background: Polyethylene glycol (PEG) is being used for the first time as an excipient in mRNA vaccines against SARS-CoV- 2 containing PEG 2000, highlighting it as a potential cause of anaphylaxis. We aim to report clinical cases of severe allergy to PEG and furthermore to assess the usefulness of skin tests (ST) performed with the commercial extract PEG 1500 for the allergy work-up of patients with suspected allergy to SARS-CoV- 2 vaccines. Method(s): We evaluated 126 patients with moderate to high risk of allergy to SARS-CoV- 2 vaccination referred to our Allergy Department from March to December 2021. ST were performed with extract PEG 1500 (Roxall), using the following methodology: prick tests with 0.1%, 1% and 10% concentrations, with readings at 30 minutes (according to manufacturer's instructions);if negative, intradermal tests (IDT) were performed with the 1/10 dilution (0.01%), except in cases of anaphylaxis, where dilutions 1/1000 and 1/100 were used (adapted from previous publication using PEG 20000). Immediate IDT readings were made at 30 minutes and delayed readings at 24 hours. The same protocol was applied to 5 healthy controls who received PEGylated vaccines. Result(s): We present 6 cases of severe PEG allergy: one near-fatal anaphylaxis after glucocorticoid injection containing PEG 3350 and five systemic allergic reactions after mRNA vaccine containing PEG 2000 (Pfizer-BioNTech or Moderna). All patients had positive immediate IDT using PEG 1500 allowing the diagnosis and the selection of vaccine without PEG. All of them were negative to polysorbate 80. One patient developed anaphylaxis following IDT 0.01%. In the remaining 120 patients, the ST using PEG 1500 were negative in immediate and delayed reading of IDT. Seven patients were positive to polysorbate 80. All healthy controls had negative ST using PEG 1500. Conclusion(s): To our knowledge this is the first case series describing the allergy work-up testing with commercial extract PEG 1500 in the scope of SARS-CoV- 2 vaccination. ST using extract PEG 1500 revealed to be a useful tool for the diagnosis of PEG allergy, since it allowed confirming six cases of severe PEG allergy, contraindicating the further administration of PEGylated vaccines. It also allowed allergy exclusion in one hundred cases that took afterwards SARS-CoV- 2 vaccines containing PEG 2000. Moreover, healthy controls had negative IDT demonstrating the reliability of the proposed procedure. Investigation should only be conducted in a specialized drug allergy centre.
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Acid deposition and particulate matter (PM) pollution have declined considerably in China. Although metal(loid) and acid deposition and PM have many common sources, the changes of metal(loid) deposition in China in the recent decade have not been well explored by using long-term monitoring. Therefore, we analyzed the dry and wet deposition of eleven metal(loid)s (including Al, As, Ba, Cd, Cu, Cr, Fe, Mn, Pb, Sr, and Zn) from 2017 to 2021 at Mount Emei, which is adjacent to the most economic-developed region in western China (Sichuan Basin (SCB)). Anthropogenic emissions contributed to over 80% of the annual wet deposition fluxes of metal(loid)s and acids (SO4 2-, NO3 -, and NH4 +) at Mount Emei, and the major source regions were the SCB, the Yunnan-Guizhou Plateau, and Gansu Province. Metal(loid) and acid deposition had similar seasonal variations with higher wet deposition fluxes in summer but higher wet deposition concentrations and dry fluxes in winter. The seasonal variations were partially associated with higher precipitation but lower pH in summer (968 mm and 5.52, respectively) than in winter (47 mm and 4.73, respectively). From 2017 to 2021, metal(loid) deposition did not decline as substantially as acid deposition (5.6%-30.4%). Both the annual total deposition fluxes and concentrations of Cr, Cu, Sr, Ba, and Pb were even higher in 2020-2021 than in 2017-2018. The inter-annual and seasonal changes implied the responses of metal(loid) deposition to anthropogenic emission changes were buffered (e.g., transformation, dilution, and degradation) by precipitation rates, acidity, natural emissions, and chemical reactions in the atmosphere, among others.Copyright © 2023 Elsevier Ltd
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Case report The first approved COVID-19 vaccines include BNT162B2 Pfizer-BioNTech and mRNA-1273 Moderna mRNA vaccines. Some severe allergic reactions to these vaccines have been report, and even though there is a lack of robust evidence, IgE-mediated hypersensitivity to excipients may be the cause of several. The excipient polyethylene glycol (PEG) is present in both, whilst Moderna further contains trometamol (or tromethamine), a buffer additive present in drug formulations and contrast media. We report the case of a 40 year-old woman, with controlled allergic rhinitis and asthma, who was referred to our Immunoallergology Department due to an anaphylactic reaction to Moderna COVID-19 vaccine. She described an episode of cervical and facial pruritus 5 minutes after receiving the first dose of vaccine, which rapidly evolved to generalized urticaria. She was promptly given intravenous (IV) clemastine with improvement of symptoms. However, 1h later she developed respiratory symptoms (dry cough, shortness of breath and wheezing). IV hydrocortisone was also given, and the patient was kept under medical supervision for 6h, after which she was discharged home. The following day, she had urticaria that resolved with oral deflazacort (60 mg). She denies exercise practice, alcohol consumption or outset of new drugs prior to vaccination. During investigation, the patient described two similar reactions in the past, 5 minutes after the administration of trometamol-containing contrast media (10 years before with an iodinated contrast and 2 years ago with a gadolinium contrast, both with trometamol). A week after the reaction all laboratory evaluation were within normal limits, including tryptase level. Skin tests were performed, 2 months after, with contrast media that contain trometamol (iopromide, iomeprol, iodixanol, ioversol, gadobutrol) and that do not (ioxitalamate, amidotrizoate, gadoterate meglumine), in accordance with the EAACI/ENDA guidelines. Iopromide and iodixanol were positive on intradermal testing (1:10 dilution), suggesting trometamol as the culprit excipient. She was advised not to receive the 2nd dose of Moderna vaccine. She received Pfizer-BioNTech vaccine at the hospital, without any reactions. This case demonstrates that an IgE-mediated reaction to trometamol may be an underlying mechanism for immediate hypersensitivity to mRNA Moderna vaccine. The risk of an allergic reaction to it increases when a previous history of hypersensitivity to contrast media exists.
ABSTRACT
SARS-CoV-2 infectious virions have been reported in exhaled breath, but their source remains elusive: breath sampling systems used to date do not separate breath aerosols by size, fail to prevent salivary/fomite contamination, or aerosol size evolution before sample capture. We hypothesised that sampling end-tidal, oral exhaled breath condensate (EBC), after separating large droplets by inertial impaction 4cm from the lips, would quantify viral loads in distal lung-derived fine aerosols (FA). We used a collector (PBM-HALE ) that captures mechanically aerosolised viruses to sample adult participants for <30 min under informed consent;cases symptomatic for <5 days (n=30) or >5 days (n=12), positive by nasopharyngeal swab RT-PCR (Ct>=13.1), were sampled in clinical triage 'red zones', or COVID-19 wards with no mechanical ventilation or open windows. Salivary alpha amylase activity (Salimetrics LLC), or SARS-CoV-2 viral load (VIASURE SARS-CoV-2 (ORF1ab and N gene)) after QIAsymhpony DSP midi extraction, was quantified in 0.2mL FA EBC fractions. No salivary alpha amylase activity was detected in healthy participant FA EBC (>1:1,750 dilution of paired saliva vs assay detection limit (n=300)). No SARS-CoV-2 RNA was detected in FA EBC (1.18mL +/- 0.32 total volume) among any COVID-19 cases (Aug 2020-Jan 2022) at limits of detection of 120 genomes/mL FA EBC or 4.72 genomes/min exhalation. No pre-extraction spike-in control reaction inhibition was observed. No ambient contamination of the alveolar FA EBC was detected with this sampling device. The alveolar fraction of orally exhaled tidal breath lacks detectable SARS-CoV-2 viral load.
ABSTRACT
Mucormycosis is an angioinvasive opportunistic fungal infection, but these have become emerging pathogens, especially in conditions with underlying predisposing risk factors in a favourable setting. With the exponential rise in COVID-19 cases, there was an increase in the number of mucormycosis cases among them. The global prevalence rate of mucormycosis in COVID-19 globally varies from 0.005 to 1.7 per million population and in India, it is approximately 0.14 cases/1000. The objective of this study is to detect the prevalence of mucormycosis with the antifungal susceptibility pattern among COVID-19 patients admitted in our hospital. A total of 347 COVID-19 and post-COVID-19 patients with symptoms suggestive of mucormycosis were included in this study. Nasal scrapings, debrided necrotic tissue, unhealthy tissue bits and biopsy tissues taken through FESS were processed for mycological examination under sterile conditions. Among the total 347 samples processed, 87(25%) were positive for fungal culture. Among the culture positves 7.8% (25) belong to mucorales. Among the total 87 fungal isolates, the majority of organism isolated was Aspergillus sp(68%), followed by Rhizopus sp (18%). Rhizopus/Aspergillus sp (5%), Mucor species (5%), Rhizomucor sp (2%), Mucor/Aspergillus sp(1%), Curvularia sp (1%) were the other fungi isolated. All the strains of Mucorales were sensitive to Posaconazole and one strain showed resistance to amphotericin B with MIC 8 microg/ml by microbroth dilution method based on CLSI M27 guidelines for Amphotericin B, and Posaconazole.Copyright © The Author(s) 2023.