SARS-CoV-2 Research Articles

Life-Threatening Spontaneous Hematoma in Unusual Sites in Patients with COVID-19 on Anticoagulant Therapy: A Case Series

Thromboembolic manifestations are a common phenomenon in patients affected by corona virus (SARS CoV-2). Recent studies have shown that patients with acute renal failure are also at a greater risk of venous and arterial thromboembolism, 15-30% in ICU, and 7% inpatient care. However, frequently unjudicial use of anticoagulants may develop severe life-threatening hematoma. In our hospital settings we had a dedicated COVID Unit with a Hemodialysis facility. Our Nephrology department had managed 381 patients being COVID positive along with renal impairment from March 2020 to January 2022. Among these patients, four patients developed spontaneous non traumatic hematoma in unusual sites. On admission all the patients received treatment according to our national guidelines for COVID-19. Cases: It is a retrospective analysis in a single-centered hospital. Four cases with confirmed COVID-19 with acute kidney injury and on anticoagulant therapy had developed sudden concealed bleeding. These patients had no previous history of anticoagulant therapy before admission. Case 1 developed hemorrhage in Right lower anterior paramedian deep parietal wall of abdomen, Case 2 had hematoma in retroperitoneal space and in lower third of Iliopsoas, Case 3 developed hemorrhage in left cerebral hemisphere, Case 4 had Intramuscular Hematoma in left rectus abdominis. Out of these four patients two of them required Hemodialysis and one of them went into shock. All patients included were male. The mean age was 57±19.64years. All the four patients were initially managed conservatively with keen monitoring and with proper volume resuscitation, blood transfusion and discontinuation of the anticoagulants. Three of the patients survived with conservative management and one patient died due to sudden massive cardiac arrest. The use of therapeutic anticoagulant can increase the risk of bleeding in atypical sites and may exhibit higher patient death with COVID-19 if not identified at early stage. So a risk-benefit ratio of usage of anticoagulants should be kept in mind and further clinical trials needed to justify its random use in COVID-19. J Bangladesh Coll Phys Surg 2024; 42: 393-400

Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2.

During the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY. To characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs). A retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: "high dose dexamethasone" (daily dose greater than 12 mg and/or for longer than 10 days), "low dose dexamethasone" (daily dose 12 mg or less for 10 days or less), and "no dexamethasone" (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use. High-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74). Acknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.

Potential hypothesis for the increased risk of Parkinson´s disease following COVID-19.

Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.

SNaPshot minisequencing for SARS CoV 2 Variant Genotyping

Abstract Introduction/Objective The SNaPshot Multiplex System (Thermo Fisher) can investigate up to fifty SNP markers simultaneously by using PCR amplification and subsequent dideoxy single base extension of an unlabeled primer and capillary electrophoresis. After electrophoresis and fluorescence detection, the alleles of a single marker appear as different colored peaks at roughly the same size in the electropherogram plot. The size of the different allele peaks vary slightly due to differences in molecular weight of the dyes. We propose a new set of primers and probes to use this system to differentiate variants of SARs Cov 2 variants. Methods/Case Report SNAPSHOT analysis was performed using the primers designed internally and analysis was done of up to 7 mutation hot spots, which were 417, 4511, 478, 484, 501, 614, and 681. By implementing the algorithm of systems and methods herein with the traces depicted in Figures, true positive and true negative outcomes for the different COVID variants can be performed, based on the highlighted peaks, which are not necessarily the most intense peaks. 10 Positive controls achieved from in stro transcript plasmid was tested then 10 viral RNA obtained through BEI Resources, NIAID was tested after mixed into 30 pooled negative PCR-swab specimens. Genmapper was used for analysis of results. 40 Korean patient samples were tested as well. Results (if a Case Study enter NA) Both In vitro transcript and derived specimens of wild type, alpha, beta, delta, gamma, kappa, omicron, and pirola showed expected results in 78/80 of the specimens. For example,delta B.1.617.2 variant showed 1 = A (green) at Primer 452R-F, 2 = G (blue): Primer 484Q-F, and 3 = A (green) at Primer 614-F. Of note, hetero type was noted in a few of the patient strains but none of the BEI strains and this may be due to a transfromation of the virus and worth investigation. Conclusion The SNaPshot® Multiplex System is a accurate system that may be applied to multiple applications including viral strain anylsis and here we can show how it may be effectively used for SARS-Cov-2 gentotyping. Using this technique, it is possible to analyze more than 50 SNPs distributed throughout the genome in a single multiplex reaction, making it an advantage when compared with traditional sequencing reaction. This is a important study that shows that this technique may be used in multiple field applictions.

One-Year Surveillance of a Patient Cohort’s Lung Ultrasonography Findings Post Mild-Moderate COVID-19 Infection

Objective: Lung involvement due to COVID-19 infection relates to patient clinical outcomes. However, little evidence exists on whether an abnormal lung sonogram, during an initial outpatient infection, may signal an abnormal immunologic response and lasting abnormalities. The aim of this study was to observe whether high-risk outpatients, previously infected with SARS CoV-2 and found to have an initial abnormal lung sonogram, had persistent diagnostic findings at a 1-year re-examination. Materials and Methods: A prospective longitudinal cohort study was performed, based on a prior study completed in January 2022 wherein 55/201 (27%) of consecutive outpatients infected with SARS-CoV-2 received therapy at an outpatient monoclonal antibody clinic and had presented with an abnormal lung ultrasound containing at least 3 apical lung B-line artifacts (LUS+). One year later, the original 55 LUS+ patients were contacted for re-examination; as a result, 14 LUS+ patients consented to a repeat LUS tospecifically recheck the apical area of the lungs for persistent B-line artifacts. The same ultrasound equipment system and imaging methodology were used for this cohort of patients. Additional data was collected regarding COVID-19 test-positive re-infection, persistent pulmonary symptoms during the past year, and COVID-19 vaccination status. Results: Of the 14 LUS+ patients, the mean cohort age was 63 ± 9 years, of which 71% were men. Over the ensuing year, 43% had persistent symptoms, 71% had updated vaccination, and 36% had a self-reported re-infection. The re-infection was reported to have occurred a median of 7 months after the initial infection. The cohort was sub-divided into those with persistent LUS+ compared to those that reverted to a normal scan. The mean age was 69 ± 10 years among those LUS+ compared to 56 ± 8 years in the normalized group. The body mass index (BMI) was 32 kg/m2 in those LUS+ compared to 27 kg/m2 in the normalized group. The cohort has 6 men and 2 women in the LUS+ group compared to 4 men and 2 women in the normalized group. One LUS+ patient out of eight reportedly had been reinfected compared to four normalized patients out of six stated being reinfected. Three LUS+ patients out of eight reported having persistent symptoms compared to three normalized patients out of six complaining of continued COVID-19 symptoms. Conclusion: Based on the 1-year repeated LUS, for this cohort, there was a high prevalence of persistent symptoms and lung abnormalities, in those who had mild-moderate outpatient COVID-19 and received monoclonal antibody therapy. The longitudinal data collection on this cohort of COVID-19 positive outpatients may suggest that individual immune responses or viral virulence factors may play a role in B-line persistence. Certainly, future LUS results may be confounded by a previous COVID-19 infection.

Impact of mechanical power on ICU mortality in ventilated critically ill patients: a retrospective study with continuous real-life data

BackgroundOver the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not accurately reflect the impact of power throughout the period of mechanical ventilatory support on intensive care unit mortality.MethodsRetrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 h were included. We extracted the mechanical power values throughout the entire mechanical ventilation in controlled modes period from the clinical information system every 2 min. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with intensive care unit mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia.ResultsThe cut-off point of mechanical power at with there is a higher increase in intensive care unit mortality was 18 J/min. The greater the number of hours patients were under mechanical power > 18 J/min the higher the intensive care unit mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hypoxemic respiratory failure. The risk of death in the intensive care unit increases 0.1% for each hour with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay.ConclusionsThe number of hours with mechanical power > 18 J/min is associated with mortality in the intensive care unit in critically ill patients. Continuous monitoring of mechanical power in controlled modes using an automated clinical information system could alert the clinician to this risk.

A computational biology approach for the identification of potential SARS-CoV-2 main protease inhibitors from natural essential oil compounds.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions: Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.

Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell function and antigen-specific CD4+ T cell responses.

Live microfilariae (mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-y. To explore further how EVs alter human APC function, we studied the effect ofmf and EVs on human elutriated monocyte-derived dendritic cells (DC) following exposure to Mf, mf-derived excretory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs. After demonstrating that the measurable responses induced by live mf could be recapitulated by EVs and EV-containing E/S, we next performed RNAseq analysis of human DC following exposure to live mf, EVs, E/S, or EV-depleted E/S. In our analyses of the data for the DC, using a false discovery rate (FDR)<0.05, EV-exposed DC had induced the expression of 212 differentially expressed genes (DEGs) when compared to unexposed DC and 157 when compared to E/S-depleted EVs. These genes were enriched in GO biological processes associated with neutrophil degranulation and 15 DEGs associated with KEGG Lysosome pathways. IPA analysis point to immune dysregulation. We next aimed to understand the intracellular processes altered by EVs and the effect these have on effector T cells. When SARS CoV-2 Membrane-specific CD4+ TCLs were assessed following EV conditioning of autologous DC and activation with the SARS CoV-2-Membrane peptide pool, we found conditioning reduced the frequency of SARS CoV-2 Membrane-specific CD3+ CD4+ CD154+ cells (p=.015). Similarly, EV-conditioning of SARS CoV-2 Membrane-specific CD3+ CD4+ cells induced fewer cell capable of producing IFN-γ (p=.045). Taken together, our data suggest a modulatory role of EVs on APC function that likely leads to defects in T cell effector function.

A-356 A hand-held microfluidic platform for rapid and sensitive identification of respiratory viruses from nasal swab samples

Abstract Background Identifying the infected individual with a fast and accurate test is essential to constrain the spread of viruses and provide the proper treatment. Antigen rapid test (ART) provides quick screening of infection for patients; however, it shows less promising in the detection of early infection and patent’s full recovery as its inferior sensitivity to the nucleic acid detection method. On the other hand, bulky and costly instrument, tedious and prolonged procedures in traditional nucleic acid testing is also unfavorable for the screening. Delta is developing a fully automated hand-held POC using molecular technology to simultaneously detect 4 targets in 20 mins. The POC can be stand-alone or linked to mobile or PC app for different application scenarios. The proprietary recipe of the lysis buffer could neutralize the inhibition in the sample with effective pathogen lysis in seconds. The microfluidic cartridge containing lyophilized reagent can be stored at room temperature. The amplification signal is detected via the optical system from the colorimetric LAMP. This study is to evaluate the performance of the POC system in detecting SARS-CoV2 (SC2), FluA and B viruses in nasal swab. In addition, the assay performance was further compared with other commercial products available. Methods The attenuated SC2 virus, FluA and B viruses were diluted with 1xTE into different concentrations. The diluted viruses were spiked into the lysis buffer in 5% v/v ratio. Nasal samples collected from donors were soaked and swirled inside the cartridges containing lysis buffer according to the manufacturers’ instructions. For commercial products without lysis buffer, direct swabs were used. The cartridges were then put into the respective devices for further testing. Results The lyophilized SC2 assay consistently detected the viruses at 1000 copies/ml (20 out of 20) in real nasal samples in the presence of Delta Lysis Buffer (containing lyophilized neutralizer). However, without Lysis buffer, there was no signal detected even in the presence of 240x LoD viruses. The whole workflow sensitivity was tested with SC2 positive samples at 1x, 4x, 10x LoD and negative samples in the nasal sample matrix on Delta hand-held system. The results were processed via embedded algorithm and displayed on device as well as on PC and mobile app respectively. Out of 79 positive samples tested, the detection rate was 100%. There was no false positive detection for 31 negative samples tested. Positive internal control indicated the valid runs. 5 major SC2 subtypes (99.8% in silico analysis of 366,707 strains), 10 FluA and 9 FluB subtypes were successfully detected. Further, Delta hand-held platform outperformed in the LoD of SC2 with 500 copies/swab comparing to the ≥50,000 copies/swab of the benchmarked commercial platforms. Conclusions The performance of the hand-held molecular detection system we developed demonstrated a rapid, sensitive, and competitive analytical performance in the respiratory panel detection. The capability of device linking to apps and clouds for data management and the extendable docking system for multiple devices to run samples simultaneously and independently, make it applicable for the infectious diseases screening in both clinical settings and for home-use.

A-240 Validation of the OSOM Flu SARS-CoV-2 Combo Home Test

Abstract Background COVID-19 and Influenza respiratory infections often cause similar symptoms, however, treatment is different for each infection. Delay in diagnosis can be fatal in some cases, therefore rapid detection and differentiation are critical for appropriate medical treatment. The OSOM Flu SARS-CoV-2 Combo Home Test is a lateral flow immunoassay intended for the qualitative and differential detection of nucleocapsid protein from SARS-CoV-2 and influenza A/B proteins using self-collected anterior nasal swab samples (self-collection is only recommended for those 14 years of age and older). An interpretation card, included with the test, is used to reliably distinguish among possible testing results. Methods A prospective study was conducted at multiple geographically distinct sites in the U.S during the 2023-2024 season for the validation of the OSOM Flu SARS-CoV-2 Combo Home Test to detect SARS-CoV-2/Flu A/Flu B in self-collected anterior nasal swab samples. The study evaluated the performance in symptomatic individuals only. A total of 703 prospective samples were evaluable for SARS. For Flu A/B, four additional subject samples were unevaluable due to comparator results not being available and a total of 699 samples were included in the data analysis. The comparator tests were FDA 510(k)-cleared molecular assays. Results Influenza A was detected with a sensitivity of 93.1% (95% CI: 84.8%-97.0%) and a specificity of 99.5% (95% CI: 98.6% - 99.8%). Influenza B was detected with a sensitivity of 89.1% (95% CI: 77.0% - 95.3%) and a specificity of 99.7% (95% CI: 98.9% - 99.9%). SARS CoV-2 was detected with a sensitivity of 87.0% (95% CI 78.6% - 92.4%) and a specificity of 99.1% (95% CI: 97.9% - 99.6%) when Ct values are standardized and 10% of samples are considered low positives, having a Ct value of ≥ 30. Conclusions With respiratory infections often showing indistinguishable symptoms and the possibility of co infection, lowering the testing hurdles for individuals to be able to perform a rapid differential test at home without the aid from a healthcare worker is the most effective way to mitigate spread and patient management from a public health perspective. Comparing the OSOM Flu SARS-CoV-2 Combo Home test to the FDA cleared comparators in a clinical setting, the OSOM Flu SARS-CoV-2 Combo Home test retains acceptable sensitivity and specificity. Using self-collected anterior nasal swabs which are minimally invasive alongside the low cost of a lateral flow immunochromatographic assay remains the most effective way to perform the serial screening testing recommended by the CDC in situations where transmission and severe outcome risk is high.

Impacto de la motivación laboral en el desempeño del personal administrativo en home office: un caso de estudio en una empresa comercializadora de plásticos.

In 2020, the world faced a severe health crisis derived from SARS CoV-2, so different social sectors found it necessary to modify and acquire new habits aimed at preserving hygiene and health. Specifically in the workplace, organizations faced situations that forced them to make decisions that significantly changed their usual work style. As a result of this situation, companies implemented different strategies in favor of staff health, one of the most used was the Home Office (working at home), which caused various problems among employees, such as increased stress, lack of communication, poor time management, poor performance, etc. In relation to the above, this research was carried out using a quantitative approach, with the application of a survey to the administrative staff of a company dedicated to the marketing of plastic items, with the purpose of knowing the working conditions of the collaborator. At home, and consequently, propose motivational strategies focused on promoting their performance and well-being at work. The results obtained reflect that the staff did not have spaces suitable for working at home, as well as difficulty communicating and interacting with colleagues, as well as the lack of time organization to carry out their work activities. Finally, recommendations are designed such as the periodic scheduling of effective meetings, discussions; actions that favorably impact the performance of collaborators.

Quality of Internet-Based Information on COVID-19 and Dentistry

Aim: Dentists and their patients were at high risk for COVID-19 infection. As websites serve as a primary information source for many, this cross-sectional study aimed to assess the validity and reliability of information provided by websites regarding COVID-19 and dentistry. Materials and Methods: An online search was conducted on Google.com using the keywords ‘SARS CoV-2 and dentistry’, ‘COVID-19 and dentistry’ and ‘Coronavirus and dentistry’. The first 50 websites for each keyword were screened in incognito mode. After excluding duplicates, inaccessible and irrelevant websites, 88 websites remained for analysis. These websites were evaluated using the Health on the Net Foundation Code of Conduct (HON code) and the Journal of the American Medical Association (JAMA) benchmarks, which assess authorship, attribution, disclosure and currency of information. Descriptive statistical analyses, chi-square tests and one-way ANOVA were performed. Results: A total of 88 websites were found suitable for quality assessment. Only three of the websites had HON code accreditation. The mean JAMA benchmark score was 3.75 ± 0.7. The majority of the websites (62.5%) were academic, with a JAMA score of 3.84 ± 0.5. News and non-profit sites had the highest JAMA scores (4.0). Significant differences in JAMA scores were observed across different types of websites ( p &lt; .05). Conclusions: The study found that the quality of websites providing information about COVID-19 and dentistry was generally high, especially among academic sites. This highlights the importance of high-quality online information to ensure that dentists and patients have access to accurate and reliable data during the pandemic.

The dimerization domain of SARS CoV 2 Nucleocapsid protein is partially disordered as a monomer and forms a high affinity dynamic complex.

The SARS-CoV-2 Nucleocapsid (N) is a 419 amino acids protein that drives the compaction and packaging of the viral genome. This compaction is aided not only by protein-RNA interactions, but also by protein-protein interactions that contribute to increasing the valence of the nucleocapsid protein. Here, we focused on quantifying the mechanisms that control dimer formation. Single-molecule Förster Resonance Energy Transfer enabled us to investigate the conformations of the dimerization domain in the context of the full-length protein as well as the energetics associated with dimerization. Under monomeric conditions, we observed significantly expanded configurations of the dimerization domain (compared to the folded dimer structure), which are consistent with a dynamic conformational ensemble. The addition of unlabeled protein stabilizes a folded dimer configuration with a high mean transfer efficiency, in agreement with predictions based on known structures. Dimerization is characterized by a dissociation constant of ~ 12 nM at 23 °C and is driven by strong enthalpic interactions between the two protein subunits, which originate from the coupled folding and binding. Interestingly, the dimer structure retains some of the conformational heterogeneity of the monomeric units, and the addition of denaturant reveals that the dimer domain can significantly expand before being completely destabilized. Our findings suggest that the inherent flexibility of the monomer form is required to adopt the specific fold of the dimer domain, where the two subunits interlock with one another. We proposed that the retained flexibility of the dimer form may favor the capture and interactions with RNA, and that the temperature dependence of dimerization may explain some of the previous observations regarding the phase separation propensity of the N protein.

Trivalent transition metal ion mediated template synthesis: In silico molecular docking, DNA binding, antimicrobial evaluation and DFT studies

In order to reduce the chances of multiple drug resistance, there is an urgent requirement for the designing of new antimicrobial agents. In this current research, series of novel hexaazamacrocyclic trivalent transition metal complexes of ChromiumIII and IronIII have been prepared by adopting the pathway of metal ion mediated template condensation. The newly synthesized macrocyclic complexes were analyzed by Infra-Red Spectroscopy, Carbon-Hydrogen-Nitrogen analyzer, UltraViolet–visible, Powder X-Ray Diffraction, Electron Paramagnetic Resonance, Magnetic Susceptibilities, Molar conductance, Electron Spray Ionisation-Mass Spectrometry and Thermogravimetric analysis techniques. The electro-lytic behaviour of the complexes was suggested by conductance (molar) values. All the complexes (T7-T12) can be formulated or represented as [MLX] X2·yH2O, where M = FeIII, CrIII and L is the macrocyclic ring resulting from 1,8-diaminonaphthalene and succinimide and X = NO3−, Cl−, CH3COO− and y = 1 or 2. All the macrocyclic complexes have been anticipated to have a penta coordinated square pyramidal shape using several physico-analytical approaches. Monomeric nature of the complexes was confirmed by CHN analysis and mass spectral data. Powder X-Ray Diffraction studies were carried out for interpreting the crystallinity of the complexes. Density Functional Theory studies were performed for energy optimization and theoretical calculations of UV & IR. The DNA interaction studies showed intercalative mode of binding is present in the newly designed complexes with the DNA. In addition to these, all the metal complexes were screened for their antibacterial and antifungal activity against pathogenic strains of bacteria and fungi, Complex T7 has effective bactericidal action against B. cereus and E. coli. Molecular docking studies were also performed on SARS Cov-2 and Mycobacterium tuberculosis. The used proteins are NSP15 Endoribonuclease from SARS CoV-2 and DNA of Mycobacterium tuberculosis H37Rv. The results revealed that complex T10 is having good binding affinity against DNA of Mycobacterium tuberculosis H37Rv.

Can CRP and Lymphocyte Count be Considered as Predictive Factors for the Prognosis of COVID-19 in Intensive Care? An Analytic Study

Introduction: SARS Cov2 infection still represents a real threat whose clinical severity results from an inadequate immuno-inflammatory reaction. The objective of our study was to determine the prognostic interest of the value of CRP and the rate of lymphocytes in the management of patients contaminated by SARS-Cov2. Material And Methods: This is a prospective, descriptive and analytical study of interest to patients with severe COVID-19, admitted to medical intensive care at the Oued Eddahab military hospital, for a period of one year. The biological parameters were analyzed on admission and during the stay in intensive care. The ROC curve was used to determine the sensitivity and specificity of CRP and lymphocytes as well as their optimal predictive threshold values. Results: 32 patients were included in our study. The average age of admissions was 65 years ± 12.38 with a sex ratio of 5.4 in favor of men. The optimal predictive threshold for the severity found was 147mg/l for CRP with a sensitization of 95% and a specificity of 83.3%, and 807/mm3 for lymphocytes with a sensitivity of 91.7% and a specificity of 95%. The odds ratio (OR) found for CRP and lymphocytes was &gt; 1. Conclusion: The CRP and the level of lymphocytes at the threshold defined above are risk factors for the severity of Sars-Cov2 infection.

Angiotensin-Converting Enzyme-2 (ACE2) Downregulation During Coronavirus Infection.

Angiotensin-converting enzyme-2 (ACE2) downregulation represents a detrimental factor in people with a baseline ACE2 deficiency associated with older age, hypertension, diabetes, and cardiovascular diseases. Human coronaviruses, including HCoV-NL63, SARS-CoV-1, and SARS CoV-2 infect target cells via binding of viral spike (S) glycoprotein to the ACE2, resulting in ACE2 downregulation through yet unidentified mechanisms. This downregulation disrupts the enzymatic activity of ACE2, essential in protecting against organ injury by cleaving and disposing of Angiotensin-II (Ang II), leading to the formation of Ang 1-7, thereby exacerbating the accumulation of Ang II. This accumulation activates the Angiotensin II type 1 receptor (AT1R) receptor, leading to leukocyte recruitment and increased proinflammatory cytokines, contributing to organ injury. The biological impacts and underlying mechanisms of ACE2 downregulation during SARS-CoV-2 infection have not been well defined. Therefore, there is an urgent need to establish a solid theoretical and experimental understanding of the mechanisms of ACE2 downregulation during SARS-CoV-2 entry and replication in the host cells. This review aims to discuss the physiological impact of ACE2 downregulation during coronavirus infection, the relationship between ACE2 decline and virus pathogenicity, and the possible mechanisms of ACE2 degradation, along with the therapeutic approaches.

In–situ self–reduction preparation of Ti3C2Tx/Ag on flexible PMMA chip for quantitative detection of SARS–CoV–2

Surface enhanced Raman scattering (SERS) has proven to be of great superiority in the assay and prevention of infectious disease attributed to its rapid and specific fingerprint recognition ability toward trace molecules. However, it is still crucial to develop portable and precise chip for the reliable realization of on–site and large–scale screening. Here, a robust in–situ reduction strategy was employed to prepare Ti3C2Tx@Ag nanocomposites, which was installed on a polymethyl methacrylate (PMMA) matrix to construct a novel flexible SERS chip with self–rectification capability. The resulting Ti3C2Tx@Ag nanocomposites exhibited both electromagnetic and chemical enhancement effects, enabling high SERS activity. In particular, the as–developed SERS chip demonstrated fascinating signal reproducibility and quantitative detection capability by conducting the intrinsic Raman signal of PMMA as an internal standard. Furthermore, the PMMA–Ti3C2Tx@Ag chip facilitated the visualization of severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) nucleocapsid (N) with ultra–low limit of detection, stressing the potential application of this smart self–rectification SERS chip with high activity in real time and rapid monitoring of sudden infectious diseases.

Comprehensive MRI assessment reveals subtle brain findings in non-hospitalized post-COVID patients with cognitive impairment.

Impaired cognitive ability is one of the most frequently reported neuropsychiatric symptoms in the post-COVID phase among patients. It is unclear whether this condition is related to structural or functional brain changes. In this study, we present a multimodal magnetic resonance imaging study of 36 post-COVID patients and 36 individually matched controls who had a mild form of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection from March 2020 to February 2022. This study aimed to investigate structural and functional brain alterations and their correlation with post-COVID symptoms and neurocognitive functions. The study protocol comprised an assessment of physical fatigue [Fatigue Severity Scale (FSS)], mental fatigue (Mental Fatigue Scale (MFS)], depression [Montgomery Asberg Depression Rating Scale (MADRS)], anxiety [Hospital Anxiety and Depression Scale (HAD)], post-COVID Symptoms Severity Score, and neurocognitive status [Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)]. The magnetic resonance imaging protocol included morphological sequences, arterial spin labeling (ASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (fMRI) sequences. Using these protocols, the assessments of macrostructural abnormalities, perfusion, gray matter density, white matter integrity, and brain connectivity were performed. Post-COVID patients had higher levels of physical fatigue, mental fatigue, depression, and anxiety than controls and showed cognitive impairment in all the RBANS domains except in Visuospatial/Construction. The subjective mental fatigue correlated with objective impaired cognitive ability in the RBANS test, particularly in the Attention domain. There were no differences between patients and controls regarding macrostructural abnormalities, regional volumes, regional perfusion metrics, gray matter density, or DTI parameters. We observed a significant positive correlation between RBANS Total Scale Index score and gray matter volume in the right superior/middle-temporal gyrus (p < 0.05) and a significant negative correlation between the white matter integrity and post-COVID symptoms (p < 0.05) in the same area. The connectivity differences were observed between patients and controls in a few regions, including the right middle frontal gyrus, an important area of convergence of the dorsal and ventral attention networks. We also noted a positive correlation between post-COVID symptoms and increased connectivity in the right temporoparietal junction, which is part of the ventral attention system. In non-hospitalized subjects with post-COVID, we did not find any structural brain changes or changes in perfusion, compared to controls. However, we noted differences in connectivity within an important area for attention processes, which may be associated with post-COVID brain fog.

A Case Demonstration of the Open Health Natural Language Processing Toolkit From the National COVID-19 Cohort Collaborative and the Researching COVID to Enhance Recovery Programs for a Natural Language Processing System for COVID-19 or Postacute Sequelae of SARS CoV-2 Infection: Algorithm Development and Validation.

A wealth of clinically relevant information is only obtainable within unstructured clinical narratives, leading to great interest in clinical natural language processing (NLP). While a multitude of approaches to NLP exist, current algorithm development approaches have limitations that can slow the development process. These limitations are exacerbated when the task is emergent, as is the case currently for NLP extraction of signs and symptoms of COVID-19 and postacute sequelae of SARS-CoV-2 infection (PASC). This study aims to highlight the current limitations of existing NLP algorithm development approaches that are exacerbated by NLP tasks surrounding emergent clinical concepts and to illustrate our approach to addressing these issues through the use case of developing an NLP system for the signs and symptoms of COVID-19 and PASC. We used 2 preexisting studies on PASC as a baseline to determine a set of concepts that should be extracted by NLP. This concept list was then used in conjunction with the Unified Medical Language System to autonomously generate an expanded lexicon to weakly annotate a training set, which was then reviewed by a human expert to generate a fine-tuned NLP algorithm. The annotations from a fully human-annotated test set were then compared with NLP results from the fine-tuned algorithm. The NLP algorithm was then deployed to 10 additional sites that were also running our NLP infrastructure. Of these 10 sites, 5 were used to conduct a federated evaluation of the NLP algorithm. An NLP algorithm consisting of 12,234 unique normalized text strings corresponding to 2366 unique concepts was developed to extract COVID-19 or PASC signs and symptoms. An unweighted mean dictionary coverage of 77.8% was found for the 5 sites. The evolutionary and time-critical nature of the PASC NLP task significantly complicates existing approaches to NLP algorithm development. In this work, we present a hybrid approach using the Open Health Natural Language Processing Toolkit aimed at addressing these needs with a dictionary-based weak labeling step that minimizes the need for additional expert annotation while still preserving the fine-tuning capabilities of expert involvement.

Online Fast Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Proliferation Through Replication

Purpose. A virus, when it infects a host organism, multiplies its ribonucleic acid (RNA) to make it more harmful. We analyze if a view-based temporal template method, the motion history image (MHI) algorithm, may be of use to extract information on the progression of viral interactions over time. Methods. We employ an alternative online processing modality to comprehend and analyze the replication dynamics of severe acute respiratory syndrome coronavirus 2 (SARS CoV 2). The data are evaluated using the computation of a quantitative algorithm, the absolute value of differences (AVD), followed by the generation of temporal template map, the MHI of viral contact. Results. We show that the MHI identifies various stages to examine cultural characteristics and information on the progression of viral interactions over time. The results are more easily obtained compared to a visual inspection of the frames constituting the recordings. MHI also has the advantage of relying on a simple algorithm. The AVD index further provides deeper insights into the dynamics of the viral interaction over time, and its measurement suggests that SARS CoV-2 virus is becoming more widespread. This study shows that the replication process damages the host cell over time, in addition to causing SARS CoV-2 to proliferate. Conclusions. The MHI provides a framework for automated feature extraction from time series data. The combined approach results in decreased computational complexity and enables online assessment of the assay. Clinical and research studies can be conducted to evaluate MHI and AVD and their utility in aiding diagnostic analysis.