anti-SARS CoV-2 Research Articles

Pre-exposure immunohematologic features of heart failure associate with COVID-19 mortality

Chronic heart failure, like diabetes, is a pro-inflammatory cardiometabolic condition, but its association with immunodeficiency is less well established. We conducted a retrospective cohort study of US Veterans infected during the first wave of COVID-19 (n = 92,533) to identify relationships between comorbidities, pre-infection immunohematologic (IH) features (based on complete blood cell count parameters), and 60-day mortality. A biomarker sub-analysis of anti-SARS CoV2 antibodies and cytokine levels was also performed (n = 44). Heart failure was independently associated with higher COVID-19 mortality and with the specific IH alterations (especially relative anemia, anisocytosis, and lymphopenia) which themselves predicted non-survival or protracted inflammation. Over half the risk conferred by heart failure was mediated by its anticipatory IH features whereas diabetes risk was unrelated to its associated IH profile. These findings indicate that heart failure is associated with a COVID-19 immunodeficiency distinct from that of diabetes which correlates with antecedent erythrocyte and lymphocyte dyshomeostasis.

Efficacy and Safety of SARS-COV-2 Vaccines in Breast Cancer Patients

Abstract Background Breast cancer (BC) is a major public health problem. COVID-19 pandemic impacted all areas of daily life, including medical care. In particular, delivering care for patients with cancer or suspected cancer during the crisis was challenging given the competing risks of death from untreated cancer versus serious complications from SARS- CoV-2, and the likely higher lethality of COVID-19 in immunocompromised patients. Aim of the Work This study aims to assess the efficacy and immunogenicity of SARS COV 2 vaccines in breast cancer patients by evaluating anti spike antibodies in vaccinated and non vaccinated patients and also through assessing the infection with covid after vaccination (in vaccinated patients) and in non vaccinated patients. The study also aims to assess the Safety of SARS COV 2 vaccine in breast Cancer patients (local and systemic Toxicity). Patients and Methods Our population consisted of 120 female patients diagnosed with early and locally advanced breast cancer, in the breast cancer unit, Clinical oncology department, Ain Shams University Hospitals. All on systemic therapy (on neoadjuvant or adjuvant treatment). Sixty vaccinated and 60 unvaccinated against COVID-19. The cutoff value of SARS COV-2 antibody is 50 BAL/mL (>/= 50 seropositive, <50 seronegative) Results Out of 120 patients, Anti-SARS COV-2 Antibody seropositivity was found to be 48 vs. 58 pts (80% vs. 96.7%) in non vaccinated Vs. Vaccinated patients, with a P-value=0.0046), which was statistically significant. The median titre in both groups was found to be 1434.5 vs. 2500, (P = 0.0026). In the 120 patients, 26 patients had covid infection with a significant difference, Non vaccinated Vs. Vaccinated: 21 vs. 5 pts (35% vs. 8.3 %, P = 0.0004). In the sixty vaccinated patients, mild local adverse events were reported such as warmness at site of injection in 17 patients, representing (28.3%) of patients, Pain 11 (18.3%), Swelling 11 (18.3%), Itch 8 (13.3%), and Redness 6 (60%) representing the least adverse event. The patients experienced mild systemic adverse events, the highest incidence was Fatigue 28 (46.7%), then Myalgia/arthralgia 17(28.3%), headache 2 (3.3%),and fever 16 (26.7%). Conclusion Anti SARS COV2 are effective and safe in localized breast cancer patients on systemic therapy.

Asymptomatic SARS-COV2 Infection or COVID-19 vaccination effect for severe multisystem inflammatory syndrome in a 6-year-old girl: case report and review of the literature

BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection.Case presentationWe describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae.ConclusionsThis case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

Humoral response to anti SARS-CoV2 vaccination at one and seven months is not different in shift workers and non-shift workers

Since previous studies, mostly performed in healthy adults, show that sleep restriction around time of vaccination impairs antibody response and shift work affects sleep, aim of the study was to test the hypothesis that the antibody response to vaccination is impaired in shift workers, when compared to non-shift workers.Employees (n = 445; mean age 44 ± 11 years; 35 % men) of the Centro Cardiologico Monzino, IRCCS (Milan, Italy) were vaccinated against SARS-CoV2 in February 2021 with an mRNA-based vaccine. Antibody titers were assayed 1 and 7 months later. Differences between groups were assessed using ANOVA, after log-transformation of variables with right-skewed distribution.We report that the antibody titer was significantly higher in shift workers (33 % of employees) compared to non-shift workers at first assay [median (IQR): 2495 (1700; 4665) vs 2060 (1619; 2970) BAU/mL, p = 0.0123], as well as at the second one, and that this difference was abolished after adjustment for previous development of symptomatic COVID-19. Results were not affected by age or sex at birth.These results show that shift workers were able to mount an unimpaired antibody response to vaccination. Since vaccinations were performed during the pandemic urgency, our retrospective study has several limitations, nevertheless it underlines the need for large prospective, controlled studies on the effects of acute and chronic sleep restriction on response to vaccination in the general population and on the impact of shift work on immune response.

Profiling the phytochemicals and anti-SARS CoV-2 activity of different Ligustrum ovalifolium Hassk aerial part extracts: An in vitro-in silico study

Profiling the phytochemicals and anti-SARS CoV-2 activity of different Ligustrum ovalifolium Hassk aerial part extracts: An in vitro-in silico study

Hospitalization Endpoint in Clinical Trials of Outpatient Settings: using Anti-SARS-COV-2 Therapy as an Example.

In response to the COVID-19 pandemic, the World Health Organization (WHO) developed a set of outcome measures for trials primarily aimed at hospitalised patients. However, a gap exists in defining outcome standards for non-hospitalised patients. Therefore, this study aims to discuss hospitalisation as a primary outcome in outpatient trials and its potential pitfalls, specifically focusing on trials related to anti-SARS-COV-2 therapy. In this narrative review, researchers thoroughly searched MEDLINE and ClinicalTrials.gov from January 2020 to December 2022, targeting Phase III randomized controlled trials involving outpatients with mild-to-moderate COVID-19. The trials were specifically related to anti-SARS-COV-2 monoclonal antibodies or antiviral agents. The study collected essential data, including the type of intervention, comparator, primary objective, primary endpoint, and the use of estimands in the trial. The search identified 12 trials that evaluated the efficacy of anti-SARS COV-2 therapies in a predefined population. Three studies used hospitalisation and death as primary endpoints in high-risk patients receiving monoclonal antibodies. Nine studies assessed the efficacy of several antiviral agents: four trials used hospitalisation and death as the main endpoints, while others used different measures such as virologic measures using the Reverse Transcription-Polymerase Chain Reaction test (RT-PCR), the eight-point WHO ordinal scale, symptom alleviation by Day 7 and time to clinical response. Choosing hospitalization as an endpoint may provide meaningful data such as the cost-effectiveness ratio of a drug. However, different hospital utilisation patterns and investigator decisions could bias clinical outcomes if no specific criteria are considered. Therefore, investigators should have clear criteria for determining variables that influence this measure.

Comparison of T cells mediated immunity and side effects of mRNA vaccine and conventional COVID-19 vaccines administrated in Jordan

ABSTRACT Various COVID-19 vaccines can affect the immune system. Discrepancies have been noted in immune system characteristics, such as T-lymphocyte levels, between vaccinated and non-vaccinated individuals. This study investigates the variations in immune responses among the four administered COVID-19 vaccines, influencing factors, and clinical outcomes in Jordan. A total of 350 adults, who were at least two doses vaccinated, were interviewed and blood samples were collected for subsequent laboratory analyses. The study involved the quantification of T-cells specifically targeting anti-SARS CoV-2 using Flow cytometry analysis. BNT162b2 (Pfizer) recipients displayed significantly higher CD3+/CD4+ T-helper cell responses (90.84%, 87.46% – 94.22%) compared to non-Pfizer-BioNTech recipients {BBIBP-CorV (Sinopharm) and Sputnik V (Gamaleya Research Institute), then ChAdOx1 nCoV-19 (AstraZeneca)} (83.62%, 77.91% − 89.33%). The CD3+/CD8+ (T cytotoxic) level was notably elevated in non-Pfizer-BioNTech recipients {Sinopharm and Sputnik V then ChAdOx1 nCoV-19 AstraZeneca (73.94%, 69.38% − 78.49%) compared to BNT162b2 (Pfizer) recipients (58.26%, 53.07% − 63.44%). The CD3+ (T-cells) level showed no significant difference between BNT162b2 recipients (73.74%) and non-Pfizer-BioNTech recipients (77.83%), with both types generating T-cells. Comparing two doses of non-Pfizer-BioNTech vaccines with the third dose of BNT162b2 recipients (Pfizer), no difference in the type of immune reaction was observed, with non-Pfizer-BioNTech recipients still stimulating endogenous pathways like cell-mediated cytotoxic effects for cells. All COVID-19 vaccines administered in Jordan were effective, with respect to the total number of T cells. Non-Pfizer-BioNTech had higher in toxic T-cells and Pfizer-BioNTech was higher in helper T-cells that stimulate plasma cells to produce antibodies.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study

BackgroundHouseholds are considered ideal settings for studying the transmission dynamics of an infectious disease. MethodsA prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. ResultsWe enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0–18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4–45.5) and fatigue (aOR, 9.3; 95% CI, 3.8–22.7) were associated with SARS-CoV-2 transmission. ConclusionsWe observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

Evaluation of SARS-CoV-2 Humoral Response Following Vaccination with ChAdOx1 nCoV-19 (Covishield™) and/or Sinopharm, BBIBP-CorV (Vero cell™).

Billions of doses of COVID-19 vaccine have been introducing in the world to prevent pandemic COVID-19. Higher efficacy but limited data are available for its longevity. We aimed to find out the IgG Anti-SARS Cov-2 antibody level among frontline healthcare workers after two doses of vaccines. A cross-sectional study was carried among 170 HCPs of Seti Provincial Hospital of western Nepal, who were more than 18 years, and had taken two doses of either one of COVID 19 vaccine. All those participants, who were on leave during the data collection tenure (1st February 2022 to 28th February 2022) and/or did not consent to participate were excluded. Mindray SARS-CoV-2 S-RBD IgG assay kit based on CLIA method, was used whose target antigen is S-RBD (spike protein of receptor binding domain) antigen. The IgG immunoglobulin is detected and cut off value ≥10 AU/ml is considered positive. Based on the recommended cut off, the antibody was present in more than 90% across both groups of vaccinee i.e. the positive antibody titer at a mean duration of 7.31 months was 93.53% overall (93.75% and 93.44% in Vero cell™ and Covishield™ vaccinees respectively). There were 3.92 times high odds of high antibody titer (≥250 AU/ml) in Covishield™ group (OR: 3.92, 95% CI: 1.86-8.26, P-value: <0.001) than in Vero cell™ group of vaccinee. Similarly, there were significant difference of high titer of antibody across groups with more than six months of elapse of vaccination (OR: 2.18, 95% CI: 1.06-4.49, P-value: <0.001) than with less than six months of elapse of vaccination. The humoral response was higher among HCPs who received two-doses vaccination with ChAdOx1 nCoV-19 (Covishield™) and/or Sinopharm, BBIBP-CorV (Vero cell™) vaccine, and among those with six or more months of elapse of vaccination. The seroprevalence of SARS-CoV-2 following two-doses vaccination among HCPs was more than nine-tenths.

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2’s spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72–90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein’s conformational arrangements. The binding free energy ΔGTOTAL of C3 (−38.0 ± 0.08 kcal/mol) and C6E (−41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2.

Is Post-COVID 19 Vaccination Antibody Level Related to Happiness and Stress Hormones?

Aim: The level of antibody production in those vaccinated against coronavirus can be affected by many different situations. There is an important balance between immune response, stress and emotional state. However, it is not known how this situation affects antibody production after vaccination. This study aimed to investigate the correlation between the antibody response induced by the COVID-19 vaccine and the hormones cortisol, a marker of the stress axis, and serotonin, a marker of happiness. &#x0D; Material and Method: Serum cortisol and serotonin levels were analyzed in those who tested positive (n=40) and negative (n=40) for Anti-SARS CoV-2 IgG induced by vaccination. Anti-SARS CoV 2 IgG, cortisol, and serotonin levels were determined by using the ELISA method. The data were compared using the Mann-Whitney U test. The value of p0.05). &#x0D; Conclusion: Consequently, no effect of the stress parameter cortisol and the happiness parameter serotonin, was found in vaccine-induced immunization. It is considered that the different antibody responses in individuals may vary depending on other factors.

Synthesis and characterization of Ag(I) and Cu(I) complexes of triphenylphosphine: crystal structures, Hirshfeld surface analyses, and molecular docking with SARS-CoV-2 and its Omicron variant

Two new coordination complexes, a Ag(I) complex [Ag(PPh3)3(Sal)] (1) and a Cu(I) complex [Cu(PPh3)3Cl] (2), have been synthesized (PPh3 = triphenylphosphine, Sal = 3,5-dichlorosalicylaldehyde). Both complexes were characterized via single crystal X-ray crystallography. Complexes 1 and 2 were crystallized in monoclinic and trigonal crystal systems, respectively, in the P21/c and P3 space groups. Both possess tetrahedral coordination geometries. DFT calculations provided structure-property information. The Hirshfeld surface analyses and 2D fingerprint plots were performed to investigate the intermolecular interactions in the crystal structures. To explore potential SARS-CoV-2 drug candidates, we have examined the molecular docking of 1 and 2 with the SARS-CoV-2 spike protein (PDB ID: 8GOP) and with the SARS-CoV-2 Omicron spike protein (PDB ID: 7WRV). Complexes 1 and 2 showed good docking results with the SARS-CoV-2 spike protein (PDB ID: 8GOP) where the binding energies (ΔG) and respective inhibition constants (K i) correlation values are −7.4 kcal/mol (4.321 µM) and −7.9 kcal/mol (5.012 µM), respectively. The molecular docking results revealed that 1 and 2 with the SARS-CoV-2 Omicron spike protein (PDB ID: 7WRV) resulted in the binding energy (ΔG) of −7.6 kcal/mol and −8.2 kcal/mol with an inhibition constant (K i) of 4.639 and 5.742 µM, respectively. The study predicts that 1 and 2 may be used as anti-SARS CoV-2 agents.

The proteolytic airway environment associated with pneumonia acts as a barrier for treatment with anti-infective antibodies

Like pneumonia, coronavirus disease 2019 (COVID-19) is characterized by a massive infiltration of innate immune cells (such as polymorphonuclear leukocytes) into the airways and alveolar spaces. These cells release proteases that may degrade therapeutic antibodies and thus limit their effectiveness. Here, we investigated the in vitro and ex vivo impact on anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) IgG1s and other IgG subclasses (IgG2 and IgG4) of the neutrophil elastase, proteinase 3 and cathepsin G (the three main neutrophil serine proteases) found in endotracheal aspirates from patients with severe COVID-19. Although the IgGs were sensitive to neutrophil serine proteases, IgG2 was most resistant to proteolytic degradation. The two anti-SARS CoV2 antibodies (casirivimab and imdevimab) were sensitive to the lung’s proteolytic environment, although neutrophil serine protease inhibitors only partly limited the degradation. Overall, our results show that the pneumonia-associated imbalance between proteases and their inhibitors in the airways contributes to degradation of antiviral antibodies.

Detection of anti-SARS CoV-2 antibodies in human serum by means of Bloch surface waves on 1D photonic crystal biochips

This study presents the development and characterization of a disposable biochip for the detection of antibodies against the SARS-CoV-2 spike protein, a well-known target for vaccine and therapeutic development. This biochip is based on a one-dimensional photonic crystal (1DPC) deposited on a plastic substrate and designed to sustain Bloch surface waves (BSW) in the visible range. The experimental phase was carried out using the biochip in conjunction with a custom-made optical read-out platform capable of real-time refractometric detection and fluorescence-based end-point measurements. Our biochip was functionalized by immobilizing the receptor-binding domain of the spike protein onto the surface using a silanization process. Human serum samples, including a negative control and a positive sample from a recovered COVID-19 patient, were tested on the biochip. The experimental results show that the biochip discriminates between positive and negative samples in a label-free refractometric mode down to a 1:10 dilution of the sera and in quantum dot amplified refractometric and fluorescence mode down to 1:100 dilution. The results demonstrate the potential of the disposable biochip for sensitive and specific detection of COVID-19 antibodies.

Following Natural Autoantibodies: Further Immunoserological Evidence Regarding Their Silent Plasticity and Engagement in Immune Activation.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological and natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, physiological nAAbs also exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR n = 1739 and anti-SARS-CoV-2 IgG n = 330) and nAAbs (anti-citrate synthase IgG, IgM n = 1739) were measured by in-house and commercial ELISAs using Croatian (Osijek) anonymous samples with documented vaccination backgrounds. The results were subsequently compared for statistical evaluation. Interestingly, the IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p < 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p = 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls vector/mRNA vaccines p = 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network.

Diagnostic performance of two commercially available coronavirus disease 2019 antibody kits: Elecsys Anti-SARS CoV-2 (Roche) and Anti-SARS-CoV-2 ELISA (IgG) (Euroimmun)

Although coronavirus disease 2019 (COVID-19) is no longer a pandemic, it still kills. The risk of a new wild variant means it is still important to monitor and assess the level of immunity in vulnerable populations. We aimed to investigate the diagnostic performance of two widely available commercial antibody testing kits. A total of 170 blood samples with different disease profiles were collected. Sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV), accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and kappa values were calculated. Receiver-operating characteristic (ROC) analyses of sensitivity and 1-specificity were performed. The area under the curve (AUC) was calculated and P less than 0.05 was considered significant. The positive likelihood ratio LR+ [sensitivity/(1 − specificity)] as a measure of the diagnostic performance of a test was calculated. Spearman's rank correlation analysis was used to compare kit results. For the Roche and Euroimmun tests, the sensitivity was 96 and 89%, the specificity was 100 and 100%, PPV was 100 and 100%, and NPV was 57 and 33%, respectively. AUC was 0.983 for Roche (P &lt; 0.001) and 0.94 for Euroimmun (P &lt; 0.001). A highly significant correlation between the two kits was found (r = 0.917, P &lt; 0.001). Even though the Elecsys Roche kit had a slightly better performance, both kits could be used for the antibody screen of a population. However, combined methods, including memory T-cell and neutralizing antibody tests, can give a better idea of an individual's immune status.

Design, synthesis, and biological evaluation of indole-2-carboxamides as SARS CoV-2 main protease inhibitors

Using a repurposing approach, a series of previously reported antiproliferative indole-based carboxamides (9–23) were reassessed for their anti-SARS-CoV-2 viral activity as main protease (SARS-CoV-2 Mpro) inhibitors. The structure of the indole-based carboxamides was validated by comparing the acquired data to previously report physicochemical and NMR spectroscopy data. The anti-SARS-CoV-2 activity of the synthesised compounds was tested in Vero-E6 cells using SARS-CoV-2 (NRC-03-nhCoV) virus. MTT cytotoxicity assay results demonstrated that compounds 9–23 had CC50 (50% cytotoxicity concentration) values ranging from 325.60 to 578.50 μM and safety indices ranging from 21.40 to 99.60. Most of the compounds examined significantly inhibited NRC-03-nhCoV virus replication, with IC50 values ranging from 3.60 μM to 15.20 μM, with compounds 11, 19, and 20 having the most potent anti-SARS-COV-2 activity. The inhibitory effect of compounds 11, 13, 14, 19 and 20 against SARS-CoV-2 Mpro was investigated. The findings of this test were consistent with the anti-SARS CoV-2 experiment. Inflammatory cytokine tests revealed that compounds 11, 19 and 20 have antiviral effectiveness against SARS-CoV-2 and can reduce hyper inflammation. Finally, docking studies of the novel compounds in the SARS CoV-2-Mpro active site revealed a good match.

Discovery of raffinose sulfate as a potential SARS CoV-2 inhibitor via blocking its binding with angiotensin converting enzyme 2

The present study aimed to characterize the possible binding sites on the SARS CoV-2 RBD-ACE2 complex and to highlight sulfated oligosaccharides as potential anti-SARS CoV-2 via inducing RBD-ACE2 complex destabilization and dissociation. By combining pharmacophore-based and structural-based virtual screening approaches we were able to discover raffinose sulfate (RS) as a potential antiviral sulfated oligosaccharide against two SARS CoV-2 variants (i.e., wild type and Omicron) (IC50 = 4.45 ± 0.28 μM and 4.65 ± 0.32 μM, respectively). Upon MD simulation, RS was able to establish stable binding at the RBD-ACE2 interface inducing a rapid dissociation. Accordingly, and by using bio-layer interferometry (BLI) assays, RS was able to significantly weaken the affinity between RBD (of both variants) and ACE2. Additionally, we found that RS has a poor cellular permeability indicating that its interaction with the RBD-ACE2 complex may be the main mechanism by which it mediates its antiviral activity against SARS CoV-2. Despite its proposed interaction with the RBD-ACE2 complex, RS did not show any inhibitory activity against ACE2 catalytic activity. In light of these findings, the RS scaffold can be further developed into a novel anti-SARS CoV-2 drug with improved activity and tolerability in comparison with other sulfated polysaccharides e.g., heparin and heparan.

Microbiological status of anti-SARS CoV-2 protective face masks

The SARS-CoV-2 pandemic situation put extreme pressure on the worldwide medical system from medical personnel to medical equipment. The protective face mask became the front line of anti-SARS-CoV-2 prevention methods, used by most of the world population, more than 7 billion people. The massive demand for face masks activated the world market, where countries from different continents increased their mask production and commercialization worldwide. Unfortunately, the focus on face mask production mostly relied on their ability to filter small-size molecules and less on their microbiological sterile status. Since bacterial structural communities could differ between various large populational groups or continents, in this study, we analyzed the microbial quality of face masks received from various countries/continents. There were analyzed the microbiological load of four types of masks, three from China and one from Romania. The bacterial density from masks was analyzed by membrane filtration and swabbing bacterial collection techniques. The results showed the Romanian mask had a smaller bacterial load than the Chinese masks. In addition, the bacterial identification showed a wide range of bacterial strains, quite different between face mask types.