Decreased Disease Severity Research Articles

Neutrophil to lymphocyte ratio and immature granulocyte: assessing for promising parameters to monitor tuberculosis-diabetes mellitus patients

Tuberculosis remains as a major global public health threat and infected more than >10 million cases worldwide. Nowadays, public have witnessed epidemiological shift between chronic and infectious disease globally. Diabetes mellitus as a non-communicable disease and on the other side, Tuberculosis as an infectious disease coexist in the same individual may became health challenge in the near future. DM’s impact on clinical presentation and treatment outcome of TB remains poorly. Detecting and managing TB patients with DM comorbidity by routine laboratory screening provides an opportunity for monitoring patients' prognosis and decreasing disease severity to better outcomes. But in facts, not all laboratory services can provide complex yet expensive assays. Studies has shown Neutrophil to Lymphocyte Ratio (NLR) and Immature Granulocyte Percent (IG%) may be an option as an easy, quick, simple, low-cost, repeatable and reliable assays to monitor TB-DM patient’s prognosis.

Evaluation of Trichoderma isolates as biocontrol measure against Claviceps purpurea

Claviceps purpurea causes ergot, a floral disease of major cereal crops, such as winter rye and winter triticale. The dark sclerotia formed by C. purpurea contain numerous toxic ergot alkaloids, which pose a major health risk for humans and animals when ingested. The countermeasures against ergot infection are currently limited to intensive tillage, seed cleaning, crop rotation or integration of optical sorting machines to remove ergot from cereals before processing. However, these practices confer only a minor protective effect and are highly energy-demanding. Thus, more effective and sustainable plant protection measures to combat ergot infections in cereals are needed. The application of Trichoderma spp. as biological control agent has already proven successful against a wide range of phytopathogenic fungi. However, there is only minor scientific evidence about its protective capacity against C. purpurea in cereal crops. In our study, we therefore investigated the antagonistic potential of several Trichoderma isolates against C. purpurea and their ability to confer protection against ergot infection. In initial in vitro tests and confrontation assays, we quantified and compared the production of iron-chelating compounds and hydrolytic enzymes as well as the antagonistic activity against C. purpurea sclerotia and mycelial cultures. Several strains showed high antifungal capacity and growth inhibitory effects towards C. purpurea. Selected Trichoderma strains were then tested for their potential to protect rye (Secale cereale) plants from ergot infection within a greenhouse trial. Rhizosphere-inoculated plants displayed a decreased disease severity compared to plants that had been sprayed with Trichoderma spores above-ground. Gene expression analysis by reverse transcription quantitative PCR also indicated the induction of systemic defense reactions. Overall, our data suggest that individual Trichoderma isolates possess a high antagonistic potential towards C. purpurea, which could be effective by direct mycoparasitism and by inducing systemic plant resistance, and therefore provide important guidance towards the development of Trichoderma treatments of cereals as biocontrol measure against ergot.Graphical abstract

A Three-Year Study of Comparative Effects of Four Organic Amendments on Soil Health Dynamics, Tomato Production, and Rhizosphere Microbial Community

ABSTRACT Tomato is a demanding crop in fertilizers, fungicides, and pesticides. Therefore, producing food with limit use of chemical farm inputs became essential to reduce the harmful effects of these chemicals in agro-ecosystems. Green manures have great potential to limit the dependency on chemical inputs and preserve the soil fertility. Two fodder radish cultivars, used as green manure, were tested, during three consecutive cropping years, for their effects on soil properties and fertility, tomato growth and production, soilborne diseases’ severity, and rhizosphere microbial community. Control treatment consisted of bovine manure and a commercial bio-activator of plant and soil systems i.e. biocat−15Ⓡ. All amended soils showed enhancement in their total nitrogen and available potassium and phosphorus levels. The highest increment in the soil organic matter and the soil carbon biomass noted using radish cv. Defender material. Before tomato planting, the monitoring of the soil microbial community structure revealed that the two green manures had increased the soil richness in actinomycetes communities but only cv. Defender had enhanced the bacterial population. For tomato growth and soilborne disease severity parameters, organic amendments had enhanced tomato growth by 17.8 to 41.7% and decreased disease severity by 46.6 to 97.3% at the second cropping year compared to the first one. The present results indicate that the four organic amendments tested would be an effective approach for improving the soil ecological environment for sustainable tomato cropping with significant enhancements of the majority of tested parameters recorded using fodder radish cv. Defender as green manure.

Effects of above ground pathogen infection and fungicide application on the root-associated microbiota of apple saplings

BackgroundThe root-associated microbiome has been of keen research interest especially in the last decade due to the large potential for increasing overall plant performance in agricultural systems. Knowledge about the impact of above ground plant disturbances on the root-associated microbiome remains limited. We addressed this by focusing on two potential impacts, foliar pathogen infection alone and in combination with the application of a plant health protecting product. We hypothesized that these lead to plant-mediated responses in the rhizosphere microbiota.ResultsThe effects of an infection of greenhouse grown apple saplings with either Venturia inaequalis or Podosphaera leucotricha as foliar pathogen, as well as the combined effect of P. leucotricha infection and foliar application of the synthetic plant health protecting product Aliette (active ingredient: fosetyl-aluminum), were studied on the root-associated microbiota. The bacterial community structure of rhizospheric soil and endospheric root material was characterized post-infection, using 16S rRNA gene amplicon sequencing. With increasing disease severity both pathogens led to changes in the rhizosphere and endosphere bacterial communities in comparison to uninfected plants (explained variance up to 17.7%). While the preventive application of Aliette on healthy plants two weeks prior inoculation did not induce changes in the root-associated microbiota, a second later application on the diseased plants decreased disease severity and resulted in differences of the rhizosphere bacterial community between infected and several of the cured plants, though differences were overall not statistically significant.ConclusionsFoliar pathogen infections can induce plant-mediated changes in the root-associated microbiota, indicating that above ground disturbances are reflected in the below-ground microbiome, even though these become evident only upon severe leaf infection. The application of the fungicide Aliette on healthy plants itself did not induce any changes, but the application to diseased plants helped the plant to regain the microbiota of a healthy plant. These findings indicate that above ground agronomic management practices have implications for the root-associated microbiome, which should be considered in the context of microbiome management strategies.

Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19

BackgroundOxidative stress is thought to play a significant role in the pathogenesis and severity of COVID-19. Additionally, angiotensin converting enzyme 2 (ACE2) expression may predict the severity and clinical course of COVID-19. Accordingly, the aim of the present study was to evaluate the association of oxidative stress and ACE2 expression with the clinical severity in patients with COVID-19.Methods and resultsThe present study comprised 40 patients with COVID-19 and 40 matched healthy controls, recruited between September 2021 and March 2022. ACE 2 expression levels were measured using Hera plus SYBR Green qPCR kits with GAPDH used as an internal control. Serum melatonin (MLT) levels, serum malondialdehyde (MDA) levels, and total antioxidant capacity (TAC) were estimated using ELISA. The correlations between the levels of the studied markers and clinical indicators of disease severity were evaluated. Significantly, lower expression of ACE2 was observed in COVID-19 patients compared to controls. Patients with COVID-19 had lower serum levels of TAC and MLT but higher serum levels of MDA compared to normal controls. Serum MDA levels were correlated with diastolic blood pressure (DBP), Glasgow coma scale (GCS) scores, and serum potassium levels. Serum MLT levels were positively correlated with DBP, mean arterial pressure (MAP), respiratory rate, and serum potassium levels. TAC was correlated with GCS, mean platelet volume, and serum creatinine levels. Serum MLT levels were significantly lower in patients treated with remdesivir and inotropes. Receiver operating characteristic curve analysis demonstrates that all markers had utility in discriminating COVID-19 patients from healthy controls.ConclusionsIncreased oxidative stress and increased ACE2 expression were correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 in the present study. Melatonin supplementation may provide a utility as an adjuvant therapy in decreasing disease severity and death in COVID-19 patients.

Biologic Therapies Decrease Disease Severity and Improve Depression and Anxiety Symptoms in Psoriasis Patients.

Psoriasis is an immune-mediated chronic skin disease that is associated with a significant psychological burden. A newer line of therapy is represented by biologic agents. Our study aimed to evaluate the effect of biologic therapies in the treatment of psoriasis concerning both disease severity and psychological comorbidity. We performed a prospective case-control comparison to evaluate the prevalence of depression and anxiety in psoriasis patients and unaffected individuals. All patients were recruited between October 2017 and February 2021. Baseline depression (PHQ-9), anxiety (GAD-7), PASI, and DLQI scores were noted. Then, we evaluated the efficacy of biologic treatment in reducing these scores at 6 months of therapy. Patients were treated with either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. 106 bio-naïve patients with psoriasis and 106 controls without the disease were included in this study. Depression and anxiety were significantly more common among psoriasis patients than in unaffected individuals (p < 0.0001). Female patients presented both depression and anxiety more frequently than men in both case and control groups. Disease severity was significantly associated with worsened depression and anxiety symptoms. Biologic therapy resulted in a significant decrease in all four scores at the 6-month mark for each patient (p < 0.0001). Only an improved PASI correlated significantly with lower depression and anxiety scores (p < 0.005), whereas a decreased DLQI did not (p > 0.955). None of the seven biologic agents used was discovered to be superior. biologic therapies are effective in decreasing both disease severity and alleviating depression and anxiety symptoms in psoriasis.

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.

Nanoparticles Enhance Solubility and Neuroprotective Effects of Resveratrol in Demyelinating Disease.

Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory treatments for MS aim to reduce inflammation with limited effects on the neurodegenerative component of this disease. The purpose of the current study is to develop a novel nanoparticle formulation of resveratrol to increase its solubility, and to assess its ability to prevent optic nerve and spinal cord degeneration in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Resveratrol nanoparticles (RNs) were made using a thin rehydration technique. EAE mice received a daily oral administration of vehicle, RNs or unconjugated resveratrol for one month. They were assessed daily for clinical signs of paralysis and weekly for their visual acuity with optokinetic responses (OKR). After one month, their spinal cords and optic nerves were stained for inflammation and demyelination and retinal ganglion cells immunostained for Brn3a. RNs were stable for three months. The administration of RNs did not have any effect on clinical manifestation of EAE and did not preserve OKR scores but reduced the intensity of the disease. It did not reduce inflammation and demyelination in the spinal cord and the optic nerve. However, RNs were able to decrease RGC loss compared to the vehicle. Results demonstrate that resveratrol is neuroprotective by reducing RGC loss. Interestingly, neuroprotective effects and decreased disease severity occurred without reduction of inflammation or demyelination, suggesting this therapy may fill an unmet need to limit the neurodegenerative component of MS.

B cells Regulation by Interferon-gamma in a Neuromyelitis Optica Spectrum Disorder animal model

Abstract Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) mediated by Th17 and auto-antibody response against the water channel protein Aquaporin-4 (AQP4). In NMOSD, B cells plays a central role regulating autoreactive T and antibody secreting cells, and the use of anti-B cells therapy is a common practice for patients. Despite this, the mechanisms of B cells response against AQP4 are poorly understood. We have demonstrated that the immune tolerance against the immunodominant AQP4 201–220peptide in mice is maintained by IFN-g, controlling disease incidence, severity, and chronicity. Actively immunization of C57BL/6 (WT) treated with neutralizing anti-IFN-g antibodies, IFN-g knockout (IFNGKO) and IFN-g receptor KO (IFNRKO) mice was induced using the AQP4 201–220peptide, showing an ascendant paralysis starting from the tail to complete hind limb paralysis. CNS histological analysis showed an increased presence of T and B cells, and the complement system in lesion sites, associated with CNS damage. CNS Th17 profile was also observed in the anti-IFN-g treated group. Conversely, IFN-g treatment in IFNGKO mice decrease disease severity with a reduction of CNS CD4 +and B cells. Remarkably, IFN-g regulates the IL-6 expression by B cells in an antigen specific fashion. B-cell depletion significantly reduced the disease incidence, T cells CNS infiltration and anti-AQP4 201–220serum antibodies. Finally, using anti-IL-6R treatment, we showed that IL-6 signaling is necessary for the B cell activation and their induction of Th17 cells. In conclusion, AQP4 201–220tolerance is strictly regulated by IFN-g and its signaling, restraining B cells pathogenicity through IL-6 signaling modulation. This work was supported by National Institutes of Health grants R21AI151438 and R01 NS099334

The effect of omega-3 supplements on the serum levels of ACE/ACE2 ratio as a potential key in cardiovascular disease: A randomized clinical trial in participants with vitamin D deficiency.

The aim of this randomized controlled clinical trial was to determine the effect of the omega-3 fatty acid supplementations 300 mg per day for 8 weeks on the serum levels of ACE/ACE2 ratio in Jordanian participants with vitamin D deficiency (VDD). The physical and clinical characteristic of individuals in both intervention and control randomized controlled clinical trial were measured and analyzed. The comparisons between the two groups and the changes in each group before and after taking omega-3 doses were studied through independent t test and paired t test, respectively. Possible factors that have a role in the changes were determined by multivariate stepwise regression. Follow-up period lasted 10 weeks. The sample consisted of 82 participants with VDD and a mean age of 37.85 ± 9.85 years. Omega-3 Supplements resulted in a significant decrease in serum ACE levels, ACE/ACE2 ratio and serum 25-hydroxy vitamin D (25OHD). While the change in serum ACE2 levels and serum triglycerides levels were insignificant. Also, a significant increase in serum LDL levels were observed. It is possible that taking high doses of omega-3 fatty acid supplementations have positive effects on the heart and circulatory system and could protect from COVID-19 or decrease disease severity, in connection with a decrease in the ACE/ACE 2 ratio. On the other hand, omega-3 supplement may have negative effect on cardiovascular system due to the significant increase in serum LDL levels.

Bactericidal and plant defense elicitation activities of Eucalyptus oil decrease the severity of infections by Xylella fastidiosa on almond plants.

The activity of Eucalyptus essential oil against eleven strains pertaining to six species of plant pathogenic bacteria was studied using growth inhibition and contact assays. All strains were susceptible to the formulation EGL2, and Xylella fastidiosa subspecies and Xanthomonas fragariae were the most sensitive. The bactericidal effect was strong causing 4.5 to 6.0 log reductions in survival in 30min at concentrations in the range of 0.75 to 15.0 μl/ml depending on the bacteria tested. Transmission electron microscopy of the formulation EGL2 against the three X. fastidiosa subspecies studied allowed the observation of a strong lytic effect on bacterial cells. In addition, the preventive spray application of EGL2 to potted pear plants subsequently inoculated with Erwinia amylovora significantly decreased the severity of infections. Almond plants treated by endotherapy or soil drenching, and then inoculated with X. fastidiosa showed a significant decrease in disease severity as well as in the levels of the pathogen, depending on the strategy used (endotherapy/soil drenching, preventive/curative). The treatment by endotherapy in almond plants induced the expression of several genes involved in plant defense. It was concluded that the reduction of infections by the Eucalyptus oil treatments was due to the combination of its bactericidal and plant defense induction activities.

Health-related quality of life of daily-life-affected benign essential blepharospasm: Multi-center observational study.

To compare Thais' health-related quality of life (HRQOL) and severity grading, efficacy and safety in daily-life-affected benign essential blepharospasm (BEB) patients at baseline and after Botulinum toxin type A (BTX-A) treatment. Prospective-observational study. BEB patients with Jankovic rating scale (JRS) at least 3 in both severity and frequency graded from 14 institutes nationwide were included from August 2020 to June 2021. Demographic data, HRQOL evaluated by the Thai version of EQ-5D-5L and NEI-VFQ-25 questionnaires, and severity grading score evaluated by Jankovic rating scale (JRS) at baseline, 1, and 3 months after the treatment were collected. The impact of the BTX-A injections and their complications were recorded. 184 daily-life-affected BEB patients were enrolled; 159 patients (86.4%) had complete data with a mean age of 61.40±10.09 years. About 88.05% were female, and 10.1% were newly diagnosed. Most of the patients had bilateral involvement (96.9%) and 12.6% had history of BEB-related accident. After BTX-A treatment, HRQOL improved significantly in 4 dimensions of EQ-5D-5L, except self-care. The EQ_VAS (mean±SD) was 64.54±19.27, 75.13±15.37, 73.8±15.85 (p<0.001) and EQ-5D-5L utility score was 0.748±0.23, 0.824±0.19 and 0.807±0.19 at baseline, 1, 3 months after treatment, respectively. From NEI-VFQ-25, HRQOL also improved in all dimensions, except eye pain. The JRS improved in all patients. Self-reported minor adverse events were 22.6%, which mostly resolved within the first month. Daily-life-affected BEB impacted HRQOL in most dimensions from both generic and visual-specific questionnaires. BTX-A treatment not only decreased disease severity, but also improved quality of life.

Modes of Action of Biocontrol Agents and Elicitors for sustainable Protection against Bacterial Canker of Tomato.

Tomato is one of the world's most commonly grown and consumed vegetables. However, it can be attacked by the Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis (Cmm), which causes bacterial canker on tomato plants, resulting in significant financial losses in field production and greenhouses worldwide. The current management strategies rely principally on the application of various chemical pesticides and antibiotics, which represent a real danger to the environment and human safety. Plant growth-promoting rhizobacteria (PGPR) have emerged as an attractive alternative to agrochemical crop protection methods. PGPR act through several mechanisms to support plant growth and performance, while also preventing pathogen infection. This review highlights the importance of bacterial canker disease and the pathogenicity of Cmm. We emphasize the application of PGPR as an ecological and cost-effective approach to the biocontrol of Cmm, specifying the complex modes of biocontrol agents (BCAs), and presenting their direct/indirect mechanisms of action that enable them to effectively protect tomato crops. Pseudomonas and Bacillus are considered to be the most interesting PGPR species for the biological control of Cmm worldwide. Improving plants' innate defense mechanisms is one of the main biocontrol mechanisms of PGPR to manage bacterial canker and to limit its occurrence and gravity. Herein, we further discuss elicitors as a new management strategy to control Cmm, which are found to be highly effective in stimulating the plant immune system, decreasing disease severity, and minimizing pesticide use.

Reducing environmentally mediated transmission to moderate impacts of an emerging wildlife disease

Abstract Emerging infectious diseases have caused population declines and biodiversity loss. The ability of pathogens to survive in the environment, independent of their host, can exacerbate disease impacts and increase the likelihood of species extinction. Control of pathogens with environmental stages remains a significant challenge for conservation and effective management strategies are urgently needed. We examined the effectiveness of managing environmental exposure to reduce the impacts of an emerging infectious disease of bats, white‐nose syndrome (WNS). We used a chemical disinfectant, chlorine dioxide (ClO2), to experimentally reduce Pseudogymnoascus destructans, the fungal pathogen causing WNS, in the environment. We combined laboratory experiments with 3 years of field trials at four abandoned mines to determine whether ClO2 could effectively remove P. destructans from the environment, reduce host infection and limit population impacts. ClO2 was effective at killing P. destructans in vitro across multiple concentrations. In field settings, higher concentrations of ClO2 treatment were needed to sufficiently reduce viable P. destructans conidia in the environment. The reduction in the environmental reservoir at treatment sites resulted in lower fungal loads on bats compared to untreated control populations. Survival following treatment was also higher in little brown bats (Myotis lucifugus), and trended higher for tricolored bats (Perimyotis subflavus). Synthesis and applications. Our results highlight that targeted management of sources for environmental transmission can be an effective control strategy for wildlife disease. We found that successfully reducing pathogen in the environment decreased disease severity and increased survival, but required higher treatment exposure than was effective in laboratory experiments, and the effects varied among species. More broadly, our findings have implications for other emerging wildlife diseases with free‐living pathogen stages by highlighting how the degree of environmental contamination can have cascading impacts on hosts, presenting an opportunity for intervention.

Evaluation of Soil Streptomyces spp. for the Biological Control of Fusarium Wilt Disease and Growth Promotion in Tomato and Banana

Fusarium oxysporum f. sp. lycopersici (Fol) and Fusarium oxysporum f. sp. cubense (Foc), are the causal agent of Fusarium wilt disease of tomato and banana, respectively, and cause significant yield losses worldwide. A cost-effective measure, such as biological control agents, was used as an alternative method to control these pathogens. Therefore, in this study, six isolates of the Streptomyces-like colony were isolated from soils and their antagonistic activity against phytopathogenic fungi and plant growth-promoting (PGP) activity were assessed. The results showed that these isolates could inhibit the mycelial growth of Fol and Foc. Among them, isolate STRM304 showed the highest percentage of mycelial growth reduction and broad-spectrum antagonistic activity against all tested fungi. In the pot experiment study, the culture filtrate of isolates STRM103 and STRM104 significantly decreased disease severity and symptoms in Fol inoculated plants. Similarly, the culture filtrate of the STRM304 isolate significantly reduced the severity of the disease and symptoms of the disease in Foc inoculated plants. The PGP activity test presents PGP activities, such as indole acetic acid production, phosphate solubilization, starch hydrolysis, lignin hydrolysis, and cellulase activity. Interestingly, the application of the culture filtrate from all isolates increased the percentage of tomato seed germination and stimulated the growth of tomato plants and banana seedlings, increasing the elongation of the shoot and the root and shoot and root weight compared to the control treatment. Therefore, the isolate STRM103 and STRM104, and STRM304 could be used as biocontrol and PGP agents for tomato and banana, respectively, in sustainable agriculture.

Physiological and Anatomical Responses of Faba Bean Plants Infected with Chocolate Spot Disease to Chemical Inducers.

Plant diseases are biotic stresses that restrict crop plants' ability to develop and produce. Numerous foliar diseases, such as chocolate spots, can cause significant production losses in Vicia faba plants. Certain chemical inducers, including salicylic acid (SA), oxalic acid (OA), nicotinic acid (NA), and benzoic acid (BA), were used in this study to assess efficacy in controlling these diseases. A foliar spray of these phenolic acids was used to manage the impacts of the biotic stress resulting from disease incidence. All tested chemical inducers resulted in a significant decrease in disease severity. They also enhanced the defense system of treated plants through increasing antioxidant enzyme activity (Peroxidase, polyphenol oxidase, β-1, 3-glucanase, and chitinase) compared to the corresponding control. Healthy leaves of faba plants recorded the lowest (p < 0.05) values of all antioxidant activities compared to those plants infected by Botrytis fabae. Moreover, the separation of proteins using SDS-PAGE showed slight differences among treatments. Furthermore, foliar spray with natural organic acids reduced the adverse effects of fungal infection by expediting recovery. The SA (5 mM) treatment produced a pronounced increase in the upper, lower epidermis, palisade thickness, spongy tissues, midrib zone, length, and width of vascular bundle. The foliar application with other treatments resulted in a slight increase in the thickness of the examined layers, especially by benzoic acid. In general, all tested chemical inducers could alleviate the adverse effects of the biotic stress on faba bean plants infected by Botrytis fabae.

Therapeutic Effect of Vitamin A Administration on Disease Severity in Hospitalized COVID-19 Patients: A Pilot Open-Labeled Randomized Clinical Trial

Background: Considering the high prevalence of the COVID-19 worldwide and since there is no effective treatment for it, the employment of complementary treatments without side effects is highlighted. So, this clinical trial aimed to assess if vitamin A injection decreases disease severity in hospitalized patients with COVID-19. Methods: In this pilot open-labeled randomized controlled clinical trial (RCT), 18 patients were instructed to take a daily dose of intramuscular vitamin A (maximum of 14 days), and 18 patients continued their common treatment protocols. For predicting mortality risk, we used the Coronavirus Clinical Characterization Consortium (4C) score. This score predicts mortality in hospitalized patients based on demographic and physiologic parameters. Based on this score, the patients were classified into four groups from low-risk to extremely high-risk groups. Results: The included participants were aged 61.43±13.54 years, and 38.8% of them were female. The findings indicated no significant differences between groups regarding baseline characteristics. In the vitamin A group, the mean 4C score was 6.86±3.37 before the study which reduced insignificantly to 6.8±3.34 at the end of the study. In the control group, the mean 4C score increased insignificantly from 7.21±2.72 to 7.28±2.39. Furthermore, the result of the one-way analysis of covariance (ANCOVA) showed that after adjusting for baseline values, the differences between groups are not significant. Conclusion: Based on the results, this study showed no significant effect of vitamin A on COVID-19 severity.

1876. COVID-19 Reinfection and Disease Severity in the New York City Health + Hospitals System

Abstract Background Though reinfection with SARS-CoV-2 is well documented, there remains uncertainty about the potential for more severe symptoms with reinfections compared to index infections. Methods Patients who received SARS-CoV-2 PCR testing between March 1, 2020 and March 1, 2021 at New York City Health and Hospitals (NYC H+H) facilities and had two positive tests &amp;gt; =90 days apart were included in the analysis. Clinical and demographic data were extracted from the electronic medical record. Manual chart review was done to confirm symptomatology, assess COVID-19 related hospital admissions, and determine WHO disease severity. Patients were then classified as unlikely reinfection, possible reinfection, or probable reinfection based on symptomatology, PCR and antibody testing, and lack of alternative diagnoses. Patients were classified as “unable to be assessed” if symptomatology could not be assessed for both episodes of PCR positivity. Figure 1:Flow chart of selection process for study inclusionFigure 2:Reinfection Classification Results During our study timeframe, 1,255,584 unique patients received at least one SARS-CoV-2 PCR test, 265 of whom had two positive tests &amp;gt; =90 days apart. We categorized 20 patients as unable to be assessed, 28 as unlikely reinfection (1 persistent PCR positivity, 27 unlikely true infection at index or second PCR-positive episode), and 217 as possible or probable reinfection. Of the 217, at their index episode 79 had an asymptomatic infection (36.4%) and 17 were severe or critical (7.8%). At their second episode, 162 patients had an asymptomatic infection (74.7%), and 5 were severe or critical (2.3%). Only 24 patients with possible/probable reinfection had a more severe COVID reinfection than index infection, and 20 of the 24 had asymptomatic index infections. Three patients were hospitalized at both episodes, and two deaths possibly attributable to COVID-19 reinfection were noted in this cohort. Figure 3:Change in WHO disease severity classification from index to second infection among probable/possible reinfection cases (n=217) Red indicates increase in disease severity from index to reinfection (n=24), blue indicates decrease in disease severity from index to reinfection (n=100), white indicates no change (n=74) and gray indicates unable to assess disease severity at index or second infection (n=19). Conclusion COVID-19 reinfection was rare in a high incidence setting among patients tested at NYC H+H facilities. Disease severity was generally milder in reinfection, although severe and critical disease occurred in a small number of patients. These findings from earlier in the pandemic (presumably wild-type and alpha variant) provide data for comparison in understanding how reinfection is evolving with newer variants. Disclosures Carlos Salama, MD, Genentech: Advisor/Consultant Gabriel Cohen, MD, Daybreak Health: Advisor/Consultant|Daybreak Health: Board Member|Daybreak Health: Ownership Interest.

Hydropriming and Osmotic Priming Induce Resistance against Aspergillus niger in Wheat (Triticum aestivum L.) by Activating β-1, 3-glucanase, Chitinase, and Thaumatin-like Protein Genes.

Priming is used as a method to improve plant growth and alleviate the detrimental effects of pathogens. The present study was conducted to evaluate the effects of different priming methods in the context of resistance to Aspergillus niger in wheat (Triticum aestivum L.). Here, we show that different priming treatments-viz., hydropriming, osmotic priming, halopriming, and hormonal priming techniques can induce disease resistance by improving the biochemical contents of wheat, including chlorophyll, protein, proline, and sugar. In addition, physiological parameters-such as root length, shoot length, fresh and dry root/shoot ratios, and relative water content were positively affected by these priming methods. In essence, hydropriming and osmotic priming treatments were found to be more potent for enhancing wheat biochemical contents, along with all the physiological parameters, and for reducing disease severity. Hydropriming and osmotic priming significantly decreased disease severity, by 70.59-75.00% and 64.71-88.33%, respectively. RT-PCR and quantitative real-time PCR analyses of potentially important pathogenesis-related (PR)-protein genes (Thaumatin-like protein (TLP), chitinase, and β-1,3-glucanase) in primed plants were evaluated: β-1,3-glucanase was most highly expressed in all primed plants; Chitinase and TLP exhibited higher expression in hormonal-, halo-, osmotic-, and hydro-primed plants, respectively. These results suggest that the higher expression of β-1,3-glucanase,&amp;nbsp;TLP, and chitinase after hydropriming and osmotic priming may increase disease resistance in wheat. Our study demonstrates the greater potential of hydropriming and osmotic priming for alleviating stress caused by A. niger inoculation, and enhancing resistance to it, in addition to significantly improving plant growth. Thus, these priming methods could be beneficial for better plant growth and disease resistance in other plants.

Pruritogens in pemphigoid diseases: Possible therapeutic targets for a burdensome symptom.

Pruritus is a hallmark feature in pemphigoid diseases, where it can be severe and greatly impact the quality of life of affected patients. Despite being a key symptom, the exact pathophysiological mechanisms involved in pruritus in pemphigoid are yet to be fully elucidated and effective therapies addressing them are limited. This review summarizes the present understanding of pruritus specific to pemphigoid diseases, especially the pruritogens that induce it, and the therapeutic options that have been explored so far. The majority of the available evidence is on bullous pemphigoid and epidermolysis bullosa acquisita. Histamine derived from basophils correlates with pruritus severity, with omalizumab demonstrating promising efficacy in pruritus for bullous pemphigoid. IL-4/-13 contribute to itch in bullous pemphigoid with dupilumab being evaluated in clinical trials. Other pruritogens of interest include substance P, tryptase, and thymic stromal lymphopoetin, with therapies targeting them requiring further investigation. Scratching behaviors contribute directly to blister formation through various mechanisms, such as pathological autoantibody recruitment, T helper cell type 1 polarization, and exposure of intracellular autoantigens. Treatments addressing these pathways may contribute to decreasing disease severity. Additional studies are needed to fully characterize how pruritus is regulated in pemphigoid diseases, to help pave the way to develop novel and effective therapeutics that will not only address pruritic symptoms but also decrease disease severity.