Features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2.

Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Methods In this study,an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS - CoV - 2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital,Guangzhou Medical University,since May 21,2021,and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t - test or the Mann - Whitney U test was used for comparison of continuous data between two groups,and the chi - square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS - CoV - 2 were enrolled,among whom there were 32 (37. 6%)pediatric patients infected with Delta variant and 53 (62. 4%)pediatric patients infected with Omicron variant,and there were no significant differences between the two groups in age,sex, body height,body weight,and comorbidities (all P > 0. 05). There were no significant differences between the two groups in alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma - glutamyl transpeptidase,total bilirubin,albumin,and cholinesterase (all P > 0. 05),and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA)than those infected with Delta variant (Z = - 2. 336,P = 0. 020). However,the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups (P > 0. 05). Among the 85 pediatric patients,10 (11. 8%)had a mild increase in liver function parameters,among whom 7 had an increase in TBA,1 had an increase in ALT, 1 had increases in ALT and AST,and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6. 3% vs 15. 1%,chi2 = 0. 691,P = 0. 406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS - CoV - 2,but further studies are needed to evaluate the long - term influence of such infection on liver function.Copyright © 2022 Editorial Board of Jilin University

Traditional Chinese Medicine Syndrome Differentiation of Delta and Omicron Variants of SARS-CoV-2 Carriers in Changsha,Hunan.

Objective: To summarize and compare the main traditional Chinese medicineTCMsyndromes of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2SARS-CoV-2 carriers to provide references for the syndrome evolution and syndrome differentiation of SARS-CoV-2 infection. Method(s):The TCM medical records of imported and local cases of infection with Delta and Omicron variants of SARS-CoV-2 in Changsha since September 23,2021 to March 27,2022 were collected,including 18 Delta variant cases and 36 Omicron variant cases. Their TCM diagnosis information and TCM pathogenesis were analyzed and compared. Result(s): The common manifestations in Delta variant cases were cough,fever,chest distress/shortness of breath,sore muscles,nausea,dry mouth,dry or sore throat,thick and greasy tongue coating,and rapid and slippery pulse. The predominant pathogenesis was dampness-heat in the upper-energizer and heat stagnation in the lesser Yang combined with dampness. The occurrence of chest distress/shortness of breath,greasy tongue coating,slippery pulse,and the proportion of dampness-heat in the upper-energizer syndrome were higher in Delta variant cases than in Omicron variant cases P<0.05. The common manifestations in Omicron variant cases were itchy and sore throat,nasal congestion,running nose,fever,mild aversion to cold,dry mouth,dizziness,slightly reddish tongue with thin white coating,and rapid or wiry pulse. The predominant pathogenesis was wind-dryness invading defensive exterior,and heat stagnation in the lesser Yang. The occurrence of white-coated tongue and the proportion of wind-dryness invading defensive exterior syndrome were higher in Omicron variant cases than in Delta variant casesP<0.05. Conclusion(s): There are certain differences in TCM syndromes and the corresponding pathogenesis between Delta variant and Omicron variant cases in Changsha,Hunan. The Delta variant of SARS-COV-2 tends to induce dampness-heat syndrome, whereas Omicron variant infection tends to elicit wind-dampness syndrome,which is expected to provide a reference for the pathogenesis evolution of SARS-COV-2 infection.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Repurposing of poly-gamma-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment

Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.

Analysis of the Solution of a Model of SARS-CoV-2 Variants and Its Approximation Using Two-Step Lagrange Polynomial and Euler Techniques

In this paper, a vaccination model for SARS-CoV-2 variants is proposed and is studied using fractional differential operators involving a non-singular kernel. It is worth mentioning that variability in transmission rates occurs because of the particular population that is vaccinated, and hence, the asymptomatic infected classes are classified on the basis of their vaccination history. Using the Banach contraction principle and the Arzela–Ascoli theorem, existence and uniqueness results for the proposed model are presented. Two different numerical approaches, the fractional Euler and Lagrange polynomial methods, are employed to approximate the model's solution. The model is then fitted to data associated with COVID-19 deaths in Pakistan between 1 January 2022 and 10 April 2022. It is concluded that our model is much aligned with the data when the order of the fractional derivative (Formula presented.). The two different approaches are then compared with different step sizes. It is observed that they behave alike for small step sizes and exhibit different behaviour for larger step sizes. Based on the numerical assessment of the model presented herein, the impact of vaccination and the fractional order are highlighted. It is also noted that vaccination could remarkably decrease the spikes of different emerging variants of SARS-CoV-2 within the population. © 2023 by the authors.

Conditional dependence structure and risk spillovers between Bitcoin and fiat currencies

This paper investigates the extreme dependence and risk spillovers between Bitcoin and the currencies of the BRICS and G7 economies. We find time-varying dependence between Bitcoin and all currencies. Moreover, when analysing risk spillovers from Bitcoin to currencies, we find that Bitcoin exercises significant power over most currencies, with the South African rand and Brazilian real holding both the highest downside and upside risk before and during the COVID-19 pandemic period, respectively. When considering risk spillovers from currencies towards Bitcoin, the Japanese yen exhibits the highest downside spillovers. Importantly, we find asymmetric spillovers between extreme upward and downward movements. • We study dependencies between Bitcoin and the currencies of the BRICS and G7 economies. • We find time-varying dependence between Bitcoin and all of the fiat currencies. • Bitcoin exercises significant power over most of the considered currencies. • We find asymmetric spillovers between extreme upward and downward movements. [ FROM AUTHOR] Copyright of Emerging Markets Review is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 Infection and Vaccination in Pregnancy: What Do We Know Now?

SARS-CoV-2 infection during pregnancy has significant implications for both mothers and their offspring. Pregnant individuals are more likely to progress to severe or critical COVID-19 than nonpregnant reproductiveaged women. Similarly, COVID-19 is associated with a number of pregnancy complications including preterm birth, hypertensive disorders of pregnancy, and cesarean delivery. These adverse outcomes and the morbidity for pregnant people with COVID-19 are closely linked to the severity of COVID-19, and the variant of SARS-CoV-2. Recent data demonstrate that the worst maternal and fetal outcomes were present during the time period of the Delta variant of SARS-CoV-2. Specifically, there was an increase in stillbirth observed in association mostly with the Delta variant due to placental damage, and a greater risk of intensive care unit admission when compared to time periods when other non-Delta strains were predominant. Like other populations, pregnant individuals with other comorbidities such as obesity and chronic hypertension are at increased risk of more severe disease. Early in the pandemic, pregnant patients were much less likely than the general population to be vaccinated, due to a lack of data for vaccine efficacy and safety in pregnancy. As reassuring data have emerged, the vaccination rate of the pregnant population has increased, resulting in decreased disease severity and improved maternal outcomes. Vaccination also has beneficial implications for early neonatal health. The long-term implications of SARSCoV- 2 infection during pregnancy for both mothers and their children remain largely unknown and are a subject of ongoing investigation.

COVID-19-Related Encephalitis in a Child with PIK3CD Defect

Introduction: COVID-19 related encephalitis has been reported in pediatric patients;however, there are no reports in patients with inborn errors of immunity (IEI). Activated PI3K Delta Syndrome (APDS) is a disease of immune dysregulation with immunodeficiency, autoimmunity, and abnormal lymphoproliferation resulting from autosomal dominant gain-offunction variants in PIK3CD or PIK3R1 genes. We investigate a family with APDS, one mother and three children, one of whom developed COVID-19 related encephalitis. Method(s): Patients were consented to an IRB-approved protocol at our institution. Medical records and detailed immunophenotyping were reviewed. Family members were sequenced for IEI with a targeted gene panel. Result(s): The index case is a 10-year-old female with a known pathogenic variant in PIK3CD (c.3061 G > A, p.Glu1021Lys), who contracted SARS-COV-2 despite one COVID-19 vaccination in the series. Her disease course included COVID-related encephalitis with cerebellitis and compression of the pons, resulting in lasting truncal ataxia and cerebellar mutism. At that time, the patient was not on immunoglobulin replacement therapy (IgRT), but was receiving Sirolimus. Besides the index case, 3 family members (2 brothers, 1 mother) also share the same PIK3CD variant with variable clinical and immunological phenotypes. All children exhibited high transitional B-cells, consistent with developmental block to follicular B cell stage. Increased non-class switched IgM+ memory B cells and skewing towards CD21lo B cell subset, which is considered autoreactive-like, was observed in all patients. Of note, the patient had low plasmablasts, but normal immunoglobulins. Of her family members, only one was receiving both sirolimus and IgRT. Conclusion(s): We describe a rare case of COVID-19-related encephalitis in a patient with inborn error of immunity while not on IgRT. This may indicate infection susceptibility because of a lack of sufficient immunity to SARS-CoV-2, unlike the rest of her family with the same PIK3CD variant.Copyright © 2023 Elsevier Inc.

Hematological features of patients with type 2 diabetes depending on the variant of SARS-COV-2

The aim of our work was to investigate the peculiarities of hematological indicators in patients with COVID-19 depending on the variant of SARS-CoV-2. A retrospective study of the electronic medical records of 19 patients with the delta variant (7 patients had comorbidity with type 2 diabetes (T2D);12 patients without T2D - control group) and 46 patients with the omicron variant (26 patients had comorbidity with T2D;20 patients without T2D - control group). No statistically significant differences were found in gender, the number of leukocytes, lymphocytes, and granulocytes in peripheral blood, C-reactive protein, and D-dimer. The results also showed a significant difference in procalcitonin level and monocyte count in patients with delta variant and T2D. A predictive model was developed using binary logistic regression to determine the SARS-CoV-2 variant based on hematological parameters (sensitivity - 76.5%, specificity - 84.8%). Thus, the peculiarities of hematological indicators of patients with T2D depending on the variant of SARS-CoV-2 (delta or omicron) were established. © P. Petakh, K. Loshak, A. Kamyshnyi.

Survival Analysis of Delta versus Omicron Variants in COVID-19 Intensive Care Unit (ICU)

Objective: COVID-19 has presented numerous epidemiological and clinical pictures from its beginning and much effort has been paid to detect the behavior of disease and its new types. Therefore, in this study, we aimed to compare the in-hospital survival time of Delta and Omicron variant patients admitted to the intensive care unit. Methods: This was a secondary data analysis of the QCOVICU data registry of 200 COVID-19 patients admitted to the ICU of Shahid Beheshti-Amir Al-Momenin Hospital of Qom City, in 2021. Likewise, time to event data, demographics, and baseline laboratory data was collected. Time of transfer to ICU, survivals, and possible predictors of hazards of death was compared within the variants of Omicron and delta. Results: Two hundred patients (62.98±19.94 years old, 94 females/106 males;100 Delta and 100 Omicron variant) participated in this study. Fifty percent of the population had died. Cross-tabulation showed comparable death rates among variants of delta and omicron (50.5% vs. 51%;p=0.999). There was a statistically significant higher time to ICU admission in Delta variant victims than in Omicron variant victims. The mean survival time of delta variant patients was 21.52 days (95% CI: 17.96 – 25.09) which was statistically higher than the mean survival of omicron patients (17.15 days, 95% CI: 13.65-20.64, p=0.018). The mean survival time of delta variant patients was statistically higher than omicron patients (21.52 vs. 17.15 days, p=0.018). Gender, age (years), and lymphocyte count were significant predictors of mortality based on the Cox regression analysis (P>0.05). There was a 5.9 times higher risk of mortality in females compared with males' gender after adjusting for other variables and a 5.6% increase in death risk with a 1-year increase in age, and a 31.8% decrease in death risk with a 1% lymphocyte percentage increase. Conclusion: Critically patients with Delta variant are getting ICU admitted later and withstand more days at ICU than Omicron patients. It seems that Omicron variant causes sudden deterioration of the patient's condition. © 2023 by SPC (Sami Publishing Company).

The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

Clinical features of patients with severe acute respiratory syndrome coronavirus 2 Delta variant infection and abnormal liver function in Guangdong Province, China. TT -? ? ? ? ? ?.

Objective To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China. Methods The patients with SARS-CoV-2 Delta variant infection who belonged to the same chain of transmission in Guangdong Province (Guangzhou and Foshan) and were admitted to Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 21 to June 18, 2021 were enrolled in this study, and the judgment criteria for liver function were alanine aminotransferase (male/female) > 50/40 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 mumol/L, gamma-glutamyl transpeptidase > 60 U/L, and alkaline phosphatase (ALK) > 125 U/L. Abnormality in any one item of the above criteria was defined as abnormal liver function, and such patients were included in analysis (the patients, aged < 18 years, who had a mild or moderate increase in ALP alone were not included in analysis). Clinical data were compared between the patients with normal liver function and those with abnormal liver function, and the etiology and prognosis of abnormal liver function were analyzed. The Mann-Whitney U test was used for comparison of continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups. Results Among the 166 patients with SARS-CoV-2 Delta variant infection, 32 (19.3%) had abnormal liver function with mild-to-moderate increases in liver function parameters, and compared with the normal liver function group, the abnormal liver function group had a significantly higher proportion of critical patients (chi2=38.689, P < 0.001) and significantly higher age and inflammatory cytokines [C-reactive protein type, serum amyloid A, and interleukin-6 (IL-6)](all P < 0.05). Among the 32 patients with abnormal liver function, 13 patients had abnormal liver function on admission (defined as primary group), while 19 patients had normal liver function on admission but were found to have abnormal liver function by reexamination after treatment (defined as secondary group). For the primary group, the evidence of abnormal liver function was not found for 3 patients (3/13, 23.1%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. Among the 19 patients in the secondary group, 9 (47.4%) had mild/common type and 10 (52.6%) had critical type, and all critical patients had the evidence of liver injury indirectly caused by the significant increases in C-reactive protein type, serum amyloid A, and IL-6 and hypoxemia;the evidence of abnormal liver function was not found for only 1 patient (1/19, 5.3%), and the possibility of toxic liver injury directly associated with SARS-CoV-2 infection was considered. All 32 patients with abnormal liver function had [JP2]significant reductions in liver function parameters after treatment including liver protection. Conclusion As for the patients with SARS-CoV-2 Delta variant infection who belong to the same chain of transmission in Guangdong Province, the critical patients show a significantly higher proportion of patients with abnormal liver function than the patients with other clinical types, and other factors except SARS-CoV-2 infection and indirect injury caused by SARS-CoV-2 infection are the main cause of liver injury.Copyright © 2022 Editorial Board of Jilin University. All rights reserved.

Descriptive analysis of the incidence rate of postacute COVID-19 syndrome in the Republic of Korea Army.

Background: This study aimed to identify the incidence rate of post-coronavirus disease-2019 (COVID-19) conditions in the Republic of Korea (ROK) Army and to investigate the trend of the incidence rate according to changes in dominant variants. Method(s): We used the results of a 19-item, self-completed survey of those who had recovered from COVID-19 in the ROK Army between March 24, 2020, and April 30, 2022. We used both descriptive and multiple logistic regression analyses to identify factors associated with the incidence rate of post-COVID-19 conditions. Result(s): Among the total of 48,623 COVID-19 episodes in the ROK Army, the overall incidence rate of post-COVID-19 conditions was 32.9%. Based on the survey, the incidence of cough was the highest at 15.4%, followed by fatigue (15.1%) and sputum (13.8%). The delta variant had the highest incidence rate of post-COVID-19 conditions at 50.7%, whereas the omicron variant had the lowest at 19.7%. Concerning the type of post-COVID-19 condition, the neuropsychiatric symptoms had the highest incidence at 27.4% when the delta variant was dominant, and the respiratory symptoms were highest at 37.3% when the omicron variant was dominant. In the case of smell and taste symptoms, the incidence rate was high at 21.1% only when the delta variant was predominant. Conclusion(s): The overall incidence rate of post-COVID-19 conditions in the ROK Army was 32.9%. When the delta variant was dominant, the overall incidence as well as the proportion of neuropsychiatric symptoms were high. However, as the omicron variant became dominant, the overall incidence decreased, but the proportion of respiratory symptoms increased.Copyright © Korean Medical Association.

Immunoglobulin replacement products in current clinical use in the United States have poor neutralizing activity against SARS-CoV-2 Omicron strains

Background: Intravenous (IV) and subcutaneous (SC) Immunoglobulin G (IG) replacement products are in wide use in patients with primary antibody deficiency syndrome (PAD). There is limited data on the levels of anti-SARS-CoV-2 spike antibodies in IG products or their ability to neutralize emerging SARS-CoV-2 variants. There is lack of data on the impact of IG therapy on serum anti-SARS-CoV-2 spike or neutralizing antibody titers in PAD patients. Method(s): We measured anti-SARS-CoV-2 anti-spike antibody levels and neutralizing titers against historical (WA1/2020) and variant (B.1.617.2 [Delta] and BA.1 [Omicron]) strains in 158 lots of 6 different IG products, collected between August 2021 to April 2022 and manufactured between December 2019 to December 2021. IG products were compared to serum from 20 healthy donors vaccinated with 2 doses of Pfizer-BioNTech mRNA vaccine. Serum anti-spike antibody level and SARS-CoV-2 neutralization activity were measured in 27 PAD patients treated with the tested IG products. Result(s): Anti-spike antibody titers started to increase in products manufactured in March 2021 and reached peak level, comparable to vaccinated healthy donors, in products manufactured in August 2021 (Fig. 1). The neutralization activity against WA1/2020 and Delta strains showed a similar pattern (Fig. 2). However, 95% of the tested products had no neutralization activity against Omicron. Until November 2021, IVIG products infused to patients in the study had anti-spike titers comparable to unvaccinated healthy donors (Fig. 3). Beginning in February 2022, IVIG products had anti-spike titers comparable to vaccinated healthy controls. Concurrent with a rise in anti-spike antibodies in IG products, PAD patients showed an increase in serum levels of anti-spike antibody and neutralizing activity against WA1/202 and Delta but not against Omicron variants. Testing of immunoglobulin replacement products neutralization activity against emerging variants BQ.1 and BQ.1.1 is underway.[Formula presented][Formula presented][Formula presented] Conclusion(s): The anti-SARS spike antibody and neutralization activity of IVIG products lags after the emergence of COVID-19 variants and currently have poor activity against Omicron strain. Because of the protracted manufacturing process, this is expected to be an ongoing challenge. As variants emerge, clinicians should consider additional means of protection for PAD patients such as vaccination, or prophylaxis with monoclonal antibodies.Copyright © 2023 Elsevier Inc.

Differential of antiviral activity between chloroquine and hydroxychloroquine sulfate against SARS-CoV-2 in vitro.

Objective To investigated the in vitro antiviral activity of chloroquine and hydroxychloroquine sulfate against different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Prototype, Beta, Delta, Omicron) by changing the sequence of drug and virus introduction. Methods Prophylactic treatment: Vero E6 cells were treated with Chloroquine or hydroxychloroquine sulfate (200.00, 150.00, 100.00, 50.00, 16.70, 5.55, 1.85, 0.62, 0.21 micromol.L-1) for 1 h, then the virus was added and incubated for another 2 h. The virus-drug mixture was repalced with fresh medium until the end of the experiment. Post-entry treatment: Vero E6 cells were incubated with virus for 2 h, then the virus was removed and the cells were cultured with drug-containing medium until the end of the experiment. Full-time treatment: Vero E6 cells were pretreated with the drug for 1 h ahead, then virus was added and incubated for another 2 h. The virus-drug mixture was discarded and the cells were cultured with drug-containing medium until the end of the experiment. After 72 h of culture, the cells were observed to see whether they became round and shed to determine the cytopathic situation, and the semi-maximum effect concentration (EC50) and drug selection index (SI) were calculated. Results Both drugs were less effective in preventing SARS-CoV-2. Chloroquine/hydroxychloroquine sulfate showed good antiviral activity under both therapeutic and full-time treatment. EC50 of hydroxychloroquine sulfate was less than chloroquine, SI was greater than chloroquine, antiviral effect of hydroxychloroquine sulfate was better than chloroquine. The antiviral effect of chloroquine (EC50 = 0.904 micromol.L-1) and hydroxychloroquine sulfate (EC50 = 0.143 micromol.L-1) was more significant against Omicron variant than other variants under therapeutic and full-time treatment conditions. Conclusion Chloroquine/hydroxychloroquine sulfate showed good antiviral activity under both therapeutic and full-time treatment, and both drugs were significantly more active against the Omicron variant than the other variants.Copyright © 2023 Authors. All rights reserved.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Structure-based virtual identification of natural inhibitors of SARS-CoV-2 and its Delta and Omicron variant proteins

Plain language summaryMutant strains of SARS-CoV-2 called 'variants of concern' (VOCs) are linked to a good ability to infect, re-infect and spread among people. They are also linked to poor ability to fight the disease and reduced effectiveness of vaccines. Delta and Omicron are important VOCs because they are difficult to control and treat. Specific resistance to some drugs used to treat COVID-19 poses a further challenge. Therefore, discovering natural or plant-derived drugs with no known resistance would be valuable to the treatment of COVID-19. In this study, we screen and identify seven plant-derived compounds that may be useful to treating COVID-19 - we identify Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A as potential candidates. Orientin, Obetrioside, Catechin and Neridienone A are identified as candidates against Delta and Omicron for the first time. Aim: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. Materials & methods: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes. Results: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness. Conclusion: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding-affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike. Tweetable We report structure-based identification of natural compounds viz., Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A against SARS-CoV-2 Mpro, Helicase and Spike as well as Delta and Omicron Spike proteins.

A comprehensive insight on the challenges for COVID-19 vaccine: A lesson learnt from other viral vaccines.

The aim of this study is to comprehensively analyze previous viral vaccine programs and identify potential challenges and effective measures for the COVID-19 vaccine program. Previous viral vaccine programs, such as those for HIV, Zika, Influenza, Ebola, Dengue, SARS, and MERS, were evaluated. Paramount challenges were identified, including quasi-species, cross-reactivity, duration of immunity, revaccination, mutation, immunosenescence, and adverse events related to viral vaccines. Although a large population has been vaccinated, mutations in SARS-CoV-2 and adverse events related to vaccines pose significant challenges. Previous vaccine programs have taught us that predicting the final outcome of the current vaccine program for COVID-19 cannot be determined at a given state. Long-term follow-up studies are essential. Validated preclinical studies, long-term follow-up studies, alternative therapeutic approaches, and alternative vaccines are necessary.

Immune Response to COVID-19 in India through Vaccination and Natural Infection.

In India, COVID-19 (Corona Virus Disease-2019) continues to this day, although with subdued intensity, following two major waves of viral infection. Despite ongoing vaccination drives to curb the spread of COVID-19, the relative potential of the administered vaccines to render immune protection to the general population and their advantage over natural infection remain undocumented. In this study, we examined the humoral and cell-mediated immune responses induced by the two vaccines Covishield and Covaxin, in individuals living in and around Kolkata, India. We also compared the immune responses induced separately by vaccination and natural infection. Our results indicate that although Covishield generates a better humoral immune response toward SARS-CoV-2, both vaccines are almost equivalent in terms of cell-mediated immune response to the virus. Both Covishield and Covaxin, however, are more effective toward the wild-type virus than the Delta variant. Additionally, the overall immune response resulting from natural infection in and around Kolkata is not only similar to that generated by vaccination but the cell-mediated immune response to SARS-CoV-2 also lasts for at least ten months in some individuals after the viral infection.

The relative prevalence of the Omicron variant within SARS-CoV-2 infected cohorts in different countries: A systematic review.

The Omicron variant of SARS-CoV-2 was detected in October 2021 and exhibited high transmissibility, immune evasion, and reduced severity when compared to the earlier variants. The lesser vaccine effectiveness against Omicron and its reduced severity created vaccination hesitancy among the public. This review compiled data reporting the relative prevalence of Omicron as compared to the early variants to give an insight into the existing variants, which may shape the decisions regarding the targets of the newly developed vaccines. Complied data revealed more than 90% prevalence within the infected cohorts in some countries. The BA.1 subvariant predominated over the BA.2 during the early stages of the Omicron wave. Moreover, BA.4/BA.5 subvariants were detected in South Africa, USA and Italy between October 2021 and April 2022. It is therefore important to develop vaccines that protect against Omicron as well as the early variants, which are known to cause more severe complications.