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.

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.

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.

Liver injury caused by SARS-CoV-2 delta and omicron-variant in Taiwan

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has recently emerged and spread globally. An outbreak of coronavirus disease 2019 (COVID-19) caused by the Delta variant occurred in Southern Taiwan in June 2021 and has been eliminated [1]. However, in April 2022, there was an outbreak of the Omicron variant in Taiwan. Fifteen patients with Omicron variant were admitted to our hospital from April 26 to May 1, 2022. We compared the clinical characteristics of the patients with the Delta variant in June 2021 and the Omicron variant in April 2022 (Table 1). These laboratory data were the first laboratory data at admission, and no anti-COVID-19 therapy was prescribed before these data. There were no differences in age (59.9 vs. 57.1 years, P = 0.96), male gender (63.6 vs. 60.0%, P = 1.00), diabetes ratio (27.3 vs. 35.7%, P = 1.00), body mass index (25.0 vs. 26.0 kg/m2, P = 1.00), pneumonia ratio (18.2 vs. 40.0%, P = 0.40) between the Delta and Omicron variants. There were also no differences in serum levels of aspartate aminotransferase (AST) (40.1 vs. 25.8 IU/L, P = 0.24) and alanine aminotransferase (ALT) (26.3 vs. 27.2 IU/L, P = 0.64) between the two groups. All the patients with the Omicron variant were symptomatic. The most common symptoms were upper respiratory tract infections (60.0%) (Supplementary Table 1). Six patients developed pneumonia without mechanical ventilator support requirement during admission (40.0%). Remdesivir, Paxlovid, or Molnupiravir were prescribed to patients according to their clinical conditions. Among the patients with the Omicron variant, nine (60.0%) had past medical history of diabetes, four (26.7%) had hypertension, three had chronic kidney disease (20.0%), and three had malignancy history (20.0%). COVID-19 might cause liver injury and lead to a more unfavorable prognosis [2]. In this study, about one-fifth of the patients suffered from liver injury, which was similar to previous studies [3]. There was no difference in liver injury between the Delta and Omicron variants in our study, which echoes previous research [4]. COVID-19 vaccination might protect against symptomatic diseases caused by the Omicron variant [5]. Vaccination rates have increased since 2021. In the study, over ninety percent of the patients have received at least two doses of vaccination. In conclusion, we demonstrated no difference in liver injury ratio between the Delta and Omicron variants. To our knowledge, this is the first report that compares the Delta and Omicron variants in Taiwan.

A Methodical Review on Omicron -a New Variant as a Drug Developer

In mid-November 2021, the new OMICRON variety was first discovered in South Africa. As of today, the OMICRON version already appeared on December 15, 2021. Around 77 countries are affected, with the bulk of cases originating in the United States, India, the United Kingdom, and South Africa. OMICRON-positive instances were also reported. The first mortality associated with the novel COVID-19 mutation was reported in the United Kingdom. Recently, a sister variant of OMICRON, 21L or BA.2, has also been discovered. Due to its enormously high number of mutations, viewed enhancement in immune evasion and transmissibility, OMICRON was developed as a new variant of concern (VOC) by the WHO on 26 November 2021. On a global pandemic scale, positive selection of SARSCoV-2 mutations appears to have begun in late 2020. Since then, the virus has been evolving on two fronts: immune evasion and enhanced transmissibility, as expressed by Delta. This review elaborates the effects of drugs in the management of OMICRON.Copyright © 2023 Society of Pharmaceutical Sciences and Research. All rights reserved.

Covid-19 in Patients Presenting with Malaria-Like Symptoms at the Korle Bu Polyclinic, Accra

Intro: Malaria is one of Ghana's most frequent illnesses and the most common cause of febrile sickness. Most infectious diseases including COVID-19 and arboviral infections mimic malaria due to the overlapping of non-specific symptoms they both share.This study investigated COVID-19 in patients presenting with malaria-like symptoms at the Korle Bu Polyclinic, Accra. Method(s): This study enrolled 300 patients presenting with malaria-like symptoms aged <= 18. After consent was obtained from study patients, two to three millilitres of whole blood, nasopharyngeal and oropharyngeal swab samples was collected for screening of Plasmodium falciparum using malaria rapid diagnostic test, microscopy and nested PCR and SARS-CoV-2 using SARSCoV-2 antigen test and Real-time PCR respectively. The whole blood sample was also used for COVID-19 antibody test and full blood count using hematological analyser. Finding(s): The detection of SARS-CoV-2 by COVID-19 Rapid Antigen Test and Real-time PCR were 60/300 (20%) and 26/300 (8.7%) respectively. Delta variant was reported in most SARS-CoV-2 positives with CT values below 30. The prevalence of malaria by microscopy, RDT and nested PCR were 7/300 (2.3%), 7/300 (2.3%) and 8/300 (2.7%) respectively. The most common symptom experienced by the study patients at the polyclinic was headache (95%;57/60). Comorbidities reported were hypertension, diabetes, Asthma, hypertension and diabetes. Most of the study patients had been previously exposure to SARS CoV-2 (113/300) and 66.7% (34/51) of AstraZeneca vaccinated patients had no antibody. Conclusion(s): Due to the synergy of symptoms, screening for COVID-19 in patients presenting with malaria-like symptoms is vital for immediate diagnosis and treatment.Copyright © 2023

On-Site Whole-Genome Sequencing of Sars-Cov-2 Reveals C3037t Mutation in Patient with Atrioventricular Nodal Reentry Tachycardia (Avnrt)

Intro: The spike protein of the SARS-CoV-2 virus targets the human cell receptor of angiotensin-converting enzyme (ACE2), including the myocardium and heart's conduction system. Patients diagnosed with COVID-19 have also been found to exhibit cardiac arrhythmia. Here, a whole-genome sequencing analysis using long-read sequencing was proposed to evaluate the virus genome in a patient who presented with AVNRT as a main presentation of COVID-19. Method(s): The sample was recovered from nasopharyngeal and oropharyngeal swab specimens of a 46-year-old female with no comorbidities who presented with palpitation, and ECG showed typical AVNRT features. The RT-qPCR of SARS- CoV-2 was confirmed positive with a CT-value of 15.82. The total RNAs were extracted and proceeded for RT-qPCR and proceeded with Oxford Nanopore Flongle sequencing. The genomics data of the virus was deposited in GISAID (EPI_ISL_3241561) and further analysed using online bioinformatics tools such as Nextclade CLI 2.3.0. Ethical approval (IREC 2021-080) for the study was obtained from IIUM Research Ethics Committee. Finding(s): Here, we reported a total of 29,775 bp near-complete whole-genome belonging to clade 21J (Delta) of AY.79 lineage (also known as B.1.617.2.79), which formed a dominant variant in Malaysia during the time of sampling. Discussion(s): While a previous study showed an association between Delta variant infection with fulminant myocarditis, the present study reported the benign AVNRT as the main presentation of SARS-CoV-2 infection. Furthermore, we observed the presence of the C3037T mutation previously described in the endomyocardial biopsy of a patient with persistent arrhythmia. Conclusion(s): Even though SARS-CoV-2 targets the respiratory tract, the present study supports the evidence that the ACE2 receptors are present in the heart. In addition, COVID19 is causing more and more damage to heart tissue, and viral transcription has been confirmed on cardiomyocytes. Further functional studies are needed to explore the associated mutations and their relation to cardiac manifestation.Copyright © 2023

Covid-19 Associated Hepatitis in Children (Cah-C) during the Rise of Delta Variant in India: A New Covid-19 Complication or a Superinfection

Intro: While the pediatric population has largely remained free of severe COVID- 19, in some situations SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). Recently, cases of hepatitis in children have caused tremendous worry across the globe, we describe a unique presentation from 2021, subsequent to asymptomatic infection of SARS-CoV-2, a unique form of severe hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association, and viral parameters of CAH-C cases, and contrast to that of MIS-C cases are presented here. Method(s): As a retrospective and follow-up case-control study we reviewed all children within 14 years presenting with "sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice. After performing all routine tests among them, those lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis (A-E) or previous underlying liver disease, and (b) multi-system involvement", being unique such cases were classified as CAH-C, and are described here. Finding(s): Among 475 children who tested positive, 37/47 cases had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers, 100% positivity for SARS-CoV-2 antibodies, and uneventful recovery. The remaining 10/47 having MIS-C had protracted illness, multiple system involvement, required admission to critical care, and a mortality rate of 30%. Among controls, only 26/50 (52%) had SARS-CoV-2 antibodies. Discussion(s): During the pandemic, various COVID-19 complications have been observed posing safety concerns, where our study identified a unique form of acute hepatitis in children designated as CAH-C. Conclusion(s): With the emergence of newer variants, including the Delta variant which predominated the second wave of infections in India and spread worldwide with changing presentations and complications, CAH-C is such new entity in children. It needs early identification and differentiation from other emerging syndromes during the ongoing pandemic for preventing adversities through timely intervention.Copyright © 2023

INVESTIGATING ANTIGENIC FEATURES OF THE SARS-CoV-2 ISOLATED IN RUSSIAN FEDERATION IN 2021-2022 BY HYPERIMMUNE MOUSE SERUM NEUTRALISATION.

Introduction. The rapid spread of a new coronavirus infection among populations in many countries worldwide has contributed to the genetic evolution of the virus, resulting in the emergence of multiple genetic variants of the SARSCoV-2 coronavirus. Mutations in the viral genome can affect the ability of the virus to bypass the immune system and complicate development of diagnostic and prophylactic drugs. Data on the neutralizing activity of the sera obtained against previously circulating genetic variants of the virus in relation to current SARS-CoV-2 strains may serve as a scientific basis for the selection of the antigens in vaccine development. The aim of this work was to study cross-reactivity of SARSCoV-2 coronavirus strains belonging to different genetic variants, which were isolated in the territory of the Russian Federation during 2020-2022 in the neutralization reaction using mouse hyperimmune sera. Materials and methods. Ten strains of SARS-CoV-2 coronavirus belonging to different genetic variants were used (three non-VOC strains, alpha, beta, gamma, delta, delta+AY, omicron 1 and omicron 2). The hCoV-19/Australia/VIC01/2020 strain (Wuhan) was included in the study as a prototypical variant. BALBc mice were immunized with inactivated concentrated antigen mixed with a 1:1 adjuvant, which was a virus-like immunostimulatory complex based on Quillaja saponaria (Quillaja saponaria). The antibody titer was determined in the neutralization reaction. Results. Essential decrease of neutralizing ability of antibodies specific to non-vOC genetic variants of SARS-CoV-2 coronavirus was revealed against beta VOC and to a lesser degree against alpha and gamma VOC variants. The differences in the neutralizing activity level of antibodies for alpha and beta VOC variants are not significant among themselves, and with gamma VOC variants - there are no significant differences. Neutralizing ability of antibodies specific to delta VOC against alpha and beta VOC variants decreased 4-fold. Neutralizing activity of sera obtained to omicron 1 and 2 variants in relation to the prototype coronavirus variant was reduced 18-fold, to the gamma variant - 12-fold, to delta variants - more than 30-fold;for other variants it was even lower. Conclusions. The results obtained testify to the presence of cross-reactivity between strains of coronavirus belonging to genetic lines Wuhan, alpha, beta, gamma;it is weaker for delta variants. Mutations in the genome of VOC omicron variants led to a significant decrease in antigenic cross-links with earlier genetic variants of the coronavirus. These findings explain the low efficacy of vaccines based on the Wuhan strain, synthetic immunogens, and recombinant proteins based on it against omicron VOC variants, which have caused a rise in morbidity since early 2022, as well as cases of re-infection of humans with new genetic variants of the coronavirus.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

Effectiveness of CoronaVac vaccine against severe acute respiratory infections (SARI) hospitalizations in Sibu District, Malaysia: A retrospective test-negative design

Introduction: The COVID-19 vaccination campaign was implemented in Sibu, Malaysia in February 2021. We assessed the effectiveness of the CoronaVac vaccine against severe acute respiratory infections (SARI) hospitalisation associated with laboratory-confirmed SARS-CoV-2 by time since vaccination. Method(s): A test-negative case-control design was employed using a web-based national information system for PCR results of SARS-CoV-2 infection and COVID-19 vaccination, and the hospitalisation dataset in Sibu Hospital. Eligible SARI cases with SARS-CoV-2 RT-PCR positive were matched to those SARI cases with negative RT-PCR tests by age and workplace. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, comorbidity, smoking and education level. Result(s): Between 15 March and 30 September 2021, in the dominance of lineages B.1.466.2 and B.1.617.2 (Delta variant), a total of 838 eligible SARI patients were identified. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3, 74.1), and 76.5% (95% CI: 45.6, 89.8) for partial vaccination (after the first dose through 14 days after the second dose) and complete vaccination (at 15 days or more after receipt of the second dose), respectively. Sensitivity analysis using propensity score matching yielded a conservative estimate of 57.4% (95% CI: 9.2, 80.1) for complete vaccination. Conclusion(s): Primary immunisation with two doses of CoronaVac vaccine provided satisfactory protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, incremental effectiveness induced by boosting, as well as performance against new variants need to be studied continuously.

Hiv Infection Increases Risk of Pasc While Covid-19 Vaccination Is Protective

Background: People with HIV (PWH) are at a higher risk of severe acute COVID-19;however, their risk of subsequently developing post-acute sequelae of SARS-CoV2 (PASC) remains unclear. Furthermore, although vaccination has been shown to be protective against PASC in the general population, few studies have evaluated its effectiveness in PWH. Method(s): We used the TriNetX health research database to source data from 69 healthcare organizations within the US. We included any adults aged >= 18 years with positive SARS-CoV-2 between January 1, 2020 and September 16, 2022 and categorized them based on their HIV status, baseline sociodemographic characteristics, comorbidities and COVID-19 vaccination status. The primary outcome was risk of PASC, compared by HIV and vaccination status after 1:1 propensity score matching. PASC was defined as either the persistence of COVID-attributable symptoms or the occurrence of new-onset health conditions at least 28 days following COVID-19 diagnosis. For all analysis, statistical significance was set at p < 0.05. Result(s): Of 3,048,792 people with confirmed SARS-CoV-2 infection, 1% (n=28,904) were PWH, with 9% of PWH (n=2592) vaccinated. At 28 days post-COVID-19 diagnosis, PWH had lower mortality compared with their non-HIV counterparts (OR 0.78, 95% CI 0.70-0.87), but higher risk of developing new-onset diabetes (DM) (OR 1.26, 95% CI 1.11-1.42), heart disease (OR 1.27, 95% 1.14-1.41), malignancy (OR 1.66, 95% CI 1.45-1.89), thrombosis (OR 1.25, 95% CI 1.12-1.39) and mental health disorders (OR 1.70 (95% CI 1.53-1.90). Furthermore, vaccinated PWH had significantly lower odds of death (OR 0.63, 95% CI 0.42- 0.93) and each new-onset PASC outcome, as follows: DM (OR 0.51, 95% CI 0.32- 0.82), heart disease (OR 0.44, 95% CI 0.29-0.67), malignancy (OR 0.43 (95% CI 0.25-0.74), thrombosis (OR 0.51, 95% CI 0.33-0.78) and mental health disorders (OR 0.49, 95% CI 0.30-0.79). The risk of PASC was higher during the pre-Delta variant period but did not vary based on CD4 count or HIV viremia. Conclusion(s): HIV infection confers a higher risk of PASC. Importantly, COVID-19 vaccination significantly lowered mortality and was protective against PASC among PWH. With the increase in the number of COVID-19 survivors, vaccination offers an effective preventive strategy to address a burgeoning public health problem. (Table Presented).

VSV-BASED COVID VACCINE FOR THE PREVENTION OF BREAKTHROUGH SARS-CoV-2 INFECTIONS

Background: More than 12 billion doses of COVID-19 vaccine administrations and over 630 million natural infections should have developed adequate levels of herd immunity over the last three years. However, there have been many new waves of coronavirus infections. The development of safe and effective vaccines to control breakthrough SARS-CoV-2 infections remain an urgent priority. We have developed a recombinant VSV vector-based vaccine to fulfill this worldwide need. Method(s): We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 recall vaccine candidate. We have constructed an attenuated recombinant VSV genome carrying the full-length Spike protein gene of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) at the N-terminus enhanced the protein expression and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) at the C-terminus of the Spike protein allowed efficient incorporation of the Spike protein into pseudotype VSV. Result(s): In immunized mice, rVSV with chimeric rVSV-msp-S-Gtc induced high levels of potent neutralizing antibodies (nAbs) and CD8+ T cell responses, while the full-length Spike with Gtc proved to be the superior immunogen. More importantly, rVSV-msp-S-Gtc-vaccinated animals were completely protected from subsequent SARS-CoV-2 challenges. Furthermore, rVSV-Wuhan and rVSV-Delta vaccines, and an rVSV-Trivalent (mixed rVSV-Wuhan, -Beta and -Delta) vaccine elicited potent nAbs against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) viruses. Heterologous boosting of rVSV-Wuhan with rVSV-Delta induced strong nAb responses against Delta and Omicron viruses, with the rVSV-Trivalent vaccine consistently inducing effective nAbs against all the SARS-CoV-2 variants tested. All rVSV-msp-S-Gtc vaccines also elicited an immunodominant Spike-specific CD8+ T cell response. Conclusion(s): rVSV vaccines targeting SARS-CoV-2 variants of concern can be considered as an effective booster vaccine in the global fight against COVID-19.