Negative Polymerase Chain Reaction Research Articles

Neurodevelopmental Outcomes in Children Vertically Exposed to Chikungunya Virus: A Two Years Follow-up Study.

To monitor by the first 24 months of life, children born to mothers with laboratory evidence of chikungunya virus (CHIKV) infection during pregnancy or up to 8 weeks before it, and to describe abnormalities in head circumference (HC), auditory and ophthalmological assessments and neuroimaging tests during the follow-up period. This is a observational, descriptive, longitudinal and prospective study of children born to mothers who had a rash and a positive test for CHIKV during pregnancy or up to 8 weeks before it. They were admitted between November 2015 and May 2019 in the outpatient multidisciplinary clinic to investigate acute exanthematous disease. The exposed children were followed up by a multidisciplinary team and underwent periodic measurements of the HC. The Denver II test was applied, in addition to transfontanellar ultrasound (TU) to evaluate neurodevelopmental outcomes during the study period. Ophthalmological and auditory examinations, echocardiography and laboratory tests were also included. We included in the study 27 children vertically exposed to CHIKV. All children had a negative polymerase chain reaction test for the virus collected at the first outpatient visit (mean age of 16.8 days and standard deviation of 8 days). No clinical condition compatible with congenital infection at birth was reported. A change in HC characterized by macrocephaly and mild global delay development was observed in a 1-year-old child whose mother was infected in the peripartum, but with normal TU. Changes in the TU were observed in 2 other children with nonspecific subependymal cystic malformation that was not evident by the cranial computed tomography. The other children monitored showed normal results in the Denver II test, in the HC and TU. No changes were identified on ocular ophthalmoscopy or auditory brainstem response test. Two children had an increase in serum ferritin levels during the first year of life, with the others' inflammatory disease markers normal. Our study added knowledge about the neurodevelopment of children exposed to CHIKV during pregnancy by a longitudinal and prospective follow-up, throughout their first 24 months of life. We did not observe a negative impact of exposure to the virus on the neurological examination, global developmental test or measurements of the HC of these children.

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

Temporal Association Between COVID-19 Immunoglobulin-G Antibody Induced Focal Cerebral Arteriopathy and New-Onset Acute Ischemic Stroke in a Pediatric: Is it Causal or Coincidental?

ABSTRACT Focal cerebral arteriopathies, vasculitis, microangiopathies, coagulopathies, and in-situ microthrombi leading to territorial infarction of neural tissues are some of the most recent instances which are reported as a consequence of the infection caused by the novel coronavirus (SARS-CoV-2). Acute ischemic stroke (AIS) is one of the major neurological manifestations that have been linked with COVID-19. We describe a case of a 5-year-old boy who had an acute-onset of bilateral arm and leg weakness due to a posterior circulatory ischemic stroke that was temporally associated with COVID-19 Immunoglobulin-G antibody-induced cerebral arteriopathies and vasculitis. Laboratory examination was suggestive of elevated D-dimer levels to 3302 ng/ml, elevated C-reactive protein to 10 mg/dl, and elevated fibrinogen levels to 433 mg/dl. He had a negative COVID-19 nasopharyngeal polymerase chain reaction and positive COVID-19 serologies. Focal cerebral arteriopathy and AIS were managed by administering early antithrombotics, steroids, and multivitamins. On routine follow-ups, the patient remained free from new neurological and functional deficits. Although many hypotheses are proposed to explain the causal relationship between the two, it could as well be sheer coincidence.

Autoimmune Sequelae After Delta or Omicron Variant SARS-CoV-2 Infection in a Highly Vaccinated Cohort

Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination. To estimate the 300-day risk of new-incident autoimmune sequelae after SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection in adults who received COVID-19 vaccines and boosters, compared with a contemporary control group without infection. This cohort study in Singapore enrolled adults from September 1, 2021, to March 7, 2022, and followed up for 300 days. Participants were adults aged 18 years or older with SARS-CoV-2 infection during the predominance of the Delta and Omicron BA.1 or BA.2 variants and were still alive at 30 days after COVID-19 diagnosis. The national SARS-CoV-2 testing registry was used to construct cohorts of adults with SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection (hereafter, cases) and a contemporaneous group with negative polymerase chain reaction or rapid antigen test results (hereafter, controls). New-incident autoimmune diagnoses after SARS-CoV-2 infection. This information was recorded in the MediClaims national health care claims database and identified 31 to 300 days after index date of infection. Risks and excess burdens were estimated using Cox proportional hazards regression model with overlap weights applied. In total, 1 766 036 adults (915 096 females [51.9%]; mean [SD] age, 49 [18] years) were included in the study population, with 480 082 (27.2%) categorized as cases and 1 285 954 (72.8%) as controls. Of these adults, 73.1% had Chinese, 13.7% Malay, and 9.9% Indian ethnicity. There were 104 179 cases and 666 575 controls included during the Delta variant-predominance transmission, while 375 903 cases and 619 379 controls were included during the Omicron variant-predominance transmission. During the Delta variant period, 81.1% of cases had completed primary vaccination; during the Omicron variant period, 74.6% of cases received boosters. No significantly elevated risk of 12 prespecified autoimmune sequelae was recorded across the Omicron and Delta variant cohorts. Elevated risks of inflammatory bowel disease (adjusted hazard ratio [AHR], 2.23; 95% CI, 1.45-3.46; P < .001) and bullous skin disorders (AHR, 4.88; 95% CI, 2.47-9.66; P < .001) were observed only in the subset of COVID-19 cases requiring hospitalization during the predominance of the Omicron variant. While elevated risk of vasculitis (AHR, 5.74; 95% CI, 1.48-22.23; P = .01) was observed in vaccine-breakthrough Omicron variant infections, no increased risk of vasculitis was observed in the corresponding subgroup who received boosters. This cohort study observed no significantly elevated long-term risk of autoimmune sequelae after SARS-CoV-2 Delta and Omicron BA.1 or BA.2 variant infection, except for a modestly increased risk of inflammatory bowel disease and bullous skin disorders in the hospitalized subgroup during the predominance of the Omicron variant. Booster vaccination appeared to mitigate the risk of long-term autoimmune sequelae.

Development and validation of supervised machine learning multivariable prediction models for the diagnosis of Pneumocystis jirovecii pneumonia using nasopharyngeal swab PCR in adults in a low-HIV prevalence setting.

The global burden of the opportunistic fungal disease Pneumocystis jirovecii pneumonia (PJP) remains substantial. Polymerase chain reaction (PCR) on nasopharyngeal swabs (NPS) has high specificity and may be a viable alternative to the gold standard diagnostic of PCR on invasively collected lower respiratory tract specimens, but has low sensitivity. Sensitivity may be improved by incorporating NPS PCR results into machine learning models. Three supervised multivariable diagnostic models (random forest, logistic regression and extreme gradient boosting) were constructed and validated using a 111-person Australian dataset. The predictors were age, gender, immunosuppression type and NPS PCR result. Model performance metrics such as accuracy, sensitivity, specificity and predictive values were compared to select the best-performing model. The logistic regression model performed best, with 80% accuracy, improving sensitivity to 86% and maintaining acceptable specificity of 70%. Using this model, positive and negative NPS PCR results indicated post-test probabilities of 84% (likely PJP) and 26% (unlikely PJP), respectively. The logistic regression model should be externally validated in a wider range of settings. As the predictors are simple, routinely collected patient variables, this model may represent a diagnostic advance suitable for settings where collection of lower respiratory tract specimens is difficult but PCR is available.

Persistence Pays: Diagnosing Tuberculous Meningitis after 11 Negative Polymerase Chain Reaction Evaluations.

Managing tuberculous meningitis (TBM) is challenging because of its poor prognosis and the difficulty in making an early diagnosis due to the low sensitivity of cerebrospinal fluid (CSF) polymerase chain reaction (PCR) evaluations. A 75-year-old woman presented with fatigue and multiple enlarged lymph nodes and was initially suspected of having metastatic cancer of unknown primary origin. Differential diagnoses included carcinomatous meningitis, neurosarcoidosis, and TBM, as suggested by the presence of multiple enhancing cerebral nodules. Despite 11 negative PCR evaluations, including nested PCR of CSF and biopsied lymph nodes within the first 3 days of empirical anti-tubercular treatment, TBM was eventually confirmed by CSF cultures 32 days later. This case highlights the need for repeated sampling.

The Impact of a Methicillin-Resistant Staphylococcus Aureus Nasal Polymerase Chain Reaction Protocol on Vancomycin Length of Therapy Among Patients With Skin and Soft Tissue Infections.

Objective: We evaluated the impact of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) protocol on the vancomycin length of therapy (LOT) for skin and soft tissue infections (SSTIs). Design: Retrospective quasi-experimental pre- and post- MRSA nasal PCR protocol implementation study. Setting: Tertiary-care academic medical center in Jacksonville, Florida. Patients: Eligible patients received empiric vancomycin for SSTIs from January 1st to September 30th 2020 (pre-implementation group) and from January 1st to September 30th 2022 (post-implementation group). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with SSTIs. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary outcomes were incidence of acute kidney injury (AKI), number of vancomycin levels collected, and hospital length of stay (LOS). Results: The study included 131 patients (pre-implementation, n = 86 and post-implementation, n = 45). There was no significant difference in vancomycin length of therapy (LOT) between implementation groups: mean LOT in days and standard deviation (SD) were 2.7 (1.9) and 2.6 (1.3), respectively, p-value 0.493. Of significance, in the post-implementation group, vancomycin LOT between patients with a negative and positive MRSA PCR were 2.3 (1.1) and 3.9 (1.6), p-value 0.006. There was no difference in secondary outcomes. Conclusion: The utilization of the MRSA nasal PCR to guide vancomycin de-escalation did not significantly change the vancomycin LOT, however in the post-implementation group there was a significant difference in vancomycin LOT between negative and positive MRSA PCRs.

Autonomic Imbalance and Elevated Inflammatory Cytokines in Long COVID: A Cross-Sectional Study.

Following an infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), many individuals fully recover. On the other hand, a few have symptoms that last for weeks, months, or even years after their initial diagnosis. Symptoms of COVID-19 persisting for four weeks and more are termed long COVID. To assess the long-term cardiovascular morbidity by battery of cardiac autonomic function tests as well as the persistence of inflammation in COVID-recovered patients three months after initial infection. Methodology: 150 patients were selected who had recovered from COVID-19 at least three months prior to the study. After obtaining informed written consent, a throat swab was tested for COVID-19, and those with negative reverse transcription polymerase chain reaction (RT-PCR) results were subjected to autonomic function testing. Serum interleukin-6 and C-reactive protein levels were determined by enzyme-linked immunosorbent assay (ELISA) test. Out of 150 subjects 36 were found to have autonomic dysfunction graded according to Ewing's criteria. Individuals with autonomic dysfunction also had significantly increased inflammatory biomarker levels. There was also significant correlation between inflammatory markers and autonomic function test and heart rate variability parameters. Even years after the COVID-19 pandemic was declared, new symptom patterns and syndromes such as 'long COVID' are appearing.A better understanding of the pathophysiological mechanisms of post-COVID manifestations that affect the autonomic nervous system, as well as customized therapeutic care, should help reduce COVID-19 sequelae, particularly if we act early in the disease.

Prevalence of Toxoplasma gondii Infections in Pregnant Women and Small Ruminants: A Molecular Diagnostic Approach

Background: Toxoplasma gondii is a globally prevalent parasite with significant health implications, particularly for pregnant women and immunocompromised individuals. Infections during pregnancy can result in serious outcomes such as miscarriage, stillbirth, or congenital disabilities. This study aimed to assess the prevalence of T. gondii infection among pregnant women and small ruminants in Al-Anbar province, Iraq, using serological and molecular diagnostic techniques. Methods: Blood samples were collected from 165 pregnant women and 100 small ruminants (sheep and goats) between January and May 2021. Serological screening was conducted using the Humatex-Toxo rapid test to detect antibodies against T. gondii. DNA was extracted from the blood samples, and nested polymerase chain reaction (PCR) targeting the T. gondii B1 gene was used for molecular detection. The infection rates were analyzed statistically using ANOVA and Chi-square tests, with significance set at p&lt;0.05. Results: The serological test identified T. gondii antibodies in 32.7% of pregnant women, while the PCR detected a higher infection rate of 40%. Among the small ruminants, PCR revealed an overall infection rate of 10%, with sheep showing a higher rate (16%) compared to goats (4%). The results indicate that PCR is more sensitive than serological testing, particularly for identifying active infections. Additionally, the higher infection rate in young women may be linked to lifestyle, environmental exposure, and dietary habits, while seasonal factors likely play a role in infection distribution. Conclusion: Nested PCR is a more effective method for detecting T. gondii in pregnant women, offering a precise tool for identifying infections and potential causes of abortion. The lower infection rates in small ruminants suggest a reduced zoonotic risk in the study area, although continued monitoring is essential. Negative PCR results may be due to inhibitors in the DNA extraction process or the parasite’s localization in tissues rather than blood. The findings highlight the importance of molecular diagnostics in public health strategies aimed at reducing T. gondii infections in high-risk populations.

TransMVAN: Multi-view Aggregation Network with Transformer for Pneumonia Diagnosis.

Automated and accurate classification of pneumonia plays a crucial role in improving the performance of computer-aided diagnosis systems for chest X-ray images. Nevertheless, it is a challenging task due to the difficulty of learning the complex structure information of lung abnormality from chest X-ray images. In this paper, we propose a multi-view aggregation network with Transformer (TransMVAN) for pneumonia classification in chest X-ray images. Specifically, we propose to incorporate the knowledge from glance and focus views to enrich the feature representation of lung abnormality. Moreover, to capture the complex relationships among different lung regions, we propose a bi-directional multi-scale vision Transformer (biMSVT), with which the informative messages between different lung regions are propagated through two directions. In addition, we also propose a gated multi-view aggregation (GMVA) to adaptively select the feature information from glance and focus views for further performance enhancement of pneumonia diagnosis. Our proposed method achieves AUCs of 0.9645 and 0.9550 for pneumonia classification on two different chest X-ray image datasets. In addition, it achieves an AUC of 0.9761 for evaluating positive and negative polymerase chain reaction (PCR). Furthermore, our proposed method also attains an AUC of 0.9741 for classifying non-COVID-19 pneumonia, COVID-19 pneumonia, and normal cases. Experimental results demonstrate the effectiveness of our method over other methods used for comparison in pneumonia diagnosis from chest X-ray images.

Predictors of Neurological Disability at Hospital Discharge for Acyclovir-treated Pediatric Herpes Simplex Virus Encephalitis.

Herpes simplex virus encephalitis (HSE) is a rare but serious neurological infection that causes neurological dysfunction. Research is lacking on the clinical predictors of neurological outcomes and the optimal duration of therapy for pediatric HSE patients. In this study of pediatric HSE patients, we identified factors predicting neurological disability at hospital discharge and examined associations of acyclovir therapy duration with neurological outcomes. This was a retrospective cohort study on 37 children diagnosed with HSE confirmed by polymerase chain reaction at age 1 month to 16 years from 2015 to 2021 in Ho Chi Minh City's Children's Hospital No. 2, Vietnam. For the acyclovir duration analysis, we examined 22 children with negative polymerase chain reaction on day 14 of treatment. Poisson regression was used to obtain the risk ratio and 95% confidence interval. The study population consisted of 73% males, with a median age of 14 months (interquartile range: 9-35). Coma at acyclovir treatment, hypotension and the need for mechanical ventilation ≥48 hours significantly predicted neurological disability in the bivariate analysis. There were no significant associations between acyclovir duration (14 vs. 21 days) and neurological outcomes, adjusting for age at diagnosis and pediatric Glasgow Coma Scale score at acyclovir initiation. We identified significant predictors of neurological disability unaffected by postacyclovir treatment factors. Among patients with negative HSE polymerase chain reaction on day 14, 14 days of acyclovir treatment may be as effective as 21 days. Additional studies on the effects of acyclovir duration are needed.

Evaluating the role of Mycobacterium tuberculosis PCR in ruling out active tuberculosis

Laboratory algorithms using Acid-Fast Bacilli staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation precautions. A retrospective case review of 52 patients with culture-confirmed pulmonary Mtb revealed 4 subjects with negative sputum Acid-Fast Bacilli smears and negative Mtb PCRs. All had significant risk factors for Mtb and had a positive interferon-gamma release assay. A negative PCR test result does not exclude an Mtb diagnosis.

Pulmonary High Resolution Computed Tomography Findings of COVID-19 Patients Using CO-RADS Classification: A Study on Pakistani Population

Background: This study aimed to use high-resolution computed tomography (HRCT) and the CO-RADS grading system to diagnose COVID-19 patients and determine severity. Methodology: A retrospective study analyzed data from 280 patients at Aziz Bhatti Shaheed Hospital Gujrat between January and August 2021. Informed consent and ethical approval were secured. Data collection used a 64-slice multi-detector CT scanner, including patients with positive and negative COVID-19 polymerase chain reaction (PCR) findings. Data were analyzed using SPSS version 23. Results: The study included more males (170, 60.7%) than females (110, 39.3%), with the most affected age group being 45-64 years. HRCT findings showed ground glass opacities in 212 cases (35.6%), consolidations in 158 cases (26.5%), Crazy paving sign in 54 cases (9.1%), pulmonary lesions in 54 cases (9.1%), interstitial lung disease in 42 cases (7.0%), pulmonary infiltrates in 32 cases (5.4%), atelectasis in 26 cases (4.4%), and pulmonary fibrosis in 18 cases (3.0%). CO-RADS classification results were: CO-RADS 1 (5, 1.8%), CO-RADS 2 (11, 3.9%), CO-RADS 3 (101, 36.1%), CO-RADS 4 (68, 24.3%), CO-RADS 5 (56, 20%), and CO-RADS 6 (39, 13.9%). PCR results were positive only in severe cases (starting from CO-RADS 2), while HRCT detected pulmonary findings even in less severe cases (starting from CO-RADS 1). Conclusion: High-resolution computed tomography accurately and quickly identifies COVID-19 infections, even when PCR findings are negative. The CO-RADS technique effectively determines the severity and spread of COVID-19. CO-RADS 3 was the most frequently reported category, with typical findings including peripheral ground glass opacities and bilateral pleural consolidations.

The Impact of Polymerase Chain Reaction Urine Testing on Clinical Decision-Making in the Management of Complex Urinary Tract Infections.

While urinary polymerase chain reaction (PCR) testing is effective in organism identification in patients with complex urinary tract infections (cUTI), limited data exists on the clinical usefulness of this test. We serially surveyed physicians treating symptomatic patients with cUTI both at presentation and after PCR, and urine culture (UC) results were available to ascertain how the test results modified the therapy. A total of 96 unique surveys completed by 21 providers were included in the data analysis. The mean age for female and male patients was 69.4 ± 15.5 and 71.6 ± 12.7 years, respectively. The test positivity and line-item concordance for UC and PCR were consistent with prior reports. The PCR results modified or confirmed treatment in 59/96 (61.5%) and 25/96 (26.0%) of the cases, respectively, with 12/29 (41.4%) and 47/67 (70.1%) having negative and positive PCR results, respectively, resulting in treatment change (difference 28.7%, p < 0.01). Of these, 55/59 (57.3%) were alterations in the antibiotic regimen. PCR use to modify treatment was similar across providers and not statistically different when stratified by patient age, gender, or prior empiric therapy. In 31/59 (52.5%) of the cases, the PCR results modified the treatment where UC would not; conversely, UC would have modified the treatment in 3/37 (8.1%) of the cases where PCR did not (difference 44.4%, p < 0.01). We find that PCR test results are used by clinicians in managing cUTI, and use of this test provides an opportunity to improve antibiotic stewardship in this difficult-to-treat subset of patients.

Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis.

This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations. A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined. Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients. On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.

Varicella-Zoster Virus-Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study.

Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND). This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2). We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.

Results of a randomized double-blind multicenter clinical trial of the efficacy and safety of the drug riamilovir for the prevention of COVID-19

Evaluation of the efficacy and safety of riamilovir as a drug for the prevention of coronavirus infection (COVID-19) in adults who have constant contact with COVID-19 patients as a result of living together. The study included 750 adult participants living with patients with confirmed polymerase chain reaction method COVID-19, who had a negative polymerase chain reaction result for the SARS-CoV-2 virus at the initial level, met the criteria for inclusion, non-inclusion and exclusion, and signed a voluntary informed consent to participate in a clinical trial. The efficacy, good tolerability and safety of the drug riamilovir for the prevention of COVID-19 infection among people who have come into contact with COVID-19 patients in a family focus of infection have been established. As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for the prevention of COVID-19 infection was established. It was shown that the relative risk of disease in the group taking riamilovir for prophylaxis was 88.96% lower than in the control group. Based on the results of a clinical trial, in October 2023 Ministry of Health of the Russian Federation approved the inclusion of a new indication (prophylaxis of COVID-19 infection) in the instructions for the medical use of the drug riamilovir (trade name - Triazavirin®).

Management outcome of a COVID-19 Positive Child with Multiple Contacts admitted in a General Intensive Care Unit-A Case Report

COVID-19 infection in paediatric patients is relatively low in Nigeria. The low index of suspicion made healthcare providers to be at risk of contracting the disease from this age group making prevention and contact tracing difficult. We report the management of a 9-month- old male child who had palatoplasty following a prior negative polymerase chain reaction (PCR) screening. The patient underwent palatoplasty for isolated cleft palate under general anaesthesia and endotracheal intubation. The patient was found to be desaturating significantly on admission to the recovery room and was subsequently taken back to the theatre with multiple attempts at intubation. A repeat PCR done was positive and subsequently, he was admitted into the ICU for ventilatory support. A chest radiograph taken on admission revealed features of severe bronchopneumonia and COVID-19 pneumonic changes. He was ventilated for 14 days and thereafter, was discharged home on a tracheostomy in good clinical condition. The mother of the child and 20 members of staff (23.5%) out of the 85 personnel who had close contact with the child in the course of treatment tested PCR positive. Contact tracing was difficult among those infected. They all recovered from the disease without complications. The treatment outcome in this COVID-19-positive child was good and contact tracing was effective in reducing the transmission of SARS-CoV-2 and limiting the impact of the outbreak. We hereby recommend preventive measures against the infection, vaccination and establishment of dedicated paediatric ICU for infectious diseases.

Treponema pallidum PCR with blood and cerebrospinal fluid of newborns exposed and not exposed to syphilis during pregnancy.

Congenital syphilis (CS) has severe adverse outcomes, including abortion and death. Diagnosis of CS in asymptomatic newborns remains difficult. This study aims to evaluate an in-house polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) and blood samples (BS) to identify T. pallidum DNA in newborns. We performed an exploratory cross-sectional study that included newborns exposed to syphilis during pregnancy (SEG) and non-exposed (SNEG) newborns, between 2019 and 2020. In-house conventional PCR for T. pallidum targeting the tpp47 gene was used to analyze CSFS and dried blood spots. BS was obtained from 54 newborns (33 SEG/21 SNEG) and CSF from 55 newborns (33 SEG/22 SNEG). Twenty-five (71.4%) SEG newborns had reactive BS rapid plasmatic reagins (RPR), and all of them had RPR titers less than or equal to the corresponding maternal titers. All RPR CSF tests were negative. PCR for T. pallidum DNA was positive in 19/33 (57.6%) BS, and in 22/33 CSF. The only SEG newborn with clinical signs of early CS had a positive CSF PCR and a negative BS PCR. Conversely, among SNEG newborns, PCR was positive in 2/21 BS and 5/22 (22.7%) CSF. T. pallidum DNA was identified using our PCR tests. The exposed group did not present abnormalities that would indicate CS. This prevented conclusions regarding sensitivity and specificity. Dried spot permitted bedside collection, easy transportation, and storage. Further research is needed to evaluate and improve the accuracy of CS low-cost PCR tests, especially for limited resource settings.

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.