Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity.

Introduction: The success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance. Methods: We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls. Results: In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients. Discussion: These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.

Should pregnant women be screened for SARS-CoV-2 infection? A prospective multicenter cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges from asymptomatic to severe infection. We aimed to compare the prevalence of COVID-19 in asymptomatic pregnant versus nonpregnant women in order to establish recommendations for a COVID-19 screening strategy. METHODS: A prospective multicenter cohort study was conducted. Asymptomatic pregnant or nonpregnant women after March 2020 (the time when COVID-19 was first detected in north Israel) were tested for SARS-CoV-2 using nasopharyngeal reverse transcription polymerase chain reaction test, anti-nucleocapsid IgG, and anti-spike IgG. Diagnosis was made if at least one test result was positive. Pregnant women were tested between 34 and 42 weeks, mostly at birth. RESULTS: Among the 297 participating women, 152 were pregnant and 145 were nonpregnant. The prevalence of asymptomatic COVID-19 was similar between the groups (4 [2.6%] and 8 [5.5%], respectively; P = 0.2). All women with COVID-19 delivered healthy appropriate-for-gestational-age babies without malformations, at term. CONCLUSIONS: The rate of asymptomatic COVID-19 in pregnant women is low and comparable to the rate among nonpregnant women. Pregnancy outcomes are favorable. Future screening programs should consider that one of 25 screened asymptomatic women will be positive.

Rapid SARS-CoV-2 Detection Using the Lucira™ Check It COVID-19 Test Kit.

The need for the early identification of SARS-CoV-2 has let to a quest for reliable tests that meet the standards of polymerase chain reaction (PCR) tests, on the one hand, and are low-cost, easy-to-use, and fast, on the other hand. One such test is the Lucira™ Check It COVID-19 Test kit ("Lucira") (Lucira Health, Inc., Emeryville, CA, USA), which utilizes real-time loop-mediated isothermal amplification technology, developed for at-home use. This study evaluated the clinical sensitivity and specificity of Lucira in identifying the virus in 190 nasopharyngeal samples collected between January and October 2021. Each sample was also subjected to RT-PCR. All negative RT-PCR results were paralleled by a negative Lucira result. Out of 90 participants who had a positive RT-PCR result, 82 (91.1%) tested positive by Lucira. Among the 72 symptomatic participants, 67 (93%) tested positive by Lucira. All samples with a positive RT-PCR result with a threshold cycle (Ct) > 36, yielded a negative Lucira result. In addition, a significant positive correlation was found between Ct and time-to-positivity with Lucira (R = 0.8612, p < 0.0001). The implementation of such a portable and affordable assay may aid in breaking the COVID-19 transmission chain.

High throughput optical modulation biosensing for highly sensitive and rapid detection of biomarkers.

Rapid, highly sensitive, and high-throughput detection of biomarkers at low concentrations is invaluable for early diagnosis of various diseases. In many highly sensitive immunoassays, magnetic beads are used to capture fluorescently labeled target molecules. The target molecules are then quantified by detecting the fluorescent signal from individual beads, which is time consuming and requires a complicated and expensive detection system. Here, we demonstrate a high-throughput optical modulation biosensing (ht-OMB) system, which uses a small permanent magnet to aggregate the beads into a small detection volume and eliminates background noise by steering a laser beam in and out of the cluster of beads. Shortening the aggregation, acquisition, and well-to-well scanning transition times enables reading a 96-well plate within 10 min. Using the ht-OMB system to detect human Interleukin-8, we demonstrated a limit of detection of 0.14 ng/L and a 4-log dynamic range. Testing 94 RNA extracts from 36 confirmed RT-qPCR SARS-CoV-2-positive patients (Ct≤40) and 58 confirmed RT-qPCR SARS-CoV-2-negative individuals resulted in 100% sensitivity and 100% specificity.

Evaluation of Factors that Affect the Performance of COVID-19 Molecular Assays Including Presence of Symptoms, Number of Detected Genes and RNA Extraction Type.

BACKGROUND AND AIMS: Rapid and accurate detection of COVID-19 is crucial for mitigation of the pandemic. We evaluated the performance of six molecular kits and the effect of several factors on the performance of the kits. MATERIALS AND METHODS: Two hundred and four nasopharyngeal samples were collected from participants aged ≥18 years at the Baruch Padeh Medical Center Poriya, Israel, between June and August 2020. Samples were tested by: Allplex 2019-nCOV Assay (Seegene), Real-Time Fluorescent RT-PCR Kit for Detecting SARS-2019-nCoV (BGI Genomics), Xpert® Xpress SARS-CoV-2 test (Cepheid), Simplexa® COVID-19 Direct Kit (Focus Diagnostics), BD SARS-CoV-2 Reagents for BD MAX™ System (BD), and Logix Smart™ Coronavirus Disease 2019 (COVID-19) Test kit (CO-DIAGNOSTICS). RESULTS: Xpert® Xpress SARS-CoV-2 test and Logix Smart™ COVID-19 Kit had the highest (91.2%) and the lowest (74.5%) sensitivity, respectively. Symptoms were a predictor of a positive result. Traditional assays had a higher minimum cycle threshold (min Ct), i.e. detected lower viral load, compared to rapid assays (p = 0.012). Samples of symptomatic participants had lower min Ct, than samples of asymptomatic participants (p < 0.001). Additionally, the more genes were detected, the lower the min Ct (p < 0.001), indicating that a greater percentage of the viral genome was amplified. CONCLUSIONS: Taken together, most assays had overall good performance. Since several factors affect the performance of kits, each laboratory must be familiar with its kit's limitations in order to produce the most reliable results.

COVID-19 Vaccination Compliance and Associated Factors among Medical Students during an Early Phase of Vaccination Rollout-A Survey from Israel.

COVID-19 is "a once-in-a-century" pandemic, bringing with it unparalleled health, social, and economic ramifications. As part of the world's efforts to restrain the pandemic, vaccine development has been expedited. This population-representative survey in Israel aimed to investigate whether the knowledge, attitudes, and vaccination status of medical students affect their intention to recommend COVID-19 vaccination (as well as reasons for refusal and acceptance of the vaccine). The questionnaire was anonymous, via Google Forms app in December 2021. One-hundred and four medical students completed the survey. Overwhelmingly, (91.3%) COVID-19 vaccination status and intention to receive the vaccine were positively associated with intention to recommend. Twenty-five percent of the students replied that they lacked knowledge regarding the vaccine. A statistically significant association was found between experiencing quarantine and the intention to be vaccinated (p = 0.034). There was a significant positive relationship between the number of symptoms from previous vaccines and the fear of COVID-19 (rs = 0.272, p < 0.01). Prior vaccination did not have an effect on COVID-19 vaccine hesitancy. This first study evaluating COVID-19 vaccine hesitancy among Israeli medical students highlighted the need for medical programs to emphasize the benefits of COVID-19 vaccination in the protection of healthcare workers and patient safety. Education, awareness campaigns, and regulation of vaccine trials could further decrease COVID-19 vaccine hesitancy and increase vaccine rates among medical students.

Tumor necrosis factor inhibitors are associated with a decreased risk of COVID-19-associated hospitalization in patients with psoriasis-A population-based cohort study.

The risk of coronavirus disease 2019 (COVID-19) and its complications among patients with psoriasis treated by tumor necrosis factor inhibitors (TNFis) remains to be decisively delineated. We aimed to assess the risk of COVID-19 infection, COVID-19-associated hospitalization, and mortality among Israeli patients with psoriasis treated by TNFi relative to other systemic agents. A population-based cohort study was conducted to compare psoriasis patients treated by TNFi (n = 1943), with those treated by methotrexate (n = 1929), ustekinumab (n = 348), and acitretin (n = 1892) regarding COVID-19 outcomes. Risk of investigated outcomes was assessed using uni- and multi-variate Cox regression analyses. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality in the TNFi group was 35.8 (95% CI, 26.1-47.9), 0.8 (95% CI, 0.0-4.2), and 0.0 per 1000 person-years, respectively. Exposure to TNFi was associated with a comparable risk of COVID-19 infection [adjusted hazard ration (HR) for TNFi vs methotrexate: 1.07 (95% CI, 0.67-1.71); TNFi vs ustekinumab: 1.07 (95% CI, 0.48-2.40); TNFi vs acitretin: 0.98 (95% CI, 0.61-1.57)]. TNFi was associated with a decreased risk of COVID-19-associated hospitalization relative to methotrexate (adjusted HR, 0.10; 95% CI, 0.01-0.82) and ustekinumab (adjusted HR, 0.04; 95% CI, 0.00-0.64), but not to acitretin (adjusted HR, 1.00; 95% CI, 0.16-6.16). No significant difference in COVID-19-associated mortality was found between the four different groups. TNFi was associated with a decreased risk of admissions due to COVID-19. Our findings substantiate the continuation of TNFi treatment during the pandemic. TNFi may be positively considered in patients with moderate-to-severe psoriasis warranting systemic treatment during the pandemic.

Full genome viral sequences inform patterns of SARS-CoV-2 spread into and within Israel.

Full genome sequences are increasingly used to track the geographic spread and transmission dynamics of viral pathogens. Here, with a focus on Israel, we sequence 212 SARS-CoV-2 sequences and use them to perform a comprehensive analysis to trace the origins and spread of the virus. We find that travelers returning from the United States of America significantly contributed to viral spread in Israel, more than their proportion in incoming infected travelers. Using phylodynamic analysis, we estimate that the basic reproduction number of the virus was initially around 2.5, dropping by more than two-thirds following the implementation of social distancing measures. We further report high levels of transmission heterogeneity in SARS-CoV-2 spread, with between 2-10% of infected individuals resulting in 80% of secondary infections. Overall, our findings demonstrate the effectiveness of social distancing measures for reducing viral spread.