Effect of SARS-CoV-2 Vaccination on Severity and Outcome of COVID-19 among Health-care Workers of a Tertiary Care Hospital in India

Introduction: SARS-CoV-2 vaccines decrease the risk of infection. However, data on the utility of vaccines in decreasing the severity of COVID-19 need to be evaluated. This study was carried out with the primary objective to assess the severity and clinical outcome of COVID-19 infections among unvaccinated and vaccinated health-care workers (HCWs). Methods: This was a hospital-based retrospective cohort study including all HCWs who developed microbiologically confirmed COVID-19 over 6 months from January 31, 2021, to July 31, 2021 (during the second wave of COVID-19 in India). Data were recorded through a questionnaire which included demographic details, primary location of work, history of vaccination with dates, comorbidities, severity of COVID-19, and outcome. HCWs who tested positive for SARS-CoV-2 before any dose of the COVID-19 vaccine were included in the "unvaccinated " group. Whereas HCWs who developed SARS-CoV-2 after a single or both doses of vaccine were included in the vaccinated group. The outcome and mortality among the vaccinated and unvaccinated groups were evaluated and compared. Results: The study included 500 HCWs who developed a microbiologically confirmed CVOID-19 infection. It was a predominantly middle-aged population with 247 unvaccinated and 253 vaccinated at the time of developing COVID-19. Only one-fourth of the population (26%) was working in the COVID-19 area and the source of COVID-19 to most was either a COVID-19 patient (39%) or a colleague (38%). Around 13% of the population had comorbidities with cardiovascular disease and diabetes being the most common. The majority of the patients were mild (71%) and most were treated at home in isolation (91%). Only 4% of the study population required intensive care. Among the vaccinated group, COVID-19 infection was predominantly mild and this difference was statistically significant as compared to the nonvaccinated. No difference was found in mortality among the two groups;however, the overall mortality was only 1%. Conclusions: SARS-CoV-2 vaccines reduce the severity of COVID-19 besides preventing infections and its spread. This can help in effective care of COVID-19 in home isolation without overburdening the health-care services. More studies including clinical parameters and microbiological components are required to understand the true extent of this protection of vaccines from severe forms of COVID-19.

Lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study

Background: Pts with R/R LBCL after first-line (1L) treatment (tx) who are unable to undergo high-dose chemotherapy (HDCT) and HSCT have poor outcomes and limited tx options. PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. Methods: Eligible pts were adults with R/R LBCL after 1L tx who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN. Bridging tx was allowed. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by liso-cel at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria and neurological events (NE) per NCI CTCAE, version 4.03. Primary endpoint was ORR per independent review committee (IRC);all pts had ≥ 6 mo followup (f/u) from first response. Results: Of 74 pts leukapheresed, 61 received liso-cel and 1 received nonconforming product. Common reasons for pre-infusion dropout included death and loss of eligibility (5 each). For liso-cel-treated pts, median age was 74 yr (range, 53-84;79% ≥ 70 yr) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively;26% had ECOG PS = 2 and 44% had HCT-CI score ≥ 3. After 1L tx, 54% were chemotherapy refractory, 21% relapsed ≤ 12 mo, and 25% relapsed > 12 mo;51% of pts received bridging chemotherapy. Median (range) on-study f/u was 12.3 mo (1.2-26.5). ORR and CR rate was 80% and 54%, respectively. Median DOR and PFS was 12.1 mo and 9.0 mo, respectively. Median OS has not been reached (Table). Most frequent tx-emergent AEs (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade (gr) 3 CRS in 1 pt (2%) and no gr 4/5 CRS. Any-grade NEs were seen in 31%, gr 3 in 5% (n = 3), and no gr 4/5 NEs;7% received tocilizumab, 3% corticosteroids, and 20% both for tx of CRS/NEs. Overall, gr ≥ 3 TEAEs occurred in 79%, with gr 5 in 2 pts (both due to COVID-19). Two pts (3%) had gr 3/4 infections and 15 (25%) had gr ≥3 neutropenia at Day 29. Conclusions: In the PILOT study, liso-cel as 2L tx in pts with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns.

Perceptions of Anxiety and Depression Among Pediatric Frontline Health care Providers During the COVID-19 Pandemic

Background: Our frontline nurses and physicians seemed to have increased anxiety at the beginning of the COVID-19 pandemic and increased depression as the year progressed. Perceptions of anxiety and depression coincided with concern for one's own health, limited knowledge of how to care for patients during a pandemic, limited personal protective equipment (PPE), and/or financial constraints. To date, there are no studies looking at pediatric frontline healthcare providers and their rates of anxiety and depression over the course of a pandemic. Furthermore, nurses and physicians have distinct roles in the emergency setting that affect their perceptions of anxiety and depression. Currently, there are limited studies comparing nurse and physician anxiety and depression rates during a pandemic. The purpose of this study was to determine if there was a difference in perceptions of anxiety and depression among our Pediatric Emergency and Urgent Care frontline providers during the COVID-19 pandemic. Methods: This was a prospective cross-sectional study at a large quaternary level 1 trauma center including 3 emergency departments and 7 urgent care sites. We used the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-2 (PHQ-2), both standardized validated screening tools for identifying anxiety and depressive disorders, respectively. The GAD-7 scores range from 0-21 points, with 0-4 considered minimal anxiety, 5-9 mild anxiety, 10-14 moderate anxiety, and 15-21 severe anxiety. PHQ-2 scores range from 0-6 points with 3-6 considered likely major depressive disorder. We surveyed healthcare providers including physicians and nurses twice with the GAD-7, once at the beginning of the pandemic in Spring 2020 and again after vaccine implementation in Spring 2021. We surveyed healthcare providers once after vaccine implementation with the PHQ-2. Results: 396 surveys were distributed in Spring 2020 and 466 surveys were distributed in Spring 2021, with one-third physician and two-thirds nurse response each time. Table 1 shows the average GAD-7 and PHQ2 scores for healthcare providers by role. The average GAD-7 score decreased for both nurses and physicians from the beginning of the pandemic to after vaccine implementation. Nurses on average had higher anxiety scores with mild score range compared to minimal score range for physicians. Nurses on average had higher depression scores compared to physicians but both roles had scores in the low likelihood range. Conclusion: Many healthcare providers perceived higher anxiety and depression levels during the pandemic. The anxiety levels appeared to decrease after vaccine implementation although hospital-wide pandemic relief efforts may have played a role in improved perceptions. Even though nurses had higher anxiety scores, the difference in the score is unlikely to be clinically significant. Our data supports rigorous mental health infrastructure during pandemic preparedness to support the sudden feelings of anxiety and depression in frontline healthcare providers.

Time Since Last Anti-CD20 Treatment Is a Major Determinant of Sars-Cov-2 Vaccine Response in a Large Cohort of Patients with B-Cell Lymphoma

[Formula presented] Background: Patients with B-cell lymphoma have poor clinical outcomes to SARS-CoV-2 infection (COVID-19) and are also more likely to have suboptimal responses to immunization. An understanding of which lymphoma patients are at greatest risk of poor COVID-19 vaccine response and what aspects of immunity are most impaired is critical for developing strategies to protect these patients from a potentially fatal infection. Methods: We enrolled 149 participants, including 129 with lymphoma and 20 age-matched controls, who received a complete COVID-19 vaccination series to assess how B- and T-cell vaccine responses vary among clinically relevant subgroups and over time. This cohort included 99 patients with prior anti-CD20 treatment, ranging from 1 week to 17 years prior, allowing us to assess relationships between timing and intensity of anti-CD20 exposure and vaccine response. The cohort also included 18 patients who began treatment with an anti-CD20-containing regimen after being fully vaccinated, in whom we are assessing the potential efficacy of a pre-therapy vaccination strategy. Peripheral blood samples were taken on average 28 days and 4 months after last vaccine dose. B-cell responses are being profiled by measuring anti-Spike serum IgG, RBD-ACE2 blocking activity, and spike-specific memory B cells. T cell assessments include quantitation of spike-specific activation and cytokine production via interferon-gamma ELISPOTs and multiparameter flow cytometry. Results: The 129 participants with lymphoma had a median age of 68, were 59% male, and 70% had either diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Thirteen percent had no therapy prior to vaccination, half had not been treated in the past six months and 36% had been treated recently or were currently being treated. Ninety-three percent received an mRNA COVID-19 vaccine. Although we did not detect a statistically significant difference in vaccine response between previously untreated lymphoma patients and controls, 3/17 were negative for blocking antibodies post-vaccine, compared to 0/20 controls (Fishers exact test p=0.09, Figure 1A). Lymphoma patients with any history of treatment had impaired serologic responses to the vaccine compared to previously untreated patients (p=0.01). Responses did not vary by specific lymphoma histology. Blocking antibodies were evident in only 45% and 3% of patients recently/currently treated with a BTK inhibitor or an anti-CD20 antibody, respectively (Figure 1A). Closely evaluating all patients who had ever received anti-CD20 antibody therapy, we found a strong linear correlation between time since last anti-CD20 treatment and RBD-ACE2 binding inhibition (p<0.0001, Figure 1B-C). T cell and memory B cell assays are ongoing as is analysis of response persistence and of the pre-therapy vaccination cohort, and results from these efforts will be included in the final presentation. Conclusions: Treatment with anti-CD20 antibodies significantly impaired COVID-19 vaccine-induced humoral responses in patients with lymphoma in a manner dependent on the time elapsed since last anti-CD20 treatment. Vaccination at least six months after anti-CD20 treatment, likely co-incident with recovery of the B-cell compartment, was associated with positive blocking antibody titers. These data suggest that booster vaccination strategies are more likely to succeed in lymphoma patients who have not received anti-CD20 treatment for at least 6 months and that those patients with recent anti-CD20 treatment may benefit most from passive immunization strategies. Forthcoming results from the pre-therapy vaccination cohort will also help inform sequencing of additional vaccine doses, passive immunization, and anti-cancer treatments. [Formula presented] Disclosures: Shree: Gilead: Other: Spouse's employment. Beygi: Kite/Gilead: Current Employment. Advani: Astellas/Agensys: Research Funding;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Bayer: Membership on an entity's Board of Directors or dvisory committees;Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees;Cell Medica: Membership on an entity's Board of Directors or advisory committees;Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding;Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen Pharmaceutical: Research Funding;Juno: Membership on an entity's Board of Directors or advisory committees;Kite Pharma: Membership on an entity's Board of Directors or advisory committees;Kura: Research Funding;Kyowa: Membership on an entity's Board of Directors or advisory committees;Merck: Research Funding;Millenium: Research Funding;Pharmacyclics: Consultancy, Research Funding;Portola Pharmaceuticals: Consultancy;Regeneron: Research Funding;Roche: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees. Khodadoust: CRISPR Therapeutics, Nutcracker Therapeutics: Research Funding;Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees;Alexion, AstraZeneca Rare Disease: Other: Study investigator. Kurtz: Roche: Consultancy;Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company;Genentech: Consultancy. Alizadeh: Bristol Myers Squibb: Research Funding;Gilead: Consultancy;Celgene: Consultancy, Research Funding;Janssen Oncology: Honoraria;Roche: Consultancy, Honoraria;Foresight Diagnostics: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;Forty Seven: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;CAPP Medical: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;Cibermed: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Levy: GigaGen: Membership on an entity's Board of Directors or advisory committees;Teneobio: Membership on an entity's Board of Directors or advisory committees;Nurix: Membership on an entity's Board of Directors or advisory committees;Dragonfly: Membership on an entity's Board of Directors or advisory committees;Apexigen: Membership on an entity's Board of Directors or advisory committees;Viracta: Membership on an entity's Board of Directors or advisory committees;Spotlight: Membership on an entity's Board of Directors or advisory committees;Immunocore: Membership on an entity's Board of Directors or advisory committees;Walking Fish: Membership on an entity's Board of Directors or advisory committees;Kira: Membership on an entity's Board of Directors or advisory committees;Abintus Bio: Membership on an entity's Board of Directors or advisory committees;Khloris: Membership on an entity's Board of Directors or advisory committees;Virsti: Membership on an entity's Board of Directors or advisory committees;BiolineRx: Membership on an entity's Board of Directors or advisory committees;BeiGene: Membership on an entity's Board of Directors or advisory committees;Quadriga: Membership on an entity's Board of Directors or advisory committees.

Impact of COVID-19 lockdown on ambient noise levels in seven metropolitan cities of India.

The paper analyzed the impact of lockdown on the ambient noise levels in the seventy sites in the seven major cities of India and ascertained the noise scenario in lockdown period, and on the Janta Curfew day in comparison to the pre-lock down period and year 2019 annual average values. It was observed that the majority of the noise monitoring sites exhibited a decrement in ambient day and night equivalent noise levels on the national Janta Curfew day and Lockdown period as compared with the normal working days attributed to the restricted social, economical, industrial, urbanization activity and reduced human mobility. A mixed pattern was observed at a few sites, wherein the ambient day and night equivalent noise levels during Janta curfew day and Lockdown period had been reported to be higher than that on the normal working days. The study depicts the noise scenario during the lockdown and pre-lockdown period for seventy sites in India and shall be instrumental in analyzing the consequences and implications of imposing lockdowns in future on the environmental noise pollution in Indian cities.

A Big Data Approach for Healthcare Analysis During Covid-19

In the present times, with the massive growth of the Internet, unbelievably enormous measures of data are in our reach. Although our lives have been changed by prepared access to boundless information, still we need to explore the use of technology in various thrust areas. In this paper, we have analyzed and classify the mental state of people to raise awareness about mental health, especially during COVID-19. I have adopted the big data approach to accomplish this project. Two standard datasets have been used for our experiments. The idea behind our work is to use propose a customized mental health solution with the use of big data approach that can be useful for health care as well. We have applied state-of-the-art classifiers algorithm and found that the CountVec with the multinomial Naïve Bayes method gives the highest accuracy in terms of precision and recall. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.