Forecasting COVID-19 Cases Using n-SARS-CoV-2 Variants

This work proposes a novel Deep Learning-based model to forecast the total number of confirmed COVID-19 cases in four of the worst-hit states of India. Along with statewide restrictions and public holidays, a novel parameter is introduced for training the proposed model, which considers the Alpha, Beta, Delta, and Omicron variants and the degree of their prevalence in each of the four states. Recurrent Neural Network-based Long-Short Term Memory is applied to the custom dataset, with the lowest Mean Absolute Percentage Error being 0.77% for the state of Maharashtra. SHapley Additive exPlanations values are used to examine the significance of the various parameters. The proposed model can be applied to other countries and can include newer variants of the novel coronavirus discovered in the future. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Digital Media Effect on Diabetic Eye Care During COVID-19 pandemic

Purpose : To gauge the impact of healthcare technology in the management of diabetic retinopathy during the COVID-19 pandemic. Methods : The study was conducted at EyeCare Consultants of New Jersey's in their two locations in NJ, Woodland Park and Edison. Eye care professionals (ECPs-two ophthalmologists, one optometrist) surveyed 400 diabetic patients during the first year of the pandemic (March 2020- February 2021). The patients all received previous instructions with CheckedUp, a patient education digital platform utilizing audiovisual and touchscreen to further educate patients, during in-office visits. The 400 diabetic patients were divided equally into two groups. To ensure the adherence of dietary and behavioral modifications related to diabetes mellitus, Group 1 received traditional phone calls while Group 2 received video calls and supplementary education with CheckedUp. Both groups had a follow-up in person in September 2021. Surveys elicited responses to gauge consistency of HbA1C management. Results : Adherence was defined as HbA1C values which remained within a target value lower than or equal to their baseline and/or <7.0% as well as compliance with medications, dietary restrictions, regular physical activity and follow-up visits. The results found a significant difference between educating the patient with a phone call versus a video call and CheckedUp. At the next follow-up visit in person: Group 1 had an adherence of 48% (96 patients) and had several patients with HbA1C values exceeding the targeted value. Group 2 had an adherence of 69% (138 patients) and were more compliant with a healthier lifestyle. They also stated that their telehealth appointment with CheckedUp helped reinforce the importance of maintaining a normal HbA1C value. Conclusions : This study illustrates the ability of digital medicine platforms to supplement virtual and in-person consultations to manage diabetic retinopathy, especially during the pandemic. Compliance is an important matter in the management and preventing progression of diabetic retinopathy. Digital tools like CheckedUp assist with optimizing patient care in these unprecedented times.

Anti-BCMA-CAR-T-Zell-Therapie bei einem Patienten mit rezidiviertem und refraktärem Multiplen Myelom nach einer COVID-19-Infektion: ein Fallbericht

Hintergrund: Über das Risiko einer Virusinfektion mit dem schweren akuten Atemwegssyndrom Coronavirus 2 (SARS-CoV-2) bei Krebspatienten, von denen viele immungeschwächt und damit anfälliger für eine Vielzahl von Infektionen sind, ist sehr wenig bekannt. Als Vorsichtsmaßnahme haben viele klinische Studien während der ersten Welle der weltweiten Pandemie des neuartigen Coronavirus (COVID-19) die Aufnahme von Patienten pausiert. In diesem Fallbericht beschreiben wir die erfolgreiche Behandlung eines Patienten mit rezidiviertem und refraktärem Multiplem Myelom (MM), der unmittelbar nach der klinischen Genesung von COVID-19 mit einer chimären Antigenrezeptor (CAR)-T-Zelltherapie mit Anti-B-Zellreifungsantigen (BCMA) behandelt wurde. Fallvorstellung: Der 57-jährige weiße männliche Patient war seit 4 Jahren an MM erkrankt und galt bei der Vorstellung zur CAR-T-Zelltherapie als pentarefraktär. Er hatte eine Immunsuppression in seiner medizinischen Vorgeschichte und er erhielt am Tag vor der COVID-19-Diagnose eine Dosis lymphdepletierender Chemotherapie (LDC). Dieser Patient konnte eine erhebliche Immunantwort gegen das SARS-CoV-2-Virus aufbauen, und antivirale Antikörper bleiben auch 2 Monate nach Erhalt einer Anti-BCMA-CAR-T-Zelltherapie noch nachweisbar. Die kürzliche SARS-CoV-2-Infektion bei diesem Patienten führte nicht zu einer Exazerbation des CAR-T-assoziierten Zytokin-Freisetzungssyndroms (CRS) und umgekehrt führte die CAR-T-Zelltherapie nicht zu Komplikationen im Zusammenhang mit COVID-19. Einen Monat nach der CAR-T-Zell-Infusion wurde bei dem Patienten ein unbestätigtes partielles Ansprechen nach den Kriterien der International Myeloma Working Group (IMWG) festgestellt. Schlussfolgerung: Unser Fall liefert einen wichtigen Kontext für die Wahl der Behandlung von MM-Patienten in Zeiten von COVID-19 sowie für die Frage, ob die CAR-T-Therapie auch bei Patienten verabreicht werden kann, die von COVID-19 genesen sind. Da die COVID-19-Pandemie weltweit anhält, ist eine umfangreiche Diskussion über die Entscheidung, ob mit der CAR-T-Zelltherapie fortgefahren werden soll, erforderlich, wobei die potenziellen Risiken und Vorteile der Therapie gegeneinander abgewogen werden müssen. Dieser Fall legt nahe, dass es möglich ist, die Anti-BCMA-CAR-T-Zelltherapie nach der Genesung von COVID-19 erfolgreich abzuschließen. Die Studie CRB-402 wurde am 6. September 2017 bei clinicaltrials.gov registriert (NCT03274219).

Suboptimal Humoral and Cellular Immune Response to SARS-CoV-2 RNA Vaccination in Myeloma Patients Is Associated with Anti-CD38 and BCMA-Targeted Treatment

Background: Multiple myeloma (MM) patients are immunocompromised due to defects in humoral/cellular immunity and immunosuppressive therapy. Reports indicate that the antibody (Ab) response in MM after 1 dose of SARS-CoV-2 RNA vaccine is attenuated. The impact of treatment on cellular immunity after vaccination remains unknown. Methods: We analyzed SARS-CoV-2 spike-binding (anti-S) IgG level in 320 MM patients receiving SARS-CoV-2 RNA vaccination. Blood and saliva were taken at multiple time points and compared with serology data of 69 age-matched vaccinated healthcare workers. We profiled SARS-CoV-2-specific T cell responses in a subset of 45 MM patients and 12 age-matched healthy controls by flow cytometry and ELIspot. All subjects were enrolled in studies approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. Results: The 320 patients (median age 68 year) received two-dose RNA vaccines (69.1% BNT162b2, 27.2% mRNA-1273). Median time to diagnosis was 60 months with a median of 2 prior treatment lines (range 0-16). We included 23 patients with smoldering MM. Patients received various treatments at vaccination with 148 (43.8%) on anti-CD38-containing treatment, 36 (11.3%) on BCMA-targeted therapy and 59 (18.4%) not on active treatment (incl. SMM patients). At the last available evaluation prior to vaccination, 131 (40.9%) exhibited a complete response. At data cutoff, a total of 260 patients (81.3%) had anti-S IgG measured >10 days after the second vaccine (median 51 days). Of these, 84.2% mounted measurable anti-S IgG levels (median 149 AU/mL). In the control group, Ab levels were significantly higher (median 300 AU/mL). Ab levels in the vaccinated MM patients with prior COVID-19 were 10-fold higher than those of patients without prior COVID-19 (p<0.001). Repeat Ab measurements up to 60 days after second vaccination confirm delayed and suboptimal IgG kinetics, particularly in patients receiving anti-MM treatment compared to controls (Figure 1). MM patients on active treatment had lower anti-S IgG levels (p=0.004) compared to patients not on therapy (median 70 vs 183 AU/mL). Notably, 41 patients (15.8%) failed to develop detectable anti-S IgG: 24/41 (58.5%) were on anti-CD38, 13/41 (31.7%) on anti-BCMA bispecific Ab therapy and 4/41 (9.8%) >3 months after CAR T. Univariate analysis showed an association of disease-related factors with absence of anti-S IgG: more previous lines of treatment (>3 lines, p=0.035;>5 lines, p=0.009), receiving active MM treatment (p=0.005), grade 3 lymphopenia (p=0.018), receiving anti-CD38 therapy (p=0.042) and receiving BCMA-targeted therapy (p<0.001). Multivariate analysis (corrected for age, vaccine type, lines of treatment, time since diagnosis, response status and lymphopenia) confirmed that anti-CD38 (p=0.005) and BCMA-targeted treatment (p<0.001) are associated with not developing detectable anti-S IgG. Clinical relevance is emphasized by 10 cases of COVID-19 after 1 (n=7) or 2 vaccine doses (n=3, all without anti-S IgG) with 1 patient passing due to respiratory failure. We studied SARS-CoV-2-specific T cell responses >2 weeks after the second vaccine in 18 MM patients with undetectable anti-S IgG (seronegative), 27 with detectable anti-S IgG (seropositive) and 12 healthy seropositive controls. We found that seropositive MM patients had CD4+CD154+ T cells producing IFNg, TNFa and IL-2 at similar levels as controls, whereas in the seronegative MM cohort CD4 T cell responses were significantly reduced (p<0.005). SARS-CoV-2-specific CD8 T cell responses were overall weaker and not different across cohorts. This data suggests that absence of detectable IgG is associated with suboptimal response of humoral and cellular immunity. Conclusion: MM patients mount a suboptimal IgG response after SARS-CoV-2 vaccination, with 15.8% of patients without detectable anti-S IgG. Ongoing analyses will highlight durability of serological protection against COVID-19. Additional data on T cell responses and immunophenotyping in the context of vaccination will be upda ed at the meeting. Implications are continuation of non-pharmacological interventions, e.g. masking/social distancing, for vulnerable patients. The findings underscore a need for serological monitoring of MM patients after vaccination and for trials assessing use of prophylactic strategies or studies exploring additional immunization strategies. [Formula presented] Disclosures: Wang: Sanofi Genzyme: Consultancy. Chari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pharmacyclics: Research Funding;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cordon-Cardo: Kantaro: Patents & Royalties. Krammer: Kantaro: Patents & Royalties;Merck: Consultancy;Pfizer: Consultancy;Avimex: Consultancy;Seqirus: Consultancy. Jagannath: Legend Biotech: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Bristol Myers Squibb: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Simon: Kantaro: Patents & Royalties. Parekh: Foundation Medicine Inc: Consultancy;Amgen: Research Funding;PFIZER: Research Funding;CELGENE: Research Funding;Karyopharm Inv: Research Funding.

Hype and hope of emerging therapies to safeguard against COVID-19 pandemic

The COVID-19 is a highly contagious disease represented with multiple non specific symptoms and caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Despite its dissemination and worsening trends researchers are still searching for the best treatment option. Timely diagnosis is the key to get more appropriate treatment regimen. Several clinical trials are ongoing to determine the efficacy and safety of existing and new therapies against Coronavirus Disease -2019 (COVID-19). These include corticosteroids, antivirals, monoclonal antibodies, interferon Alpha 2b and other immune modulators. In addition to treatment, efficacious and safe vaccines are required to slow viral transmission and to prevent further morbidity and mortality. The vaccination is useful tool to get control over the virus. Although, mass immunisation campaigns are ongoing in many countries, global coverage is crucial for getting the pandemic under control. This descriptive review collated the information on current diagnostics tools for determination of COVID-19 infection and available preventive and therapeutic strategies based on the ongoing clinical trials data and published literature.

Digital media effects on glaucoma eye care during COVID-19

Purpose : Gauge the impact of digital medicine and associated tools on glaucoma management and medication adherence during the COVID-19 pandemic. Methods : The study was conducted at EyeCare Consultants of New Jersey's two locations in Woodland Park and Edison, NJ. Eye care professionals (ECPs) (two ophthalmologists & two optometrists) surveyed 100 glaucoma patients during the first several months of the COVID-19 pandemic (March - August 2020). All those surveyed received previous digital instruction with CheckedUp, a patient education digital platform utilizing auditory, visual, and touch elements to engage patients with eyecare education during prior in-person visits. All patients were randomized into two groups: Group 1 received traditional phone calls while Group 2 received video calls (video with ECP and screen share of CheckedUp) during the pandemic to ensure adherence with ocular medications and address acute issues during this time period. All patients in Group 2 were shown the same glaucoma educational videos in English using the CheckedUp platform. Both groups received followup with an in-person visit in August. Surveys elicited responses to gauge consistency of ocular medication use. Results : Adherence was defined as daily compliance with the glaucoma medication throughout the five-month period. The survey results demonstrated a significant difference between Group 1 and Group 2. Adherence during months without in-person office visits were compared to self-reported adherence for the same five-month time period in the year prior to the COVID-19 pandemic. Group 1's overall adherence was 64% (32/50 patients) at the August in-person visit and revealed that several patients used their drops inconsistently or differently from their prescribed regimen. Group 2's overall adherence was 90% (45/50 patients) at the August in-person visit and patients demonstrated continued comprehension of glaucoma risk and the importance of consistent medication use. A majority of Group 2 patients also commented that the ECP video call with CheckedUp helped reinforce the importance of eye pressure control in glaucoma. Conclusions : This study illustrates the ability of digital medicine platforms to supplement in-person office visits to manage glaucoma, even during a pandemic such as COVID-19. Compliance remains an important issue in the medical management of glaucoma and digital solutions like CheckedUp assist with optimizing patient care.

Psychological Well-Being of Indian Mothers during the COVID-19 Pandemic: The Roles of Self-Compassion, Psychological Inflexibility, and Parenting Stress

This study explored the associations among psychological well-being (PWB), self-compassion, psychological inflexibility (PI), and parenting stress (PS) in 242 urban Indian mothers of children 10 years old and younger in the context of the COVID-19 pandemic. Regression analysis revealed that greater self-compassion (SC), less PS, and greater psychological flexibility were associated with psychological well-being among the participants. Findings from this study contribute to research on maternal mental health by showing that, even in the context of the COVID-19 crisis, SC, PI, and PS are related to the PWB of urban Indian mothers, thus highlighting a need for evolving gender-based policies and emphasizing specific interventions for this vulnerable population. © 2021 Hogrefe Publishing.

Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report.

BACKGROUND: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. CASE PRESENTATION: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. CONCLUSION: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).

MM-239: A Tertiary Center Experience of Multiple Myeloma Patients with COVID-19: Lessons Learned and the Path Forward

Context: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 100,000 deaths in the United States. Our institution has treated over 2,000 COVID-19 patients during the pandemic in New York City. Objective: We explored the population of myeloma patients who developed COVID-19 to identify risk factors tied to poor outcomes. Design: We performed a retrospective study of a cohort of 58 patients with a plasma cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020 and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics, including persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. Setting: A large tertiary care cancer center in New York at the epicenter of the COVID-19 pandemic in the USA. Patients: Patient charts were analyzed retrospectively. Patients had MM or SMM and COVID-19. Results: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years;52% of patients were male, and 63% were non-white. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (CKD, 24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (>70 years), male sex, and cardiovascular risk were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-white race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. Median time to PCR negativity was 43 (range 19–68) days from initial positive PCR. Conclusions: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on patient outcome. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia were associated with higher mortality. These findings pave a path to the identification of vulnerable patients who need early intervention to improve outcomes of myeloma patients in future outbreaks of COVID-19. The majority of myeloma patients mounted a specific antibody response to SARS-CoV-2.