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Profiling immune responses across several dimensions, including time, patients, molecular features, and tissue sites, can deepen our understanding of immunity as an integrated system. These studies require new analytical approaches to realize their full potential. We highlight recent applications of tensor methods and discuss several future opportunities.
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Communicable Diseases , Immunity , HumansABSTRACT
Background. COVID-19 reinfection is generally defined as having 2 positive SARS-CoV-2 tests greater than 90 days apart. The clinical implications and impact of COVID-19 reinfection are not completely understood. We evaluated clinical and demographic characteristics of patients with COVID-19 reinfection. Methods. All SARS-CoV-2 polymerase chain reaction (PCR) tests performed at Joint Base San Antonio (JBSA), from March 27, 2020 through January 19, 2022 were analyzed. COVID-19 reinfection was defined as having 2 positive PCR tests >90 days apart. Available data for comorbidities, travel, COVID-19 vaccination status, SARS-CoV-2 genotype, symptoms, hospitalization, and treatments were compared for first and second infections. Results. A total of 310,704 SARS-CoV-2 PCR tests performed of which 25,543 (8.2%) were positive at JBSA during the study period. Patients with COVID-19 reinfection (n=532;4.2%) were identified and 266 (50%) charts reviewed. The mean age was 36.5 (+/-15) years and approximately half were males and active duty members (Table 1). The median time from first to second infection was 326 days (IQR 160-385). Patients were predominantly unvaccinated (91.4%) at initial infection, however unvaccinated status was less common (40.2%) at second infection (40.2%;P<0.0001).A significantly higher proportion of patients were symptomatic at first infection (88.3%) compared to second infection (51.5%;P< 0.001). Pneumonia diagnosis was significantly higher (4.9% vs. 0.4%;P=0.0011) whereas hospitalization was similar (2.6% vs. 2.3%;P=0.0788) for first compared to second infection. Among hospitalized patients, critical illness was common for first infection (57.1%) but none of the patients were critically ill with their second infection. A third episode of infection was rarely observed (1.5%). Of 80 genotype samples available, 14 (30%) were paired samples. Among all paired samples different genotypes were responsible for reinfection (Table 2). Conclusion. Patients with COVID-19 reinfections were less likely to be symptomatic, had lower severity of illness, and typically had a different SARS-CoV-2 genotype at second infection. Reinfection occurred despite COVID-19 vaccination in many patients, which highlights the need to develop novel strategies for vaccination.
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Background: COVID-19's physical distancing mandates have increased the likelihood of experiencing social isolation and loneliness for residents in long-term care (LTC), especially those living with dementia. Social isolation correlates with health risks, including depression and cognitive decline. Telepresence robots can be remotely driven and facilitate social interactions through videoconferencing. Researchers have begun to explore opportunities of using these robots in the healthcare field;however, there is a research gap on examining factors influencing their implementation in LTC from the perspectives of key stakeholders. This qualitative descriptive study focuses on exploring LTC staff and leadership teams' perspectives on facilitators and barriers to implementing telepresence robots. Method(s): We employed purposive and snowballing methods to recruit 22 participants from two LTC homes in British Columbia, Canada: operational and unit leaders, and interdisciplinary staff including nursing staff, care aides and allied health practitioners. Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis. Semi-structured interviews were conducted by virtual meetings. Thematic analysis was performed to identify themes. Result(s): Analysis of the data produced three themes: (a) perceived needs and values for family-resident connections, (b) engagement through conversation and partnership, and (c) confidence with training and timely support. Based on the findings and CFIR guidance, we offer a preliminary conceptual tool "START": Share benefits and successes;Tailor policies and plans with staff partners;Acknowledge and address staff concerns;Repeated training and demonstrations;and Timely technical support. Conclusion(s): This study offers pragmatic insights into staff and leadership teams' perceptions of facilitators and barriers of implementing telepresence robots in LTC. The complexity of technology implementation will require executive and leadership teams to consider additional factors beyond the Plan-Do-Study-Act (PDSA) cycle. Copyright © 2022 the Alzheimer's Association.
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Objectives: The objectives are to describe cultural factors pertinent to working with migrant youth, recognize the diversity of ethnicities and languages in this population, and review children's narratives of trauma and resilience. Treatment experiences will be described. Method(s): Significant differences exist between the cultures of Central American countries such as Guatemala, Honduras, and El Salvador, and between subpopulations within Mexico. According to the National Institute of Statistics and Geography (INEGI), in 2015 there were 11.3 million Indigenous inhabitants in Mexico alone with 364 linguistic variations. A team interviewed 76 children, ages 8 to 12 years, at Tapachula (port of entry from Guatemala to Mexico), and Ciudad Juarez (port of entry from Mexico to the United States). In their own voices, children provided narratives of their experiences on the journey. A treatment team in El Paso studied 50 migrant children living in shelters between 2016 and 2019, looking at reasons for referral, diagnoses, medications, psychotherapy, and motivations for leaving the home country. Result(s): In 2019, there were 52,000 children who migrated toward the United States, and more than 30,000 were under the age of 11 years. This number increased 9-fold with the COVID-19 pandemic. Their narratives, incorporating legends and family stories, reflect the types of adversity they faced, including poverty, violence, corruption, environmental calamities, hunger, and death of loved ones. But they also reflect factors of resilience such as family, culture, faith, and will. Treatment of children in shelters revealed many reasons for referral, numerous psychiatric diagnoses, and stressors prior to migration, during the trip and upon arrival. Cultural factors such as commitment to family, community, and faith have been found to mitigate traumatic experiences. For many, finding strength through adversity gives meaning to their struggle. Conclusion(s): Great diversity and significant cultural and linguistic differences exist between countries and groups of Indigenous peoples within Latin America. Migrant children often suffer serial traumas during all phases of the journey. Treatment involves many diagnoses, medications, and psychotherapies. However, cultural factors contribute to resilience in this population. DEI, PTSD, EBP Copyright © 2022
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Objectives: Transforming access to and quality of mental health treatment for children exposed to serious trauma and adversity in North Carolina (NC) began with a pilot program from 2006 to 2009 followed by legislative annual funding in 2013. The aims were to develop and sustain an implementation platform that: 1) focuses on disseminating an array of 5 effective target treatments across NC for children and families exposed to child abuse/trauma;2) promotes sustainability in diverse settings;and 3) utilizes implementation science to assure positive treatment outcomes. Maintaining quality training and coaching of providers serving underserved, vulnerable populations is a critical need during difficult times of Medicaid changes and the COVID-19 syndemic. Method(s): The NC Child Treatment Program (NCCTP) in the Center for Child and Family Health has trained the following number of cohorts of Medicaid-enrolled community mental health providers in trauma-focused CBT (26), parent-child interaction therapy (PCIT, 17), child-parent psychotherapy (8), structured psychotherapy for adolescents responding to chronic stress (SPARCS, 9), and problematic sexualized behavior (1). The NCCTP builds on the National Child Traumatic Stress Network (NCTSN) learning collaborative to create a roster of highly trained providers in each treatment. Strategies used before and during the syndemic include: agency teams are provided intense training and engage in quality improvement (QI) activities focused on use of standardized assessments, achievement of fidelity and clinical outcomes, enhancing organizational capacity, stakeholder outreach, data tracking, and provision of ongoing clinical and implementation supports. Result(s): A total of 888 clinicians have been rostered in the 5 treatment models to date across 100 counties (https://www.ncchildtreatmentprogram.org). The data and lessons learned will be presented for client-level clinical outcomes, training, and service transformation generally and specific to the impact of COVID-19 and racial/other disparities. Conclusion(s): The NCCTP has built capacity to improve the health and well-being of traumatized children across our state by increasing access to and supporting the changing and challenging needs of trained, dedicated, community providers. TRA, P, CC Copyright © 2022
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The outbreak caused by SARS-CoV-2 has taken many lives worldwide. Although vaccination has started, the development of drugs to either alleviate or abolish symptoms of COVID-19 is still necessary. Here, four synthetic peptides were assayed regarding their ability to protect Vero E6 cells from SARS-CoV-2 infection and their toxicity to human cells and zebrafish embryos. All peptides had some ability to protect cells from infection by SARS-CoV-2 with the D614G mutation. Molecular docking predicted the ability of all peptides to interact with and induce conformational alterations in the spike protein containing the D614G mutation. PepKAA was the most effective peptide, by having the highest docking score regarding the spike protein and reducing the SARS-CoV-2 plaque number by 50% (EC50) at a concentration of 0.15 mg mL-1. Additionally, all peptides had no toxicity to three lines of human cells as well as to zebrafish larvae and embryos. Thus, these peptides have potential activity against SARS-CoV-2, making them promising to develop new drugs to inhibit cell infection by SARS-CoV-2.
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BACKGROUND: Autologous stem cell transplantation (ASCT) for multiple myeloma (MM) entails sudden life changes including acute symptom burden, changes in physical function, and shifting caregiver dynamics. Several studies have shown that anxiety, insomnia, and distress rise in the initial weeks following ASCT before slowly recovering. Long-term consequences of these acute exacerbations include persistent quality of life (QOL) impairments (El-Jawahri 2016), post-traumatic stress disorder (Griffith 2020), and the usage of potentially inappropriate medications (PIMs) for symptom management (Banerjee 2021). We have recently completed a pilot study of digital life coaching (DLC), whereby life coaches work with patients via phone calls and text messages to provide longitudinal support, education, and accountability to meet wellbeing-related goals. Our pilot study of 15 patients demonstrated the feasibility of DLC during this period, with bidirectional patient-coach engagement occurring every 5-7 days even during index hospitalizations for ASCT (Banerjee 2021). Based on these positive results, we have now launched a randomized Phase 2 study of DLC versus usual care among patients with MM undergoing ASCT. STUDY DESIGN: Our study is registered at clinicaltrials.gov as NCT04589286. We plan to enroll 60 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. However, neither smartphones nor specific mobile apps are required for study participation. All patients, including those in the control arm, receive brief wellness-related tips with each request for PRO data as outlined below. As shown in the Figure, patients in the DLC arm are paired with a trained life coach beginning at Day -10 before ASCT. Coaches use structured frameworks to assist patients longitudinally with identifying and accomplishing wellbeing-related goals. Specific coaching topics can vary from week to week and are set by each patient. In addition to weekly coach-led phone calls, patients are encouraged to maintain bidirectional communication via phone/text/email as often as desired. Patients in the control arm do not receive access to DLC. Our primary endpoint is the total usage of sedative-class PIMs - including lorazepam, temazepam, zolpidem, and other similar medications - prescribed for anxiety or insomnia during each of 4 four-week study subperiods identified in the Figure. Secondary endpoints include patient-reported outcome (PRO) assessments of QOL (PROMIS Global Health), distress (NCCN Distress Thermometer), and insomnia (PROMIS Sleep Disturbances 4A). PRO assessments are collected exclusively using automated REDCap emails every 1-2 weeks as shown in the Figure. PROGRESS TO DATE: As of the data cutoff (7/31/21), 19 patients have enrolled onto our study and 5 have completed all follow-up. The median age of enrolled patients is 62 (range: 31-77), with 26% of patients aged 70 or older. As shown in our pilot study (Banerjee 2021), PRO collection via automated REDCap emails is feasible. Specifically, of 93 email-based requests for PRO assessments as of the data cutoff, 92 (99%) have been completed. Analyses of PRO assessment responses and PIM usage will be conducted after study completion. DISCUSSION: Improving patient wellbeing during the acute peri-ASCT period is an unmet need in multiple myeloma. Published supportive strategies during this time include music therapy (Bates 2017), acupuncture (Deng 2018), palliative care (El-Jawahri 2017), and programmed hospital room lighting (Valdimarsdottir 2018). DLC may offer unique advantages given its easy accessibility and unified patient-facing interface across hospital/clinic/home transitions. These strengths may be particularly relevant in light of the COVID-19 pandemic, where home-based follow-up after ASCT has become more common. That being said, broadening the accessibility of DLC to include patients with limited English proficiency or patients without personal cell phones are important priorities for fu ure studies. In summary, our randomized Phase 2 study of DLC versus usual care is ongoing. If shown to reduce PIM prescription rates while improving wellbeing-related PRO trajectories longitudinally, DLC may become a standard of care for patients with hematologic malignancies undergoing ASCT. [Formula presented] Disclosures: Banerjee: Pack Health: Research Funding;SparkCures: Consultancy;Sanofi: Consultancy. Knoche: Amgen: Honoraria. Brassil: Abbvie: Research Funding;Astellas: Research Funding;BMS: Research Funding;Daiichi Sankyo: Research Funding;Genentech: Research Funding;GSK: Research Funding;Sanofi: Research Funding;Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Lo: Oncopeptides: Consultancy;EUSA Pharma: Consultancy. Chung: Caelum: Research Funding. Wong: Amgen: Consultancy;Genentech: Research Funding;Fortis: Research Funding;Janssen: Research Funding;GloxoSmithKlein: Research Funding;Dren Biosciences: Consultancy;Caelum: Research Funding;BMS: Research Funding;Sanofi: Membership on an entity's Board of Directors or advisory committees. Wolf: Adaptive Biotechnologies: Consultancy;Teneobio: Consultancy;Sanofi: Consultancy;Amgen: Consultancy. Martin: Oncopeptides: Consultancy;Sanofi: Research Funding;Amgen: Research Funding;Janssen: Research Funding;GlaxoSmithKline: Consultancy. Shah: Bluebird Bio: Research Funding;GSK: Consultancy;Janssen: Research Funding;Indapta Therapeutics: Consultancy;BMS/Celgene: Research Funding;CareDx: Consultancy;CSL Behring: Consultancy;Kite: Consultancy;Nektar: Research Funding;Karyopharm: Consultancy;Amgen: Consultancy;Oncopeptides: Consultancy;Poseida: Research Funding;Precision Biosciences: Research Funding;Sanofi: Consultancy;Sutro Biopharma: Research Funding;Teneobio: Research Funding.
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Background The coronavirus pandemic has resulted in major changes to the way children and their families carry about their daily lives. Public health measures have instructed families to stay at home to avoid spreading the infection and as such parents have faced the added challenge of combing educating and caring for their children with working from home. Recent literature highlights a possible increase in child abuse during the coronavirus (SARS-CoV-2) pandemic. Objectives In view of the concerns raised in the literature, Gloucestershire Paediatric Unscheduled Care Presentations were reviewed to determine local trends and to provide reassurance/ concerns as to any local or developing issues. Managing minor illnesses and reducing accidents is identified as one of the six key high impact areas of the DOH 2018 report which promotes timely interventions to support parents in keeping their children healthy and safe. Injury surveillance is an important component in detecting vulnerable children and their families' and is critical in informing local government policy and public health measures for its prevention. Methods Data was collected on all unscheduled care attendances (in children <16 years) taking place at Gloucestershire NHS foundation Trust's Emergency Department (ED) and Paediatric Assessment Unit (PAU) across each financial year (April - March). These were categorised according to 11 different injury/illness presentations. Any relevant changes during the pandemic (2020 - 2021) were highlighted and investigated further. Each dog bite presentation was explored according to patient demographic and location of bite. Each burn presentation was stratified according to patient demographics and type of burn and fracture numbers were compared across the months of the pandemic according to patient age. Results We have observed a 3-fold proportional increase in dog bites with a significant spike during the first lockdown. There was a disproportional increase in younger children (<5 years) being bitten to the head/face. Our data showed an overall reduction in fractures by 30% in 2020 in comparison to 2019. There was a considerable reduction in older child (>11 years). Younger children have presented in similar numbers thought to be due to an increase in trampoline use. There was an overall increase in burns by 10% in 2020 compared to 2019. Thermal contact burns were the most common burn in all age groups apart from <1year, where scalds from hot drinks predominated. The highest incidence of burns during the summer of 2020 was in the 6-11 years olds which may reflect increased BBQ usage in the summer weather and potentially reduced supervision. Conclusions Gloucestershire ED and PAU has seen upwards trends in burns and dog bites during the pandemic indicative of the burden and stressors placed on households. However, these injuries suggest a lack of supervision and safety in the home and are a safe-guarding concern. Injuries are a preventable cause of morbidity in the paediatric population. This data collection highlights the needs not only in strengthening our public health measures but also in strengthening the services responsible for investigating judiciously safeguarding concerns, detecting vulnerable families, protect children from maltreatment and promoting their overall welfare.
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In November 2019, scholars and practitioners from ten higher education institutions celebrated the launch of the iKudu project. This project, co-funded by Erasmus[superscript +], focuses on capacity development for curriculum transformation through internationalisation and development of Collaborative Online International Learning (COIL) virtual exchange. Detailed plans for 2020 were discussed including a series of site visits and face-to-face training. However, the realities of the COVID-19 pandemic disrupted the plans in ways that could not have been foreseen and new ways of thinking and doing came to the fore. Writing from an insider perspective as project partners, in this paper we draw from appreciative inquiry, using a metaphor of a mosaic as our identity, to first provide the background on the iKudu project before sharing the impact of the pandemic on the project's adapted approach. We then discuss how alongside the focus of iKudu in the delivery of an internationalised and transformed curriculum using COIL, we have, by our very approach as project partners, adopted the principles of COIL exchange. A positive impact of the pandemic was that COIL offered a consciousness raising activity, which we suggest could be used more broadly in order to help academics think about international research practice partnerships, and, as in our situation, how internationalised and decolonised curriculum practices might be approached.
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BACKGROUND: Patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM) face sudden exacerbations of anxiety, insomnia, and other symptoms within the initial weeks following ASCT. Even as these symptoms abate in subsequent months, long-term consequences include post-traumatic stress disorder (Griffith 2020), quality of life (QOL) impairments (El-Jawahri 2016), and chronic reliance on higher-risk medications such as benzodiazepines (Banerjee 2020). These findings are particularly relevant to MM patients given their older age at diagnosis, longer expected post-ASCT survival, and poorer QOL at baseline compared with other cancer patients (Kent 2015). Compared to other integrative interventions in the peri-ASCT setting, life coaching transcends a symptomatic focus while directly addressing the root determinants of impaired QOL. Life coaches work with patients using structured frameworks (Figure 1A) to provide longitudinal support, education, and accountability to meet patient-identified wellness goals. Digital life coaching (DLC) combines the strengths of life coaching with the capabilities of digital health by channeling patient-coach communication through patients' personal phones. Compared to in-person coaching, DLC is location-agnostic and allows patients to work their coaches more conveniently and frequently. DLC is feasible among ASCT survivors (Chen 2016) but has not yet been studied in the active peri-ASCT setting. We are conducting a pilot study of a 16-week DLC subscription to assess its feasibility and effects on QOL during an intensive period spanning from pre-ASCT hospitalization through Day +100 after ASCT. If successful, we plan to then pursue a randomized Phase II study comparing DLC versus usual care in the peri-ASCT setting. METHODS: Our study is registered at clinicaltrials.gov as NCT04432818. We plan to enroll 27 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. Notably, neither ownership of a smartphone nor installation of a specific mobile app is required for patient enrollment. Enrolled patients will receive unlimited access to a certified life coach beginning at Day -5 before ASCT;bidirectional communication is encouraged via phone, text, or email. The life coaches will reach out at least once per week to help patients accomplish self-identified goals such as symptom management, stress reduction, and physical activity. Our study's primary endpoint is ongoing patient engagement, defined as least one patient-initiated outreach to their coach during each of four 4-week study subperiods. Our study's secondary endpoints include patient-reported outcome (PRO) assessments of QOL, distress, and sleep disturbances (to be collected using electronic surveys every 1-2 weeks as shown in Figure 1B). Exploratory endpoints include benzodiazepine usage and rates of electronic/phone communication with patients’ treatment teams. We will analyze endpoints using descriptive methods, including stratification of secondary & exploratory endpoints by DLC usage and specific 4-week study subperiod. PROGRESS TO DATE: Of 18 approached patients as of the data cutoff (8/1/20), 15 (83%) have expressed interest. Reasons for non-enrollment include skepticism about the value of interactions with coaches who do not themselves have MM. Of the 15 patients who have expressed interest in the study, the median age is 65 (range: 50-81) and all but one patient report owning a personal smartphone. All 6 patients with finalized ASCT hospitalization dates have been enrolled and paired with life coaches. Adherence to weekly electronic PRO assessments has been 100% (n = 9 timepoints) to date, consistent with previous studies (Wood 2013). CONCLUSIONS: Our pilot study is ongoing. Our findings to date suggest that certain MM patients are phone-savvy and would be interested in digital health tools, which will continue to gain prominence in light of the ongoing COVID-19 pandemic. Strengths of DLC include it scalability across institutional lines and its ability to reach patients at home in an integrative manner. Results of this study will inform innovative approaches to support the wellbeing of patients with hematologic malignancies, both in the peri-transplantation setting and beyond. [Formula presented] Disclosures: Brassil: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Wong: Janssen: Research Funding;Roche: Research Funding;Amgen: Consultancy;Sanofi: Membership on an entity's Board of Directors or advisory committees;GSK: Research Funding;Bristol Myers Squibb: Research Funding;Fortis: Research Funding. Wolf: Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martin: Seattle Genetics: Research Funding;AMGEN: Research Funding;GSK: Consultancy;Sanofi: Research Funding;Janssen: Research Funding. Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding;GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.
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Covid-19 placed unprecedented stresses on food supply chains. Farms faced bottlenecks for some inputs, notably seasonal labour. Processing was disrupted by labour shortages and shutdowns, especially in meat processing. Air freight, important for fruits and vegetables, was severely disrupted. Demand from restaurants and food service collapsed, while retail food demand surged. Yet supply chains in the developed world have been remarkably resilient to date. Store shelves were replenished as stockpiling behaviour subsided and as supply chain actors expanded operating hours, increased staff, simplified the product range and found alternative suppliers. This rapid recovery was facilitated by policy decisions to reduce border waiting times, to streamline certification procedures and to relax regulations on trade in food. Importantly, policymakers have so far mostly avoided a repeat of the mistakes of the 2007-2008 food price crisis, which was greatly exacerbated by export bans. Some bottlenecks remain, and there may be new supply risks as Covid-19 spreads in Latin America. Overall, the biggest risk to food security is not food availability, but consumers' loss of income. Safety nets and food assistance are essential to avoid an increase in hunger, especially in developing countries.
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Background: Patients with multiple myeloma (MM) experience acute quality of life (QOL) exacerbations following autologous stem cell transplantation (ASCT) that can lead to long-term complications. Life coaching can improve QOL in a structured & personalized manner. We investigated the feasibility of a digital life coaching (DLC) platform, where coaching is accomplished through phone calls and text messages, for patients with MM during ASCT. Methods: Our pilot study (clinicaltrials.gov ID: NCT04432818) enrolled adult patients with MM, English proficiency, and cellphone ownership (smartphone not required). The 16-week DLC program, beginning at Day -5 before ASCT, included unlimited digital access to a certified life coach to help with identifying and accomplishing wellness-related goals. Our primary outcome was ongoing DLC engagement (≥ 1 bidirectional conversation every 4 weeks). Secondary outcomes were ePRO assessments of QOL (PROMIS Global Health), insomnia (PROMIS Sleep Disturbances), and distress (NCCN DT). Electronic patient-reported outcome (ePRO) assessments were delivered via automated REDCap emails every 1-2 weeks. Results: Of 18 screened patients, 15 (83%) enrolled in our study;2 patients dropped out before initiating DLC (including 1 who was unable to connect with her coach between Day -5 and 0). Of 13 remaining patients, median age was 65 (range 50-81) and 23% had an ECOG performance status of 1 (remainder 0). DLC conversations occurred a mean of every 7.6 days (range 3-28) overall and every 6.5 days (range 2.8-14) during the initial 28- day period including high-dose melphalan and hospitalization. 80% of patients maintained ≥ 1 conversation every 4 weeks. Selected ePRO results (mean ± standard error) are shown in the table. Conclusions: Certain MM patients are able to engage digitally with a life coach and complete email-based ePRO assessments during and after ASCT. Limitations of our study include selection bias and the Day -5 start date, which may be too late logistically and symptom-wise (given our ePRO findings suggestive of peak distress pre- ASCT). DLC may play an innovative and scalable role given the emphasis on remotely delivered care during the COVID-19 pandemic. A Phase II randomized study of DLC versus usual care is under way (clinicaltrials.gov ID:.
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Background: New SARS-CoV-2 variants with mutations in the spike glycoprotein have arisen independently at multiple locations and may have functional significance. The combination of mutations in the 501Y.V2 variant first detected in South Africa include the N501Y, K417N, and E484K mutations in the receptor binding domain (RBD) as well as mutations in the N-terminal domain (NTD). Here we address whether the 501Y.V2 variant could escape the neutralizing antibody response elicited by natural infection with earlier variants. Methods: We were the first to outgrow two variants of 501Y.V2 from South Africa, designated 501Y.V2.HV001 and 501Y.V2.HVdF002. We examined the neutralizing effect of convalescent plasma collected from adults hospitalized with COVID-19 using a microneutralization assay with live (authentic) virus. Whole genome sequencing of the infecting virus of the plasma donors confirmed the absence of the spike mutations which characterize 501Y.V2. We infected with 501Y.V2.HV001 and 501Y.V2.HVdF002 and compared plasma neutralization to first wave virus which contained the D614G mutation but no RBD or NTD mutations. Results: We observed a reduction in antibody activity ranging from 6-fold to knockout for the 501Y.V2 (B.1.351) relative to the B.1.1 variant derived from the first wave of the pandemic in South Africa. Conclusion: This observation indicates that 501Y.V2 may escape the neutralizing antibody response elicited by prior natural infection. It raises a concern of potential reduced protection against re-infection and by vaccines designed to target the spike protein of earlier SARS-CoV-2 variants.
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The recent outbreak caused by SARS-CoV-2 continues to threat and take many lives all over the world. The lack of an efficient pharmacological treatments are serious problems to be faced by scientists and medical staffs worldwide. In this work, an in silico approach based on the combination of molecular docking, dynamics simulations, and quantum biochemistry revealed that the synthetic peptides RcAlb-PepI, PepGAT, and PepKAA, strongly interact with the main protease (Mpro) a pivotal protein for SARS-CoV-2 replication. Although not binding to the proteolytic site of SARS-CoV-2 Mpro, RcAlb-PepI, PepGAT, and PepKAA interact with other protein domain and allosterically altered the protease topology. Indeed, such peptide-SARS-CoV-2 Mpro complexes provoked dramatic alterations in the three-dimensional structure of Mpro leading to area and volume shrinkage of the proteolytic site, which could affect the protease activity and thus the virus replication. Based on these findings, it is suggested that RcAlb-PepI, PepGAT, and PepKAA could interfere with SARS-CoV-2 Mpro role in vivo. Also, unlike other antiviral drugs, these peptides have no toxicity to human cells. This pioneering in silico investigation opens up opportunity for further in vivo research on these peptides, towards discovering new drugs and entirely new perspectives to treat COVID-19.Communicated by Ramaswamy H. Sarma.