Building Research Capacity in Primary Care Practices That Serve Predominantly Racial and Ethnic Minority Populations

In this commentary, we report on lessons learned over 2 years (2020-2022) from conducting primary care research through a novel alliance of an ACO consisting of independent practices, a health plan, and several academic researchers, with the support of a private foundation. Am J Manag Care. 2023;29(6):In Press _____ Takeaway Points The process of collaborating on research was mutually beneficial for a network of independent practices and a group of academic researchers. * The process benefited the practices by facilitating more precise thinking about quality improvement, motivating the staff, and enabling readiness for health system change. * The process benefited the researchers by illuminating nuances of clinical and organizational workflow and revealing the practices' in-depth understanding of the communities they serve. * If practices have more federally funded opportunities to consistently participate in research, it could help speed greater adoption of payment reform models to promote health equity at the state and national levels. _____ A 2021 National Academies of Sciences, Engineering, and Medicine report, Implementing High-Quality Primary Care, has called out the persistent "neglect of basic primary care research" in the United States.1 A 2020 study by the RAND Corporation found that primary care research represents only 1% of all federally funded projects (including projects funded by the National Institutes of Health, the Agency for Healthcare Research and Quality [AHRQ], and the Veterans Health Administration).2 However, innovation in primary care is central to advancing health care delivery. Leaders in health care innovation recently called for CMS to test a proposal for primary care payment reform in accountable care organizations (ACOs) composed of independent practices (ie, practices not owned by hospitals).3 By innovating in independent practices, these leaders argued that CMS would provide incentives for those practices to stay independent, thereby potentially decreasing the vertical market consolidation that contributes to rising health care costs.3 Yet these same practices may have less experience with the kind of systematic innovation that leads to generalizable insights, because what little funding is available for primary care research is mostly awarded to large academic medical centers.1 AHRQ's practice-based research networks have not fully addressed this gap, as they have struggled to find infrastructure and maintain funding.1 In this commentary, we report on the lessons we learned over 2 years (2020-2022) from conducting primary care research through a novel alliance of an ACO consisting of independent practices, a health plan, and several academic researchers, with the support of a private foundation. [...]ACPNY found that experience with research facilitates innovation and readiness for health system change (lesson 1C).

Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient.

Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patient with hypogammaglobulinemia. Following mAb treatment, the patient did not clear the infection. During viral persistence, SARS-CoV-2 acquired three novel spike mutations. Neutralization and mouse protection analyses demonstrate a complete viral escape from REGN-COV at the expense of ACE-2 binding. Final clearance of the virus occurred upon reduction of the immunosuppressive regimen and total IgG substitution. Serology suggests that the development of highly neutralizing IgM rather than IgG substitution aids clearance. Our findings emphasise that selection pressure by mAbs on SARS-CoV-2 can lead to development of escape variants in immunocompromised patients. Thus, modification of immunosuppressive therapy, if possible, might be preferable to control and clearance of the viral infection.

Veterans' ambulatory care experience during COVID-19: veterans' access to and satisfaction with primary care early in the pandemic.

BACKGROUND: The COVID-19 pandemic caused widespread changes to healthcare, but few studies focus on ambulatory care during the early phase of the pandemic. We characterize veterans' ambulatory care experience, specifically access and satisfaction, early in the pandemic. METHODS: We employed a semi-structured telephone interview to capture quantitative and qualitative data from patients scheduled with a primary care provider between March 1 - June 30, 2020. Forty veterans were randomly identified at a single large urban Veterans Health Administration (VHA) medical center. The interview guide utilized 56 closed and open-ended questions to characterize veterans' perceptions of access to and satisfaction with their primary care experience at VHA and non-VHA primary care sources. We also explored the context of veterans' daily lives during the pandemic. We analyzed quantitative data using descriptive statistics and verbatim quotes using a matrix analysis. RESULTS: Veterans reported completing more appointments (mean 2.6 (SD 2.2)) than scheduled (mean 2.3 (SD 2.2)) mostly due to same-day or urgent visits, with a shift to telephone (mean 2.1 (SD 2.2)) and video (mean 1.5 (SD 0.6)). Among those who reported decreased access to care early in the pandemic (n = 27 (67%)), 15 (56%) cited administrative barriers ("The phone would hang up on me") and 9 (33%) reported a lack of provider availability ("They are not reaching out like they used to"). While most veterans (n = 31 (78%)) were highly satisfied with their VHA care (mean score 8.6 (SD 2.0 on a 0-10 scale), 9 (23%) reported a decrease in satisfaction since the pandemic. The six (15%) veterans who utilized non-VHA providers during the period of interest reported, on average, higher satisfaction ratings (mean 9.5 (SD 1.2)). Many veterans reported psychosocial effects such as the worsening of mental health (n = 6 (15%)), anxiety concerning the virus (n = 12 (30%)), and social isolation (n = 8 (20%), "I stay inside and away from people"). CONCLUSIONS: While the number of encounters reported suggest adequate access and satisfaction, the comments regarding barriers to care suggest that enhanced approaches may be warranted to improve and sustain veteran perceptions of adequate access to and satisfaction with primary care during times of crisis.

Impaired immune response drives age-dependent severity of COVID-19.

Severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe COVID-19 and show that the age-dependent disease severity is caused by the disruption of a timely and well-coordinated innate and adaptive immune response due to impaired interferon (IFN) immunity. Aggravated disease in aged mice was characterized by a diminished IFN-γ response and excessive virus replication. Accordingly, adult IFN-γ receptor-deficient mice phenocopied the age-related disease severity, and supplementation of IFN-γ reversed the increased disease susceptibility of aged mice. Further, we show that therapeutic treatment with IFN-λ in adults and a combinatorial treatment with IFN-γ and IFN-λ in aged Ifnar1-/- mice was highly efficient in protecting against severe disease. Our findings provide an explanation for the age-dependent disease severity and clarify the nonredundant antiviral functions of type I, II, and III IFNs during SARS-CoV-2 infection in an age-dependent manner. Our data suggest that highly vulnerable individuals could benefit from immunotherapy combining IFN-γ and IFN-λ.

Antibody escape and global spread of SARS-CoV-2 lineage A.27.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

Case Series: Convalescent Plasma Therapy for Patients with COVID-19 and Primary Antibody Deficiency.

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.

Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants.

The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient's escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.

Implementation of Video Visits During COVID-19: Lessons Learned From a Primary Care Practice in New York City.

Background: During the height of the coronavirus (COVID-19) pandemic, there was an unprecedented demand for "virtual visits," or ambulatory visits conducted via video interface, in order to decrease the risk of transmission. Objective: To describe the implementation and evaluation of a video visit program at a large, academic primary care practice in New York, NY, the epicenter of the COVID-19 pandemic. Design and participants: We included consecutive adults (age > 18) scheduled for video visits from March 16, 2020 to April 17, 2020 for COVID-19 and non-COVID-19 related complaints. Intervention: New processes were established to prepare the practice and patients for video visits. Video visits were conducted by attendings, residents, and nurse practitioners. Main measures: Guided by the RE-AIM Framework, we evaluated the Reach, Effectiveness, Adoption, and Implementation of video visits. Key results: In the 4 weeks prior to the study period, 12 video visits were completed. During the 5-weeks study period, we completed a total of 1,030 video visits for 817 unique patients. Of the video visits completed, 42% were for COVID-19 related symptoms, and the remainder were for other acute or chronic conditions. Video visits were completed more often among younger adults, women, and those with commercial insurance, compared to those who completed in-person visits pre-COVID (all p < 0.0001). Patients who completed video visits reported high satisfaction (mean 4.6 on a 5-point scale [SD: 0.97]); 13.3% reported technical challenges during video visits. Conclusions: Video visits are feasible for the delivery of primary care for patients during the COVID-19 pandemic.

Experiences of Home Health Care Workers in New York City During the Coronavirus Disease 2019 Pandemic: A Qualitative Analysis.

Importance: Home health care workers care for community-dwelling adults and play an important role in supporting patients with confirmed and suspected coronavirus disease 2019 (COVID-19) who remain at home. These workers are mostly middle-aged women and racial/ethnic minorities who typically earn low wages. Despite being integral to patient care, these workers are often neglected by the medical community and society at large; thus, developing a health care system capable of addressing the COVID-19 crisis and future pandemics requires a better understanding of the experiences of home health care workers. Objective: To understand the experiences of home health care workers caring for patients in New York City during the COVID-19 pandemic. Design, Setting, and Participants: From March to April 2020, a qualitative study with 1-to-1 semistructured interviews of 33 home health care workers in New York City was conducted in partnership with the 1199SEIU Home Care Industry Education Fund, a benefit fund of the 1199 Service Employees International Union United Healthcare Workers East, the largest health care union in the US. Purposeful sampling was used to identify and recruit home health care workers. Main Outcomes and Measures: Audio-recorded interviews were professionally transcribed and analyzed using grounded theory. Major themes and subthemes were identified. Results: In total, 33 home health care workers employed by 24 unique home care agencies across the 5 boroughs of New York City participated. Participants had a mean (SD) age of 47.6 (14.0) years, 32 (97%) were women, 21 (64%) were Black participants, and 6 (18%) were Hispanic participants. Five major themes emerged: home health care workers (1) were on the front lines of the COVID-19 pandemic but felt invisible; (2) reported a heightened risk for virus transmission; (3) received varying amounts of information, supplies, and training from their home care agencies; (4) relied on nonagency alternatives for support, including information and supplies; and (5) were forced to make difficult trade-offs in their work and personal lives. Conclusions and Relevance: In this qualitative analysis, home health care workers reported providing frontline essential care, often at personal risk, during the COVID-19 pandemic. They experienced challenges that exacerbated the inequities they face as a marginalized workforce. Interventions and policies to better support these frontline health care professionals are urgently needed.