Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.
Methods
We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.
Results
Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.
Conclusions
Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.
Psychological sense of community within psychosocial rehabilitation clubhouse programs was examined using concept mapping with 18 members and 18 staff from 10 programs. Members identified four concepts: Recovery, social connections, membership, and tasks and roles. Members described hope and healing as aspects of recovery. Members' views on sense of community focused on the rehabilitation and social nature of the program. Staff also identified four concepts: Affiliation and support for members, shared experiences, clubhouse organization, and task and roles. The staff concept of clubhouse organization, which incorporated the ideas of leadership and organization of physical space and the concept of task and roles, was based on ideas of shared responsibility and clubhouse procedures. Staffs' views on sense of community strongly reflected their formal training in clubhouse principles. The relation of these concepts to McMillan and Chavis' theoretical framework for sense of community is discussed and recommendations for practice provided.
A novel curriculum such as the QuIPS pathway provides an important opportunity to develop and test new assessment tools for curricula in systems-based practice and practice-based learning and improvement. The authors also hope that by bringing together local QI and patient safety experts and stakeholders during the curricular development process, they have laid the groundwork for the creation of a more pervasive curriculum that will reach all MCW students in the future. The model may be generalizable to other U.S. medical schools with scholarly pathways as well.
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