Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries (preprint)

Prior evidence has suggested the multisystem symptomatic manifestations of post-acute COVID-19 condition (PCC). Here we conducted a network cluster analysis of 24 WHO proposed symptoms to identify potential latent subclasses of PCC. Individuals with a positive test of or diagnosed with SARS-CoV-2 after 09/2020 and with at least one symptom within ≥ 90 to 365 days following infection were included. Sub-analyses were conducted among people with ≥ 3 different symptoms. Summary characteristics were provided for each cluster. All analyses were conducted separately in 9 databases from 7 countries, including data from primary care, hospitals, national health claims and national health registries, allowing to validate clusters across the different healthcare settings. 787,078 persons with PCC were included. Single-symptom clusters were common across all databases, particularly for joint pain, anxiety, depression and allergy. Complex clusters included anxiety-depression and abdominal-gastrointestinal symptoms. Substantial heterogeneity within and between PCC clusters was seen across healthcare settings. Current definitions of PCC should be critically reviewed to reflect this variety in clinical presentation.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study. (preprint)

Purpose/ Background Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. Methods A prospective and randomized clinical study was conducted in 60 patients during two periods, October 2018 - September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using Cardiopulmonary Exercise Test (CPET) and the 6-minute walk test (6MWT) were evaluated. Results Prehabilitation reduce postoperative complications (17.4% vs 33.3%, p=0.22) and hospital stay (5.74 vs 6.67 days, p=0.30). 6MWT showed a significant improvement in prehabilitation group (+78.9 meters). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+ 68.9 meters vs - 27.2 meters, p=0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+ 0.79 METs vs - 0.84 METs, p=0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p<0.001)). Conclusion Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. Strong correlation was observed between CET and 6MWT, which allows validation 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patiens when other more specific and expensive tests are not available. Registration number Registered in ClinicalTrials.gov in August 2018 with registration number NCT03618329. Initial results published in Supportive Care in Cancer:Effect of home‐based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID‐19 pandemic. DOI: 10.1007/s00520-021-06343-1

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: An application of the RE-AIM/PRISM extension for sustainability and health equity (preprint)

Background: The COVID-19 pandemic necessitated rapid changes in the delivery of care across public primary care settings in rural Guatemala in 2020. In response, a hypertension program implemented within the public primary care system required multiple adaptations, providing an illustrative example of dynamic implementation amidst changing context in an under-resourced setting. This study describes the evolvability of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care) during the COVID-19 pandemic and discusses implications for health equity and sustainability. Methods: This convergent mixed methods analysis assessed implementation across five Ministry of Health districts during the initial phase of the pandemic. Qualitative and quantitative data were collected, analyzed, and integrated, informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation Maintenance) Framework’s extension for sustainability, and its contextual enhancement, PRISM (Pragmatic, Robust, Implementation and Sustainability Model). For RE-AIM, we focused on the “Implementation” domain, operationalizing it qualitatively as continued delivery and adaptations to the EBI and implementation strategy, and quantitatively as the extent of delivery over time. We conducted 18 in-depth interviews with health providers / administrators (n=8) and study staff (n=10) and performed a matrix-based thematic-analysis. Qualitative results informed the selection of quantitative implementation summarized as behavior over time graphs. Quantitative implementation data and illustrative quotes are presented as joint displays. Results: In relation to implementation, several organic adaptations hindered delivery, threatened sustainability, and may have exacerbated health inequities. Planned adaptations enhanced program delivery and may have supported improved equity and sustainability. Salient PRISM factors that influenced implementation included “Organizational perspective of the EBI”, “Fit” and “Implementation and sustainability infrastructure”. Facilitators to continued delivery included the perception that the EBI is beneficial, program champions, and healthcare team organization. Barriers included the perception that the EBI is complicated, competition with other primary care activities, and temporary suspension of services due to COVID-19. Conclusions: Multi-level contextual changes led to numerous adaptations of the EBI and implementation strategy. Systems thinking approaches may shed light on how a program’s sustainability and its equitable delivery are influenced by adaptations over time in response to dynamic, multi-level contextual factors. Trial registration: NCT03504124

The WHO-TDR Dissemination and Implementation Massive Open Online Course (MOOC): Evaluation and Lessons Learned from Eight Low-and Middle-Income Countries. (preprint)

Introduction Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, we report on the feasibility of this MOOC, which was implemented during the SARS COVID-19 pandemic from April- November 2020.Methods Participants completed pre- and post- training questionnaires to assess self-reported D&I competencies, general research skills, and research mentor access and quality. D&I competencies were measured by use of a scale developed for a US-based training program, with change in competency scores assessed by paired t test. We used univariate statistics to analyze the data for all other outcomes.Results Of the 247 participants enrolled, 32 (13%) completed all MOOC components. D&I competency scores suggest improvement for those who had complete pre- and post-assessments. Trainee’s average score on the full competency scale improved 1.45 points (0-5 scale) from pre- to post-test; all four subscales also showed evidence of improvements. There were small but not significant increases in competencies for grant writing, proposal/ manuscript writing and presentations from pre- to post-test assessment. 40% of trainees reported access to a research mentor and 12% reported access to a D&I specific mentor. Participants reported barriers (e.g., unstable internet access and challenges due to COVID-19) and facilitators (e.g., topical interests, collaboration with colleagues) to completing the MOOC.ConclusionsAlthough COVID-19 affected program usage and completion, the MOOC was feasible and effective, showing that among LMIC participants completing the course, there was improvement in D&I competency scores. Recommendations for future D&I trainings in LMICs should include 1) adding more topic specific modules (i.e., NCD research, general research skills) for scalability; 2) fostering more collaboration with participants across LMICs; and 3) establishing partnerships with D&I mentors for course participants. 

PIMS-TS Innate Cell Signature and Immunophenotype, Description and Comparison with a Cohort of Healthy Children, Kawasaki Disease, Severe Viral and Bacterial Infections. (preprint)

A new clinical syndrome named as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) has been described. This new disease is a main cause of hospital and pediatric intensive care unit (PICU). We made a prospective-retrospective observational study to describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS (from March 2020 to September 2020). They were compared with previous cohorts of healthy controls and children admitted to PICU because bacterial infection, viral infection and Kawasaki disease (KD). Two hundred and forty seven children were studied: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 KD and 13 PIMS-TS. PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p =0,000). Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression (p = 0,000). Also, CD11a and CD11b were highly expressed compare to other severe viral or bacterial infections (p = 0,000). In conclusion, we describe and compare for the first time the innate cellular response of children with PIMS-TS with other severe forms of viral or bacterial infection and KD. These data should be further studied and may facilitate the diagnosis and management of these patients. 

The impact of population mobility on COVID-19 incidence and socioeconomic disparities at the sub-city level in 314 Latin American cities (preprint)

Background Little is known about the impact of changes in mobility at the sub-city level on subsequent COVID-19 incidence or the contribution of mobility to socioeconomic disparities in COVID-19 incidence. Methods We compiled aggregated mobile phone location data, COVID-19 confirmed cases, and features of the urban and social environments to analyze linkages between population mobility, COVID-19 incidence, and educational attainment at the sub-city level among cities with >100,000 inhabitants in Argentina, Brazil, Colombia, Guatemala, and Mexico from March to August 2020. We used mixed effects negative binomial regression to examine longitudinal associations between changes in weekly mobility (lags 1-6 weeks) and subsequent COVID-19 incidence at the sub-city level, adjusting for urban environmental factors. Findings Among 1,031 sub-cities representing 314 cities in five Latin American countries, 10% higher weekly mobility was associated with 8.5% (95% CI 7.4% to 9.5%) higher weekly COVID-19 incidence the following week. This association gradually declined as the lag between mobility and COVID-19 incidence increased and was not different from the null at a six-week lag. We found evidence that suggests differences in mobility reductions are a driver of socioeconomic disparities in COVID-19 incidence. Interpretation Lower population movement within a sub-city is associated with lower risk of subsequent COVID-19 incidence among residents of that sub-city. Implementing policies that reduce population mobility at the sub-city level may be an impactful COVID-19 mitigation strategy that takes equity into consideration and reduces economic and social disruption at the city or regional level. Funding Wellcome Trust

Description and comparison of PIMS-TS innate cell signature and immunophenotype with a cohort of healthy children, severe viral and bacterial infections and Kawasaki Disease (preprint)

A new clinical syndrome associated to SARS-CoV-2 has been described in children. It has been named as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). This new disease is a main cause of hospital and pediatric intensive care unit (PICU). In this work we describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS. Also, we compare it with healthy controls and children admitted to PICU because bacterial infection, viral infection and Kawasaki disease. We made a prospective-retrospective observational study in a tertiary pediatric hospital. Children admitted to PICU because of PIMS-TS from March 2020 to September 2020 were consecutively included. They were compare with previous cohorts from our center. A total of 247 children were included: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 Kawasaki disease and 13 PIMS-TS. PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p =0,000). At the same time, we describe a differential expression of CD64, CD11a and CD11b. Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression compared to all groups (p = 0,000). Also, proteins involved in leukocyte tissue migration, like CD11a and CD11b were highly expressed compare to other severe viral or bacterial infections (p = 0,000). In PIMS-TS this increased CD11a expression could be a sign of the activation and trafficking of these leukocytes. These findings are congruent with an inflammatory process and the trend of these cells to leave the bloodstream. In conclusion, we compare for the first time the innate cellular response of children with PIMS-TS with other severe forms of viral or bacterial infection and Kawasaki disease. Our findings define a differential cell innate signature. These data should be further studied and may facilitate the diagnosis and management of these patients.