Learning competing risks across multiple hospitals: one-shot distributed algorithms.

OBJECTIVES: To characterize the complex interplay between multiple clinical conditions in a time-to-event analysis framework using data from multiple hospitals, we developed two novel one-shot distributed algorithms for competing risk models (ODACoR). By applying our algorithms to the EHR data from eight national children's hospitals, we quantified the impacts of a wide range of risk factors on the risk of post-acute sequelae of SARS-COV-2 (PASC) among children and adolescents. MATERIALS AND METHODS: Our ODACoR algorithms are effectively executed due to their devised simplicity and communication efficiency. We evaluated our algorithms via extensive simulation studies as applications to quantification of the impacts of risk factors for PASC among children and adolescents using data from eight children's hospitals including the Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, Children's Hospital of Colorado covering over 6.5 million pediatric patients. The accuracy of the estimation was assessed by comparing the results from our ODACoR algorithms with the estimators derived from the meta-analysis and the pooled data. RESULTS: The meta-analysis estimator showed a high relative bias (∼40%) when the clinical condition is relatively rare (∼0.5%), whereas ODACoR algorithms exhibited a substantially lower relative bias (∼0.2%). The estimated effects from our ODACoR algorithms were identical on par with the estimates from the pooled data, suggesting the high reliability of our federated learning algorithms. In contrast, the meta-analysis estimate failed to identify risk factors such as age, gender, chronic conditions history, and obesity, compared to the pooled data. DISCUSSION: Our proposed ODACoR algorithms are communication-efficient, highly accurate, and suitable to characterize the complex interplay between multiple clinical conditions. CONCLUSION: Our study demonstrates that our ODACoR algorithms are communication-efficient and can be widely applicable for analyzing multiple clinical conditions in a time-to-event analysis framework.

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-ß and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Characterisation of internal tremors and vibration symptoms.

OBJECTIVES: To describe the experiences of patients who have postacute sequelae SARS-CoV-2 infection with internal vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from individuals belonging to its Facebook group with a history of COVID-19 suffering from vibrations and tremors. SETTING AND DESIGN: A narrative analysis was performed on 140 emails and 450 social media comments from 140 individuals collected as a response to a call to >180 000 individuals participating in Survivor Corps between 15 July and 27 July 2021. We used common coding techniques and the constant comparative method for qualitative data synthesis and categorising emails. Coded data were entered into NVivo V.12 to identify recurrent themes, theme connections and supporting quotations. Comments were analysed using Word Clouds, generated with R V.4.0.3 using quanteda, wordcloud and tm packages. MAIN OUTCOME MEASURES: Patient-reported long COVID symptom themes and domains related to internal tremors and vibration. RESULTS: The respondents' emails represented 22 themes and 7 domains pertaining to their experience with internal tremor and vibrations. These domains were as follows: (1) symptom experience, description and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment and (7) impact on individuals' lives and livelihood. There were 22 themes in total, each corresponding to one of the broader domains. Among the responses, many described symptoms that varied in location, timing and triggers, occurred soon after their COVID-19 infection, and were markedly debilitating. There were often frustrating experiences with the healthcare system. CONCLUSIONS: This study describes key themes and experiences among a group of people reporting long COVID and having a prolonged and debilitating symptom complex that prominently features internal tremors and vibrations.