Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis.

OBJECTIVE: To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC). DESIGN: Prospective, observational cohort study of subjects with PASC. SETTING: Academic tertiary centre from five clinical referral sources. PARTICIPANTS: Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19. EXPOSURES: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR. OUTCOMES MEASURES: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load. RESULTS: We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6-11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1-6)) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically active PASC subphenotypes: a high burden constitutional symptoms (21.9%), a persistent loss/change of smell and taste (20.6%) and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001) as well as referral source for enrolment. Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. CONCLUSIONS: We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.

Novel Pharmacological Treatment Options of Steroid-Refractory Graft-versus-Host Disease.

Background: Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously. Objectives: This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. Study Design. The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies. Results: While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide. Conclusion: While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.

Physical and psychological effects of cadaveric dissection on undergraduate medical students.

OBJECTIVE: To assess the physical and psychological effects of human cadaveric dissection on undergraduate medical students and to observe the role of counseling in this regard. METHODS: The quasi-experimental study was carried out on undergraduate medical students of Foundation University Medical College, Rawalpindi, Pakistan. The batch of 2010 was designated as the control group, while the experimental group comprised the batch of 2011. The 2010 batch began dissection without prior counseling, whereas the batch of 2011 was provided counseling ahead of dissection. At the end of the academic year, both the batches were assessed for the effects of dissection, and preference for it. This was done through a pre-designed questionnaire. The results were analysed using SPSS 10. RESULTS: The control group had 84 (48.55%) students, while there were 89 (51.44%) students in the experimental group. Overall, there were 138 (79.76%) girls and 35 (20.23%) boys. The students experienced multiple physical symptoms, but, 140 (80.9%) of them agreed that the symptoms disappeared spontaneously. Multiple psychological problems were also encountered. The percentage of students experiencing these problems was more in the control group as compared to the experimental group (n=56; 63% vs n=41; 49%). The difference was not statistically significant (p <0.062). Despite all the problems, 153 (88.4%) of the students wanted to continue dissections, and 80.9% preferred cadaveric specimen rather than plastic models for studying anatomy. In the experimental group 82 (97.6%) students agreed that the initial preparatory discussions were helpful in overcoming their psychological problems. CONCLUSION: Multiple physical and psychological problems are associated with cadaveric dissection, but the latter can be significantly decreased with effective counseling. In spite of all problems, the students still prefer dissection over plastic models and other audio-visual aids.