Family Caregiver experience of caring COVID-19 patients admitted in COVID hospital of B. P. Koirala Institute of Health Sciences, Nepal (preprint)

Background: Informal caregivers played a substantial role in caring the COVID-19 patients during hospitalization in Nepal. This study attempted to understand the family caregiver’s experiences while attending their relatives in a COVID-19 Hospital of Nepal. Methods: A descriptive phenomenological approach was used to understand the caregiver’s experience of attending and supporting their relatives admitted to the COVID-19 hospital of B. P. Koirala Institute of Health Sciences.13 caregivers of COVID-19 positive were purposively selected from January to March 2022. A face-to-face interview was conducted in a caregiver residential facility using the interview schedule developed by the department for the purpose of data collection after obtaining ethical clearance from the Institutional review committee of B. Koirala Institute of Health Sciences (B.P.K.I.H.S). Data were audio recorded and manually analyzed. Results: 13 caregivers (6 male and 7 female) participated in the study. The result was summarized under the five domains: Challenges encountered Changes in Physical and Mental Health, Changes in roles and responsibilities, Positive experiences, and Things that could make Caregiving tasks easier. The major challenges were a financial burden, communication problems, stigmatized attitude, Insecurity and vulnerability, substandard accommodation facility, and visitor restriction policy. A wide range of negative emotions, as well as unmet physical health needs, was reported. Changes in family and occupational roles as a result of the caregiving process cause additional stress to the caregivers. Despite all, they tried to positively cope and adapt to the difficult situation and acknowledged the effort of health personnel and other significant members of the family. Provision of essential medical and basic services/facilities within the hospital, reconstruction of open accommodation facility, maintaining a proper channel of communication, and visitation allowance were suggested as care facilitators to make caregiving tasks easier. Conclusions: This study highlights the role of caregivers is very crucial during the time of health crisis.

Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients (preprint)

Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection related disease and mortality. To understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 COVID 19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine-specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cell was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.

ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury (preprint)

Unlike many mammalian vital organs, the lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, which primarily targets epithelial cells in the airways and alveoli. Quiescent lung-resident epithelial progenitors proliferate, migrate, and differentiate following lung injury, participating in two distinct reparative pathways: functionally beneficial regeneration and dysplastic tissue remodeling. Intrapulmonary airway-resident basal-like p63 + progenitors are one such progenitor cell type that migrates from the airways to form ectopic bronchiolar tissue in the alveoli, generating honeycomb-like cysts that fail to resolve after injury. Though this phenomenon is now well described, the cell-autonomous signals that drive dysplastic alveolar remodeling remain uncertain, a question made especially salient by observations that p63 + progenitors also expand dramatically upon diffuse alveolar damage in humans resulting from a variety of insults including SARS-CoV-2-induced ARDS. Here we show that the master basal cell transcription factor ΔNp63 is required for the immense migratory capacity of intrapulmonary p63 + progenitors and consequently for the dysplastic repair pathway manifest by these cells. We further demonstrate that ΔNp63 restricts the fate plasticity of intrapulmonary p63 + progenitors by regulating their epigenetic landscape, and that loss of ΔNp63 alters the deposition of active and repressive histone modifications at key differentiation gene loci, allowing ΔNp63 KO progenitors to proceed towards airway or alveolar differentiation depending on their surrounding environment. These insights into the regulatory mechanisms of dysplastic repair and intrapulmonary p63 + progenitor fate choice highlight potential therapeutic targets to promote more effective alveolar regeneration following severe lung injuries.