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Antibodies to SARS-CoV-2 are essential for protection or reduction in severity of subsequent disease. We studied antibody responses to spike protein receptor-binding domain (S1-RBD) and nucleocapsid (N) in a population-based sample of COVID-19 cases in Costa Rica. As part of the RESPIRA study, we selected an age-stratified random sample of PCR-confirmed COVID-19 cases diagnosed from March 2020 to July 2021. Antibodies were determined with multiplex serology in 794 unvaccinated subjects diagnosed 3 days to 17 months before recruitment to investigate immune response to natural infection. In addition, neutralizing antibodies were determined in 136 randomly selected participants. We estimated antibody positivity and GMTs by time since diagnosis and explored determinants using multivariate regression. Most participants tested 15-29 days after PCR diagnosis were seropositive for N (90%) and S1-RBD antibodies (96%) and had the highest GMTs for both antibodies. Only 42% of subjects tested one year after infection were seropositive for N antibodies, compared to 97% for S1-RBD. GMTs for neutralizing antibodies peaked 15-89 days after infection and declined but remained positive for 95% of subjects thereafter. In multivariate models, antibodies were significantly higher among men and increased with age and severity of the clinical presentation. The correlation of multiplex and neutralizing antibodies was high (0.72 [95% CI = 0.63-0.79]) and stronger among women. A robust immune response against N and S1-RBD is elicited by COVID-19 a few days after infection. While S1-RBD antibodies are present after > 1 year, N antibodies decline significantly. Antibody levels are higher in men and increase with age and severity of disease. The different immune response patterns by sex warrant further investigation. RESPIRA Study ClinicalTrials.gov ID: NCT04537338 (3 September 2020).

Decreased susceptibilities of Plasmodium falciparum towards the endoperoxide antimalarial artemisinin are linked to mutations of residue C580 of Kelch13, which is the homologue of the redox sensor Keap1 in vertebrates. Here, we addressed whether mutations alter the artemisinin susceptibility by modifying the redox properties of Kelch13 or by compromising its native fold or abundance. Using selection-linked integration and the glmS ribozyme, efficient down-regulation of Kelch13 resulted in ring-stage survival rates around 40%. While the loss of a potential disulfide bond between residues C580 and C532 had no effect on the artemisinin suceptibility, the thiol group of C473 could not be replaced. We also established a protocol for the production of recombinant Kelch13. In contrast to cysteine-to-serine replacements, common field mutations resulted in misfolded and insoluble protein. In summary, not the redox properties but impaired folding of Kelch13, resulting in a decreased Kelch13 abundance, is the central parameter for mutant selection. Competing Interest Statement The authors have declared no competing interest.

Abstract Background The incidence of colorectal carcinoma (CRC) in patients ≤50 (early-onset-CRC, EOCRC) years is increasing. Given their different phase of life, younger individuals may face specific challenges in terms of body image, professional life, and psychosocial support. However, tailored programs for EOCRC patients are lacking in Germany. JUMP-START, a prospective study at the National Center for Tumor Diseases (NCT) Heidelberg in collaboration with the AIO (Arbeitsgemeinschaft internistische Onkologie) and the foundation for young adults with cancer in Germany aims to identify the specific needs of EOCRC patients and improve multiprofessional care. Materials and Methods Semi-structured interviews were conducted until content saturation, based on an interview guide focused on challenges related to diagnosis, utilization of support programs, and unmet needs. The interview guide was developed in an expert and patient panelist discussion. Qualitative analysis was performed with MAXQDA, using a content structuring qualitative content analysis according to Kuckartz. Results Forty-three EOCRC patients were screened, and 14 participants were interviewed at NCT Heidelberg between October 2023 and January 2024. Three main themes emerged: (1) The impact of CRC diagnosis at an early age on psychological and physical health, daily routine, and future perspectives, (2) Experiences with care service access and utility, and (3) Expectations for a multiprofessional care at a dedicated EOCRC center. Conclusions EOCRC patients highlighted various age-group-specific challenges related to diagnosis and treatment. Tailored multiprofessional programs may optimize care for EOCRC patients. Graphical Abstract Graphical Abstract