INVESTIGATION OF RECOVERY FOLLOWING SARS-COV-2 INFECTION: CLINICAL DISEASE, PATHOGENESIS, AND IMMUNE DURABILITY
Bibliographic record
Abstract
SARS-CoV-2 continues to present unique challenges to global health as a proportion of \npeople recovering from COVID-19 deal with prolonged symptoms and the threat of re-infection \nwith antigenically divergent variants. Throughout my three project objectives, I address the \nunknowns of SARS-CoV-2 recovery utilizing both preclinical and clinical studies of COVID-19 \nrecovery addressing post-acute sequelae of COVID-19 (PASC) and immune durability. In \nObjective 1, Syrian hamsters were infected with SARS-CoV-2 and sampled over one-year to \nassess viral load, pathology, antibody levels, and gene expression profiles by RNA sequencing. \nLong-term analysis of infected hamsters indicated persistent SARS-CoV-2 RNA and protein \nmonths after acute infection, prolonged lung damage, sustained complement activation pathways\nand neutrophils present in the lungs, along with dysregulation of serotonin secretion genes in the \nbrain of previously infected hamsters. In Objective 2, I investigated the clinical characteristics \nand systemic immune profiles of individuals recovering from COVID-19 using a cross-sectional \nstudy in humans. Participants were recruited across five groups including those with and without \nPASC from the Saskatoon area to provide information on their COVID-19 experience and \nprovide a blood sample. Antibody responses were assessed by ELISA and viral neutralization \nassays, and cytokine profiles were determined by Ella SimplePlex Immunoassay. Individuals \nwith PASC had decreased levels of neutralizing antibodies toward SARS-CoV-2 and Omicron \nBA.1. Sex analysis indicated that female PASC participants had sustained inflammatory \ncytokines such as GM-CSF following COVID-19 while males had decreasing concentrations \nover time. Lastly, in Objective 3, I utilized homologous variant re-inoculations in C57Bl6/J mice \nusing the Alpha variant of SARS-CoV-2 to understand the durability of long-term immunity at \nchallenge. Mice were protected from re-infection at both day 21 and 56 post-primary infection. \nHowever, by day 84 mice were susceptible to re-infection indicating decayed protective immune \nresponses. Overall, key attributes of recovery after SARS-CoV-2 infection were identified \nincluding viral antigen persistence, prolonged lung damage, dysregulated immune responses, sex \ndifferences, and decaying protection from re-infection. Taken together, these findings may be \napplied to PASC diagnostic development, treatment evaluation, as well as public health policies \nand vaccine regimens for vulnerable groups with higher susceptibility to PASC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".