During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific ...information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its post-acute sequelae, the impact of remote learning or periods of quarantine on education and well-being of children, and the contribution of schools to viral circulation in the community. The risk for infections that may occur within schools is related to the incidence of SARS-CoV-2 infections within the local community. Thus, persistent suppression of viral circulation in the community through effective public health measures including vaccination is critical to in-person schooling. Evidence suggests that the likelihood of transmission of SARS-CoV-2 within schools can be minimized if mitigation strategies are rationally combined. This article reviews evidence-based approaches and practices for the continual operation of in-person schooling.
Nonsteroidal anti‐inflammatory drugs (NSAIDs) exert their analgesic and anti‐inflammatory effects by inhibiting the cyclooxygenase (COX)‐1 and/or COX‐2, enzymes involved in biotransformation of ...arachidonic acid into prostanoids. It was previously reported that some NSAIDs alter populations of bacteria in the gut and modify the way that NSAIDs work in the body. Here we directly compared the impact of NSAIDs, selective (celecoxib) and non‐selective (naproxen) for COX‐2 inhibition, on the composition of the gut microbiota in mice. We conducted a longitudinal study in adult male C57BL/6 mice that were fed ad libitum with a regular chow or with a diet containing celecoxib or naproxen for three weeks. Naproxen caused significant COX‐1 inhibition as reflected by a ~70% inhibition of urinary thromboxane metabolite (TxM), an in vivo index of COX‐1 activity, and a 60% inhibition of a COX‐1/COX‐2 urinary prostaglandin (PG)E2 metabolite (PGEM), as measured by LC‐MS/MS. The treatment with celecoxib caused a significant 40% reduction of PGEM, but had no significant effect on TxM. Fecal samples were collected on day zero and day 21, DNA purified, 16S rRNA gene segments amplified using V1V2 primers, and amplicons sequenced. Community structure was compared using UniFrac, which generates distances between all pairs of samples as shared distances on a common phylogenetic tree, allowing assessment of clustering and gradients in community composition. For the unweighted analysis, the control group did not show a significant change over time (p=0.34; Permutational Multivariate Analysis of Variance Using Distance Matrices (‘Adonis’ function in R)), while a strong change was seen for naproxen (p=0.007; Adonis), and a lesser change was seen for celecoxib (p=0.023; Adonis). For the weighted analysis, the control group again did not change (p=0.31; Adonis), naproxen showed a trend (p= 0.089; Adonis), and no change was seen with celecoxib (p= 0.23; Adonis). Analysis of specific lineages showed strong longitudinal changes in some sequence clusters (operational taxonomic units), including Bacteroidetes S24‐7 and Clostridiales both p values < 10−4). Moreover, we observed that naproxen caused gastroenteropathy in mice. The stomach of naproxen‐treated mice showed pyloric mucosal erosion and ulcers while the small intestine showed ulceration, inflammation in the lamina propria and epithelium, and thickening and blunting of the villi. Significantly fewer and less severe lesions were observed in mice treated with celecoxib both in the stomach and in the intestine. Thus, both NSAIDs have an impact on the composition of the gut microbiota, with the stronger effects seen for naproxen versus celecoxib. Effects were most evident in the unweighted analysis, indicating a greater effect on community membership than on their relative proportions. These data are consistent with the hypothesis that microbial dysbiosis is involved in the NSAID‐induced enteropathy that is more common with non‐isoform selective than COX‐2 selective NSAIDs.
Support or Funding Information
This work was supported by NIH grant U54 HL117798 to Garret A. FitzGerald.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related adverse effects, given ...the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine-specific receptor binding domain (RBD) IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here we report a series of divergent omics signals that invites additional hypotheses testing. SIGNIFICANCE STATEMENT: The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on the immune response elicited by repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunizations was profiled by immunophenotypic, proteomic, and metabolomic approaches in a clinical pilot study of small sample size. A SARS-CoV-2 vaccine-specific immune response was evident irrespective of concomitant NSAID consumption. The information gathered may inform the design of a definitive clinical trial.
PDF
