Comprehensive nationwide mapping of the deadly SARS-CoV-2 epidemic in nursing homes

In a recent study published in natural aging According to the journal, researchers are using fatality rate (CFR , 209–35%) were analyzed from three SARS-CoV-2 outbreaks in nursing homes in Belgium. -19) after vaccination.

study: Immunovirological and environmental screens reveal actionable risk factors for fatal COVID-19 in post-vaccination nursing home outbreaks. Image Credit: Ground Picture/Shutterstock.com

Background

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Epidemic is Associated with High Mortality in Nursing Home Residents Due to the Effects of Older Age, Frailty, Comorbidities, Polypharmacy, and Weakened Immune Function .

The COVID-19 vaccine has immunized everyone, including the elderly, against the severe effects of COVID-19. However, the factors that increase the risk of death after SARS-CoV-2 infection in COVID-19 vaccinees have not been fully investigated and require further research.

About research

In the current national surveillance study, researchers investigated risk factors and genetic mutations for fatal COVID-19 after vaccination.

Detect SARS-CoV-2 from nasopharyngeal swabs obtained from participants using quantitative polymerase chain reaction (PCR) and perform whole genome sequencing (WGS) to determine the causative SARS-CoV-2 A mutant was identified.

In addition, Phylogenetic analysis was performed to determine the genetic clade. The primary outcome was COVID-19 related mortality, assessed using World Health Organization (WHO) criteria.

Multivariate logistic regression modeling was performed for demographic and clinical profiling of novel coronavirus disease (COVID-19). Mortality predictors were validated using Kaplan-Meier statistics and Cox proportional hazards regression modeling.

In addition, nCounter digital transcriptomics was used to assess the immunovirological profile of nasal mucosal cells to identify potential biomarkers of post-vaccination life-threatening COVID-19 that could be targeted for therapeutic drug development. identified.

In addition, environmental aerosol sampling was also performed. This finding was compared to publicly accessible RNA sequencing (RNA-seq) datasets. Nursing homes provided participants’ medical records for analysis of demographic and clinical data.

All participants had received Pfizer’s BNT162b2 vaccine. In addition, the sensitivity analysis included only PCR-positive and two-dose BNT162b2 vaccinated his BNT162b2 vaccinees.

result

The most predictive models of COVID-19-related mortality included age, male sex, interferon beta 1 (IFNB1), host angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 open reading frame 7a (ORF7a) transcripts, SARS-CoV-2 gamma and mu variants and late onset of infection (SARS-CoV-2 positive by PCR 1 week after SARS-CoV-2 onset).

This finding indicates that IFNB1-targeted therapies may be developed and that treatment should be initiated early in infection to achieve better outcomes.

Each SARS-CoV-2 outbreak is characterized by different causative SARS-CoV-2 variants of concern (VOC), i.e. gamma and delta, and variants of interest (VOI), i.e. Mu , derived from the same introduction event. SARS-CoV-2 was confirmed in aerosol samples from spaces used by residents and staff up to 52 days after initial infection. Similar results were also observed in sensitivity analyses.

Apart from interferon-λ2 (IFNL2) and IFNB1, genes mainly expressed by cells of the innate immune system were elevated, including (i) genes expressed by macrophages and monocytes; [C-X3-C motif chemokine receptor 1 (CX3CR1); tumor necrosis factor superfamily number 15 (TNFSF15); C-type lectin domain containing 6A (CLEC6A); intelectin 1; and leukocyte immunoglobulin-like receptor b5 (LILRB5)](ii) dendritic cells [X-C motif chemokine receptor 1 (XCR1)]and (iii) natural killer cells [Thy-1 cell surface antigen (THY1); cadherin 5; the cluster of differentiation 160 (CD160); beta-1,3-glucuronyltransferase 1 (B3GAT1); the neural cell adhesion molecule 1 (NCAM1); and C-C motif chemokine ligand 3 (CCL3)].

In addition, the B lymphocyte gene is [complement receptor type 2 (CR2), CD19, CD70, CD79A, CD79B, and paired box 5 (PAX5)]regulatory T lymphocytes [prostaglandin E receptor 4 (PTGER4) and forkhead box P3 (FOXP3)]and cytotoxic T lymphocytes (PTGER4 and eomesodermin) were significantly increased in lethal COVID-19.

The results of this study showed that among older vaccinees, lethal novel coronavirus infection (COVID-19) is characterized by exacerbated innate and cell-mediated immune responses. In contrast, fatal novel coronavirus infection (COVID-19) reduced major histocompatibility complex (MHC) class I activity at the functional, epigenomic, and transcriptome levels.

The most downregulated genes represent epithelial and mucosal cells (CD9, polymeric immunoglobulin receptor (PIGR), and mucin-1 (MUC1)), which contribute to SARS-CoV-2-associated epithelial and mucosal damage. showing.

Moreover, antisense SARS-CoV-2 is selectively elevated in lethal cases, indicating enhanced intracellular viral replication. Increased interferon regulatory factor 7 (IRF7) and leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) expression and decreased IRF3 expression were also observed, with a significant increase in regulators. T cells (Treg) and helper 17 cell (Th17) differentiation pathways.

The findings also indicated that interleukin-6 signaling could be a ‘downstream’ therapeutic target for COVID-19 patients who overexpress IFNB1.

Conclusion

Overall, the findings highlight risk factors and genetic mutations that underlie the deadly novel coronavirus disease (COVID-19). The results inform drug development, contribute to risk estimates for lethal COVID-19, help devise tailor-made strategies, and -19) may reduce the health burden.