Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute as well. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30-70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordinal and ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39-3.46) for increasing severities of the disease, although the OR decreased to 1.77 (95% CI, 1.09, 2.87) after adjustment for age, sex, sampling site and interval between blood sampling and diagnosis. Conclusions Measures of individual exposures to immunotoxic PFASs included PFBA that accumulates in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of more severe course of CIVID-19. Given the low background exposure levels in this study, the role of PFAS exposure in COVID-19 needs to be ascertained in populations with elevated exposures.</p

Author Correction:Vitamin D status and severity of COVID-19 (Scientific Reports, (2022), 12, 1, (19823), 10.1038/s41598-022-21513-9)

Sanne Grundvald Boelt was omitted from the author list in the original version of this Article. The Author Contributions section now reads: “A.A. contributed to the conception and idea of the work. N.M.N., A.S.C., L.B. and A.A. contributed to the design of the study. N.M.N., A.S.C., L.B. S.G.B contributed to the acquisition of data. N.M.N., A.H., L.B., S.G.B and T.G.J. contributed to the analyses of the data. All authors contributed to the interpretation of the data and the results in the manuscript. N.M.N. drafted the manuscript, made Fig. 1, T.G.J. made Fig. 2. All the authors revised the manuscript critically and has approved the final version.” The original Article has been corrected.</p

Vitamin D status and severity of COVID-19

We explored the association between COVID-19 severity and vitamin D status using information from Danish nation-wide health registers, the COVID-19 surveillance database and stored blood samples from the national biobank. 25-hydroxyvitamin D (25(OH)D) was measured using tandem mass spectroscopy. The association between 25(OH)D levels and COVID-19 severity, classified hierarchical as non-hospitalized, hospitalized but not admitted to an intensive care unit (ICU), admitted to ICU, and death, was evaluated by proportional odds ratios (POR) assuming proportionality between the four degrees of severity. Among 447 adults tested SARS-CoV-2 positive in the spring of 2020, low levels of 25(OH)D were associated with a higher risk of severe COVID-19. Thus, odds of experiencing more severe COVID-19 among individuals with insufficient (25 to &lt; 50 nmol/L) and sufficient (≥ 50 nmol/L) 25(OH)D levels were approximately 50% of that among individuals with deficient levels (&lt; 25 nmol/L) (POR = 0.49 (95% CI 0.25–0.94), POR = 0.51 (95% CI 0.27–0.96), respectively). Dividing sufficient vitamin D levels into 50 to &lt; 75 nmol/L and ≥ 75 nmol/L revealed no additional beneficial effect of higher 25(OH)D levels. In this observational study, low levels of 25(OH)D were associated with a higher risk of severe COVID-19. A possible therapeutic role of vitamin D should be evaluated in well-designed interventional studies.</p

Optimization and evaluation of a live virus SARS-CoV-2 neutralization assay

Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These assays are instrumental in defining vaccine and therapeutic antibody potency, immune evasion by viral variants, and post-infection immunity. Here we describe the development, optimization and evaluation of a live virus microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates are pre-incubated with serial diluted antibody and added to Vero E6 cells. Replicating virus is quantitated by enzyme-linked immunosorbent assay (ELISA) targeting the SARS-CoV-2 nucleocapsid protein and the standardized 50% virus inhibition titer calculated. We evaluated critical test parameters that include virus titration, assay linearity, number of cells, viral dose, incubation period post-inoculation, and normalization methods. Virus titration at 96 hours was determined optimal to account for different growth kinetics of clinical isolates. Nucleocapsid protein levels directly correlated with virus inoculum, with the strongest correlation at 24 hours post-inoculation. Variance was minimized by infecting a cell monolayer, rather than a cell suspension. Neutralization titers modestly decreased with increasing numbers of Vero E6 cells and virus amount. Application of two different normalization models effectively reduced the intermediate precision coefficient of variance to <16.5%. The SARS-CoV-2 microneutralization assay described and evaluated here is based on the influenza virus microneutralization assay described by WHO, and are proposed as a standard assay for comparing neutralization investigations

Neutralisation of the SARS-CoV-2 Delta sub-lineage AY.4.2 and B.1.617.2 + E484K by BNT162b2 mRNA vaccine-elicited sera

AbstractSeveral factors may account for the recent increased spread of the SARS-CoV-2 Delta sublineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. Here, we evaluate the sensitivity of AY.4.2 to neutralisation by sera from Pfizer/BioNTech (BNT162b2) vaccine recipients. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sublineages. In contrast, the more rare B.1.617.2+E484K variant showed a significant &gt;4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.</jats:p

Neutralisation of the SARS-CoV-2 Delta variant sub-lineages AY.4.2 and B.1.617.2 with the mutation E484K by Comirnaty (BNT162b2 mRNA) vaccine-elicited sera, Denmark, 1 to 26 November 2021

Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sub-lineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. We evaluated the sensitivity of AY.4.2 to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients in Denmark in November 2021. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sub-lineages. Conversely, the less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.</jats:p

Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute to an association with disease severity. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30–70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an unadjusted odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39–3.46) for increasing severities of the disease. Among those hospitalized, the fully adjusted OR for getting into intensive care or expiring was 5.18 (1.29, 20.72) when based on plasma samples obtained at the time of diagnosis or up to one week before. Conclusions Measures of individual exposures to immunotoxic PFASs included short-chain PFBA known to accumulate in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of a more severe course of COVID-19. Given the low background exposure levels in this study, the role of exposure to PFASs in COVID-19 needs to be ascertained in populations with elevated exposures. </jats:sec