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Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

Eleven fungicides were screened, over three seasons, for efficacy against crucifer downy mildew, Peronospora parasitica, on cabbage seedlings grown in 24-modular polystyrene trays. Starting 10 days after emergence, seedlings were treated with weekly foliar applications of fungicide formulations. Percentage disease severity was assessed weekly using a visual rating scale; the area under the disease progress curve (AUDPC) was calculated for each treatment. A single assessment of final disease severity was an inadequate parameter for comparison of fungicide efficacy. However, AUDPC facilitated clear separation of treatments and provided an integrated measure of disease control. The mixture of cymoxanil and mancozeb was consistently found to be the most effective fungicide against crucifer downy mildew. Other fungicides that provided control included systemics (oxadixyl as a mixture with mancozeb and propamocarb) and protectants (mancozeb, chlorothalonil and cupric hydroxide). All metalaxyl-based fungicides were ineffective.

The way in which fungal populations respond to fungicides used for their control, and hence the risk of disease control failures due to resistance, depends primarily on the type of genetic variability available. Existing evidence indicates that the type of variability differs with the chemical rather than with the organism. With most systemic fungicides and antifungal antibiotics, high resistance can be obtained by mutation of a major gene. The population response is then qualitative and a high or moderate resistance risk is involved, depending on the effect of the major gene on fitness. Mathematical models are available, on the basis of which the establishment of resistance and the loss of effectiveness of a fungicide of this group can be predicted. With a few systemics and some protectants, a practically significant decrease of sensitivity requires the interaction of several genes, each of a rather minor effect: the response is quantitative and the resistance risk is low th moderate. In this situation, the combination of degree of resistance and fitness loss varies greatly and this has not permitted the construction of suitable mathematical models so far. Finally, there is no evidence that pathogenic fungi possess genes for resistance to most protectant fungicides, which involve a low resistance risk, if any. Selection of forms less sensitive to fungicides of this group does not seem to have taken place, in spite of many years of repeated use.