Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors

Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group,but the results were not statistically significant(adjusted hazard ratio 0.71,95%CI 0.50-1.00;P=0.0508).Conclusion:Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies.Throughout the decay phase,from the acute phase to the half-year follow-up visit,short-term and low-dose corticosteroids did not significantly affect humoral responses,except for accelerating the waning of short-lived antibodies.

Use of angiotensin-converting enzyme inhibitors and angiotensin Ⅱ receptor blockers in context of COVID-19 outbreak:a retrospective analysis

The possible effects of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin Ⅱ receptor blockers(ARBs)on COVID-19 disease severity have generated considerable debate.We performed a single-center,retrospective analysis of hospitalized adult COVID-19 patients in Wuhan,China,who had definite clinical outcome(dead or discharged)by February 15,2020.Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes.The medical records from 702 patients were screened.Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication,40 patients were receiving ACEI/ARB as part of their regimen,and 61 patients were on antihypertensive medication other than ACEI/ARB.We observed no statistically significant differences in percentages of in-hospital mortality(28%vs.34%,P=0.46),ICU admission(20%vs.28%,P=0.37)or invasive mechanical ventilation(18%vs.26%,P=0.31)between patients with or without ACEI/ARB treatment.Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes.Our findings confirm the lack of an association between chronic receipt of reninangiotensin system antagonists and severe outcomes of COVID-19.Patients should continue previous antihypertensive therapy until further evidence is available.

Design and synthesis of 2-aminobenzimidazoles as potential BACE1 inhibitors

Fragment-based drug discovery （FBDD） has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad （Asp228 and Asp32） of D-site amyloid precursor protein cleaving enzyme 1 （BACE1）. A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 pM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/$2＇ pockets well.

Efficient normalization for quantitative evaluation of the driving behavior using a gated auto-encoder

Driving behavior normalization is important for a fair evaluation of the driving style.The longitudinal control of a vehicle is investigated in this study.The normalization task can be considered as mapping of the driving behavior in a different environment to the uniform condition.Unlike the model-based approach as in previous work,where a necessary driver model is employed to conduct the driving cycle test,the approach we propose directly normalizes the driving behavior using an autoencoder(AE)when following a standard speed profile.To ensure a positive correlation between the vehicle speed and driving behavior,a gate constraint is imposed in between the encoder and decoder to form a gated AE(gAE).This approach is model-free and efficient.The proposed approach is tested for consistency with the model-based approach and for its applications to quantitative evaluation of the driving behavior and fuel consumption analysis.Simulations are conducted to verify the effectiveness of the proposed scheme.