A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste

ImportanceEarly treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19. ObjectiveTo determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms. DesignFrom June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial. SettingSingle site, academic medical center, outpatient setting in Connecticut, USA. ParticipantsOf 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms. InterventionTreatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo. Main Outcomes and MeasuresThe primary outcome was reduction of 4-day log10 nasopharyngeal swab viral load by 0.5 log10 compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus. ResultsParticipants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo. Conclusions and relevanceThe camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19. Trial registration: Clinicaltrials.gov, NCT04353284 (04/20/20)(https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1) Key PointsO_ST_ABSQuestionC_ST_ABSWill early treatment of COVID-19 with a repurposed medication, camostat mesylate, improve clinical outcomes? FindingsIn this phase 2 randomized, double-blind placebo-controlled clinical trial that included 70 adults with early COVID-19, the oral administration of camostat mesylate treatment within 3 days of diagnosis prevented the loss of smell/taste and reduced the duration of illness. MeaningIn the current COVID-19 pandemic, phase III testing of an inexpensive, repurposed drug for early COVID-19 is warranted.

Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19

BackgroundLimited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease. Research QuestionWhat are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection? Study Design and MethodsWe conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching. ResultsEarly CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28-0.96]; P=0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P=0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to - 0.4]; P=0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P=0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients. InterpretationEarly administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.

Tracking Smell Loss to Identify Healthcare Workers with SARS-CoV-2 Infection

BackgroundHealthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals, like HCW. MethodsWe performed a prospective cohort study, tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, novel behavioral at-home assessment of smell function with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and RT-qPCR testing to identify SARSCoV-2 infection. ResultsSARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. Among the 17 infected HCW, 53% reported smell loss, and were more likely to report smell loss than COVID-negative HCW on both the at-home assessment and the screening questionnaire (P < .01). 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among COVID-positive HCW who reported smell loss (P < .01). ConclusionsIn this prospective study of HCW, self-reported changes in smell using two different measures were predictive of COVID-19 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

The effect of membrane protein NMHC ⅡA on invasion and metastasis of bladder cancer cells / 国际检验医学杂志

Objective Non-muscle myosin heavy chain ⅡA (NMHC ⅡA ) plays a significant role in tumor progression and metastasis .Our prior study showed that the expression of NMHC ⅡA was much higher in human bladder cancer sample than that in adjacent tissue .The increased level of NM HC ⅡA expression was correlated with worse prognosis .However ,the role of NMHC ⅡA is unknown in the invasion and metastasis of bladder cancer .Methods RT-PCR and western blotting were used to examine NMHC ⅡA expression lev-els in normal bladder epithelial cells and bladder cancer cell lines .T he migration and invasion ability of cells was tested by wound healing assay and Transwell invasion assay ,respectively .Results Our study showed that knockdown of NMHC ⅡA inhibited migration and invasion in bladder cancer cell line .Conclusion The study indicated that NM HC ⅡA expression increased the invasion and metastasis ability of bladder cancer cell line in vitro .

[A new approach to accelerate DR image enhancement based on CUDA].

Multiscale pyramid image enhancement algorithm is an usual way to enhance the Digital Radiography (DR) images. However, the process of enhancement takes much of time because of the fine resolution of DR images. A new method of accelerating DR image enhancement based on Compute Unified Device Architecture (CUDA) is presented in this paper. This method completes a large amount of convolution operations in spatial domain involved in the multiscale pyramid image enhancement algorithm by using the Graphic Processing Unit (GPU). The experimental results show that the proposed method is very efficient for accelerating DR image enhancement.