Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study.

Background: The pandemic of coronavirus disease 2019 (COVID-19) resulted in grave morbidity and mortality worldwide. There is currently no effective drug to cure COVID-19. Based on analyses of available data, we deduced that excessive prostaglandin E2 (PGE2) produced by cyclooxygenase-2 was a key pathological event of COVID-19. Methods: A prospective clinical study was conducted in one hospital for COVID-19 treatment with Celebrex to suppress the excessive PGE2 production. A total of 44 COVID-19 cases were enrolled, 37 cases in the experimental group received Celebrex as adjuvant (full dose: 0.2 g, bid; half dose: 0.2 g, qd) for 7-14 days, and the dosage and duration was adjusted for individuals, while seven cases in the control group received the standard therapy. The clinical outcomes were evaluated by measuring the urine PGE2 levels, lab tests, CT scans, vital signs, and other clinical data. The urine PGE2 levels were measured by mass spectrometry. The study was registered and can be accessed at http://www.chictr.org.cn/showproj.aspx?proj=50474. Results: The concentrations of PGE2 in urine samples of COVID-19 patients were significantly higher than those of PGE2 in urine samples of healthy individuals (mean value: 170 ng/ml vs 18.8 ng/ml, p < 0.01) and positively correlated with the progression of COVID-19. Among those 37 experimental cases, there were 10 cases with age over 60 years (27%, 10/37) and 13 cases (35%, 13/37) with preexisting conditions including cancer, atherosclerosis, and diabetes. Twenty-five cases had full dose, 11 cases with half dose of Celebrex, and one case with ibuprofen. The remission rates in midterm were 100%, 82%, and 57% of the full dose, half dose, and control group, respectively, and the discharged rate was 100% at the endpoint with Celebrex treatment. Celebrex significantly reduced the PGE2 levels and promoted recovery of ordinary and severe COVID-19. Furthermore, more complications, severity, and death rate were widely observed and reported in the COVID-19 group of elders and with comorbidities; however, this phenomenon did not appear in this particular Celebrex adjunctive treatment study. Conclusion: This clinical study indicates that Celebrex adjuvant treatment promotes the recovery of all types of COVID-19 and further reduces the mortality rate of elderly and those with comorbidities.

Associations of clinical characteristics and treatment regimens with the duration of viral RNA shedding in patients with COVID-19.

OBJECTIVE: The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, but the factors influencing viral RNA shedding, which would help inform optimal control strategies, remain unclear. METHODS: The clinical course and viral RNA shedding pattern of 267 consecutive symptomatic COVID-19 patients admitted to the hospital from January 20, 2020 to March 15, 2020 were evaluated retrospectively. RESULTS: The median duration of viral RNA shedding was 12 days (interquartile range 8-16 days) after the onset of illness. Of the 267 patients included in this study, 65.2% had viral RNA clearance within 14 days, 88.8% within 21 days, and 94.4% within 28 days. Older age (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.98-1.00; p = 0.04), time lag from illness onset to hospital admission (HR 0.91, 95% CI 0.88-0.94; p < 0.001), diarrhea (HR 0.59, 95% CI 0.36-0.96; p = 0.036), corticosteroid treatment (HR 0.60, 95% CI 0.39-0.94; p = 0.024), and lopinavir/ritonavir use (HR 0.70, 95% CI 0.52-0.94; p = 0.014) were significantly and independently associated with prolonged viral RNA shedding. CONCLUSIONS: Early detection and timely hospital admission may be warranted for symptomatic COVID-19 patients, especially for older patients and patients with diarrhea. Corticosteroid treatment is associated with prolonged viral RNA shedding and should be used with caution. Lopinavir/ritonavir use may be associated with prolonged viral RNA shedding in non-severe patients; further randomized controlled trials are needed to confirm this finding.

Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial.

BACKGROUND: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. METHODS: Our study (ClinicalTrials.gov: NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FINDINGS: This study successfully enrolled 86 patients with mild/moderate COVID-19, with 34 randomly assigned to receive LPV/r, 35 to arbidol, and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoint, the rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid, was similar between groups (all p > 0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest computed tomography (CT) at days 7 or 14 (all p > 0.05). At day 7, 8 (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group, and 2 (11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical (p = 0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. CONCLUSIONS: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FUNDING: This study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004, and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).