ABSTRACT
BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.
Subject(s)
COVID-19 Drug Treatment , Glucocorticoids/therapeutic use , Hospitalization , Methylprednisolone/therapeutic use , Pharynx/chemistry , RNA, Viral/isolation & purification , Virus Shedding , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , CD3 Complex , CD8-Positive T-Lymphocytes , COVID-19/blood , COVID-19/therapy , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Disease Progression , Early Medical Intervention , Extracorporeal Membrane Oxygenation , Female , Humans , Killer Cells, Natural , Lymphocyte Count , Male , Middle Aged , Oxygen Inhalation Therapy , Patients' Rooms , Pharynx/virology , Proportional Hazards Models , Respiration, Artificial , SARS-CoV-2 , Single-Blind Method , T-Lymphocyte Subsets , T-Lymphocytes , Time Factors , Treatment OutcomeABSTRACT
A green method to synthesize cinnolines by 6π electrocyclic reaction with alkenyl amines and TBN has been developed. TBN plays a dual role both as a nitrogen atom source and an oxidant in this procedure. Relevant mechanism experiments reveal that the reaction proceeds through electrocyclic reaction and with diazo hydroxide as a key intermediate.