Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Clinical characteristics, treatment, and prognosis of 74 2019 novel coronavirus disease patients in Hefei: A single-center retrospective study.

ABSTRACT: Since December 2019, pneumonia caused by a novel coronavirus (SARS-CoV-2), namely 2019 novel coronavirus disease (COVID-19), has rapidly spread from Wuhan city to other cities across China. The present study was designed to describe the epidemiology, clinical characteristics, treatment, and prognosis of 74 hospitalized patients with COVID-19.Clinical data of 74 COVID-19 patients were collected to analyze the epidemiological, demographic, laboratory, radiological, and treatment data. Thirty-two patients were followed up and tested for the presence of the viral nucleic acid and by pulmonary computed tomography (CT) scan at 7 and 14 days after they were discharged.Among all COVID-19 patients, the median incubation period for patients and the median period from symptom onset to admission was all 6 days; the median length of hospitalization was 13 days. Fever symptoms were presented in 83.78% of the patients, and the second most common symptom was cough (74.32%), followed by fatigue and expectoration (27.03%). Inflammatory indicators, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of the intensive care unit (ICU) patients were significantly higher than that of the non-ICU patients (P < .05). However, 50.00% of the ICU patients had their the ratio of T helper cells to cytotoxic T cells (CD4/CD8) ratio lower than 1.1, whose proportion is much higher than that in non-ICU patients (P < .01).Compared with patients in Wuhan, COVID-19 patients in Anhui Province seemed to have milder symptoms of infection, suggesting that there may be some regional differences in the transmission of SARS-CoV-2 between different cities.

THE THERAPEUTIC EVALUATION AND MECHANISM ON TREATING BRONCHIAL HYPER-RESPONSIVENESS COUGH BY ZIYINQINGRE PRESCRIPTION.

OBJECTIVE: Discussing the effects of Ziyinqingre prescription on the level of airway resistance (Rrs), airway response threshold (Dmin), airway conductance (sGrs) and the level of inflammatory cytokines interleukin-4 (IL-4) and interferon-γ (IFN-γ) of the bronchial hyper-responsiveness (BHR) cough patients. METHOD: 84 subjects diagnosed as BHR were randomly divided into 42 Chinese Traditional medicine group and 42 control group. The Chinese Traditional Medicine group received Ziyinqingre prescription twice a day and the control group received 10mg Montelukast Sodium tablets once a day for two weeks. Observe the clinical symptoms improvement and the changes of the level of the Rrs, Dmin, sGrs and IL-4, IFN-γ. RESULTS: After receiving the medicine, the symptoms of the Chinese medicine group were obviously alleviated, the outcome was more satisfied than that of the control group. Compared with the control group, the level of Dmin increased and sGrs level decreased more obviously (P<0.05); the level of IL-4 decreased and IFN^level increased more obviously in the Chinese medicine group (P<0.05). CONCLUSION: Ziyinqingre prescription can not only improve BHR patients' symptoms, but reduce the level of bronchial responsiveness, which proved a better curative effect of Chinese medicine. The mechanism is probably due to relieving the airway inflammation by keeping the balance between Th1 and Th2 cells.

[Effect of Ziyinqingsang decoction on interleukin-4 and -5 levels in peripheral blood mononuclear cells of children in acute stage of cough variant asthma].

OBJECTIVE: To observe the effect of Ziyinqingsang decoction on the levels of interleukin-4 (IL-4) and IL-5 in the peripheral blood mononuclear cells (PBMCs) in children with cough variant asthma (CVA) in the acute stage. METHODS: Thirty children with CVA in the acute stage were given Ziyinqingsang decoction for 2 weeks. The IL-4 and IL-5 levels in the PBMCs were determined using ELISA before and after the treatment, and the changes of the clinical symptoms were observed. RESULTS: The levels of IL-4 and IL-5 in the PBMCs was 89.69∓13.82 ng/l and 12.17∓0.43 ng/ml before the treatment, which were significantly reduced to 72.18∓14.89 ng/l and 5.81∓0.31 ng/ml after the treatment (P<0.05). The symptoms including coughing, pharyngodynia, and pharyngo-itch were all improved obviously (P<0.05). CONCLUSION: Ziyinqingsang decoction ameliorates the symptoms of CVA in the acute stage probably by decreasing the levels of IL-4 and IL-5 in the PBMCs of the children.

[Effect of modified shegan mahuang decoction on cytokines in children patients with cough and variant asthma].

OBJECTIVE: To study the influence of modified Shegan Mahuang Decoction (SGMH) on cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-13 in children suffered from cough and variant asthma (C&VA). METHODS: One hundred and fifty-four children with C&VA were randomly assigned to two groups: 79 in the treatment group were medicated orally with SGMH one dose per day taking in twice; 75 in the control group were medicated with Montelukast once a day in dose of 4 mg for children aged from 2 to 5 years and 5 mg for those from 6 to 14 years, the medication for all was given 4 weeks. Serum contents of cytokines, including TNF-alpha, IL-10 and IL-13, in patients were measured before and after treatment. Besides, serum contents of these cytokines in 45 healthy children were measured for control. RESULTS: Serum levels of TNF-alpha and IL-3 in the treatment group were 2510 +/- 1500 ng/L and 60.76 +/- 23.67 ng/L, and in the control group, 2890 +/- 1410 ng/L and 61.56 +/- 20.37 ng/L, respectively, all were significantly higher than those of healthy (709 +/- 280 ng/L and 39.49 +/- 3.09 ng/L, P < 0.01); but level of IL-10 was significant lower in the two patient groups than that in control (1546 +/- 1434 ng/L and 1823 +/- 1314 ng/L vs 7123 +/- q2641 ng/L, P < 0.01). After treatment, the levels of TNF-alpha and IL-13 decreased and IL-10 increased significantly in the treatment group, and showed significant different to those in the control group respectively (960 +/- 420 ng/L, 43.67 +/- 12.37 ng/L and 6834 +/- 2216 ng/L vs 2610 +/- 1220 ng/L, 50.56 +/-19.56 ng/L and 2529 +/- 1223 ng/L, P < 0.01). Clinical efficacy between groups also showed that the total effective rate in the treatment group was significantly better (86.07% vs. 42.67%, P < 0.01). CONCLUSION: SGMH can regulate the serum levels of TNF-alpha, IL-10 and IL-13, and shows evident clinical effect in treating children's C&VA.

[Influence of Minkeqing oral liquid on IL-6, IL-8, ET-1, TX-B2 in blood and to observe bronchoalveolar lavage fluid of the rat with inhalating ovalbumin].

OBJECTIVE: To observe the effect on infantile allergic cough with Minkeqing oral liquid (Minkeqing) and to study its cell molecular biologic mechanism. METHOD: The rat model was induced by inhalating ovalbumin; then the effects of Minkeqing on IL-6, IL-8, ET-1, TX-B2 in the blood and the bronchoalveolar lavage fluid (BALF) of the animal model were observed. RESULT: Minkeqing could reduce the levels of IL-6,IL-8,ET-1,Tx-B2 in the blood and BALF of the animal model. CONCLUSION: Minkeqing has the significant function of inhibiting the release of inflammatory mediums.

Pharmacokinetic and pharmacodynamic profiles of the antitussive principles of Glycyrrhizae radix (licorice), a main component of the Kampo preparation Bakumondo-to (Mai-men-dong-tang).

We examined the pharmacokinetic and pharmacodynamic properties of liquiritin apioside, a main antitussive component of Glycyrrhizae radix (licorice), with regard to its antitussive effect in guinea pigs. The peak plasma concentration of the unchanged compound was observed 15 min after the administration of liquiritin apiosaide. The plasma concentration then gradually decreased and was almost undetectable 4 h after administration. Liquiritigenin, a des-glycoside of liquiritin apioside, appeared in the plasma 2 h after the administration of liquiritin apioside and remained for more than 6 h after administration. The plasma concentration of unchanged liquiritigenin was observed 15 min after administration and then gradually increased for more than 6 h after administration. When the antitussive effects of liquiritin apioside, liquiritin and liquiritigenin, at respective doses of 30 mg/kg, p.o., were examined 1 h after administration, liquiritin apioside and liquiritigenin caused a significant reduction in the number of capsaicin-induced coughs. However, at the same dose, liquiritin had no significant effect on the number of capsaicin-induced coughs. On the other hand, when the antitussive effects of liquiritin apioside, liquiritin and liquiritigenin, at doses of 30 mg/kg, p.o., were examined 4 h after administration, each caused a more than 40% reduction in the number of capsaicin-induced coughs. The present results suggest that G. radix (licorice) may produce a persistent antitussive effect, and that liquiritin apioside plays an important role in the earlier phase, while liquiritigenin, which is a metabolite of liquiritin apioside and liquiritin, plays an important role in the late phase.

Iron supplementation inhibits cough associated with ACE inhibitors.

Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.