| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
125-196 |
DRI_Background |
denotes |
Covid-19 is a new coronavirus disease first described in December 2019. |
| T2 |
197-254 |
DRI_Challenge |
denotes |
This respiratory illness is severe and potentially fatal. |
| T3 |
255-331 |
DRI_Outcome |
denotes |
Severe cases make up to 15%, lethality ranges between 1.5 and more than 10%. |
| T4 |
332-432 |
DRI_Challenge |
denotes |
What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. |
| T5 |
433-537 |
DRI_Background |
denotes |
During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. |
| T6 |
538-784 |
DRI_Background |
denotes |
The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. |
| T7 |
785-955 |
DRI_Approach |
denotes |
Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 h after infection. |
| T8 |
956-1141 |
DRI_Background |
denotes |
In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. |
| T9 |
1142-1357 |
DRI_Outcome |
denotes |
In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. |
| T10 |
1358-1454 |
DRI_Approach |
denotes |
Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. |
| T11 |
1455-1599 |
DRI_Challenge |
denotes |
From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. |
| T12 |
1600-1918 |
DRI_Background |
denotes |
Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. |
| T13 |
1919-2115 |
DRI_Approach |
denotes |
Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. |
| T14 |
2116-2237 |
DRI_Background |
denotes |
By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. |
| T15 |
2238-2446 |
DRI_Approach |
denotes |
This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. |
| T16 |
2447-2552 |
DRI_Background |
denotes |
Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. |
| T17 |
2553-2613 |
DRI_Outcome |
denotes |
Inhalation was well tolerated without relevant side effects. |
