Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion
In this study, we focus on how CQ inhibits autophagy and directly compare its effects to those of BafA1. We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle.
Furthermore, CQ induces an autophagy-independent severe disorganization of the Golgi and endo-lysosomal systems, which might contribute to the fusion impairment. Strikingly, HCQ-treated mice also show a Golgi disorganization in kidney and intestinal tissues.
Altogether, our data reveal that CQ and HCQ are not bona fide surrogates for other types of late stage lysosomal inhibitors for in vivo experiments. Moreover, the multiple cellular alterations caused by CQ and HCQ call for caution when interpreting results obtained by blocking autophagy with this drug. (R1)
CQ can cause involuntary movements, myoclonus
On the 5th hospital day, his COVID-19 showed improvement with regression of infiltrates on chest radiography and decreasing ferritin (1,642.99 ng/mL, NV = 21.81–274.66 ng/mL).
However, the patient was noted to have involuntary movements that prompted referral to the movement disorders service. On examination, bilateral, asynchronous, irregular myoclonus of the upper limbs was noted (Supplementary Video 1 in the online-only Data Supplement).
He was also bedbound due to moderate to severe myoclonus of the bilateral proximal lower limbs, most prominent during attempts to stand from a sitting position (Supplementary Video 2 in the online-only Data Supplement). (R2)
Video 1
Video 2
Case 1
A boy aged 12 presented with persistent protrusion of the tongue with fasciculation, excessive salivation, and difficulty in swallowing. The previous day he had been given an injection of chloroquine phosphate together with two tablets by mouth and had repeated the dose of tablets the next morning. (R3)
Case 2
A girl aged 16 was admitted to hospital one evening by the nurses. She had abdominal pain, nausea, fever, and poor appetite, and was given two tablets of chloroquine and two tablets of paracetamol. The next morning she was seen by the doctor, who diagnosed urinary tract infection.
She was then given a triple dose of sulphonamide tablets and an injection of dipyrone. Later that afternoon she developed protrusion of the tongue, the neck was involuntarily pulled to one side, and her speech was slurred. These symptoms abated during the next 48 hours, though all treatment apart from chloroquine was continued. (R3)
Case 3
A civil servant aged 26 presented with paraesthesia of the right side of the face and neck. There was no previous history of fits. The previous day he had had a fever and had taken two tablets of chloroquine and two tablets of aspirin. On examination the neck was drawn to the right and there was fasciculation of the facial muscles. His blood pressure was 140/100 mm Hg and a diagnosis of stroke was considered. He was admitted to hospital and developed protrusion of the tongue that evening. (R3)
Case 4
A housewife aged 19 presented with typical symptoms of malaria -fever, headache, aches and pains, and palpitation. Chloroquine phosphate 4 ml intramuscularly, chloroquine tablets, two daily for four days, and aspirin two tablets three times daily were prescribed. Two days later she presented with twitching of the left side of the face and difficulty in keeping her eyes open. She could not open her mouth fully. (R3)
Case 5
A young nurse aged 23 had malaria and was given chloroquine phosphate 4 ml intramuscularly and two tablets of chloroquine. After three hours she complained of involuntary turning of the neck to one side. Later protrusion of the tongue and excessive salivation developed. She had used chloroquine in the past without any such reaction. She was known to be a timid person and the possibility of hysteria was raised. (R3)
Headache, visual disturbances, gastrointestinal upset, and pruritus
Four cases of involuntary movements induced by amodiaquine were recently reported.' Chloroquine is similar to amodiaquine and both are used effectively in the treatment of malaria. Chloroquine has many well-recognised, minor side effects including transient headache, visual disturbances, gastrointestinal upset, and pruritus. T wave changes in the electrocardiogram (without evidence of cardiovascular damage), visual symptoms, and mild skin eruptions3 have been noted in patients given large doses of chloroquine over a period. Long-term chloroquine treatment also frequently causes retinopathy (R3)