USE OF CHLOROQUINE IN ASYMPTOMATIC ELDERLY COVID19 PATIENTS, A PLACEBO OR RATHER A SOURCE OF COMPLICATIONS: A CASE REPORT

elderly subjects without comorbidities.

He had digestive side effects which were controlled with symptomatic treatment. Later, he presented neurological signs on the fifth day of treatment, first he presented dizziness with incoherent speech then he had a partial right hemicorps deficit, the Glasgow score has been calculated at 13. Cerebral CT scan showed hyper density within the upper longitudinal sinus suggestive of venous thrombosis (figure 4); it has also viewed left external capsular ischemic lacunar lesions. Electrocardiogram showed a sinus rhythm without any abnormalities (figure 5). Laboratory test showed hyponatremia at 123mEq/l, elevated blood cell count and a high C reactive protein level. A urinary tract infection was identified with a negative culture. The patient was treated with low molecular weight heparin LMWH and ceftriaxone 2g per day. A second control injection scan was carried out after 24 hours and confirmed persistent venous thrombosis without any worsening of images. No endovascular intervention has been performed. After 48H, following rehydration, the Glasgow score improved to 15 and the body deficit has regressed. The biological parameters also improved as resumed in table 1. PCR covid19 test being negative twice at the 9 th and 10 th day of treatment respectively, patient was deemed suitable for discharge and commenced Rivaroxaban 20 mg daily for three months and salicylic acid 75 mg per day. Evolution was favourable.

Discussion:-
CVT is a rare cause of stroke which nearly represents 0, 5 percent of all stroke cases (1,5,6,8). Most series reported predominance in young people (7,8,23,24). Clinical symptoms are highly variable and are summarized in table 2; the most common are headache and alteration of mental status (1).
Risk factors are listed in table 3. In our case, dehydration and urine infection seemed to be the anticipating factors.
The superior sagittal sinus is the more frequently reported location (1). Deep CVT have usually a poor prognosis leading to death or severe neurologic sequalae (5,6,9).
In a pooled analysis, cerebrovascular disease was found to be associated with a _2.5-fold increased disease severity in patients with COVID-19 (15). Authors hypothesized that like all six beta coronaviruses already identified; SARS cov2 is also neurotropic (12). The physiopathological mechanisms would associate direct brain invasion by the virus or a mediated penetration via the angiotensin converting enzyme 2 ''ACE2'' ( 12,13 ), Which would trigger a massive neuro inflammatory cascade more or less associated with damage caused by systemic inflammation and hypoxia. Simultaneous immune injury has been also suggested as an additive factor in the neuropathology. Wu and al have identified coagulation abnormalities that may increase the risk of neurological complications in patients infected with covid19 (19). A few cases of CVT have been reported in covid19 positive patients' series. Asadipooya and Simani reported 1 case, as did Li and al. Daniel D Cavalcanti reported three fatal CVT in young previously healthy people. UK and Spanish authors reported younger cases of CVT with good prognosis (2).
As for imaging diagnosis, we used in our case a non-contrast computed tomography (NCCT) which was suggestive for CVT, followed by a contrast enhanced CT (CECT) that confirmed CVT.
Despite CT is widely used as the first line neuroimaging test, it usually remains insensitive depending on the time of its realization and the presence or absence of venous anatomical variations. CECT may show the classic ''empty delta'' sign. CT venography CTV may strengthen the diagnostic arsenal in late-onset cases. However, magnetic resonance imaging MRI is more sensitive for the detection of CVT than CT at each stage of thrombosis (1). Thus, it's recommended as the initial neuroimaging test by the ACC (8).
Concerning the treatment, our patient was initially treated by LMWH according to the guidelines (8), and then switched to continue oral anticoagulation by rivaroxaban for three months.
Neither the ACC (2011 guidelines), nor the European stroke organization endorsed by the European Academy of neurology in 2017 recommended the use of direct oral anticoagulants DOA in CVT regarding the lack of evidence (8,14). Nevertheless, several publications, even for small cohorts, have shown that the use of DOA was safe and that there was no inferiority or excess risk of hemorrhage compared to warfarin in this indication (14). In our case, after almost three months of follow up, our patient was well without any hemorrhagic complication.

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Was the introduction of chloroquine justified?
Referring to the literature, it has been found that people of all ages are generally susceptible to the new virus covid19, but the elderly and patients with multiple chronic diseases have the highest rates of severe illness and mortality (18).
Chloroquine (CQ) was first shown to effectively suppress Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in in vitro assay ( 21,22 ), and has been subsequently suggested to be efficacious in slowing the deterioration of pneumonia, improving lung imaging results, decreasing viral load, and thus shorten disease duration.
Hydroxychloroquine HXQ was preferred over chloroquine as adjunctive emergency treatment since the first release of this guidance (13th of March, 2020), taking also into account that therapy would be likely required mostly in older patients and/or in case of severe disease. The initial clinical study that suggested a shorter viral shedding in hydroxychloroquine-treated patients (compared to controls) had however several major limitations (small sample size, non-homogeneous compared groups, and rather late HXQ administration) making it a very weak evidence base. Recovery trial has stopped enrolling patients on the 5th of June after finding no beneficial effect of hydroxychloroquine (9600 mg over 10 days) in patients hospitalized with COVID-19 (4).Moreover, based on the encouraging '' in vitro ''results, clinical trials of chloroquine were conducted in hospitals in Beijing and Guangdong province, and the results showed that chloroquine phosphate may be effective in treating covid19 (22). Xuelin Sunand al published a paper on March that guides using of chloroquine phosphate in elderly covid19 positive patients, they recommended for patients with a bodyweight of more than 50 kg, chloroquine phosphate 500 mg orally, bid, for 7 days, for those with a bodyweight of 50 kg or less, 500 mg, bid, on the 1 st and 2nd days, and 500 mg daily on the 3rd to 7th days.
Cheng Cui and al proposed a physiologically based pharmacokinetic model(PBPK) to optimize the use of CQ in covid19 patients (17). They thus recommended 250mg bid during 5 days for geriatrics (65 to 98 years old), cirrhotic, patients whose glomerular filtration ratio GFR is less than 30ml/mn or between 30 and 60, pregnant women and children. Our 90 years old patient had a GFR 38 ml/mn, with no comorbidies. Despite lack of symptoms at admission, He has an estimated 20 per cent pulmonary parenchymal damage which has increased to 40 percent ( figure 3) under chloroquine therapy 500 mg bid during 10 days, associated with azithromycin 500mg the 1 st day followed by 250mg from 2 nd to 7 th day.
Instead of radiological improvement, the patient experienced hypoglycemia and digestive side effects with nausea, abdominal cramps, vomiting, diarrhea and anorexia contributing to dehydration, severe hyponatremia, which most likely contributed to the CVT. Table 1:-Evolution of biologic parameters during hospitalization.

Conclusion:-
It might be wiser not to use chloroquine in asymptomatic, previously healthy, elderly Covid 19 patients with mild or moderate pneumonia and to restrict therapeutic intervention to thromboembolic prophylaxis in high-risk subjects, with close monitoring. Viral load study could be a selection criterion, as chloroquine could be proposed in patients with a very high viral load especially in the presence of co-morbidities.