Amantadine in the prevention of SARS-CoV-2
An observational study has shown that amantadine is an effective drug in the treatment of symptoms caused by SARS-CoV-2 .
It has been observed that patients with Parkinson’s disease who were prescribed with amantadine as part of their treatment and were infected with the coronavirus did not develop the symptomatology caused by COVID-19 [11, 12].
In recent literature, there are few clinical cases related to the hypothetic role as preventive use of amantadine.
Aranda et al. studied a total of 15 patients of different ages who presented symptoms compatible with COVID-19. The average age of the patients studied was 48 ± 16 years. Ten of them were women and the rest were men. Four percent were suffering from hypertension and three percent from type 2 diabetes mellitus. Only one person reported cardiac disease. The main symptoms they reported were fever, dyspnea, headache, nausea and nasal congestion. Ten of the patients lost their sense of taste and smell. The treatment consisted of 100 mg of amantadine, one tablet in the morning and one in the evening, for a period of 14 days. Most of them were prescribed 500 mg of azithromycin, 200 mg of celecoxib and 500 mg of aspirin for a period of 6 days. Three patients had to receive nebulizations with ipratropium bromide/salbutamol, 3 times a day for 5 days. Two of the patients were administered oxygen (4Lpm) because their oxygen saturation was below 90%. All patients recovered with amantadine treatment and none had to go to the hospital for mechanical ventilation. Family members who were in contact with them were prescribed amantadine 100 mg twice daily as a prophylactic measure .
Cortés presents a 75-year-old woman with Parkinson’s disease diagnosed 17 years previously is presented. Under medical supervision by her neurologist, the patient was receiving opicapone, 50 mg/day, pramipexole, 2.1 mg/day, levodopa, 1000 mg/day, benserazide, 250 mg/day and amantadine, 100 mg/day and for hyperthyroidism levothyroxine, 25 mg/day. Five years ago, the patient was diagnosed with gastric cancer treated surgically (Billroth II gastrectomy) and with chemotherapy before and after surgery, currently without recurrence of her cancer. After 7 days with a fever oscillating between 37.5 and 38.8 °C together with an unusual sporadic cough, mild diarrhea and fatigue, the patient’s husband was diagnosed by PCR with COVID-19 which led to his hospital admission with a diagnosis of SARS-CoV-2 infection with bilateral pneumonia. Despite drug treatment and the administration of high-flow oxygen with a Monaghan mask, he died 5 days after admission. The female patient and wife of the above, did not present any symptoms of coronavirus infection: neither fever, nor cough, nor diarrhea, nor anosmia, despite having lived with her husband in a very intimate way, sharing a bed and exposed to the aerosols produced by her husband’s persistent cough. Once her husband was admitted to hospital, she was isolated at the home of her daughter, who, after the death of her father, assumed the role of main caregiver. Both her daughter and her daughter’s husband tested negative for COVID-19 by PCR .
Rejdak et al. studied 22 patients (10 with multiple sclerosis, 5 with Parkinson’s disease and 7 with cognitive impairment) positive for SARS-CoV-2 and were receiving treatment with amantadine or memantine (100 mg q.d and 10 mg b.i.d, respectively) for at least 3 months prior to exposure to infection. All patients were tested after reported person-to-person contact with SARS-CoV-2 infected subjects and confirmed viral infection with SARS-CoV-2 PCR testing of upper and lower respiratory tract specimens. All of them were in quarantine for two weeks from the exposure documented, and none developed clinical manifestations of infectious disease. They also reported no significant change in neurological status in the course of primary nervous system disease .
Aranda et al. conducted a clinical study of a 57-year-old person who presented cold symptoms and body pain, with glucose levels of 200 mg/dL, and was prescribed paracetamol (500 mg every 6 h) and naproxen (550 mg daily for 5 days). The patient continued with his treatment for type 2 diabetes mellitus. Due to the persistent cough, azithromycin (500 mg) was added for a period of 3 days; however, the symptomatology continued, so it was decided to perform a real-time PCR test for SARS-CoV-2, which was positive. The treatment prescribed was 100 mg of amantadine twice a day for 14 days. His asymptomatic relatives (wife and daughter) positive for SARS-CoV-2 were prescribed 100 mg of amantadine twice daily as a preventive measure. The patient improved satisfactorily on the sixth day of treatment. The wife and daughter were symptom-free during the 14 days of treatment with amantadine .
Table 1 shows cases where amantadine has been used as a treatment and family members have been administered this drug as a measure to prevent them from getting symptoms from SARS-CoV-2 infection
Currently, there are a group of investigators who subscribe to the hypothesis that amantadine offers a protective effect to prevent the replication of the virus in patients who are taking it regularly.
Tipton and Wszolek from the Mayo Clinic suggest that “we must explore all possible options to prevent and seek treatment for COVID-19. The use of low-cost and readily available drugs is a low-risk and cost-effective approach. We propose amantadine and memantine as two possible candidates” . Aranda-Abreu et al. demonstrate that amantadine blocks the viroporin channel of COVID-19, preventing the release of the viral nucleus in the cell cytoplasm and states that “the use of amantadine when the first symptoms of COVID-19 occur can mitigate the effects of the disease” .
In addition, Smieszek et al., conclude that “amantadine could be used as a potent agent to lower viral load if administered early enough in the course of COVID-19 infection and that the cumulation in lysosomes, if effective could reduce viral load, decrease organ spread within the host and decrease the severity and progression of associated disease.” They suggest that more studies are needed to examine the role of amantadine .
Rejdak and Grieb in a study of patients with a range of neurological disorders concluded that “although their study had limitations due to the small sample size and cross-sectional approach, it indicated that the adamantanes amantadine or memantine exert a protective antiviral effect” and that, if confirmed, adamantanes could be useful in limiting SARS-CoV-2 infection and its clinical neurological sequelae” .
Cimolai expressed a view that, although not commonly discussed, the adamantanes should also be reevaluated at least in preliminary in vitro studies for various human coronaviruses . Araujo et al. concluded that ‘‘In the absence of a vaccine or medication to help prevent or decrease the effects of the disease, we suggest that amantadine may reduce the effects of COVID-19” . Wiwanitkit says there are many classic drugs that might be useful for management of COVID-19. Amantadine is an antiviral agent that is in that category. Its exact effect has to be further studied .