From the moment of treatment introduction, stabilization occurred within 24 hours in 69% of patients, and within 48 hours in 91% of patients. Between 24 and 48 hours full remission of disease symptoms occurred in 43% of cases. In total, 93% of patients did not require hospital admission during the treatment. None of the patients died and by the end of the treatment, all patients experienced remission of COVID-19.
Despite a high rate of pneumonia in the group of treated patients (53%), only one person was treated in the hospital (oxygen therapy), after amantadine was introduced. Three other people were referred to the hospital for pneumonia treatment. None of the patients died. As of the completion of the observation, none of the patients sought medical assistance with post COVID-19 syndrome (the condition two months after the end of treatment). Exemplary X-rays of the patient made before the treatment and during treatment are presented in Fig. 4.
One of early COVID-19 studies showed that survival rates for patients with pneumonia can be as low as 55% . Even though it was conducted at early stages of the pandemic when hospitals did not use currently accessible drugs and procedures, it can be easily compared to the ambulatory treatment regime in Poland that follows no recommendations for particular treatment .
Groups of both our study and the one cited above can be compared since they have similar mean ages (57 years). In the cited article, 37% of patients had comorbidities, 22% had pneumonia, and the mortality rate was 13%. In the studied group subject to this article, 64% of patients had comorbidities, 53% had pneumonia, and 80% of patients were overweight (as mentioned earlier, such persons are burdened with a 113% greater risk of hospital admission in the case of COVID-19) , but none have died, and just 7% required hospitalization. This may suggest that treatment with amantadine hydrochloride can reduce the risk of death and hospitalization level.
Remarks concerning the use of the considered variants and observations
If an evident improvement does not occur after 2-3 days and no complete stabilization of the patient’s condition is achieved, it may be suspected that complications, such as pneumonia, have already developed. Such patients must be carefully examined, and lung auscultation is absolutely necessary. In doubtful cases, CT (computer tomography) or at least an X-ray must be performed, as they might reveal inflammatory lesions that are not identified upon a stethoscope examination. If lesions are found during auscultation, antibiotic therapy is required with antibiotics administered intramuscularly or intravenously plus low molecular weight heparin. Steroids are administered according to the patient’s condition.
In many patients blood pressure drops or transient cardiovascular failure might occur at the breakthrough moment after the introduction of amantadine treatment, i.e. on 3-4 day. Patients may not develop high temperature and the disease symptoms begin to resolve, but at the same time, some poor tolerance of exercise may occur – even walking which lasts a maximum of 1-2 days.
Limitations of the study
Within the analysis performed by this study, attention should be paid to its significant limitations, which include: the lack of study randomization, the low number of the study population, the lack of blinding and control groups and the lack of concrete endpoints for the evaluation of the efficacy of amantadine. The final outcome results were not confirmed with the presence of IgM and IgG antibodies against COVID-19 after the completion of the treatment.
The use of antibiotics and other therapies may also distort the results of the analysis. Antibiotic treatment was not a standard in the study group, and all patients did not receive identical therapy. In some cases it was introduced empirically by other primary care physicians.
The most important limitation we acknowledge out of the ones listed above is lack of randomization. Randomized trials are standard clinical studies, as they improve the credibility of the results, particularly when factors with strong prognostic significance may affect the endpoints. In this case, such a factor may be the presence of the coexistence of pneumonia and/or the use of antibiotic therapy. On the other hand, this observational analysis was fully retrospective, and post factum randomization was not possible. It can also be noticed that randomized trials may also raise some reservations of ethical nature, in particular in the period of coronavirus, when the patient’s benefit from a given therapy (even an experimental one) is unquestionable in the opinion of the supervising physician. This type of problem is discussed in the work of K. Bielecki .
The second limitation of the work presented here is the lack of controlled conditions and the lack of blinding in the study. This could have affected the result of the study, as some patients were convinced of the efficacy of the medication and thus they reported for treatment on purpose (they even travelled large distances to get it). Therefore the placebo effect cannot be excluded. It is also important that some of the patients expected (had high hopes) that the medication would help them – hence the possibility of “therapeutic misconception”. Such a misconception might also have occurred among the patients who administered the medication and evaluated/registered the course of the disease. This may be the source of errors in the evaluation of the condition of the patients that could not be detected or avoided without double blinding of the study.
It must also be stressed that the analysis was not planned before the commencement of the treatment. As a result, the post-hoc construction of the study might have been subconsciously made in such a way that could prove the expected thesis on the basis of the possessed data. Additionally, there were no precisely defined control points, such as: the avoidance of pneumonia and the lack of the necessity of hospitalization, including respiratory therapy. The lack of patient mortality also poses limitations to the study caused by expediency.
Finally, all the patients could not have been guaranteed one uniform standard of treatment, its methodology and the control of the treatment effects, because of their place of residence and/or the type of consultation they were subject to (face-to-face or on the phone).