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\begin{document}

\title{Post-COVID worsening of Parkinson's disease patient.}



\author[1]{Aliaksandr Boika}%
\author[1]{Mikhail Sialitski}%
\author[1]{Veranika Chyzhyk}%
\author[1]{Vladimir Ponomarev}%
\author[2]{Elena Fomina}%
\affil[1]{Affiliation not available}%
\affil[2]{The Republican Research and Practical Center for Epidemiology and Microbiology}%


\vspace{-1em}



  
  \date{May 16, 2024}


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\begin{abstract}
Background The theory of ``hit and run'' raises a possibility of novel
COVID19-associated Parkinsonism cases, as well as worsening of symptoms
in patients with pre-existing Parkinson's Disease (PD). Aim/method To
demonstrate that the COVID19 infection may lead to long lasting
immunological and neurological changes at PD patients.%
\end{abstract}%



\sloppy


\textbf{Key Clinical Message}

Worsening of clinical symptoms after COVID-19 illness as well as
misregulation of CD4 and CD8 T cells numbers may be revealed at post
COVID-19 period at PD patients. Immunological changes may be a
background for clinical worsening of the patient.

\textbf{Key words:} Post-COVID-19, Parkinson's Disease, motor symptoms,
non-motor symptoms, immunology.

Background

With the global coronavirus disease 2019 (COVID-19) pandemic under way,
the full effect of the virus infection on affected individuals with and
without underlying health conditions is still far from clear. However,
there is an on-going accumulation of scientific data about an impact of
the COVID-19, on the patients with health conditions that might be
exacerbated by the virus, such as Parkinson's disease (PD). The theory
of ``hit and run'' {[}1{]} raises a possibility of novel
COVID19-associated Parkinsonism cases, as well as worsening of symptoms
in patients with pre-existing Parkinson's Disease (PD). Here we present
a short clinical study of a patient suffering from PD, whose
neurological condition was significantly impacted by the COVID19
infection, even upon recovery from the novel virus.

Aims of the study

To investigate whether the COVID19 infection may lead to long lasting
immunological and neurological changes at PD patients.

Methods and results

A clinical case of a 39-year-old man with a 2-year history of
Parkinson's disease was observed at our Centre. The Study was approved
by local Ethics Committee and Study Agreement was voluntary signed by
the subject at the beginning. Section III of the Unified Parkinson's
Disease Rating Scale (MDS-UPDRS) of the International Society for
Movement Disorders (2008) was used for assessment of severity of the
patients' motor symptoms. The symptoms were recorded at 26 in the
off-period (after a 12-24 hour break in taking antiparkinsonian drugs)
and at 17 in the on-period (1 hour after medication was taken).
Non-motor symptoms data according to the following scales was: Hamilton
Depression Rating Scale (HDRS)-7, the Pittsburgh Sleep Quality Index
(PSQI)-5, the Epworth Sleepiness Scale (ESS)-7, Non\emph{-} Motor
Symptoms Scale (NMS)-7, The 39-item Parkinson's Disease Questionnaire
Summary Index (PDQ-39SI)-39.8.

Magnetic resonance imaging of brain was normal.

The treatment of the patient included Pramipexolum (prolonged form) 2,25
mg daily and Amantadinum 300 mg daily with marked improvement of
neurological symptoms. It is noteworthy that even though the primary use
of Amantadinum is the treatment of dyskinesia associated with
parkinsonism, the drug also has marked anti-viral properties, against
type A influenza virus in particular {[}2{]}\textbf{.}

Three weeks after the examination, the patient informed us that he was
suffering from COVID-19 (positive PCR-test and bilateral polysegmental
pneumonia on CT-scan).

Two weeks later PCR-retest was negative and the pneumonia symptoms were
absent. However, the patient began to exhibit general weakness,
depression, loss of appetite, multiple joint pain and increased
clumsiness and heaviness of the body. The patient was prescribed an
anti-inflammatory drug tenoxicam 20 mg daily for 10 days, which did not
yield positive results.

The second examination was performed two months after the first visit.
Anti-parkinsonian therapy was the same through the course of the
treatment. In addition to previous neurological signs, cogwheeling of
the right leg and intensified bradykinesia on finger tapping of the right
hand were found. The overall score of the third part of the UPDRS scale
amounted to 31 in the off-period and 22 in the on-period, which marks
worsening of the condition. Passive and active rotation in the right hip
joint was painful, which was a new symptom that we have not observed
before in this patient.

Patients' non-motor symptoms were also worse : HDRS-8, PSQI-5, ESS-8,
NMS-6, PDQ-39SI-41.3.

Misregulation of CD4 and CD8 T cells numbers was also revealed as an
additional finding at post COVID-19 period: CD4+CD25hiCD127- - 0.023
(normal ranges (NR) 0.05-0.15), \selectlanguage{russian}СD62L+CD45RA- - 0.607 (NR 0,18-0,54),
СD62L+CD45RA+ - 0.122 (NR 0,15-0,38), CD62L-CD45RA+ - 0.052 (NR
0,08-0,31).

Conclusion

Our data is in agreement previously published information, that there is
substantial worsening of motor and non-motor symptoms during mild to
moderate COVID-19 illness in a cohort of patients with PD {[}3{]}. We
found post-COVID-19-related immunological changes three weeks after the
end of an acute episode. Several previously published studies point to
only reduction of both CD4 and CD8 T cells in moderate and severe
COVID-19 cases, whereas our observations point towards more long-term
immunological changes {[}4, 5{]}. We think that these changes may be a
background for clinical worsening of the patient. It is a main finding
of the present study.

This case demonstrates also quite a short time recovery from COVID-19
and associated pneumonia, which could indicate a possible positive
effect of Amantadinum against the virus. This fact can be important when
investigating drug repurposing for COVID19 treatment {[}6{]}. It is a
second finding.

Although the data on the effect of COVID19 infection on the patients
with neurological disorders such as PD is still quite scarce, as the
data further accumulates, there might be a need for more comprehensive
guidelines for treating long-term neurological and immunological
complications of COVID-19 in patients with PD and other neurological
disorders.

\textbf{Conflict of Interest:} Authors declare no conflicts of interest

\textbf{Sources of Funding Statement:} N/A

\textbf{Acknowledgements:} none

\textbf{Author' contribution:} 1) Research project: A. Conception
(Aliaksandr V. Boika, Mikhail M. Sialitsk), B. Organization (Mikhail M.
Sialitski, Vladimir V. Ponomarev, C. Execution (Mikhail M.
Sialitski,Veranika A. Chyzhyk , Elena G. Fomina);

2) Manuscript: A. Writing of the first draft (Veranika A. Chyzhyk), B.
Review and Critique (Aliaksandr V. Boika, Vladimir V. Ponomarev)

\textbf{References}

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