We report a case of severe worsening of PD symptoms in the form of rigidity, akinesia, and foot dystonia, as the sole presenting features of COVID-19 infection. The patient was afebrile and lacked any of the cardinal features of the disease in the beginning. After a normal initial workup, the patient was found to be positive for COVID-19, which was incidentally requested. Other features of COVID-19 infection later ensued, with fever and respiratory symptoms. A gradual improvement occurred during the recovery phase without any specific therapy, apart from his usual anti-PD medications and treatment of COVID-19 infection as per MOH protocol.
Because of the unexplained, rapidly progressive worsening of PD symptoms, in a previously controlled PD patient, we believe that this presentation could be related to neuro-invasive potential of SARS-CoV-2, through sharing the same receptor angiotensin-converting enzyme 2 (ACE2), which can be found in the brain and mediate the disease process [3, 4].
The impact of COVID-19 on PD is largely speculative and coming mainly from case reports and case series. Generally, COVID-19 can affect PD through worsening of motor as well as non-motor symptoms, worsening of pre-existing dyspnea due to respiratory distress, as dyspnea may exist in up to 39% of PD patients, or through the development of new-onset parkinsonism [5].
Recently, four single-case reports have been published [6,7,8,9] describing the development of acute parkinsonism following COVID-19 infection. All four cases developed parkinsonian symptoms within 5–32 days of initial SARS-CoV-2 infection, and they showed evidence of reduced function of the nigrostriatal dopamine system, on brain imaging, similar to PD. Two of them [8, 9] developed these symptoms after only relatively mild COVID-19 infection, while the other 2 [6, 7] had moderate to severe infection requiring hospitalization, similar to our case.
Another community-based case control study of 12 PD patients in Italy [10] who developed COVID-19 suggested substantial worsening of motor and non-motor symptoms during mild to moderate COVID-19 illness, which is in line with our case; however, our case is unique in the aspect that worsening of PD was the sole initial presenting feature of COVID-19, in the absence of its common cardinal features. Furthermore, a 2021 study [11] of 10 PD cases from Wuhan, China, showed that worsened outcome was linked to older age, longer PD duration, and late stage PD.
Three potential mechanisms have been proposed for the rapid development of parkinsonism following COVID-19; first, a vascular insult from a hypercoagulable state associated with severe COVID-19 can directly damage the nigrostriatal system, akin to vascular parkinsonism. Second, systemic inflammation can trigger neuroinflammation and nigral dopamine neuron injury. Midbrain dopamine neurons express high levels of the ACE2 receptor and are believed to be vulnerable to SARS-CoV-2. Third, neurotropic features of SARS-CoV-2 can cause viral RNA to invade the brain. Neuropathological studies using immunostaining for aggregated α-synuclein have suggested that the PD starts in the olfactory system or in enteric nerves and then propagates to other brain regions [12,13,14].
Moreover, other additional factors in our case could be the increased levodopa requirement during acute illness, old age, being on advanced therapies, and having possible genetic PD that can make the patient vulnerable to immunologically mediated neuronal damage.
