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Acceleration of sporadic Creutzfeldt–Jakob disease progression by COVID requires evidence from appropriately designed studies


The aim of this letter to the editor is to discuss the influence of SARS-CoV-2 infection on the progression of sporadic Creutzfeldt–Jakob disease (sCJD). A 73-year-old male was diagnosed with sCJD based on the clinical presentation, cerebral MRI, FDG–PET, and elevated 14-3-3 in cerebrospinal fluid. One month earlier he had suffered a slight COVID-19 infection. It was concluded that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of sCJD.

To the Editor


We read with interest the article by Alloush et al. about a 73-year-old male with sporadic Creutzfeldt–Jakob disease (sCJD) beginning 1 month after mild SARS-CoV-2 infection [1]. The diagnosis of sCJD was based on the clinical presentation, cerebral MRI, FDG–PET, and positive 14-3-3 test [1]. It was concluded that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of sCJD [1]. The study is appealing but raises concerns and comments.

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The major limitation of the study is that the diagnosis sCJD was not confirmed by autopsy. Clinical diagnostic criteria of sCJD include a combination of characteristic neuropsychiatric symptoms and signs, elevated cerebrospinal fluid (CSF) proteins 14-3-3, high CSF tau protein, EEG, MRI, and real-time quaking-induced conversion (RT-QuIC) [2], but the definite diagnosis is made by autopsy. The sensitivity and specificity of the tests used do not exceed 92% and 95%, respectively [3].

A second limitation of the study is that the CSF was not tested for SARS-CoV-2 by PCR. A negative nasopharyngeal swab test does not rule out cerebral SARS-CoV-2 infection. A negative PCR for SARS-CoV-2 in the CSF would have ruled out infectious SARS-CoV-2 encephalitis. Immune encephalitis caused by SARS-CoV-2 infection could have been excluded by the absence of antibodies associated with immune encephalitis and normal CSF levels of cytokine, chemokines, and glial factors.

We disagree with the statement that there was a rapid deterioration as the patient died 4 months after the disease onset [1]. The average duration of symptoms in patients with sCJD is 4 months of disease duration [4], so there is no acceleration or worsening of neurological deterioration or shortened survival. At the same time, the study design (case report) is not suitable for the conclusion that when a sCJD patient is infected with SARS-CoV-2, neurological decline is accelerated, worsened and, consequently, overall survival is shortened [1]. From a single patient and the lack of a control group, such conclusions remain unsupported. Whether SARS-CoV-2 infection actually worsens and accelerates that sCJD needs to be investigated by a multicentre design in patients with autopsy-confirmed sCJD.


Overall, the elegant study has several limitations that put the results and their interpretation into perspective. Addressing these issues would strengthen the conclusions and could improve the status of the study. Before a supportive relationship between SARS-CoV-2 and sCJD can be established, appropriate studies with a prospective, multicentre design need to be conducted. The diagnosis of sCJD must be confirmed by an autopsy.

Availability of data and materials

All data reported are available from the corresponding author.



Creutzfeldt–Jakob disease


Cerebrospinal fluid


Magnetic resonance imaging


Positron emission tomography


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JF: design, literature search, discussion, first draft, critical comments. All authors have read and approved the manuscript.

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Correspondence to Josef Finsterer.

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Finsterer, J. Acceleration of sporadic Creutzfeldt–Jakob disease progression by COVID requires evidence from appropriately designed studies. Egypt J Neurol Psychiatry Neurosurg 59, 159 (2023).

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