Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients admitted to hospital during the COVID-19 epidemic in South Africa

  1. Angharad G Davis
  2. Marise Bremer
  3. Georgia Schäfer
  4. Luke Dixon
  5. Fatima Abrahams
  6. Rene T Goliath
  7. Mpumi Maxebengula
  8. Alize Proust
  9. Anesh Chavda
  10. John Black
  11. Robert J Wilkinson
  12. And the HIATUS Study Consortium

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Abstract

Neurological manifestations of COVID-19 are increasingly described in the literature. There is uncertainty whether these occur due to direct neuroinvasion of the virus, para-infectious immunopathology, as result of systemic complications of disease such as hypercoagulability or due to a combination of these mechanisms. Here we describe clinical and radiological manifestations in a sequential cohort of patients presenting to a district hospital in South Africa with neurological symptoms with and without confirmed COVID-19 during the first peak of the epidemic. In these patients, where symptoms suggestive of meningitis and encephalitis were most common, thorough assessment of presence in CSF via PCR for SARS-CoV2 did not explain neurological presentations, notwithstanding very high rates of COVID-19 admissions. Although an understanding of potential neurotropic mechanisms remains an important area of research, these results provide rationale for greater focus towards the understanding of para-immune pathogenic processes and the contribution of systemic coagulopathy and their interaction with pre-existing risk factors in order to better manage neurological disease in the context of COVID-19. These results also inform the clinician that consideration of an alternative diagnosis and treatment for neurological presentations in this context is crucial, even in the patient with a confirmed diagnosis COVID-19.

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    SciScore for 10.1101/2021.05.14.21254691: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The study was approved by the Faculty of Health Sciences Human Research Ethical Committee of the University of Cape Town (HREC 207/2020) and by the ethical review board at Livingstone Hospital.
    Consent: Written informed consent was taken from the patients where possible in those with capacity to consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingTwo dimensional images were retrieved and independently viewed using a picture archive and communication system (PACS) by a blinded neuroradiologist using a standardised case report form.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Each run included a positive control (PC), which for sgRNA runs included a sample from a previously positive patient, a human specimen extraction control (HSC; e.g. HeLa cell RNA) as well as a no template control (NTC, i.e. water).
    HeLa
    suggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)
    Software and Algorithms
    SentencesResources
    All analysis was performed within GraphPad Prism (version 9, Prism for MacOS) software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There were several limitations to this study. Given the pragmatic nature of its design, only data on investigations indicated as part of routine clinical care were available for analysis, resulting in an incomplete laboratory and radiological data set. This includes cerebral imaging, which was not performed in all participants, and in instances where it was, contrast was not given in the majority (23/26) of cases. Factors related to coagulation, such as D-Dimer levels, would have provided interesting comparison of patients presenting with complications such as stroke with and without confirmed COVID-19. In contrast, laboratory procedures related to the discovery of SARS-CoV2 in CSF were thorough and robust, which reassures that despite multiple runs, the negative findings are reliable. Although small, this pragmatic observational cohort study contributes knowledge to our increasing understanding of COVID-19 management. Through systematic analysis of CSF in patients presenting with neurological symptoms in a context where incidence of SARS-CoV2 infection is high we have demonstrated that although cases within the literature exist, direct neurotropic invasion of the CNS is uncommon. This includes suspected cases of meningitis and encephalitis, syndromes most aligned to direct neurotropic mechanism. This considered, neurological presentations in cases of COVID-19 continue to be reported, and lead to morbidity and mortality in patients affected. The results from our study suggest...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.05.14.21254691v1 on medRxiv