@article{Davis2021a,
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. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). GS received funding through the EDCTP2 (TMA2018SF-2446 - KSHV/HIV morbidity). RJW receives support from Francis Crick Institute which is funded by UKRI (FC0010218); Wellcome (FC0010218) and CRUK (FC0010218). He is additionally supported EDCTP (RIA2017T-2019 109237). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 203135/Z/16/Z, 104803; 203135; 222574]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data archived},
author = {Davis, Angharad G and Bremer, Marise and Sch{\"{a}}fer, Georgia and Dixon, Luke and Abrahams, Fatima and Goliath, Rene T and Maxebengula, Mpumi and Proust, Alize and Chavda, Anesh and Black, John and Wilkinson, Robert J},
doi = {10.1101/2021.05.14.21254691},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davis et al. - 2021 - Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {may},
pages = {2021.05.14.21254691},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{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}},
url = {https://doi.org/10.1101/2021.05.14.21254691},
year = {2021}
}

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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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). GS received funding through the EDCTP2 (TMA2018SF-2446 - KSHV/HIV morbidity). RJW receives support from Francis Crick Institute which is funded by UKRI (FC0010218); Wellcome (FC0010218) and CRUK (FC0010218). He is additionally supported EDCTP (RIA2017T-2019 109237). This research was funded in whole, or in part, by the Wellcome Trust [Grant numbers 203135/Z/16/Z, 104803; 203135; 222574]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data archived","author":[{"propositions":[],"lastnames":["Davis"],"firstnames":["Angharad","G"],"suffixes":[]},{"propositions":[],"lastnames":["Bremer"],"firstnames":["Marise"],"suffixes":[]},{"propositions":[],"lastnames":["Schäfer"],"firstnames":["Georgia"],"suffixes":[]},{"propositions":[],"lastnames":["Dixon"],"firstnames":["Luke"],"suffixes":[]},{"propositions":[],"lastnames":["Abrahams"],"firstnames":["Fatima"],"suffixes":[]},{"propositions":[],"lastnames":["Goliath"],"firstnames":["Rene","T"],"suffixes":[]},{"propositions":[],"lastnames":["Maxebengula"],"firstnames":["Mpumi"],"suffixes":[]},{"propositions":[],"lastnames":["Proust"],"firstnames":["Alize"],"suffixes":[]},{"propositions":[],"lastnames":["Chavda"],"firstnames":["Anesh"],"suffixes":[]},{"propositions":[],"lastnames":["Black"],"firstnames":["John"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]}],"doi":"10.1101/2021.05.14.21254691","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Davis et al. - 2021 - Spectrum of neurological manifestations and systematic evaluation of cerebrospinal fluid for SARS-CoV2 in patients.pdf:pdf","journal":"medRxiv","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"may","pages":"2021.05.14.21254691","publisher":"Cold Spring Harbor Laboratory Press","title":"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","url":"https://doi.org/10.1101/2021.05.14.21254691","year":"2021","bibtex":"@article{Davis2021a,\r\nabstract = {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. {\\#}{\\#}{\\#} Competing Interest Statement The authors have declared no competing interest. {\\#}{\\#}{\\#} Funding Statement AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). GS received funding through the EDCTP2 (TMA2018SF-2446 - KSHV/HIV morbidity). 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All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. 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