SARS-CoV-2 was considered a worldwide health problem due to its rapid spread and lethality. Almost 3 years after the beginning of the pandemic period, people who were infected and survived are still presenting sequelae. Neurological manifestations caused by SARS-CoV-2 were identified in approximately 10% of people infected and hospitalized11 Meppiel E, Peiffer-Smadja N, Maury A, Bekri I, Delorme C, Desestret V, et al. Neurologic manifestations associated with COVID-19: a multicentre registry. Clin Microbiol Infect. 2021;27(3):458-66. https://doi.org/10.1016/j.cmi.2020.11.005
https://doi.org/10.1016/j.cmi.2020.11.00...
. It has been suggested that SARS-CoV-2 can infect the central nervous system through olfactory and vagus nerves. Then, it releases cytokines, increasing the sympathetic nervous system activity and maintaining the inflammatory response22 Baptista AF, Baltar A, Okano AH, Moreira A, Campos ACP, Fernandes AM, et al. Applications of non-invasive neuromodulation for the management of disorders related to COVID-19. Front Neurol. 2020;11:573718. https://doi.org/10.3389/fneur.2020.573718
https://doi.org/10.3389/fneur.2020.57371...
. Anti-inflammatory exacerbated response, pain, fatigue, cognitive issues, and physical deterioration are outcomes frequently involved in the central nervous system dysfunctions after SARS-CoV-2 infection22 Baptista AF, Baltar A, Okano AH, Moreira A, Campos ACP, Fernandes AM, et al. Applications of non-invasive neuromodulation for the management of disorders related to COVID-19. Front Neurol. 2020;11:573718. https://doi.org/10.3389/fneur.2020.573718
https://doi.org/10.3389/fneur.2020.57371...
,33 Pilloni G, Bikson M, Badran BW, George MS, Kautz SA, Okano AH, et al. Update on the use of transcranial electrical brain stimulation to manage acute and chronic COVID-19 symptoms. Front Hum Neurosci. 2020;14:595567. https://doi.org/10.3389/fnhum.2020.595567
https://doi.org/10.3389/fnhum.2020.59556...
.
Noninvasive and safe strategies, such as transcranial direct current stimulation, might be an alternative to managing inflammatory response and neurological symptoms. Neuromodulation of the left dorsolateral prefrontal cortex seems to present the potentiality to decrease the recovery time of the neurological disabilities generated by SARS-CoV-2 through different mechanisms22 Baptista AF, Baltar A, Okano AH, Moreira A, Campos ACP, Fernandes AM, et al. Applications of non-invasive neuromodulation for the management of disorders related to COVID-19. Front Neurol. 2020;11:573718. https://doi.org/10.3389/fneur.2020.573718
https://doi.org/10.3389/fneur.2020.57371...
. The sympathetic and parasympathetic autonomic nervous system response seems to be involved in inflammatory modulation44 Schmaußer M, Hoffmann S, Raab M, Laborde S. The effects of noninvasive brain stimulation on heart rate and heart rate variability: a systematic review and meta-analysis. J Neurosci Res. 2022;100(9):1664-94. https://doi.org/10.1002/jnr.25062
https://doi.org/10.1002/jnr.25062...
. It is important to mention that in experimental models and preliminary data in human beings, vagus nerve stimulation attenuates inflammation, modulating activity of cholinergic anti-inflammatory pathways55 Azabou E, Bao G, Bounab R, Heming N, Annane D. Vagus nerve stimulation: a potential adjunct therapy for COVID-19. Front Med (Lausanne). 2021;8:625836. https://doi.org/10.3389/fmed.2021.625836
https://doi.org/10.3389/fmed.2021.625836...
.
There are at least six drugs approved by the Food and Drug Administration to treat SARS-CoV-2: paxlovid, molnupiravir, fluvoxamine66 Wen W, Chen C, Tang J, Wang C, Zhou M, Cheng Y, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and paxlovid) for COVID-19:a meta-analysis. Ann Med. 2022;54(1):516-23. https://doi.org/10.1080/07853890.2022.2034936
https://doi.org/10.1080/07853890.2022.20...
, remdesivir, baricitinib77 Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795-807. https://doi.org/10.1056/NEJMoa2031994
https://doi.org/10.1056/NEJMoa2031994...
, and dexamethasone88 RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704. https://doi.org/10.1056/NEJMoa2021436
https://doi.org/10.1056/NEJMoa2021436...
, which have decreased the recovery time and accelerated an improvement in clinical status of patients infected by SARS-CoV-2. It has been hypothesized that their actions are related to reducing inflammatory-mediated injury and improving lymphocyte counts.
There are at least nine ongoing clinical trials registered in adults99 US National Institutes of Health. ClinicalTrials.gov; 2020 [cited on Mar 6, 2020]. Available from: https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=tdcs&cntry=&state=&city=&dist=
https://clinicaltrials.gov/ct2/results?c...
. All the trials are designed to use transcranial direct current stimulation without pharmacological association to treat patients infected by SARS-CoV-2. We expect that future clinical trials are designed using transcranial direct current stimulation as an associated strategy with pharmacological treatment to generate a booster. In this sense, if transcranial direct current stimulation shows efficacy to recover central nervous system dysfunctions generated by SARS-CoV-2, we could start discussions to insert this tool in the public health system.
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Funding: none.
REFERENCES
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1Meppiel E, Peiffer-Smadja N, Maury A, Bekri I, Delorme C, Desestret V, et al. Neurologic manifestations associated with COVID-19: a multicentre registry. Clin Microbiol Infect. 2021;27(3):458-66. https://doi.org/10.1016/j.cmi.2020.11.005
» https://doi.org/10.1016/j.cmi.2020.11.005 -
2Baptista AF, Baltar A, Okano AH, Moreira A, Campos ACP, Fernandes AM, et al. Applications of non-invasive neuromodulation for the management of disorders related to COVID-19. Front Neurol. 2020;11:573718. https://doi.org/10.3389/fneur.2020.573718
» https://doi.org/10.3389/fneur.2020.573718 -
3Pilloni G, Bikson M, Badran BW, George MS, Kautz SA, Okano AH, et al. Update on the use of transcranial electrical brain stimulation to manage acute and chronic COVID-19 symptoms. Front Hum Neurosci. 2020;14:595567. https://doi.org/10.3389/fnhum.2020.595567
» https://doi.org/10.3389/fnhum.2020.595567 -
4Schmaußer M, Hoffmann S, Raab M, Laborde S. The effects of noninvasive brain stimulation on heart rate and heart rate variability: a systematic review and meta-analysis. J Neurosci Res. 2022;100(9):1664-94. https://doi.org/10.1002/jnr.25062
» https://doi.org/10.1002/jnr.25062 -
5Azabou E, Bao G, Bounab R, Heming N, Annane D. Vagus nerve stimulation: a potential adjunct therapy for COVID-19. Front Med (Lausanne). 2021;8:625836. https://doi.org/10.3389/fmed.2021.625836
» https://doi.org/10.3389/fmed.2021.625836 -
6Wen W, Chen C, Tang J, Wang C, Zhou M, Cheng Y, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and paxlovid) for COVID-19:a meta-analysis. Ann Med. 2022;54(1):516-23. https://doi.org/10.1080/07853890.2022.2034936
» https://doi.org/10.1080/07853890.2022.2034936 -
7Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795-807. https://doi.org/10.1056/NEJMoa2031994
» https://doi.org/10.1056/NEJMoa2031994 -
8RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704. https://doi.org/10.1056/NEJMoa2021436
» https://doi.org/10.1056/NEJMoa2021436 -
9US National Institutes of Health. ClinicalTrials.gov; 2020 [cited on Mar 6, 2020]. Available from: https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=tdcs&cntry=&state=&city=&dist=
» https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=tdcs&cntry=&state=&city=&dist=
Publication Dates
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Publication in this collection
20 Feb 2023 -
Date of issue
2023
History
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Received
01 Nov 2022 -
Accepted
14 Dec 2022