Objective Anxiety, fatigue and depression are common neurological manifestations after COVID-19. So far, post-COVID complications were treated by rehabilitation, oxygen therapy and immunotherapy. Effects of neurofeedback on post-COVID complications and their potential interrelatedness have not been studied yet. In this pilot study, we investigated the effectiveness of neurofeedback (Othmer method) for treatment of fatigue, anxiety, and depression after COVID-19. Methods 10 participants met inclusion criteria for having positive anamnesis of at least one of the following complications following COVID-19: fatigue, anxiety, and depression which were measured by questionnaires. ANOVA was used for calculating differences in questionnaire score before and after neurofeedback. Pearson’s correlation coefficient was used to calculate correlations between anxiety, depression and fatigue. Results After five neurofeedback sessions, there came to significant reduction of severity of post-COVID anxiety and depression persisting for at least one month. Effect of neurofeedback on fatigue was insignificant. Severity of anxiety, fatigue and depression as well as reductions in depression and fatigue were positively correlated with each other. Conclusion These findings showed effectiveness neurofeedback for reducing anxiety and depression after COVID-19 and for studying correlations between neurological complications after COVID-19. However, since our pilot clinical trial was open-label, it is hard to differentiate between neurofeedback-specific and unspecific effects on our participants. Future randomized controlled trials with more robust sample are necessary to investigate feasibility of neurofeedback for post-COVID neurological complications. The study has identification number trial ID ISRCTN49037874 in ISRCTN register of clinical trials (Retrospectively registered).

Transcranial alternating current stimulation (tACS) and neurofeedback (NFB) are two different types of non-invasive neuromodulation techniques, which can modulate brain activity and improve brain functioning. In this review, we compared the current state of knowledge related to the mechanisms of tACS and NFB and their effects on electroencephalogram (EEG) activity (online period/stimulation period) and on aftereffects (offline period/post/stimulation period), including the duration of their persistence and potential behavioral benefits. Since alpha bandwidth has been broadly studied in NFB and in tACS research, the studies of NFB and tACS in modulating alpha bandwidth were selected for comparing the online and offline effects of these two neuromodulation techniques. The factors responsible for variability in the responsiveness of the modulated EEG activity by tACS and NFB were analyzed and compared too. Based on the current literature related to tACS and NFB, it can be concluded that tACS and NFB differ a lot in the mechanisms responsible for their effects on an online EEG activity but they possibly share the common universal mechanisms responsible for the induction of aftereffects in the targeted stimulated EEG band, namely Hebbian and homeostatic plasticity. Many studies of both neuromodulation techniques report the aftereffects connected to the behavioral benefits. The duration of persistence of aftereffects for NFB and tACS is comparable. In relation to the factors influencing responsiveness to tACS and NFB, significantly more types of factors were analyzed in the NFB studies compared to the tACS studies. Several common factors for both tACS and NFB have been already investigated. Based on these outcomes, we propose several new research directions regarding tACS and NFB.

Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8–47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.

Theoretical considerations related to neurological post-COVID complications have become a serious issue in the COVID pandemic. We propose 3 theoretical hypotheses related to neurological post-COVID complications. First, pathophysiological processes responsible for long-term neurological complications caused by COVID-19 might have 2 phases: (1) Phase of acute Sars-CoV-2 infection linked with the pathogenesis responsible for the onset of COVID-19-related neurological complications and (2) the phase of post-acute Sars-CoV-2 infection linked with the pathogenesis responsible for long-lasting persistence of post-COVID neurological problems and/or exacerbation of another neurological pathologies. Second, post-COVID symptoms can be described and investigated from the perspective of dynamical system theory exploiting its fundamental concepts such as system parameters, attractors and criticality. Thirdly, neurofeedback may represent a promising therapy for neurological post-COVID complications. Based on the current knowledge related to neurofeedback and what is already known about neurological complications linked to acute COVID-19 and post-acute COVID-19 conditions, we propose that neurofeedback modalities, such as functional magnetic resonance-based neurofeedback, quantitative EEG-based neurofeedback, Othmer’s method of rewarding individual optimal EEG frequency and heart rate variability-based biofeedback, represent a potential therapy for improvement of post-COVID symptoms.

Phosphene is the experience of light without natural visual stimulation. It can be induced by electrical stimulation of the retina, optic nerve or cortex. Induction of phosphenes can be potentially used in assistive devices for the blind. Analysis of phosphene might be beneficial for practical reasons such as adjustment of transcranial alternating current stimulation (tACS) frequency and intensity to eliminate phosphene perception (e.g., tACS studies using verum tACS group and sham group) or, on the contrary, to maximize perception of phosphenes in order to be more able to study their dynamics. In this study, subjective reports of 50 healthy subjects exposed to different intensities of retinal tACS at 4 different frequencies (6, 10, 20 and 40 Hz) were analyzed. The effectiveness of different tACS frequencies in inducing phosphenes was at least 92 %. Subject reported 41 different phosphene types; the most common were light flashes and light circles. Changing the intensity of stimulation often induced a change in phosphene attributes. Up to nine phosphene attributes changed when the tACS intensity was changed. Significant positive correlation was observed between number of a different phosphene types and tACS frequency. Based on these findings, it can be concluded that tACS is effective in eliciting phosphenes whose type and attributes change depending on the frequency and intensity of tACS. The presented results open new questions for future research.