As we recover from the effects of the coronavirus disease (COVID-19) pandemic, the medical community globally is seeing the emergence of another challenge, which is the neuropsychiatric consequences of patients with long COVID. As COVID-19 recovered patients battle the challenges of emotional, persistent cognitive, and autoimmune symptoms such as fatigue, depression, brain fog, anxiety, and sleep disturbances, which are now potentially being recognized as part of a more complex multisystem disorder, it is crucial to pay attention to new developments that this novel coronavirus is causing. The growing evidence clearly highlights biological mechanisms such as microvascular injury, neuroinflammation, neurotransmitter disruption, and immune dysregulation. Still, there are systemic issues such as the absence of properly defined clinical frameworks, a lack of diagnostic tests, and healthcare systems that lack interdisciplinary coordination and collaboration, which have left many patients either underdiagnosed or without support. Our perspective paper calls attention to the urgent need for integrated care models, emphasizing the role nursing can play in symptom management and early recognition of any new symptoms in patients. We also focus on a reimagined approach to treating such patients by improving the collaboration between healthcare specialists in neurology and psychiatry. We believe that without such a coordinated effort in responding to the threat of long COVID, there will be a silent wave of chronic disability in the future.

Post-Acute COVID-19 Syndrome, Neuropsychiatric disorders, Etiology; Cognitive dysfunction, Neuroinflammation, Nursing care, Health services accessibility.

Since the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan in December 2019, which caused COVID-19, the world has seen multiple variants of the virus.[1] Researchers and scientists have been able to develop multiple strategies, including vaccine development, nanomedicine development, and novel therapeutics, including the use of artificial intelligence to fight the pandemic that caused mayhem in the normal day-to-day lives of individuals globally.[2,3] Today, almost five years since that first case, as the acute threat of the pandemic takes a back seat from making global headlines, another silent epidemic is rising to the surface: the long-term neuropsychiatric consequences of COVID-19 infection. This has been labelled as long COVID by experts due to the enduring and long-lasting nature of symptoms of the initial infection.[4-6] Many of these symptoms are cognitive or psychiatric and have emerged as a significant neurological public health burden. A graphical representation of the neuropsychiatric issues related to long COVID is shown in Figure 1. The clinical infrastructure, diagnostic methods, and public planning have been facing shortcomings and appear unprepared for this emerging challenge. The question that needs to be evaluated and answered is whether we are ready for the next wave, not the infection, but one of chronic disability.

Figure 1: Illustrative representation of the neuropsychiatric fallout of long COVID

The scope of the problem: Recent data from the World Health Organization (WHO) suggests that for every 100 patients who had COVID-19, about six develop long COVID.[7] Data from 2022 from the Centers for Disease Control and Prevention (CDC) estimates that almost 6.9% of adults in the United States of America (USA) developed long COVID.[8] Another study estimates that about 400 million people are suffering from long COVID globally cumulatively.[9] Researchers have demonstrated that almost one in three people who are affected by COVID-19 develop or experience neuropsychiatric symptoms, which include brain fog, fatigue, memory loss, anxiety, depression, and psychosis.[10,11] The study by Taquet et al. in 2022 showed that the risk of psychotic disorders, seizures, and cognitive deficits was elevated when compared to that of influenza, thus proving the unique neurotropism of SARS-CoV-2.[11] Their study also highlighted that out of the 1.2 million patients included in the study, most patients were of a working-age population, indicating the significant impact of long COVID on the workforce, economy, and quality of life.[11] This is going to put additional strain on the global economic burden caused by neurological diseases.[9,12] Through this paper, the authors aim to highlight the biological, clinical, nursing, and systemic challenges and recommend readiness strategies in overcoming the dangers of long COVID.

For this perspective article, a targeted review of literature between January 2020 and July 2025 was conducted. Databases in the search included PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, PsycINFO using keyword combinations “long COVID,” “post-COVID condition,” “neuropsychiatric,” “cognitive impairment,” “neuroinflammation,” “nursing care,” “health systems,” and “preparedness.” We focused on prioritizing systematic reviews, meta-analyses, large cohort studies, and papers related to policy matters that reported on cognitive or neuropsychiatric outcomes of long COVID. Further in the process, additional sources were identified by manually screening the reference lists of selected articles. Global organizations such as the WHO and the CDC were scanned for more information. The inclusion criteria were as follows: (a) peer-reviewed research papers published in English between January 2020 and November 2025, (b) reporting cognitive, neuropsychiatric, or psychological sequelae of long COVID, (c) articles that addressed nursing implications on healthcare systems, and (d) articles focusing on adult or mixed populations. Seminal or legacy papers were also included as necessary. Based on our findings, we organized this perspective article into four distinct domains as follows:

1. Biological mechanisms
2. Clinical challenges
3. Nursing perspectives
4. Systemic preparedness

1. Biological mechanisms of neuropsychiatric issues in long COVID :

The neuropsychiatric symptoms of long COVID have a distinct correlation with other underlying biological mechanisms. Research has proven the processes of neuroinflammation, microvascular endothelial injury, autoimmunity, dysautonomia, and neurotransmitter disruption.[13-19] Contemporary evidence points to additional layers of complexity in the disease process. Mitochondrial impairment has been shown to play a vital role in contributing to the many neurological symptoms, such as fatigue, vascular issues, or cognitive disturbances, associated with long COVID.[20] The study by Szögi et al.[21] focused on identifying novel biomarkers and found reduced levels of circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in patients with long COVID. They proved the crucial role of long-term mitochondrial dysfunction in the pathogenesis of long COVID. Epigenetic modifications, such as altered DNA methylation patterns due to pulmonary viruses such as SARS-CoV-2, can create a long memory of infection within immune and neural cells, thereby aiding in sustaining vulnerability even after viral load clearance.[22-24] Studies have highlighted a critical aspect linking SARS-CoV-2 in accelerating the pathways of neurodegeneration, such as enhanced tau phosphorylation and α-synuclein aggregation, thus raising concerns for long-term dementia, including Alzheimer’s and Parkinson’s dementia.[25-29]

These findings highlight the multifactoral and systemic nature of long COVID. An all-inclusive framework linking immune dysregulation, vascular injury, viral persistence, and cellular dysfunction is needed to explain the wide-ranging neuropsychiatric presentation and to create pathways for future therapeutic targets. In Table 1, we list some of the biological mechanisms and the systemic correlations in long COVID.

Table 1: Biological mechanisms and symptom correlates in long COVID

2. Clinical challenges in diagnosis and management:

Coming to an accurate diagnosis and developing a practical management of the neuropsychiatric sequelae in long COVID presents us with complex and persistent challenges. These challenges point to the long-standing gaps in the manner in which psychiatric and cognitive symptoms are studied, coded, and treated in different healthcare systems globally. We present three key issues that, from our perspective, stand out.

• Symptom overlap with psychiatric and neurological disorders: Patients who have long COVID often present with cognitive symptoms such as poor concentration (brain fog), lapses in memory, along with fatigue, anxiety, or depression. These symptoms have a considerable overlap with primary psychiatric disorders (for example, major depressive disorder, generalized anxiety disorder) and with neurologic syndromes (for example, mild cognitive impairment or post-concussive syndrome).[30] This can be challenging as it burdens the healthcare team and complicates diagnosis, thereby leading to errors by clinicians who can misdiagnose and attribute cognitive dysfunction to stress or burnout or psychiatric comorbidity instead of recognizing it as a potential neuropsychiatric manifestation of long COVID. Such misdiagnosis can delay correct therapeutic interventions.
• Lack of validated tools: Currently, the standardized diagnostic frameworks for cognitive and neuropsychiatric conditions post-COVID are in their infancy. Even though we have instruments such as the Montreal Cognitive Assessment (MoCA), mini-mental state examination (MMSE), and NEUROSCREEN, which have been proposed and applied in research and clinical use, we do not have a validated consensus tool that is tailored towards neuropsychiatric assessment in long COVID or there os inconsistency in the application of the International Classification of Diseases (ICD) diagnostic codes.[31-35] This lack of synchronization and coordination in clinical practice often leads to limitations in cross-study comparability, which further weakens decision-making in the clinical setting.
• Under-recognition and stigma in patient encounters: Many patients have concerns that, due to various factors such as excessive workload on the clinicians, their cognitive or psychiatric complaints may go unnoticed or completely ignored by the clinicians as being transient or psychosomatic. Often, patients may appear high-functioning in the short clinical interactions but are struggling in real-world scenarios, including at work, caregiving, or multitasking.[36] Such a perception of under-recognition and illegitimacy tends to fuel stigma, thus discouraging patients from seeking the care they need and eroding overall trust in the healthcare system. Nurses can play an important role in helping overcome this stigma, as they often spend more time with patients and can validate and document these symptoms, thereby underscoring the importance of multidisciplinary care teams.

Studies have been documenting the severity, prevalence, and persistence of neurological and psychiatric sequelae in patients with COVID-19 infection. These include patient-led surveys, large-scale retrospective cohort studies using electronic health records (EHR), systematic reviews, and meta-analyses from 2021 to 2025, as seen in Table 2. Altogether, these studies highlight and reinforce the nature of clinical challenge in front of us and provide an evidence base to develop standardized diagnostic and management protocols.

Table 2: Key studies highlighting the clinical challenges of long COVID

3. Nursing perspective:

• The frontline role: Nurses are the backbone of clinics and hospitals and are often the first point of contact and those who interact the most with the patients. So, from the nursing perspective, long COVID symptoms can present a multidimensional care challenge that can extend beyond clinical symptom management. As nurses spend a lot of their duty time in patient care, they are well-trained to identify any subtle changes in the patient’s symptoms, whether cognitive or emotional, that can sometimes go unnoticed in a brief physician-patient encounter. Nurses can play a crucial role in advocating for more rigorous neuropsychiatric assessment and pushing for guiding interdisciplinary care pathways.
• Early recognition and monitoring of subtle symptoms: Nurses play a critical role in detecting early signs and symptoms that can be overlooked, such as brain fog, irritability, short-term memory lapses, or sleep disturbances in long COVID patients. Routine conversations and repeated observations during hospital stays, or follow-ups in outpatient clinic visits, have put nurses in a unique situation to spot subtle behavioural or cognitive changes that may go under-reported by patients. Such vigilance provides early recognition and assists in creating opportunities for timely referrals to psychiatry or neurology-related services.
• Holistic interventions in everyday care: Nurses are uniquely positioned to implement more holistic interventions in low-resource settings, such as pacing strategies, nursing care plans, maintaining symptom diaries, and providing supportive education, thereby drastically improving patient agency and reducing psychological burden. A recent study noted that in dementia care in the post-pandemic era, nurses can play a key role in tracking neuropsychiatric symptoms and help maintain therapeutic consistency, which can, in turn, be applied to the broader population of patients with long COVID.[55]
• Gaps in training and the need for standardized frameworks: The absence of formal nursing frameworks for dealing with the challenges of long COVID can hinder the provision of a standardized nursing care delivery model. Despite their frontline position, nurses have reported feeling undertrained to manage post-COVID psychiatric or cognitive symptoms.[41,56]. Without well-established and clear protocols, the current approaches to assessment and management of such patients remain inconsistent, which in turn leads to variability in quality of care locally and globally. The need for developing evidence-based guidelines and integrating nurse specialists in long COVID clinics, both in resource-rich and low-resource settings, is all the more essential today.

4. Systemic preparedness:

As we are seeing improvement in recognition of long COVID as being clinically relevant, there is an insufficiency being noticed in overall systemic preparedness. The current fragmented nature of healthcare delivery, gaps in interdisciplinary collaboration, and shortages in workforce readiness tend to limit health systems in responding efficiently. Select key issues as described below help illustrate the challenges:

• Patchy access to long COVID clinics: Many tertiary hospitals or academic institutions in developed countries have launched long COVID clinics.[57-60] Even with this development, access can be inconsistent, especially in low-resource or rural areas. Patients can end up with long wait times for appointments, broken referral pathways, and ever-increasing financial burdens.[61-63] Data from the USA and European Union (EU) countries suggest that patients can frequently go undiagnosed or receive inadequate treatment due to the lack of standardization in the referral system or uneven geographic distribution of services.[64]
• Lack of integration between psychiatry and neurology: The separation of clinical specialities, especially neurology and psychiatry, in traditional healthcare often leads to issues related to the care of patients with long COVID.[65] Cognitive symptoms fall under neurology, but psychiatric specialists manage associated depression or anxiety, and there is often minimal coordination between these two specialties. This, in turn, can delay diagnosis, cause duplication of services, and cause economic burden on patients. Researchers have emphasized integrating neuropsychiatric approaches and acknowledged the biological and psychosocial overlap in patients with long COVID.[9,66]
• Workforce training deficiencies: Healthcare professionals, including physicians, nurses, and allied health workers, have reported limited training and a lack of confidence in managing patients with long COVID symptoms. Insufficient continuing education, lack of standardized clinical guidelines, and the general stigma associated with post-viral syndromes drastically increase these deficiencies. Surveys have shown that there is an urgent need for workforce-wide educational initiatives to overcome under-preparedness in identifying emotional and cognitive symptoms.[41,56]
• Policy-level changes and multidisciplinary unit models: The emergence of long COVID highlights the need for changes at the policy level to have an effective change at the care level by incorporating integration of different disciplines, including neurology, psychiatry, cardiology, pulmonology, rehabilitation, and nursing expertise into a single multidisciplinary unit of care. Select long COVID centers in the USA and the UK have successfully demonstrated the potential such an integrated care system has on improved patient outcomes.[64,66] International policy initiatives from global organizations such as the WHO and the CDC call for an increase in investments in long COVID research, standardization of diagnostic frameworks, and simplifying reimbursements, all while better understanding the complexity of post-COVID care of patients.[7,8]

With growing evidence on the interlinkage of COVID and neuropsychiatric symptoms, we must move towards an integrated structure of diagnosis, treatment, research, and healthcare policy. To address this, we need to first acknowledge that the brain and mind function together, shaped by immunological, viral, and psychosocial factors, and we need to bridge the traditional divide between neurology and psychiatry. Below are five strategies that can prove essential to address this moving forward:

Standardized diagnostic frameworks: The most crucial step for advancing care is the development of a standardized diagnostic framework. Current instruments, such as the MoCA and Hospital Anxiety and Depression Scale (HADS), are not validated specifically for long COVID neuropsychiatric sequelae.[67] Patients have to deal with inconsistent assessments, and cross-study comparability is limited due to a lack of harmonized criteria. It is important to add new ICD-11 categories of cognitive and psychiatric symptoms to emerging post-COVID conditions, as has been advised by the WHO.[7,9]. Incorporation of neurocognitive screening should be added as a standard diagnostic protocol.[34]

Multidisciplinary clinics: Multidisciplinary clinics play an important role in healthcare. Improved patient outcomes, especially in post-COVID care, have been noted by the integration of different disciplines such as neurology, psychiatry, pulmonology, cardiology, rehabilitation, and nursing.[64,66] Such setups streamline referral and provide continuity of care while validating patient experience.

Longitudinal biomarker studies: Research in the near future should focus on biomarkers and the natural evolution of the coronavirus to understand the underlying biological aspects of long COVID.[68] Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), inflammatory cytokines, and other neuroimaging biomarkers are currently being studied for their diagnostic and prognostic potential in patients with long COVID neurological and psychiatric symptoms.[69,70,71] By distinguishing post-COVID cognitive impairment from non-COVID psychiatric illness with biomarker-driven pathways, we can develop targeted therapeutics and group patients for clinical trials.

Public awareness and destigmatization: The need of the hour is for the destigmatization of psychiatric symptoms of long COVID to improve patient outcomes. The focus in public health campaigns at the grassroots should be to educate that the neuropsychiatric sequelae are biological and not psychosomatic.[72,73] Awareness drives help reduce barriers to care and encourage patients to seek timely help. Timely incorporation of inputs from patient advocacy groups in policy and clinical guidelines will help ensure the interventions reflect real-world needs.[8,74]

Role of artificial intelligence and digital tools in rehabilitation: Digital health tools and artificial intelligence (AI) have shown promise in assessment and rehabilitation. AI-driven cognitive screening applications, wearable remotely monitored devices, and integration of machine learning models in the detection of relapses will transform the delivery of care and patient outcomes.[75-77]

In the post-COVID pandemic era, the emergence of long COVID is redefining the challenges in healthcare. There is an urgency of preparedness that cannot be overlooked. Globally, a new wave of chronic and disabling conditions is threatening us if decisive actions are not taken now. Systematic screening, early recognition, and proactive monitoring have to be actively scaled at primary and specialty care settings. We have to face this head-on collaboratively. As doctors and nurses play a critical role on the frontline, more research into biomarker discovery and novel therapeutic trials is needed. Policy has to be renewed so that patients are not left to go from door to door in search of quality care. The use of emerging technological tools in AI should be used to better assist in addressing the issues to safeguard global neurological and mental health and prepare us for the next public health crisis.

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Corresponding Author:
Kevin Morris
Department of Research and Development, Aklun Biotech, Nagpur, India
Editor-in-Chief, Medtigo Journal of Neurology and Psychiatry, USA
Morris Lifesciences and Technologies, Research Center, Nagpur, India
Email: morriskevin2508@gmail.com

Co-Author:
Walencia Olympia Pereira
College of Nursing and Health Sciences, Azusa Pacific University, California, USA

WOP and KM contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles. WOP and KM were involved in the Original Draft preparation, and Writing, Review & Editing to refine the manuscript. KM oversaw the Supervision of the work, ensuring accuracy and completeness. WOP and KM approved the final manuscript for submission to the journal.

Not applicable

The authors declare no conflicts of interest

The guarantor of this study was Kevin Morris, MD

https://doi.org/10.63096/medtigo3084243

Pereira WO, Morris K. The Neuropsychiatric Fallout of Long COVID: Clinical, Biological, and Health-System Readiness Challenges. medtigo J Neurol Psychiatr. 2025;2(4):e3084243. doi:10.63096/medtigo3084243 Crossref