Severe Acute Respiratory Syndrome Coronavirus 2 is Penetrating to Dementia Research

Abstract

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus infectious disease 2019 (COVID-19), which was first reported in Wuhan, China, in late December, 2019. Despite the tremendous efforts to control the disease, SARS-CoV-2 has infected 1,5 million people and caused the death of more than a hundred thousand people across the globe as of writing. Recently, Mao et al. [1] investigated the penetration potential of SARS-CoV-2 into the central nervous system in 214 patients. They reported that 36.4% of the patients had some neurologic findings which are ranged from nonspecific manifestations, e.g., dizziness, headache, and seizure, to specific manifestations, e.g., loss of sense of smell or taste, and stroke. Whether these common symptoms in their patients are related to SARS-CoV-2 infection is not known. However, it is important to mention here that dramatic neurologic symptoms, i.e., depressed level of consciousness, seizure, and stroke, are common in the patients at the late stage of the disease, accounting for increased mortality rate in severely affected patients. Nevertheless, to objectively delve into the direct relation between the neurologic symptoms and COVID-19, medical comorbidities of patients should also be considered [2]. Further studies are needed because we are in the midst of an ongoing pandemic of COVID-19, and neurologists may be confronted with new-onset neurologic symptoms owing to COVID-19. SARS-CoV-2 penetrates via human angiotensin-converting enzyme-2 receptor (ACE-2) that was also utilized by severe acute respiratory syndrome coronavirus (SARS CoV) [3]. Glial cells and neurons have been reported to express ACE-2 receptors, which make them a potential target of COVID-19. It was indicated that SARS CoV causes neuronal death by invading the brain via olfactory epithelium [4]. The electron microscopy, immunohistochemistry, and real-time reverse transcription- PCR findings have corroborated the presence of SARS-CoV in the brain tissue [4] and cerebrospinal fluid [5]. Together, it can be speculated that SARS-CoV-2 can affect the brain by penetrating the brain via the cribriform plate, which can account for the early findings of the COVID-19 like altered sense of smell or hyposmia. Because SARS-CoV-2 causes severe respiratory symptoms in people aged 60 years and older, it has important implications for patients with Alzheimer’s disease (AD) [6]. Therefore, in the countries that have taken action to the virus, clinic studies of AD have been stopped to protect the patients. However, rigorous quarantine of elders has aborted clinic trials and experimental studies conducted with transgenic animals. Transgenic models are quite expensive; the loss of these animals has costly consequences. There is no doubt that this storm will stop, but its catastrophic effects on dementia research will continue for a time. Thus, dementia researchers and pharmaceutical companies should determine an emergency action plan to exit the chaos of this pandemic. Here, we listed some challenges in dementia research during the COVID-19 outbreak and table some suggestions. All countries try to control SARS-CoV-2 by social distancing. Therefore, neurology clinics were closed, and routine examination of Alzheimer’s patients was stopped. However, the lockdown of patients with AD caused clinical studies to stop. which has severely affected dementia research. Additionally, the arrest of experimental studies due to the closing of universities in two hundred countries also deprives experimental achievements. The closing of universities may lead to data loss, death of expensive transgenic animals, international researchers to be faced with visa problems, and be lost the laboratory staff whose contract has expired [7]. It is impossible that forecasting when this COVID-19 pandemic will end is impossible and thus, it is essential that a solution be developed to continue dementia studies on Alzheimer’s patients. Remote monitoring of the patients with the use of technology is in the lead of possible solutions. Clinicians can continue to follow their patients by telemedicine [8], but extended lockdown of patients may cause depression in both patients and their caregivers [9]. It is also known that movement restriction exacerbates AD symptoms [10]. The monitorization of the patient in this condition with telemedicine would not provide objective data. In addition, when patients living in rural areas are considered, it will not be a surprise that reaching equally all patients is impossible. Therefore, a collective action plan protecting dementia research during the COVID-19 outbreak should be prepared by a consortium of pharmaceutical companies, researchers, clinicians, and patients. Data loss is in the lead of expected problems during the COVID-19 outbreak. For example, the planned ending dates of phase 2/3 trials of gantenerumab (Roche) and solanezumab (Lilly) were missed [11]. It is highly essential that patients be monitored from their homes with telemedicine to protect them. Nonetheless, it is not sufficient for the continuation of clinical trials and experimental studies. We suggest that patients of phase trails should be isolated in fully-equipped nursing homes managed by qualified personnel. In this way, the patients can be more effectively protected from SARS-CoV-2 and the depression caused by the lockdown.Young family members going out for basic needs could infect older family members. Also, patients with AD pay less attention to hand hygiene, which makes them more susceptible to SARS-CoV-2. Moreover, cats have recently been shown to be infected by SARS-CoV-2 [12]. Patients with AD may not follow directions of neurologists on telemedicine and thus, the interaction of Alzheimer’s patients with pets can cause a dangerous scenario. Consequently, the lockdown of patients with dementia in their homes might not be an appropriate exit strategy for the future of dementia research. On the other hand, it is important to mention here that the nursing home capacity of the United States may not be sufficient for 5,8 million Alzheimer’s patients aged 65 years and older [13]. Thus, we highlight that only the patients involved in the clinic trails should be followed in the nursing homes. The other patients can be monitored with telemedicine from their homes. The data will hardly be lost in patients isolated in nursing homes. In this strategy, secondary risk factors affecting the clinic trails like depression are also removed. The motivations of clinicians and researchers is as important as the patients in the catastrophic atmosphere of the outbreak. Governments, media, and funders can support the motivations of clinicians and researchers. For example, research funders and pharmaceutical companies can extend project deadlines and provide an additional promotion to the researchers who have completed their clinic trails. Consequently, a global action plan should be prepared to block SARS-CoV-2 penetration to dementia research. At first glance, it may be thought that the most appropriate strategy for patients with dementia is social isolation in their homes during the outbreak as in healthy young people and elders. However, we suggest that isolating patients with dementia in fully-equipped nursing homes can be a more appropriate exit strategy for the protection of dementia patients and research.

Neuropsychiatric Symptoms in Elderly With Dementia During COVID-19 Pandemic: Definition, Treatment, and Future Directions

“…In order to avoid increasing antipsychotic usage and dosages, physical restraint techniques have been used to control agitation ( 26 ). Other specific programs, which included selective, personalized isolation for those who cannot comply with current isolation guidelines, have been described ( 29 , 30 ). However, behavioral dyscontrol in patients with dementia largely exceeds the resources provided by nursing homes ( 31 ), and systematic application of personalized isolation may be difficult to implement.…”

Cognitive and Neuropsychiatric Manifestations of COVID-19 and Effects on Elderly Individuals With Dementia

“…Although some procedures could be still performed through telemedicine such as clinical Research and clinical trials Perform follow-up evaluation to COVID-19 survivors to examine the presence of long-term neuropsychiatric and cognitive complications evaluations and neuropsychological testing, this type of research usually requires the presence of patients to undergo blood draw, lumbar puncture or neuroimaging, among others. Basic laboratories conducting experimental research in the Alzheimer's field have also been affected by COVID-19, as the sudden lack of staff due to lockdown forced ongoing experiments to be stopped and transgenic animals to die, with the resulting loss of valuable data (Bostanciklioglu, 2020). Besides, research funding is currently being diverted into COVID-19 research, leaving dementia researchers with less funding opportunities to continue their projects.…”

Behavioral and Psychological Effects of Coronavirus Disease-19 Quarantine in Patients With Dementia

“…Changes in neuropsychiatric symptoms in subjects with dementia may exacerbate the psychological effects of lockdown in their caregivers, situation which may further worsen patients' behavioral symptoms, acting in a vicious loop of mutual increase of psychiatric burden. Finally, confinement reduces access to physical exercise or even physiotherapy, and movement restriction exacerbates symptoms of dementia (13,14). In turn, lack of activities and global cognitive and physical stimulation may cause delirium in individuals with dementia, contributing further to morbidity.…”