What We Know Now About Long Covid Syndromes?

It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.

NO CSF BIOMARKER EVIDENCE OF PERSISTING CNS INFECTION AFTER SARS-CoV-2 INFECTION

Background: Neurocognitive symptoms are common in acute as well as convalescent (post-acute sequelae of COVID-19 [PASC]) COVID-19, but mechanisms of CNS pathogenesis are unclear. The aim of this study was to investigate cerebrospinal fluid (CSF) biomarker evidence of CNS infection, immune activation and neuronal injury in convalescent compared with acute infection. Method(s): We included 68 (35% female) patients >=18 years with CSF sampled during acute (46), 3-6 months after (22) SARS-CoV-2 infection or both (17), and 20 (70% female) healthy controls from longitudinal studies. The 22 patients sampled only at 3-6 months were recruited in a PASC protocol. CSF N-Ag was analyzed using an ultrasensitive antigen capture immunoassay platform (S-PLEX SARS-CoV-2 N Kit, Meso Scale Diagnostics, LLC. Rockville, MD). Additional analyses included CSF beta2-microglobulin (beta2M)], IFN-gamma, IL-6, TNF-alpha neurofilament light (NfL), and total and phosphorylated tau. Log-transformed CSF biomarkers were compared using ANOVA (Tukey post-hoc test). Result(s): Patients sampled during acute infection had moderate (27) or severe (19) COVID-19. In patients sampled at 3-6 months, corresponding initial severity was 10 (mild), 14 (moderate), and 15 (severe). At 3-6 months, 31/39 patients reported neurocognitive symptoms;8/17 patients also sampled during acute infection reported full recovery after 3-6 months. CSF biomarker results are shown in Figure 1. SARS-CoV-2 RNA was universally undetectable. N-Ag was detectable only during acute infection (32/35) but was undetectable in all follow up and control samples. Significantly higher CSF concentrations of beta2M (p< 0.0001), IFN-gamma (p=0.02), IL-6 (p< 0.0001) and NfL (p=0.04) were seen in acute compared to post-infection. Compared to controls, beta2M (p< .0001), IL-6 (p< 0.0001) and NfL (p=0.005) were significantly higher in acute infection. No biomarker differences were seen post-infection compared with controls. No differences were seen in CSF GFAp, t-tau or p-tau. Conclusion(s): We found no evidence of residual infection (RNA, N-Ag), inflammation (beta2M, IL-6, IFN-gamma, TNF-alpha), astrocyte activity (GFAp) or neuronal injury (NfL, tau) 3-6 months after initial COVID-19, while significantly higher concentrations of several markers were found during acute infection, suggesting that PASC may be a consequence of earlier injury rather than active CNS damage. CSF beta2M, IL-6, IFN-gamma and NfL were significantly lower after 3-6 months than during acute COVID-19 and not different from healthy controls. (Figure Presented).

Trajectory of Post-Covid Neurocognitive Recovery in People Living with and without Hiv

Background: Neurocognitive dysfunction is common in long COVID and in people living with HIV (PWH). It is unknown whether PWH experience different disturbances in neurocognitive function following COVID-19 compared to HIVseronegative people. Method(s): The amfAR-Johns Hopkins University COVID Recovery Study is a prospective observational cohort study consisting of four groups: participants who had SARS-CoV-2 infection for the first time within 30 days prior to enrollment with HIV (PWH, arm 1) and without HIV (arm 2);participants with no history of SARS-CoV-2 infection with HIV (arm 3) and without HIV (arm 4). 93.5% of the cohort had received a COVID-19 vaccine prior to enrollment. Cognitive tests were administered at 1-and 4-months post symptom onset (arms 1-2) or post-enrollment (arms 3-4) in seven domains. Age standardized scores (all tests) and age-sex-and education-standardized scores (verbal fluency) were obtained. Standardized scores were compared using the Mann-Whitney U Test and the Kruskal-Wallis test. Result(s): PWH scored lower than HIV-seronegative participants at 1 and 4 months post-COVID on three tests: the Hopkins Verbal Learning Test-Revised (HVLT-R) learning (M1, p=0.011, M4, p=0.015), HVLT-R memory (M1, p=0.029, M4, p=0.007), and category-cued verbal fluency (VF;M1&4, p< 0.001). For the majority of timepoints, PWH who were post-COVID produced equivalent scores as PWH who never had COVID (p-levels > 0.05). Comparing post-COVID HIV-seronegative people to those who never had COVID, post-COVID participants scored lower than never-COVID participants on the Oral Trail Making Test part A (OTMT) test of processing speed at month 1 (p=0.033). Between month 1 and 4, HIV-seronegative people who were post-COVID showed improvements in HVLT-R Recognition (p=0.039), OTMT A (p=0.003), and OTMT B test of executive function (p=0.032). Conclusion(s): Neurocognitive scores in PWH were independent of COVID status, suggesting that higher frequencies of post-COVID neurocognitive dysfunction in PWH compared to HIV-seronegative people are due to HIV-associated factors more so than COVID. HIV-seronegative, post-COVID people demonstrate diminished recognition memory, processing speed, and executive function at 1 month post-COVID that improves by 4 months. Post-COVID neurocognitive dysfunction is present, if temporary, even in a highly vaccinated cohort of people.

One year overview of follow-up in a post-covid consultation of critical patients with covid-19

Introduction: Long-term clinical management and evolution of a cohort of critical COVID-19 survivors has not been well described. Method(s): We report a prospective observational study of COVID-19 patients admitted to ICU between March to August 2020. The follow-up comprised symptoms, pulmonary function test, 6-minute walking test (6MWT, and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-covid19 syndrome was performed at 1-year. Result(s) and Conclusion(s): A total of 181 patients were admitted at the ICU during the study period. They were predominantly middle-aged (median [IQR] of 61 [52;67] years old) male (66.9%) with a median of ICU stay of 9 (5- 24.2) days. Twenty percent of them died in the hospital and 39 were not able to be included, a final cohort of 105 patients initiated the follow-up. At one year, 32.2% persist with respiratory alterations and needed to continue the follow-up. 10% still had severe lung diffusing (DLCO) involvement (<60%) and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) of symptoms of 5.77 (4.66) and 61.3% meet criteria for post-covid syndrome at one-year. During the follow-up 46 patients were discharge and 16 were transfer to others consultations. Other conditions such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%) and lung cancer (1%) have been identified. A high use of healthcare resources is observed in the first year of these critical survivors after hospital discharge.

Providing Comprehensive Services to Treat Patients and the Inpatient Psychiatric Bed Crisis

Objectives: A growing mental health crisis and a shortage of inpatient psychiatric beds have resulted in a surge of patients' boarded' in emergency departments awaiting acute inpatient psychiatric placement. This delays care and causes a further burden on already stressed emergency services. In June 2020, the Centers for Disease Control and Prevention (CDC) reported an increased incidence of anxiety and depressive disorders since March of 2020, in comparison to pre-pandemic data. This has further exacerbated the shortage of psychiatric beds nationwide. In addition, staff shortages at state psychiatric hospitals in the Commonwealth of Virginia led to temporary closures to admissions. State facilities in VA provide care for our most vulnerable population, including (involuntary) patients on a temporary detention order (TDO). Carilion Clinic implemented the Comprehensive Psychiatric Emergency Program (CPEP) in August 2020 with the goal of early identification and robust treatment of psychiatric patients while in the ED. Since implementation of the CPEP, providers have been able to redirect patients away from burdened state psychiatric facilities by rapid stabilization of patients in the ED. Patients were able to step down to a less restrictive environment, often no longer meeting criteria for TDO. This study aims to assess the rate of TDO releases pre- and postimplementation of the CPEP at Carilion Clinic. Method(s): A pilot program was launched in August 2020 at Carilion Roanoke Memorial Hospital through a collaboration of the Departments of Emergency Medicine and Psychiatry. The staff was comprised of a psychiatrist, a psychiatric nurse practitioner, and a social worker. Data was collected from May 2020 to June 2021 from the Epic electronic medical record and included all patients in the ED on a TDO, ages six and above. Patients who no longer met criteria for a TDO were released from involuntary status and either redirected as a voluntary patient to an inpatient psychiatric unit or discharged to the community. The rate of TDO releases three months prior to CPEP implementation was assessed and compared to the TDO release rate post-CPEP implementation. Result(s): Prior to CPEP implementation, the TDO release rate was 7%, amounting to four patients released from a TDO per month. After implementation of CPEP, the TDO release rate increased to 19%, equating to thirteen patients released from a TDO per month during the pilot period. This led to a decrease in the number of patients that would have previously been admitted to a state psychiatric facility. Patients who benefitted from implementation of the CPEP were those with conditions in the following categories: chronic mental illness (32%), individual/family crisis (24%), neurocognitive disorders (20%), substance use disorder (18%), autism spectrum disorders and intellectual/developmental disabilities (6%). Conclusion/Implications: Implementation of the Comprehensive Psychiatric Emergency Program (CPEP) in Carilion Clinic' Emergency Department was successful in reducing the number of state psychiatric admissions by redirecting 11% more involuntary patients to voluntary status. The results of this study highlight the benefits of having in-house psychiatry teams dedicated to early triage, rapid treatment, and comprehensive case management for psychiatric patients in the emergency department. References- CDC, National Center for Health Statistics. Indicators of anxiety or depression based on reported frequency of symptoms during the last 7 days. Household Pulse Survey. Atlanta, GA: US Department of Health and Human Services, CDC, National Center for Health Statistics;2020. https:// www.cdc.gov/nchs/covid19/pulse/mental-health.htm.

Similarities and differences between post-COVID-19 syndrome and fibromyalgia

It is estimated that 4% of people infected with COVID-19 will develop post-COVID-19 Syndrome (PC 19). PC 19 is defined as the presence of unexplained signs and symptoms developed during the illness and persistent beyond 12 weeks. Fibromyalgia (FM) is defined as generalized musculoskeletal pain of more than three months duration and is accompanied by other alterations such as fatigue and neurocognitive disorders. Clinically, both pathologies are similar, they share asthenia, myalgia, mental slowness, attention deficit, execution, and processing. The average age of incidence, the predominance in the female sex and the prevalence are similar in both groups. In PC 19 there is a clear relationship between the infection and the appearance of symptoms. In FM its etiology is unknown and various mechanisms are postulated as the cause, but among all of them, it is worth highlighting infections, mainly viral ones, as triggers of the symptom picture. At the present time, we do not know how the symptoms occur in both diseases, so we have no treatment, except symptomatic. So far we have seen the similarities, but there are also differences. In PC 19, only a third of the patients have generalized pain, a fact that is present in 100% of patients with FM and that defines the disease This leads us to conclude that although both coincide in many aspects, they are not the same clinical picture, but given its characteristics, it seems logical to include it in the group of central sensitization diseases. (DOLOR. 2022;37:91-5) Copyright © 2022 Publicaciones Permanyer. All rights reserved.

Inpatient psychiatric care of COVID-19 infected patients in a Hungarian general hospital

Introduction: during the study period (08/02/2021 - 11/05/2021) the Centre of Psychiatry in the Jahn Ferenc South-pest Hospital (CP-JFSH) was one of the two psychiatric wards in Budapest, specialized for the treatment of COVID-19 infected psychiatric patients. Objective(s): the aim of the study was to survey the characteristics and evaluate the outcome of the COVID-19 infected psychiatric patients treated in the CP-JFSH. Method(s): retrospective analysis of the files of COVID-19 infected psychiatric patients admitted to the CP-JFSH in a 3 month period. In addition to demographic data, diagnostic distribution, co-morbidities, date of infection, method of detection of the virus, presence of pneumonia, severity of infection, outcome, treatment, vaccination data were evaluated. Result(s): in the study period 124 COVID-19 infected psychiaric patients were admitted to the CP-JFSH. The gender distribution was aproximately equal, the mean age of the patients was 62.8+/- 15.7 years. Majority of the patients suffered from major neurocognitive disorder followed by schizophrenia spectrum disorder. Most common co-morbidities were cardiovascular diseases and diabetes. Pneumonia was present in 41% of the patients. Majority of the patients were already infected at the time of admission, detected with the first PCR examination and haven't been vaccinated yet. Thirty-one percent of the patients suffered from moderate to severe COVID-19 illness. COVID-19 specific therapy (favipiravir, remdesivir, fluvoxamin) was introduced in 57%. Mortality was 12% while the relaps rate 4%. Conclusion(s): comparing with inpatient mortality rate published in the literature, mortality rate was higher among psychiatric patients, underlining the need for special attention of this population.

BENIGN PARTIAL ROLANDIC EPILEPSY FOLLOWING SARS-COV-2 INFECTION AND NEUROCOVID-19 EXPERIENCE: A CASE STUDY

Background Early evidence described by a number of scholars worldwide suggests that neu-roCOVID-19 has both mild [e.g. loss of smell (anosmia), loss of taste (ageusia), neurological tics (heterophilia), visual disturbances, headaches, dizziness, disorien-tation] and more severe sequelae (e.g. cognitive impairment, seizures, delirium, psychosis, strokes). Long-term neurological problems or neurological deficits may also occur. The aim of this study was to describe the examination and neurother-apy of a boy following SARS-CoV-2 infection and NeuroCOVID-19 in whom neurological tics and motor automatisms as well as cognitive impairment, particularly attention deficit disorder, developed as a consequence. Case study: We present a boy K.S., 7 years old, without any neurodevelopmental disorders, following a SARS-CoV-2 infection in May 2021 and the contraction of neuro-COVID-19 confirmed by a genetic test for the quantitative detection of neutralising antibodies (responsible for immunity) in the IgG class against SARS-CoV-2. The boy had relatively mild pseudomonal symptoms of the illness: temperature 38.5, runny nose, cough, muscle aches, headaches and general weakness. He was treated symptomatically and recovered after 2 weeks. Two months later, at the beginning of July 2021, neurological tics consisting of an upward turning of the eyeballs to the left appeared. These tics intensified in August 2021 and were accompanied by motor automatisms consisting of the left hand stiffening in salute-like position, while at the same time there was an inclination of the head to the left. In September 2021, after exertion in the swimming pool, an epileptic seizure occurred which caused the boy to start drowning. In the days that fol-lowed the above described tics and motor automatisms increased. He also developed sleep disorders, which consisted of him waking up several times during the night, during which time neurological tics and motor automatisms also ap-peared. Gradually, cognitive dysfunctions, especially attention deficits and behavioural changes, joined in, making it impossible for the boy to function independently at school and in many situations of daily life. Neurophysiological examination: qEEG, ERPs and sLORETA tomography performed on 11.09.2021 using automatic seizure activity detection software showed the pres-ence of the neuromarker benign partial rolandic epilepsy (BPERS) and neurocog-nitive disturbances resembling the symptoms of attention deficit hyperactivity disorder (ADHD), compared with the neuromarkers of children with this condition (n=100) from the normative database of the Human Brain Index (HBI) in Switzer-land. Detection of the neuromarkerBPERS was helpful in selecting an individu-alised neurostimulation protocol. The patient participated in 20 neurofeedback sessions using (1) SMR reinforcement, theta inhibition;(2) theta inhibition, B1 reinforcement (15-18 Hz);(3) qEEG-guided neurofeedback. Neurostimulation with neurofeedback was conducted twice a week, for 15-20 minutes gradually increasing to 30-40 minutes per session. The patient also received individual goal-directed psychotherapy After successive sessions of neurofeedback, a gradual reduction neurological symptoms was observed. By the end of neu-rotherapy, neurological tics, motor automatisms, neurocognitive disorders and behavioural disturbances had completely disappeared. The patient functions well in school and achieves very good results. Conclusions: HBI methodology was helpful in finding functional neuromarkers of benign partial Rolandic epilepsy and disturbed cognitive control. Therefore, it was possible to offer more effective neurorehabilitation of the disorders, which contribute to a better quality of life for the patient.

QUALITY OF LIFE IN CANCER SURVIVORS LIVING IN NURSING HOMES

Introduction Our objective was to compare the quality of life (QOL) in residents according to their cancer status, using questionnaires adapted to potential neurocognitive disorders (NCD) presence. Methods This multicenter cross-sectional study included residents aged 70 years and older able to communicate, with an estimated necessary number of subjects of 352. The study was conducted in two steps: first including residents with cancer and next a control group randomly selected among residents without any history of cancer matched on NCD and dependence status. QoL was assessed with different scales: QolAD if NCD, otherwise WHOQOL-OLD and QLQC30+ELD14 in the cancer group. Results Due to the COVID pandemic, the study was terminated early, and only 70 included residents had complete analyzable data. The participants had a median age of 85 years [70-99] and 20 were male. Regarding dependence status, 20 had an ADL between 0-2, 15 an ADL between 2.5-4.5, 34 an ADL between 5-6. Among the 42 residents in the cancer group, mostly cancer survivors. 13/42 residents in the cancer group had NCD (vs. 7/28 in the control group), 19/42 in the cancer group reported pain (vs. 16/28 in the control group). Conclusions Various obstacles have prevented from completing the study: low resident eligibility, difficulty in obtaining written consent, and finally the COVID pandemic which limited the availability of the nurse investigators and had impacted residents' QOL. This study could be redone at a distance from this pandemic if possible.

ONSET OF COGNITIVE DISORDERS FEW DAYS AFTER A COVID-19 INFECTION DISEASE: DIFFICULTIES TO SET A DIAGNOSIS IN MIDDLE AND LOW-INCOME COUNTRIES

Introduction The coronavirus disease 2019 (COVID-19) was first known by its respiratory symptoms. Neurological complications are increasingly seen and described. Our case emphasizes the difficulties of differential diagnosis between encephalitis and post-traumatic stress disorder (PTSD) in SARS-COV2 patients. Case report A healthy 62 years old man tested positive for COVID-19 during a travel procedure. He was admitted to hospital because of a sudden drop of oxygen saturation from 99% to 89% with pulmonary CT scan showing a parenchymal bilateral ground-glass lesions and consolidative opacities of about 50% of lung while the patient remained asymptomatic. After he has been discharged from hospital he developed isolated executive disorders. Post COVID-19 encephalitis or PTSD were questioning. Discussion and conclusion Our patient had an acute hypoxemia which is well known to be associated with executive disorders such as in acute respiratory distress. But these signs appeared after the COVID-19 came negative hence the executive disorders were likely to be related to direct brain infection or to a non-infectious condition like the PTSD. Functional neuroimaging is then the gold standard to rule out a brain damage.

Dying Wish: A Case of Controversial Covid Vaccination Near the End of Life

Background: This case describes the circumstances of an older woman and her daughter faced with the dilemma of whether or not to receive the COVID-19 vaccine at the end of life. Methods: Ms. V was a 90-year-old woman with past medical history of major neurocognitive disorder, asthma, and hypertension on home hospice after experiencing a rapid decline beginning in November 2020. By January 2021, she had significantly deteriorated with a prognosis of weeks. At this time, the COVID-19 vaccine had become available to high-risk individuals and their household members. Because Ms. V lacked capacity to make her medical decisions, her daughter and healthcare power of attorney, Ms. B, had to determine her wishes. Ms. V's goals were comfort care and to avoid hospitalization. Although she had worked as a nurse, she had declined her annual influenza vaccine in the past. However, Ms. B felt that her mother would have wanted to help her children and caretakers get the vaccine, which would only be possible if she got the vaccine first. Results: Extensive conversations with Ms. V's children, hospice team, and geriatrician were held utilizing the 4-box approach to ethical decision making.1 Ms. B decided that her mother would have wanted to receive the vaccine for the main purpose of also vaccinating her children, who both had advanced heart failure and were at high risk for complications from COVID-19. She received one dose of the Pfizer COVID-19 vaccine and died ten days later. Her children and live-in caregiver all received the Pfizer Covid-19. Conclusion: Although Ms. V had previously refused annual influenza vaccinations, her daughter felt that her mother would have gotten the vaccine to provide protection for her children and caregiver. While it was acknowledged that Ms. V would probably gather little immunity benefit from the vaccine due to her poor prognosis, her daughter felt that the benefits of the entire household receiving the vaccine outweighed any potential risks. Her family called this final act of protection her dying wish.

Daytime Hypersomnolence in COVID-19: A Case Report and Literature Review

Coronavirus infectious disease 2019 (COVID-19) is confirmed to develop neurocognitive complications. In the present paper, we describe two patients with laboratory-confirmed COVID-19 and excessive daytime sleepiness. In the present study, we reported two laboratory-confirmed cases of COVID-19 with excessive daytime sleepiness. Patients had drowsiness and mild confusion on presentation. In both cases, CNS infections, including meningitis and encephalitis, were ruled out. Both patients’ symptoms remarkably improved following the therapeutic course indicating the direct effect of SARS-CoV2 in sleep modulating centers on the brain. COVID-19 should be considered in patients with excessive daytime sleepiness and drowsiness in the current outbreak.