Neuropsychiatric side of the COVID-19

The latest data shows the wide spectrum of various neuropsychiatric manifestations of COVID-19 often persisting after its acute phase. Neuropsychiatric complications of COVID-19 include various neural impairments (fatigue, headache, dizziness, anxiety, cognitive dysfunction, sleep and mood disturbances, muscle soreness, stroke, seizures, encephalitis, ataxia, myelitis, anosmia, ageusia, Guillain-Barré syndrome, and Miller Fisher syndrome) as the development of a full clinical picture of psychiatric diseases (psychotic, anxiety, and affective spectrum). Symptoms of post-COVID syndrome may persist even a year after discharge and are associated with a high risk of suicidal behavior in virus survivors. Currently, possible mechanisms of COVID-19 effect on the central nervous system include indirect (cytokine storm, hypoxia, acute respiratory distress syndrome, neuroinflammation, postinfection autoimmunity) and possible direct COVID-19-induced neuronal/vascular damage (including direct PAMP-like effect of SARS-CoV-2 components on Toll-like receptors of glia). Autoimmune and immunopathological links of COVID-19 pathogenesis also may play a role in its neuropsychiatric complications. COVID-19 is known for high rates of morbidity and mortality. Early recognition of neuropsychiatric manifestations, adequate treatment, and long-term follow-up are needed to provide efficient patient care. © 2023 Elsevier Inc. All rights reserved.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.

Persistence of IgG COVID-19 antibodies: A longitudinal analysis.

Background and aim: The kinetics of antibody production in response to coronavirus disease 2019 (COVID-19) infection is not well-defined yet. This study aimed to evaluate the antibody responses to SARS-CoV-2 and its dynamics during 9-months in a cohort of patients infected during the first phase of the pandemic. As a secondary aim, it was intended to evaluate the factors associated with different concentrations of IgG antibodies. Methods: A prospective cohort study was conducted from June 2020 to January 2021. This study recruited a convenience sample of adult individuals who where recently diagnosed with COVID-19 and were living in mainland Portugal. A total of 1,695 blood samples were collected from 585 recovered COVID-19 patients up to 9 months after SARS-CoV-2 acute infection. A blood sample was collected at baseline and three, 6 and 9 months after SARS-CoV-2 acute infection to assess the concentration of IgG antibody against SARS-CoV-2. Results: The positivity rate of IgG reached 77.7% in the first 3 months after symptom onset. The IgG persists at all subsequent follow-up time-points, which was 87.7 and 89.2% in the 6th and 9th months after symptom onset, respectively. Three distinct kinetics of antibody response were found within the 9 months after infection. Kinetic 1 (K1) was characterized by a constant low IgG antibody concentration kinetic (group size: 65.2%); kinetic 2 (K2), composed by constant moderate IgG kinetic (group size: 27.5%) and kinetic 3 (K3) characterized by higher IgG kinetic (group size: 7.3%). People with ≥56 years old (OR: 3.33; CI 95%: [1.64; 6.67]; p-value: 0.001) and symptomatic COVID-19 (OR: 2.08; CI 95%: [1.08; 4.00]; p-value: 0.031) had higher odds of a "Moderate IgG kinetic." No significant association were found regarding the "Higher IgG kinetic." Conclusion: Our results demonstrate a lasting anti-spike (anti-S) IgG antibody response at least 9 months after infection in the majority of patients with COVID-19. Younger participants with asymptomatic disease have lower IgG antibody positivity and possibly more susceptible to reinfection. This information contributes to expanding knowledge of SARS-CoV-2 immune response and has direct implications in the adoption of preventive strategies and public health policies.

Vaccination effects on post-infection outcomes in the Omicron BA.2 outbreak in Shanghai.

Omicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

Results of Comparative Serological Studies of Post-Infection and Post-Vaccination Immunity Characteristics to SARS-CoV-2 in Kidney and Liver Recipients

Introduction. Immunocompromised individuals, such as kidney and liver recipients, are at high risk for a severe course of COVID-19, which explains the special interest in this category of patients in conditions of high incidence of this infection and mass vaccination with available vaccines. Purpose. To study the characteristics of humoral post-infection and post-vaccination immunity to SARS-CoV-2 in kidney and liver recipients based on qualitative and quantitative serotesting. Materials and methods. The study of characteristics of post-infection immunity was carried out in the group of immunocompromised individuals (n=213) including kidney (n=177) and liver (n=26) recipients with PCR confirmed COVID-19, while the study of post-vaccination immunity was carried out in the group of kidney (n=56) and liver (n=12) recipients immunized with Sputnik V (Russia) or Vero Cell (China). In comparative studies, a simple randomized sample was used of immunocompetent patients who recovered from COVID-19 (n=163), corresponding in age and gender to that of the recipients examined, as well as a convenient sample of immunocompetent individuals vaccinated with Sputnik V (n=257) and Vero Cell (n=160). Serotesting for the detection of IgG to S and N proteins of SARS-CoV-2 was carried out by ELISA. Reliable intervals for proportions were calculated using the Wald method. The significance of the detected differences was assessed by the χ2 (chi-square) method. Results. The paper presents data on comparative serological testing of kidney and liver recipients recovered from COVID-19. The detection rate of post-infectious IgG to N and S proteins of SARS-CoV-2 was found to be 88.1% in the group of kidney recipients, 91.3% in the group of liver recipients, and 91.7% in the group of immunocompetent individuals. At the same time, the proportion of N protein seropositive subjects in all groups of observation was lower in comparison with that to S protein, with a significant difference in the group of kidney recipients (59.9% and 86.4%, respectively, p<0.001). The overall dynamics of the decrease in proportion of seropositive individuals during the observation period up to 12 months from the onset of clinical manifestations of infection in both groups of recipients and in the group of immunocompetent individuals had common patterns, however, seroprevalence rates for IgG to N protein significantly differed over time (9–12 months from the onset of the disease) and were much higher in the group of immunocompetent individuals (p<0.001). Despite the presence of general patterns of post-infection antibody response formation, seroprevalence rates to SARS-CoV-2 and the duration of post-infection antibody persistence were slightly lower in the group of kidney recipients than in the group of liver recipients and in immunocompetent individuals. The immunological efficacy of vaccination (the proportion of individuals with post-vaccination antibodies) in the group of kidney recipients was significantly lower (p<0.001) than in the group of immunocompetent patients after both Sputnik V (68.0% and 98.8%, respectively) and Vero Cell (58.1% and 95.0%, respectively) immunization. In liver transplant recipients, there were no significant differences with immunocompetent individuals in terms of post-vaccination response. Conclusion. The data obtained indicate certain differences in characteristics of post-infection and post-vaccination antibody response due to patients' immune status. © 2022, Professionalnye Izdaniya. All rights reserved.

Direct, indirect, post-infection damages induced by coronavirus in the human body: an overview.

Background: Severe acute respiratory syndrome Coronavirus-2 invades the cells via ACE2 receptor and damages multiple organs of the human body. Understanding the pathological manifestation is mandatory to endure the rising post-infection sequel reported in patients with or without comorbidities. Materials and methods: Our descriptive review emphasises the direct, indirect and post-infection damages due to COVID-19. We have performed an electronic database search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with selective inclusion and exclusion criteria. Results: The included studies substantiated the extensive damages in the multiple organs due to direct and indirect consequences of COVID-19. After an apparent recovery, the prolonged presentation of the symptoms manifests as post-COVID that can be related with persisting viral antigens and dysregulated immune response. Conclusion: A few of the symptoms of respiratory, cardiovascular, and neuropsychiatric systems that persist or reappear as post-COVID manifestations. Vaccination and preventive programs will effectively reduce the prevalence but, the post-COVID, a multisystem manifestation, will be a significant tribulation to the medical profession. However, the issue can be managed by implementing public health programs, rehabilitation services, and telemedicine virtual supports to raise awareness and reduce panic.

Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.

ChAdOx1 nCoV-19 Immunogenicity and Immunological Response Following COVID-19 Infection in Patients Receiving Maintenance Hemodialysis.

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) were found to have a decreased immune response following mRNA COVID-19 immunization. ChAdOx1 nCoV-19 was a promising COVID-19 vaccine that performed well in the general population, but the evidence on immunogenicity in ESRD with HD patients was limited. Moreover, the immunological response to COVID-19 infection was inconclusive in patients with ESRD and HD. The aim of this study was to investigate the immunogenicity of ChAdOx1 nCoV-19 vaccination and the immunological response after COVID-19 infection in ESRD patients with HD. The blood samples were obtained at baseline, 1-month, and 3-month follow-up after each shot or recovery. All participants were measured for anti-spike IgG by the ELISA method, using Euroimmun. This study found a significant increase in anti-spike IgG after 1 month of two-shot ChAdOx1 nCoV-19 vaccination, followed by a significant decrease after 3 months. On the other hand, the anti-spike IgG was maintained in the post-recovery group. There was no significant difference in the change of anti-spike IgG between the one-shot ChAdOx1 nCoV-19-vaccinated and post-recovery groups for both 1-month and 3-month follow-ups. The seroconversion rate for the vaccinated group was 60.32% at 1 month after one-shot vaccination and slightly dropped to 58.73% at the 3-month follow-up, then was 92.06% at 1 month after two-shot vaccination and reduced to 82.26% at the 3-month follow-up. For the recovered group, the seroconversion rate was 95.65% at 1 month post-recovery and 92.50% at 3-month follow-up. This study demonstrated the immunogenicity of two-dose ChAdOx1 nCoV-19 in ESRD patients with HD for humoral immunity. After COVID-19 infection, the humoral immune response was strong and could be maintained for at least three months.

A Comparative Study of Nine SARS-CoV-2 IgG Lateral Flow Assays Using Both Post-Infection and Post-Vaccination Samples.

BACKGROUND: Since the SARS-CoV-2 pandemic, lateral flow assays (LFA) detecting specific antibodies have entered the market in abundance. Despite being CE-IVD-labeled, the antigenic compounds of the assays are often unknown, the performance characteristics provided by the manufacturer are often incomplete, and the samples used to obtain the data are not detailed. OBJECTIVE: To perform a comparative evaluation of nine lateral flow assays to detect IgG responses against SARS-CoV-2. For the evaluation, a carefully designed serum panel containing post-infection samples and post-vaccination (both mRNA vaccine and inactivated virus vaccine) samples was used. RESULTS: The sensitivity of the assays overall ranged from 9 to 90.3% and the specificity ranged from 94.2 to 100%. Spike protein-containing assays performed generally better than the assays with only nucleocapsid protein. The sensitivity of some assays was higher on post-infection samples, while other assays had a higher sensitivity to post-vaccination samples. CONCLUSION: A comparative approach in the verification of LFAs with an adequately designed serum panel enabled the identification of the antigens used in the assays. Sensitivities differed between post-infection and post-vaccination samples, depending on the assays used. This demonstrates that the verification of assays must be performed with samples representative of the intended use of the assay.

Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19.

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: A case-control study.

BACKGROUND AND AIM: Because acute infectious gastroenteritis may cause post-infection irritable bowel syndrome and functional dyspepsia and the severe acute respiratory syndrome coronavirus-2 affects gastrointestinal (GI) tract, coronavirus disease-19 (COVID-19) may cause post-infection-functional GI disorders (FGIDs). We prospectively studied the frequency and spectrum of post-infection-FGIDs among COVID-19 and historical healthy controls and the risk factors for its development. METHODS: Two hundred eighty patients with COVID-19 and 264 historical healthy controls were followed up at 1 and 3 months using translated validated Rome Questionnaires for the development of chronic bowel dysfunction (CBD), dyspeptic symptoms, and their overlap and at 6-month for IBS, uninvestigated dyspepsia (UD) and their overlap. Psychological comorbidity was studied using Rome III Psychosocial Alarm Questionnaire. RESULTS: At 1 and 3 months, 16 (5.7%), 16 (5.7%), 11 (3.9%), and 24 (8.6%), 6 (2.1%), 9 (3.2%) of COVID-19 patients developed CBD, dyspeptic symptoms, and their overlap, respectively; among healthy controls, none developed dyspeptic symptoms and one developed CBD at 3 months (P < 0.05). At 6 months, 15 (5.3%), 6 (2.1%), and 5 (1.8%) of the 280 COVID-19 patients developed IBS, UD, and IBS-UD overlap, respectively, and one healthy control developed IBS at 6 months (P < 0.05 for all except IBS-UD overlap). The risk factors for post-COVID-19 FGIDs at 6 months included symptoms (particularly GI), anosmia, ageusia, and presence of CBD, dyspeptic symptoms, or their overlap at 1 and 3 months and the psychological comorbidity. CONCLUSIONS: This is the first study showing COVID-19 led to post-COVID-19 FGIDs. Post-COVID-19 FGIDs may pose a significant economic, social, and healthcare burden to the world.

Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). AIMS OF REVIEW: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology. KEY SCIENTIFIC CONCEPTS OF REVIEW: The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment.

INTRODUCTION: An infection by COVID-19 triggers a dangerous cytokine storm, so tocilizumab has been introduced in Italy as an agent blocking the cytokine storm. This paper aims to describe the one-year survival of ICU patients treated with tocilizumab. METHODS: This observational study enrolled all patients confirmed to be infected by COVID-19 who were admitted to the ICU in our center. We offered tocilizumab to all non-septic patients if they did not present any contraindications. RESULTS: We enrolled 68 ICU patients in our center on 72 occasions during the enrollment period; we excluded four patients due to study criteria. The one-year mortality hazard ratio of treated patients was 0.64, with a confidence interval of 0.31 to 1.19, with p = 0.169. Among the survivors, 32 of 35 patients answered the phone interview (14 patients in the treated group and 18 in the untreated group); overall, the effect of COVID-19 on quality of life was 58.14%. These effects were lower in the tocilizumab group, with p = 0.016 *. CONCLUSIONS: Our observational data follow the most relevant largest trial. Patients treated with tocilizumab had lower rates of new-onset symptoms later COVID-19 ICU hospitalizations. As reported by recent medical literature, the presence of these symptoms suggests that a follow-up program for these types of patients could be useful.

Fatigue Symptoms Associated With COVID-19 in Convalescent or Recovered COVID-19 Patients; a Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence and prognosis of post-acute stage SARS-CoV-2 infection fatigue symptoms remain largely unknown. AIMS: We performed a systematic review to evaluate the prevalence of fatigue in post-recovery from SARS-CoV-2 infection. METHOD: Medline, Embase, PsycINFO, CINAHL, Web of Science, Scopus, trial registries, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for studies on fatigue in samples that recovered from polymerase chain reaction (PCR) diagnosed COVID-19. English, French, and Spanish studies were included. Meta-analyses were conducted separately for each recruitment setting. RESULTS: We identified 41 studies with 9,362 patients that recovered from COVID-19. Post-COVID-19 patients self-report of fatigue was higher compared to healthy controls (risk ratio (RR) = 3.688, 95%CI [2.502, 5.436], p < .001). Over 50% of patients discharged from inpatient care reported symptoms of fatigue during the first (event rate [ER] = 0.517, 95%CI [0.278, 0.749]) and second month following recovery (ER = 0.527, 95%CI [0.337, 0.709]). Ten percent of the community patients reported fatigue in the first-month post-recovery. Patient setting moderated the association between COVID-19 recovery and fatigue symptoms (R2 = 0.11, p < .001). Female patients recovering from COVID-19 had a greater self-report of fatigue (odds ratio [OR] = 1.782, 95%CI [1.531, 2.870]). Patients recruited through social media had fatigue above 90% across multiple time points. Fatigue was highest in studies from Europe. CONCLUSION: Fatigue is a symptom associated with functional challenges which could have economic and social impacts. Developing long-term planning for fatigue management amongst patients beyond the acute stages of SARS-CoV-2 infection is essential to optimizing patient care and public health outcomes. Further studies should examine the impact of sociodemographic, pandemic-related restrictions and pre-existing conditions on fatigue.

Myasthenia gravis associated with novel coronavirus 2019 infection: A report of three cases.

Several neurological presentations have been reported following coronavirus 2019 (COVID-19) infection. This case report describes three myasthenia gravis (MG) patients presented following COVID-19 infection. We report three adult patients with myasthenic Gravis and COVID-19 infection. The patients are between 38 and 61 years old. Case 1 is a 61-year-old woman with progressive dysphagia, nasal speech, ocular ptosis, diplopia, and proximal muscle weakness for 10 days. She had a COVID-19 infection 6 weeks ago. Case 2 is a 57-year-old man with clinical symptoms of muscular fatigability, diplopia, ptosis, and dysphagia for a week and a positive COVID-19 infection 10 days ago. Case 3 is a 38-year-old woman with fatigability, ptosis, dysphagia, and a diagnosis of COVID-19 infection 4 weeks ago. All patients had a positive RT-PCR for COVID-19 infection by nasopharyngeal swab test and a high-level acetylcholine receptor antibody in the serum. All patients were treated with pyridostigmine and prednisolone with a favorable outcome. MG may appear following COVID-19 infection, and the role of molecular mimicry and latent MG activation should be considered the cause of the disease onset.

Durable antibody response one year after hospitalization for COVID-19: A longitudinal cohort study.

OBJECTIVES: Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of antibody titres decline and seroreversion. METHODS: Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients' discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively. RESULTS: 80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.059 [0.05-0.067], p < 0.001), inversely with WHO severity score (coefficient [95% CI] -0.042 [-0.079/-0.004], p = 0.033), and there was a trivial positive association with age (coefficient [95% CI] 0.002 [0-0.005], p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.091 [0.078-0.105], p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53-0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00-1.33; p = 0.062). CONCLUSION: Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals.

BACKGROUND & AIMS: Chronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle. METHODS: HepG2-NTCPsec+ cells were inoculated with HBV. Supernatants of infected cells were transferred to naïve cells. Inhibition of infection was determined in primary and secondary infected cells by high-content imaging of viral and cellular factors. Novel antivirals were triaged in cells infected with cell culture- or patient-derived HBV and in stably virus replicating cells. HBV internalisation and target-based receptor binding assays were conducted. RESULTS: We developed an HBV platform, screened 2,102 drugs and bioactives, and identified 3 early and 38 late novel HBV life cycle inhibitors using infectious HBV genotype D. Two early inhibitors, pranlukast (EC50 4.3 µM; 50% cytotoxic concentration [CC50] >50 µM) and cytochalasin D (EC50 0.07 µM; CC50 >50 µM), and 2 late inhibitors, fludarabine (EC50 0.1 µM; CC50 13.4 µM) and dexmedetomidine (EC50 6.2 µM; CC50 >50 µM), were further investigated. Pranlukast inhibited HBV preS1 binding, whereas cytochalasin D prevented the internalisation of HBV. Fludarabine inhibited the secretion of HBV progeny DNA, whereas dexmedetomidine interfered with the infectivity of HBV progeny. Patient-derived HBV genotype C was efficiently inhibited by fludarabine (EC50 0.08 µM) and dexmedetomidine (EC50 8.7 µM). CONCLUSIONS: The newly developed high-content assay is suitable to screen large-scale drug libraries, enables monitoring of the entire HBV life cycle, and discriminates between inhibition of early and late viral life cycle events. LAY SUMMARY: HBV infection is an incurable, chronic disease with few available treatments. Addressing this unmet medical need has been hampered by a lack of suitable cell culture models to study the entire viral life cycle in a single experimental setup. We developed an image-based approach suitable to screen large numbers of drugs, using a cell line that can be infected by HBV and produces large amounts of virus particles. By transferring viral supernatants from these infected cells to uninfected target cells, we could monitor the entire viral life cycle. We used this system to screen drug libraries and identified novel anti-HBV inhibitors that potently inhibit HBV in various phases of its life cycle. This assay will be an important new tool to study the HBV life cycle and accelerate the development of novel therapeutic strategies.

Impact of COVID-19: urging a need for multi-domain assessment of COVID-19 inpatients.

OBJECTIVE: To retrospectively analyse data obtained from the multi-domain assessment of hospitalized COVID-19 patients, to describe their health status at discharge, and to investigate whether subgroups of patients, more specific ICU patients and older adults (> 70 years), had more (or less) risk to experience specific impairments. METHODS: Retrospective case series in the University Hospitals Leuven, Belgium of confirmed COVID-19 patients 'after surviving an ICU-stay', 'aged ≥ 70 years', or 'aged < 70 years with a length of hospitalization > 7 days'. Exclusion criteria were 'unwilling to cooperate', 'medically unstable', or 'palliative care policy'. Following tests were used: 'Five Times Sit To Stand Test', 'hand grip dynamometry', 'Barthel index', 'Swallowing screening', 'Montreal Cognitive Assessment', 'Hospital Anxiety and Depression Scale', and 'Nutritional Risk Screening 2002'. RESULTS: One or more tests were obtained in 135/163 patients (83.3%). Physical impairments were present in 43.2-82.8% of the patients. Median BI was 10/20 indicating limited self-dependency. Swallow impairments were present in 3/53 (5.7%) and 24/76 (31.6%) had risk of malnutrition. Impaired memory was seen in 26/43 (60.5%) and 22/47 (46.8%) had elevated anxiety/depression scores. Older adults had more physical, functional, and cognitive impairments. ICU patients had a lower hand grip force. CONCLUSION(S): The high prevalence of physical, cognitive, psychological, and functional impairments in hospitalized COVID-19 patients, both ICU and non-ICU patients, indicates that assessment of impairments is imperative. These results imply that rehabilitation and follow-up is essential for these patients. This paper proposes a short, workable assessment composed with known outcome measures to assess different domains of COVID-19 patients.