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.

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.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

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.

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.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Protection by Vaccines and Previous Infection Against the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades immunity conferred by vaccines and previous infections. METHODS: We used a Cox proportional hazards model and a logistic regression on individual-level population-wide data from the Czech Republic to estimate risks of infection and hospitalization, including severe states. RESULTS: A recent (≤2 months) full vaccination reached vaccine effectiveness (VE) of 43% (95% confidence interval [CI], 42%-44%) against infection by Omicron compared to 73% (95% CI, 72%-74%) against Delta. A recent booster increased VE to 56% (95% CI, 55%-56%) against Omicron infection compared to 90% (95% CI, 90%-91%) for Delta. The VE against Omicron hospitalization of a recent full vaccination was 45% (95% 95% CI, 29%-57%), with a recent booster 87% (95% CI, 84%-88%). The VE against the need for oxygen therapy due to Omicron was 57% (95% CI, 32%-72%) for recent vaccination, 90% (95% CI, 87%-92%) for a recent booster. Postinfection protection against Omicron hospitalization declined from 68% (95% CI, 68%-69%) at ≤6 months to 13% (95% CI, 11%-14%) at >6 months after a previous infection. The odds ratios for Omicron relative to Delta were 0.36 (95% CI, .34-.38) for hospitalization, 0.24 (95% CI, .22-.26) for oxygen, and 0.24 (95% CI, .21-.28) for intensive care unit admission. CONCLUSIONS: Recent vaccination still brings substantial protection against severe outcome for Omicron.

Long COVID-19 syndrome: a 14-months longitudinal study during the two first epidemic peaks in Southeast Brazil.

BACKGROUND: A growing number of long COVID cases after infection have been reported. By definition, long COVID is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, the profile and timeline of which remains uncertain. METHODS: In this work, in-home, outpatient and hospitalized COVID-19 positive patients were monitored for up to 14 mo to establish the prevalence of long COVID symptoms and their correlation with age, pre-existing comorbidities and course of acute infection. The longitudinal study included 646 positive patients who were monitored once a month. RESULTS: From the whole population, 50.2% presented with long COVID syndrome. Twenty-three different symptoms were reported. Most frequent were fatigue (35.6%), persistent cough (34.0%), dyspnea (26.5%), loss of smell/taste (20.1%) and frequent headaches (17.3%). Mental disorders (20.7%), change in blood pressure (7.4%) and thrombosis (6.2%) were also reported. Most patients presented with 2-3 symptoms at the same time. Long COVID started after mild, moderate and severe infection in 60, 13 and 27% of cases, respectively, and it was not restricted to specific age groups. CONCLUSIONS: Older patients tended to have more severe symptoms, leading to a longer post-COVID-19 period. The presence of seven comorbidities was correlated with the severity of infection, and severity itself was the main factor that determined the duration of symptoms in long COVID cases.

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.

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.