A qualitative exploration of active ingredients and mechanisms of action of an online singing programme with mothers experiencing postnatal depression during the COVID-19 pandemic: SHAPER-PNDO study. (preprint)

Background Social distancing restrictions and the suspension of in-person treatment and support contributed to an increase in postnatal depression during the coronavirus disease 2019 (COVID-19) pandemic. Creative health interventions can help to alleviate anxiety and depression, with studies showing that singing is particularly effective for supporting the mental health of new mothers. We adapted an in-person group singing programme (Breathe Melodies for Mums (M4M)) to online delivery during the COVID-19 pandemic to support the mental health of new mothers, and, in a feasibility study, found improvements in postnatal depression (PND) symptoms at 6-month follow up. The current qualitative study aimed to explore how and why M4M-online impacted the mental health of those taking part.Methods We took a theory-based approach using the Ingredients in Arts in Health (INNATE) Framework of ‘active ingredients’ and the Multi-level Leisure Mechanisms Framework of ‘mechanisms of action’ to identify and categorise intervention components and change mechanisms. Iterative consensus building between three researchers were complemented by qualitative semi-structured online interviews with 24 women experiencing PND symptoms who took part in M4M-online. Data were analysed inductively using reflexive thematic analysis.Results Consistency was found between the online and in-person interventions in active ingredients relating to project design, content, programme management and the composition of the group. Key differences were in the social and contextual ingredients. Psychological, social and behavioural mechanisms for improved mental health and wellbeing included: 1) Increased self-confidence as a mother, 2) Increased positive emotional responses, 3) A supported change in identity, 4) Reduced loneliness and isolation, 5) Increased social bonding and connections with family and 6) Enhanced sense of time through new routines.Conclusions Participating in online group singing can support new mothers experiencing PND by triggering psychological, social and behavioural responses that lead to improved mental health. Key programme features are identified which can be used to design future online creative health interventions or tailor in-person activities for remote delivery to support populations who may face practical and social barriers to attending in-person.

Clinical characterization of new-onset chronic musculoskeletal pain in Long COVID: a cross-sectional study (preprint)

Purpose: New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life. Patients and methods: 30 adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers, and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire - short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L). Results: New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro- inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower ; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores. Conclusion: New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.

Clinical Reasoning: A 23-Year-Old Man With Progressive Asymmetric Weakness and Numbness.

We report a case of a 23-year-old man who presented with progressive asymmetric weakness and numbness in his distal extremities over 4 months, with initial symptoms starting days after a coronavirus 2019 (COVID-19) vaccine booster. Initial neurologic examination was notable for distal weakness of both upper and lower extremities that was more pronounced on the left, complete areflexia, and decreased distal sensation to pinprick and vibration without loss of proprioception. Nerve conduction studies demonstrated a generalized, non-length-dependent, sensorimotor, demyelinating polyneuropathy, with conduction block seen in multiple compound muscle action potentials. Sensory nerve action potentials were normal in absolute terms but had asymmetric amplitudes.Based on the patient's nerve conduction studies, he was diagnosed with a specific immune-mediated neuromuscular disorder. He was started on intravenous immunoglobulin, but within days of the first infusions experienced a rare and potentially life-threatening complication. He received appropriate treatment and was started on alternative immunotherapy, after which his symptoms improved.Our case exemplifies the features of a specific subtype of a more common immune-mediated neuromuscular diagnosis with unique elements of history, examination, and nerve conduction studies that required interpretation in the clinical context. We also discuss a rare side effect of a commonly used immunotherapy and its risk factors and comment on the likelihood that this diagnosis may be related to a preceding COVID-19 vaccine booster.

Rare case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma.

We describe the first case of anti-CV2 paraneoplastic polyneuropathy associated with lung adenocarcinoma. Our patient presented with progressive unsteadiness and numbness involving bilateral upper and lower limbs. He had symmetrical length-dependent lower motor neuron pattern of weakness and numbness involving both small and large fibres with prominent sensory ataxia. An extended workup for the polyneuropathy involving a serum paraneoplastic antineuronal antibody panel showed a positive reaction for anti-CV2 antibody. CT scan of the thorax, abdomen and pelvis revealed a right upper lung nodule and histopathological examination of the nodule revealed lung adenocarcinoma. He was scheduled for chemotherapy following his discharge and there was improvement of his sensorimotor polyneuropathy following his chemotherapy.

Development of Moral Injury in ICU Professionals During the COVID-19 Pandemic: A Prospective Serial Interview Study.

OBJECTIVES: During the COVID-19 pandemic, ICU professionals have faced moral problems that may cause moral injury. This study explored whether, how, and when moral injury among ICU professionals developed in the course of the COVID-19 pandemic. DESIGN: This is a prospective qualitative serial interview study. SETTING: Two hospitals among which one university medical center and one teaching hospital in the Netherlands. SUBJECTS: Twenty-six ICU professionals who worked during the COVID-19 pandemic. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: In-depth interviews with follow-up after 6 and 12 months. In total, 62 interviews were conducted. ICU professionals narrated about anticipatory worry about life and death decisions, lack of knowledge and prognostic uncertainty about COVID-19, powerlessness and failure, abandonment or betrayal by society, politics, or the healthcare organization, numbness toward patients and families, and disorientation and self-alienation. Centrally, ICU professionals describe longitudinal processes by which they gradually numbed themselves emotionally from patients and families as well as potentially impactful events in their work. For some ICU professionals, organizational, societal, and political responses to the pandemic contributed to numbness, loss of motivation, and self-alienation. CONCLUSIONS: ICU professionals exhibit symptoms of moral injury such as feelings of betrayal, detachment, self-alienation, and disorientation. Healthcare organizations and ICU professionals themselves should be cognizant that these feelings may indicate that professionals might have developed moral injury or that it may yet develop in the future. Awareness should be raised about moral injury and should be followed up by asking morally injured professionals what they need, so as to not risk offering unwanted help.

Neuromyelitis Optica Spectrum Disorder After BIBP COVID-19 Vaccine: A Case Report (preprint)

Background: With the availability of the COVID-19 vaccine, post-vaccination neurological complications have occasionally been reported. Case presentation: We present a case of neuromyelitis optica spectrum disorder (NMOSD) that developed 1 month after the second dose of BIBP COVID-19 vaccine (SARS-CoV-2-Vaccine [Vero Cell] Inactived). The patient presented itching, numbness of the hand and right side of the face, associated with nausea, vomiting and hiccups. Brain MRI showed lesions in the area postrema, medulla, and bilateral hypothalamus, typical of NMOSD. Serum antibodies to anti-AQP4 and anti-MOG were negative. Conclusions: The pathogenesis of NMOSD development and the vaccine is still unknown. The presentation of NMOSD is generally aggressive and disabling, it is important for the neurologist to be attentive to the highly variable clinical presentation after vaccination against COVID-9 for early diagnosis and effective treatment.

COVID-19 is associated with high blood glucose levels: Diabetic neuropathy during the SARS-CoV-2 pandemic (preprint)

Background: The nerves in the legs and feet are most frequently damaged by diabetic neuropathy. The COVID-19 infection is associated with a high risk of neuropathy symptoms. Case Presentation: On July 12, 2022, a 58-year-old black female retiree with significant symptoms of numbness and muscle weakness in the hands and legs was brought into the emergency room. 17 years prior, she received a type 2 diabetes mellitus diagnosis. Metformin 1.5 g twice a day and glibenclamide 10 mg twice a day were part of her therapy regimen. When she was admitted to the emergency room, she described a one-day history of shortness of breath, frequent urination, excessive thirst, hyperglycemia, excessive appetite, fever, headache, and dehydration. A chest X-ray showed bilateral diffuse, patchy airspace opacities that could be caused by multifocal pneumonia or viral pneumonia. She started receiving 1000 mL of fluid resuscitation (0.9% normal saline) as soon as she was moved to the critical care unit, along with a drip-in insulin infusion. Conclusion: Diabetes, infections like COVID-19, poor vitamin levels, and other factors can all contribute to diabetic neuropathies. According to the Centers for Disease Control and Prevention, patients with type 2 diabetes mellitus are much more likely to experience severe morbidity and death from coronavirus disease-19. Symptoms of diabetic neuropathy continued for months after a COVID-19 infection test resulted in a positive result.

Impaired B cell recall memory and reduced antibody avidity but robust T cell response in CVID patients after COVID-19 vaccination (preprint)

Purpose: Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2 specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients. Methods: We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pTFH) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine. Results: SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. 100% of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen specific CD4+CD154+CD137+CXCR5+ pTFH cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pTFH did not correlate with antibody response or avidity. Conclusion: Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.

Contemporary Management of Unexpected Arterial Thrombosis and Acute Limb Ischemia in a Young Male Patient with COVID-19: A Case Report and Literature Review (preprint)

Background The spread of severe acute respiratory syndrome coronavirus 2 has resulted in coronavirus disease 2019 (COVID-19) pandemic, raising significant concerns. COVID-19 can lead to thrombotic complications such as acute limb ischemia (ALI). In patients with COVID-19, thrombotic complications may increase the risk of morbidity and mortality. The frequency of ALI has reduced worldwide, and the hypercoagulable condition remains an infrequent cause of limb ischemia. Patients with COVID-19 have a 35–45% thromboembolic complication rate. In many studies, the virus launches a second attack between 7 and 14 days after symptom onset, possibly causing hypercoagulability. If conservative treatment fails, various surgical methods, including thromboembolectomy, thrombolysis, and thrombosuction, can be performed to treat ALI.Case Presentation: We report the case of a 37-year-old man who presented with a 2 weeks history of right foot pain, toes blackish discoloration, and numbness. He tested positive for COVID-19 10 days prior to his presentation. Computed tomography angiography (CTA) of the lower limbs revealed near-complete occlusion of the right popliteal artery with single-vessel posterior tibial artery runoff. The patient was brought to a hybrid operating room, and diagnostic angiography confirmed the diagnosis. He underwent popliteal artery thromboembolectomy and intraoperative thrombolysis through a posterior approach. A completion angiography demonstrated a patent popliteal artery with a 2-vessels patency to the foot. His postoperative recovery was uneventful. After surgery, the popliteal, anterior tibial, and posterior tibial arteries were all palpable. The patient was discharged home on antiplatelet therapy with frequent postoperative follow-ups during the last 1 year in our outpatient clinic.Conclusions In mild ALI symptoms, unfractionated heparin can be used with vigilant follow-up. Open and endovascular procedures are currently used to treat patients with acute limb ischemia, and technological advancements continue to make interventions easier and safer.

Longitudinally extensive transverse myelitis following ChAdOx1 nCoV-19 vaccine.

Transverse myelitis (TM) has been reported in association with various vaccinations. Herein we describe a case of longitudinally extensive transverse myelitis (LETM) associated with vaccination with ChAdOx1 nCoV-19 (COVISHIELD) vaccine. A 59-year-old woman with no prior co-morbidities presented with lower extremity numbness, weakness, acute urinary retention, and constipation. Numbness gradually extended up to the lower costal margin with band like sensation. She had received the vaccine 5 days prior to the onset of the symptoms. Extensive diagnostic evaluation effectively ruled out causes other than vaccination-associated transverse myelitis. Following treatment with intravenous methylprednisolone, the patient made a significant recovery. TM may be associated with vaccination against the novel ChAdOx1 nCoV-19 vaccine and we believe this to be the first report from India of LETM associated with this vaccine.

Interaction of compounds derived from the Chinese medicinal formula Huangqi Guizhi Wuwu Tang with stroke-related numbness and weakness targets: An in-silico docking and molecular dynamics study.

Huangqi Guizhi Wuwu Tang (HGWT) is a traditional Chinese herbal formula used for managing post-stroke symptoms. Existing research have supported the use of this formula particularly for stroke-related numbness and weakness (SRNW); however, their mechanisms of actions are not fully understood. This study aims to investigate the molecular mechanisms of components from HGWT targeting specific proteins related to numbness and weakness through computational docking and molecular dynamics (MD) simulations. A total of 786 compounds from HGWT were retrieved from a herbal compound database and docked against a candidate SRNW target protein, with the asernestioside B (HQ068)-mitogen-activated protein kinase 3 (MAPK3) complex predicted to exhibit the highest binding affinity (-10.4 kcal/mol) and number of ligand-receptor contacts. Subsequent molecular dynamics (MD) simulations were performed in triplicate on the apo-MAPK3 protein and asernestioside B -bound form in a solvated system for 200 ns per trajectory to ascertain the stability of the enzyme-ligand complex, and to determine the structural impact of ligand binding. The stability of the complex and overall tertiary structural changes were characterized using root-mean-square deviation (RMSD), radius of gyration (Rg), root-mean-square fluctuation (RMSF) calculations Differences in the RMSF of apo and ligand-bound MAPK3 were most prominent in three major regions: (a) activation loop Asp184:Pro213 (b) MAPK3 insertion site Gly262:Ala291 and (c) loop region at the C-terminus Tyr334:Pro356. Lower values of RMSF for the HQ068-bound protein at the activation loop suggest that HQ068 binding stabilizes MAPK3 in a different conformation in this region compared to the apo protein. Free energy calculations of the asernestioside B-MAPK3 complex revealed key residues contributing to the interaction, which include Pro264, Gln 266, Asp268 and Thr288. These key residues may play an integral role in the binding of selective modulators or substrates of extracellular signal-regulated kinase (ERK) within the MAPK cascade. Overall, this study provides a mechanistic overview of compounds from HGWT. Modelling predicted that asernestioside B may act with high potency against MAPK3, while exhibiting a favourable ADMET profile, and this compound should be explored as a potential agent to alleviate SRNW-related symptoms in future studies.

Unusual manifestation of COVID-19-associated pulmonary aspergillosis, A case report (preprint)

A young man, a recent coronavirus patient, was readmitted with hypoesthesia and dysarthria following a rapid deterioration of respiratory symptoms. The brain and lung CT scans revealed ischemia and cavitary lung lesions. Clinical suspicion for aspergillus leads to prompt treatment, confirmed by biopsy. Neurologic and pulmonary symptoms resolved ultimately.

Intrafamilial Spread and Altered Symptomatology of SARS-CoV-2, During Predominant Circulation of Lineage B.1.1.7 Variant in Israel.

The dynamics of intrafamilial spread of SARS-CoV-2 during January-February 2021 when variant B.1.1.7 predominated were compared with data from April to May 2020, when other circulating variants prevailed. Much higher intrafamilial transmission rates among all age groups, in particular in young children, and lower rates of sensory impairment were demonstrated during January-February 2021.

Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients (preprint)

Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19+ patients, 78 COVID-19- acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.

Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study.

OBJECTIVE: The Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world data are scarce. Bell's palsy, herpes zoster, Guillain-Barré syndrome (GBS) and other neurological complaints in proximity to vaccination have received special public attention. We compared their rates among vaccinated and unvaccinated individuals. METHODS: Individuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical cohort study in a health maintenance organization insuring 1.2 million citizens. Each vaccinee was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of Bell's palsy, GBS, herpes zoster or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review. RESULTS: Of 406 148 individuals vaccinated during the study period, 394 609 (97.2%) were eligible (11 539 excluded). A total of 233 159 (59.1%) were matched with unvaccinated controls. Mean follow was 43 ± 15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR 0.96, CI 0.54-1.70), one versus zero cases of GBS, 151 versus 141 cases of herpes zoster (RR 1.07, CI 0.85-1.35) and 605 versus 497 cases of numbness or tingling (RR 1.22, CI 1.08-1.37), respectively. DISCUSSION: No association was found between vaccination, Bell's palsy, herpes zoster or GBS. Symptoms of numbness or tingling were more common among vaccinees. This study adds reassuring data regarding the safety of the BNT162b2 vaccine.

EFFICACY OF THE MEASLES-MUMPS-RUBELLA (MMR) VACCINE IN THE REDUCING THE SEVERITY OF COVID-19: AN INTERIM ANALYSIS OF A RANDOMISED CONTROLLED CLINICAL TRIAL (preprint)

BackgroundCOVID-19 is still a challenge, both with regard to its treatment and to the actual efficacy of the vaccines available to date, especially with the emergence of new variants. We evaluated the efficacy of the measles-mumps-rubella (MMR) vaccine in preventing SARS-CoV-2 infection and severity of COVID-19 in health workers. MethodsThis analysis includes data from one ongoing blinded, randomized, placebo-controlled trial with participants aged 18-60 years were randomly assigned to receive the MMR vaccine or a placebo. The primary efficacy analysis included all participants with a positive nasopharyngeal RT-PCR test since their inclusion. ResultsThe MMR vaccine did not prevent the SARS-CoV-2 infection. Participants in the MMR group, compared with those in the placebo group, had a 48% risk reduction in symptomatic COVID-19 (RR = 0.52; 95% CI: 0.33-0.83; p=0.004) and a 76% risk reduction in COVID-19 treatment (RR = 0.24; 95% CI: 0.06 - 0.88; p = 0.020) with one dose and a 51% risk reduction in COVID-19 symptoms (RR = 0.49; 95% CI: 0.31 - 0.78; p = 0.001) and a 78% risk reduction in COVID-19 treatment (RR = 0.22; 95% CI: 0.06 - 0.82; p = 0.015) with two doses. ConclusionsThis interim analysis of an ongoing clinical trial suggests that compared with a placebo, the vaccine reduces the risk of COVID-19 symptoms and reduces the need for COVID-19 treatment. Clinical Trials RegistryBrazilian Clinical Trials Registry (ReBEC n{degrees} RBR-2xd6dkj - https://ensaiosclinicos.gov.br/rg/RBR-2xd6dkj). HIGHLIGHTSO_LIThe MMR vaccine can stimulate the innate immunity inducing a nonspecific protection against other infections, called heterologous immunity. C_LIO_LIRepeated exposure to the antigen (innate immune response training) results in an extension of the action time of this immune response (innate immune response memory) and consequently in protection against other infections (heterologous immunity) for a longer time. C_LIO_LIThe MMR vaccine has been used by national immunization programs in the world for many years, it is very safe and can be stored and distributed at 2-8{degrees}C, making it particularly suitable for global distribution. C_LIO_LIAmong participants who received at least one dose, compared with those in the placebo group, participants in the MMR group had a significant risk reduction in symptomatic COVID-19 and of cases requiring treatment. C_LIO_LIThe use of MMR vaccine can be useful in several populations in the world that do not have access to the COVID-19 vaccine and in a future epidemic or pandemic as an emergency measure until specific treatments or vaccines for each case are available to the general population. C_LI

Internet Use impact on Physical Health during COVID-19 pandemic in Bangladesh: A Web-based Cross-sectional study (preprint)

BackgroundBangladesh ranked fifth largest internet user in Asia. Past studies on internet use have focused on its impact on mental health, with little known about its impact on the physical health of individuals during COVID-19 pandemic. Hence, this study examines the impact of Internet use frequency on physical health during the Covid-19 lockdown in Bangladesh. MethodsA web-based cross-sectional study on 3242 individuals aged 18 and above was conducted from 2nd August - 1st October 1, 2020, during the lockdown in Bangladesh. The survey covers demographics, Internet use frequency and physical health questions. Multiple linear regression analyses were used to examine the impact of internet use frequency on physical health. ResultsThe result indicated that 72.5%, 69.9%, 65.1% and 55.3% reported headache, back pain, numbness of the fingers and neck pain, respectively. The multivariable analyses showed increased physical health impact among regular (coefficient {beta} =0.52, 95% confidence interval [CI]: 0.18-0.85, P=0.003), frequent ({beta} = 1.21, 95%CI: 0.88-1.54, P < .001) and intense ({beta} = 2.24, 95%CI: 1.91-2.57, P < .001) internet users. Other factors associated with physical health scores were gender, income (in Taka), occupation, regions, and working status. ConclusionFrequent, intensive, and extensive use of the internet were strong predictors of increased physical health problems, and the study suggests the need for raising awareness of physical health problems triggered by high internet users among the high socioeconomic group in Bangladesh.

Guillain-Barré syndrome after COVID-19 in Japan.

We report the first case of Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection in Japan. A 54-year-old woman developed neurological symptoms after SARS-CoV-2 infection. We tested for various antiganglioside antibodies, that had not been investigated in previous cases. The patient was diagnosed with GBS based on neurological and electrophysiological findings; no antiganglioside antibodies were detected. In previous reports, most patients with SARS-CoV-2-infection-related GBS had lower limb predominant symptoms, and antiganglioside antibody tests were negative. Our findings support the notion that non-immune abnormalities such as hyperinflammation following cytokine storms and microvascular disorders due to vascular endothelial damage may lead to neurological symptoms in patients with SARS-CoV-2 infection. Our case further highlights the need for careful diagnosis in suspected cases of GBS associated with SARS-CoV-2 infection.

COVID-19 associated central nervous system manifestations, mental and neurological symptoms: a systematic review and meta-analysis.

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.

Why Appreciation of Pulmonary Vitamin D Metabolism Should Temper Expectations for Vitamin D Supplementation to Reduce Disease Severity and Improve Clinical Outcome of COVID-19 (preprint)

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.