Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

Encephalitis as a post-COVID-19 complication: causation or association?

Case Report: Although the coronavirus disease 2019 (COVID-19) affects the respiratory system, neurological complications in children have been reported. Neurological manifestations in children with acute COVID-19 infection are rare and range from headaches, transverse myelitis, strokes, and encephalitis which presents as a part of Multisystem Inflammatory Syndrome in Children (MIS-C). However, encephalitis presenting post-COVID-19 in the absence of MIS-C in children has not been described. Case presentation: A 9-year-old Hispanic female with no past medical history presented with altered mental status and seizures. Associated symptoms prior to seizures included worsening headaches and vomiting. Initial labs were significant for an elevated erythrocyte sedimentation rate of 32 mm/hr, C-reactive protein of 2 mg/dL, and white blood cell (WBC) count of 28 000 cells/mcl with neutrophilia. Comprehensive metabolic panel was normal. Computed tomography of the head and urine drug screen were normal. Magnetic resonance imaging of the brain demonstrated diffusion restriction in the left frontal lobe as well as mild leptomeningeal enhancement concerning for meningoencephalitis. Lumbar puncture (LP) showed pleocytosis (WBC 169 cells/mcl, 76% neutrophils), elevated glucose 77 mg/dl, normal protein 56 mg/dl, and elevated myelin basic protein indicative of a demyelinating disease. Infectious workup was significant for a positive COVID-19 immunoglobulin (Ig) G (19.66), positive Mycoplasma pneumoniae (M. pneumoniae) IgM (0.87 units/L), with an equivocal IgG (0.11 units/L). Autoimmune workup was negative. She received dexamethasone 0.15 mg/kg/dose for 1 day, followed by methylprednisolone (10 mg/kg/dose) for 3 days and oral prednisone for 5 days resulting in significant improvement. Although CSF cultures returned negative, she received a 7-day course of doxycycline for a possible coexisting M. pneumoniae infection. Repeat LP showed improving pleocytosis, and lymphocytic predominance. Discussion: In this case report, rapid neurological recovery after administration of corticosteroids in the presence of positive COVID-19 IgG and demyelinating disease was suggestive of encephalitis presenting post- COVID-19 infection. Although M. pneumoniae can present with neurological symptoms (e.g., encephalitis), repeat titers at follow-up after recovery did not show the expected 4-fold increase in IgG, making it less likely the cause of this presentation. The proposed pathophysiology of COVID-19-mediated encephalitis includes direct invasion of the nervous system, immune-mediated cytokine response, and molecular mimicry between coronaviruses and neuronal proteins causing demyelination. The mainstay treatment includes immunomodulators such as corticosteroids, Intravenous Immunoglobulin, monoclonal antibodies (eg., rituximab), or plasma exchange. Conclusion: COVID-19 infection should be considered when evaluating a patient with meningoencephalitis or post-infectious encephalitis.

Neurologic Manifestations of COVID-19

Coronavirus disease (COVID-19) caused by a new coronavirus, SARS-CoV-2, has become a serious health problem throughout the world. Although COVID-19 primarily presents as an acute respiratory tract infection, many neurological findings have also been described in patients. Neurological findings are classified into three groups as central, peripheral nervous system and musculoskeletal system. The most common central nervous system symptom is headache. Encephalitis, encephalopathy, seizures, acute ischemic stroke are also seen. The most common symptoms in the peripheral nervous system are loss of smell and taste. Myalgia, myositis and rhabdomyolysis also can be seen in musculoskeletal system involvement. Awareness of the neurological symptoms by physicians will be beneficial in early diagnosis and treatment of the disease.

Neurological Manifestations of Multisystem Inflammatory Syndrome in Children

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 first reported from South East London has a wide spectrum of neurological signs and symptoms including headache, impaired consciousness, aseptic meningitis, encephalitis, seizure, ataxia, and stroke. It is important to diagnose these patients as soon as possible and treat them with a multidisciplinary ap-proach. A few studies have reported post-discharge follow-up data in MIS-C patients with neurological symptoms most of whom showed neurological improvement. Long-term follow-up of MIS-C patients is required to determine possible neurological sequelae. Copyright © 2022 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

Neurological Manifestations In COVID-19 Patients: An Imaging Review

Background: The COVID-19 pandemic that started in late 2019, has posed a great health challenge to India rapidly elevating our country to the second most affected nation after the United States. While the respiratory manifestations of COVID-19 are widely-known, there is paucity of information on its neurological manifestations in Indian literature. The imaging features of the diverse neurological presentations such as stroke, encephalitis, demyelination, hemorrhages and vascular involvement are reviewed in this article. Objective of the review is to discuss the spectrum of neuroimaging features in COVID-19. Method(s): Multiple publications from systematic and cohort studies on neuroimaging are reviewed in this article. Due permission was obtained from the publishers to reproduce the illustrations because of lack of adequate neuroimaging data in our country. Result(s): Ischemic infarcts, micro-hemorrhages, parenchymal hematomas and white matter changes, both diffuse and focal were the most common manifestations. Acute necrotizing hemorrhagic encephalitis, features resembling posterior reversible encephalopathy syndrome (PRES) and acute demyelinating encephalomyelitis (ADEM), arterial dissections, dural sinus and deep venous thrombosis were reported. Olfactory bulb and white matter signal ratios were elevated in anosmic patients. Micro-structural changes such as remyelination and neurogenesis indicated processes of repair. Conclusion(s): Ischemic and hemorrhagic lesions are the most common neuroimaging abnormalities in COVID-19 patients, though 40% of the studies are normal. Awareness of the imaging features is essential for management of these patients in the current pandemic. Severity of illness and risk of spread of infection are major constraints for neuroimaging. Copyright © 2022 International Medical Sciences Academy. All rights reserved.

Rare case of post-COVID transverse myelitis

Case Report: Acute transverse myelitis (TM) is a rare inflammatory disease that typically presents asweakness, sensory alterations, and bowel or bladder dysfunction. Among the causes of TM are infections, paraneoplastic syndromes, or autoimmune conditions of CNS. Postinfectious TM can develop secondary to a viral or bacterial infection. SARS-CoV-2 is a recently discovered viral illness, and sequelae due to COVID-19 infection are still being studied. There is scarce literature relating the two conditions, and it is imperative to raise awareness. A 72-year-old man with hypertension and GERD, completely independent in ADL, was brought to the ED with sudden onset of bilateral lower extremity weakness. He reported symptoms started with difficulty climbing stairs that rapidly progressed to inability to ambulate independently and were associated with bilateral thigh soreness. Nine days prior, he developed fever and generalized malaise, and two days later, SARS-CoV-2 PCR and Ag tests were positive. He received azithromycin, Paxlovid, and dexamethasone as treatment. Upon evaluation, the patient was afebrile and hemodynamically stable. Neurological examination was remarkable for spasticity and hyperreflexia at bilateral lower limbs, clonus, preserved motor strength with adequate sensation to soft touch, and intact vibration and proprioception in all extremities. Cranial nerves were intact. These findings were consistent with an upper motor neuron lesion. On imaging, the Head CT scan was unremarkable. Thoracic/Lumbar Spine MRI was significant for distal thoracic and conus areas with central homogeneous brightness compatible with nonspecific myelitis. Laboratories showed leukocytosis without neutrophilia or bandemia, thrombocytosis, and elevated CRP. HIV and RPR tests were negative. A lumbar puncture for CSF analysiswas remarkable for mild monocytic pleocytosis (7 cell/muL), an increased level of total proteins (56 mg/dL), and normal glucose (57 mg/dL). CSF culture and gram stain were negative. CSF cytology yielded few lymphocytes and few monocytes and was negative for malignant cells. The meningoencephalitis panel was negative. Based on these findings, a clinical diagnosis of postinfectious myelitis secondary to COVID-19was made. The patient was treated with intravenous Methylprednisolone 1 g daily for five days. On follow-up, lower extremity weakness resolved completely, and he resumed his daily physical activities. Patients with COVID-19 infection can present with neurologic manifestations such as headache, myalgias, dizziness, dysgeusia, and anosmia. This case hopes to raise awareness of less commonly known neurological manifestations of SARS-CoV-2 infection and how the early recognition of symptoms can help expedite the diagnosis and treatment of the condition to avoid long-term sequelae. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.

An Unusual Case Presentation of MOG-Positive Acute Disseminated Encephalomyelitis (ADEM) in a Preschool Child

Introduction: An unusual case presentation of MOG-positive Acute Disseminated Encephalomyelitis (ADEM) in a preschool child following meta-pneumo viral infection responded to the combination of immune modulatory treatment with a favourable outcome. Material: Three-year-old female child presented with acute encephalopathy, high fever, vomiting, starring episodes, floppiness, and left abducent nerve palsy with rapid deteriorating GCS necessitating intubation and ventilation. Two weeks earlier, she was treated for suspected CNS infection with 10 days of antibiotics in the PICU with a positive meta-pneumo-virus. On admission, she had a GCS score of 6 with left-sided increased tone, bilateral hyperreflexia, and bilateral extensor response and on Day 14 demonstrated hyperkinetic movements of the upper and lower limbs. Method(s): Serum MOG antibody positive, CSF MOG low positive, metabolic investigations, Mycoplasma, EBV, Influenza, corona PCR, SARS-COV-2 Antibody, viral CSF panel unremarkable. MRI brain demonstrated T2 hyperintense signal in bilateral medial thalami and brain stem with a normal spine. Progressive changes were shown on repeated MRI Brains on day 4 and day 14 suggestive of multifocal changes involving deep cortical and subcortical white matter bilaterally with a new short segment of the spinal lesion at the T8 level. Repeated EEG and ambulatory EEG showed a diffusely slow background with intermittent slow runs of slow waves suggestive of generalized cerebral dysfunction. Result(s): After receiving the combination of high pulse steroids with a taper over 10 weeks, IVIG and 10 cycles of plasmapheresis she demonstrated gradual and remarkable clinical improvement over 10-12 weeks with a minimal focal neurological deficit. Conclusion(s): Initial differentiating CNS infection, metabolic disease and ADEM may be clinically challenging. Her clinical presentation, investigations and imaging were in keeping with the diagnosis of MOG-positive ADEM. Previous CNS infection may be related. MOG-positive ADEM treated with the early combination of immunomodulation may lead to positive clinical outcomes.

A Series of Catastrophic Events

Case report - Introduction: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening disease occurring in up to 1% of antiphospholipid syndrome (APS) cases. It was first defined in 1992 and remains a difficult to treat entity with a mortality rate of 37%. We describe a patient with systemic lupus erythematosus (SLE) and CAPS presenting with simultaneous multi-organ injuries who was successfully managed with 'triple' therapy including cyclophosphamide. Case report - Case description: A 42-year-old female presented to her local hospital with chest pain and worsening vision. She had a background of SLE, triple antibody-positive APS (previous DVT, pregnancy loss and strokes), hypertension, a metallic mitral valve, a previous myocardial infarction and pre-existing visual impairment due to a prior intra-cerebral bleed related to anticoagulation. Examination revealed a faint malar rash, cortical blindness and long tract neurological signs. Her ECG showed ischaemic changes and the admission troponin was significantly raised (3773ng/L). An echocardiogram showed new left ventricular dysfunction and a subsequent cardiac MRI was in keeping with coronary artery disease. Investigations showed an acute kidney injury, newly deranged liver function tests and a raised INR (>11, with no bleeding). Complement was normal with a low dsDNA titre. Urinalysis revealed proteinuria and a protein creatinine ratio measured 176mg/mmol. MRI diffusion weighted brain imaging showed acute bilateral occipital and left fronto-parietal infarcts. She had symptoms of a lupus flare with arthralgia and a butterfly facial rash. COVID-19 PCR tests were negative and she had not been recently vaccinated. She was diagnosed with CAPS and transferred to St Thomas' hospital intensive care. On arrival, she received 1mg intravenous vitamin K followed by triple therapy for CAPS: an unfractionated heparin infusion, oral prednisolone 40mg daily, 5 days of plasma exchange and, given her background of SLE, she was treated with intravenous cyclophosphamide (according to the EUROLUPUS regimen). Intravenous methylprednisolone was avoided due to a previous hypertensive encephalopathy reaction. She responded rapidly. Her troponin fell from a peak of 5054 to 294ng/ L, her creatinine settled at a new baseline (232umol/L) and her liver function normalised. She was switched back to warfarin due to her metallic valve and started on aspirin for cardiovascular secondary prevention. She required physical and occupational therapy due to her strokes but recovered well. Case report - Discussion: According to the 2003 criteria, CAPS can be classified as definite when there is evidence of: -3 organs involved, development of manifestations simultaneously or within a week, confirmation by imaging and/or histopathology of small vessel occlusion and positive antiphospholipid antibodies. Probable CAPS is when 3 out of the 4 criteria are present. In this case, three organs were confirmed to be involved with imaging showing cerebral and cardiac ischaemia. Her creatinine rose from a base of 190 to 289umol/L coupled with a high protein creatinine ratio confirming renal involvement. A Budd-Chiari syndrome was also suspected due to deranged liver function tests and INR, though imaging performed after therapy did not confirm this. A biopsy of any of these four organs was not feasible given the severity of her presentation and coagulopathy. There are no randomised controlled trials but data from the CAPS registry guides treatment and management follows a logical approach: anticoagulation to treat thrombosis, glucocorticoids for inflammation and plasma exchange (or IVIG) to remove the circulating autoantibodies. Triple therapy was associated with a reduced mortality compared to no treatment (28.6% versus 75%, respectively). Following analyses from the CAPS registry we also chose to treat with cyclophosphamide, which is associated with improved survival in patients with SLE. This decision was based on the clinical features of an SLE flare as opposed to serological grounds. There have b en reports of rituximab and eculizumab being used successfully in CAPS, though generally as a last resort. As complement activation is seen in animal models of antiphospholipid syndrome thrombosis and rituximab is often used in refractory SLE, they may prove to be promising agents for refractory CAPS. Case report - Key learning points: 1. Prompt recognition and early treatment is vital in managing CAPS 2. Triple therapy with anticoagulation, glucocorticoids and plasma exchange / IVIG is associated with better survival in CAPS 3. Cyclophosphamide is associated with better survival in patients with CAPS and concomitant SLE.

Increased cerebral blood flow and neuroinflammation post COVID-19

Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.

Coagulopathy and thromboembolism in children with COVID-19 - pathophysiology, thrombotic risk, clinical manifestations, and management

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the beginning of the pandemic, it has been generally accepted that children infected with SARS-CoV-2 either stay asymptomatic or present benign symptoms. Yet SARS-CoV-2 is widely known to cause serious consequences in children and adolescents. Complications may develop during infection, several weeks afterwards, or in the course of multisystem inflammatory syndrome in children (MIS-C). MIS-C manifests with fever, gastrointestinal, cardiovascular and/or neurological symptoms. Moreover, thromboembolism is a relatively common complication of COVID-19 and MIS-C. The purpose of this work was to review current reports on thromboembolic complications among children who underwent SARS-CoV-2 infection. Among the published cases of MIS-C, thromboembolic incidents ranged from 1.4% to 6.5%, taking the form of a brain infarct, deep vein thrombosis, pulmonary embolism, or splenic infarct. Several mechanisms leading to thrombosis in COVID-19 in children are considered. The development of acute infection in the lungs results in local clot formation in the pulmonary microcirculation, leading to perfusion disturbances. ADAMTS13 activity is also mildly reduced in patients infected with SARS-CoV-2, increasing the risk of microthrombosis. COVID-19-associated coagulopathy is characterized by elevated D-dimers and fibrinogen levels. Significantly increased D-dimers probably represent activation of coagulation caused by viremia and cytokine storm, as well as possible organ dysfunction. The treatment of thromboembolism in children includes low and high molecular weight heparins and acetylsalicylic acid. Pediatricians should be aware of the possible multiple complications associated with COVID-19 in children, including thromboembolic incidents. Copyright © 2022 Sciendo. All rights reserved.

Neurologic Manifestations of COVID-19.

Coronavirus disease (COVID-19) caused by a new coronavirus, SARS-CoV-2, has become a serious health problem throughout the world. Although COVID-19 primarily presents as an acute respiratory tract infection, many neurological findings have also been described in patients. Neurological findings are classified into three groups as central, peripheral nervous system and musculoskeletal system. The most common central nervous system symptom is headache. Encephalitis, encephalopathy, seizures, acute ischemic stroke are also seen. The most common symptoms in the peripheral nervous system are loss of smell and taste. Myalgia, myositis and rhabdomyolysis also can be seen in musculoskeletal system involvement. Awareness of the neurological symptoms by physicians will be beneficial in early diagnosis and treatment of the disease. Copyright © 2022 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

A Case of cryptococcal meningoencephalitis in an immunocompetent patient with Chiari I malformation

Case Report: Over 90% of cases of cryptococcal meningoencephalitis present in immunocompromised patients, with the majority of those being in patients with AIDS. However, this infection can also occur in patients with other immunocompromised states, such as steroid use, malignancy, rheumatologic diseases, and use of immunosuppressive medications. Delay in diagnosis can often lead to rapid neurological deterioration and mortality. Case: A young, otherwise immunocompetent patient, with a history of Chiari I malformation and recent COVID- 19 infection presented with syncope following two weeks of headaches, generalized body aches and weakness after COVID-19 diagnosis. Physical exam demonstrated an isolated CN VI palsy. Head imaging revealed new right caudate infarcts, and a cerebellar tonsillar descent compatible with history of Chiari I malformation. Initial lumbar puncture (LP) was deferred due to congenital brain herniation. Over the next few days, the patient continued to show increasing neurological deficits such as truncal ataxia and increased mood instability. The patient was transferred to the Intensive Care Unit, and LP was obtained under special neuro-critical care direction. Due to increased opening pressures and yeast on gram stain, cryptococcus was suspected and later confirmed. Although anti-fungal therapy was initiated, the patient continued to deteriorate, leading to cardiac arrest, intubation, and placement of lumbar drain. The patient unfortunately did not demonstrate neurologic recovery following arrest and progressed to brain death. Discussion(s): While cryptococcal meningoencephalitis is overwhelmingly a disease of immunocompromised patients, it can occur in immunocompetent hosts, and delay in diagnosis and treatment can lead to adverse and fatal outcomes. This patient had no known underlying conditions besides a recent mild COVID-19 infection and underlying Chiari I malformation, neither of which are known to be associated with cryptococcal meningoencephalitis. These factors may however have played a role in his disease and progression. Copyright © 2023 Southern Society for Clinical Investigation.

A case of post coronavirus disease 2019 (COVID-19) multisystem inflammatory syndrome in adults (MIS-A) presenting as fever and seizures

Background/Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of a severe associated condition, multisystem inflammatory syndrome in adults (MIS-A). Initially identified in children as MIS-C, literature regarding the clinical manifestations, illness progression, and treatment of MIS-A are limited. Method(s): This study describes a case of MIS-A presenting as fever and seizures. She was initially given steroids and IVIG, and due to recurrence of fever, she was later treated with tocilizumab. Result(s): The patient was a 55-year- old Filipino female presenting to the emergency department with five days of fever, headache, and disorientation. Lumbar tap was done, which showed elevated opening pressure, normal leukocyte count, normal glucose, slightly elevated protein, and no microorganisms. She was admitted and managed as a case of viral encephalitis. On hospital day 6, she had sudden onset of head-jerking and further decrease in sensorium, hence she was transferred to the intensive care unit. Brain MRI was unremarkable, and subsequent immune-mediated encephalitis was considered. The patient underwent methylprednisolone pulse therapy and IVIG infusion, which provided immediate improvement of sensorium and resolution of fever episodes. Her condition stabilized, and she was transferred out of intensive care. She underwent physical and occupational rehabilitation as preparation for discharge. Two weeks after infusion therapy, on hospital day 26, patient had recurrence of fever episodes and persistence of elevated inflammatory markers. The patient had reported a previous COVID-19 infection 10 weeks prior to admission and received a booster dose of Moderna (Spikevax) COVID-19 vaccine three weeks prior. She tested positive for ANA (1:640, nuclear speckled), while the rest of the autoimmune antibody tests were negative. She was diagnosed as MIS-A based on the following: documented fever (>=38 degrees centigrade) for >=24 hours prior to hospitalization;new-onset neurologic signs and symptoms including seizures and encephalopathy in a patient without prior cognitive impairment;elevated CRP, ferritin, IL-6, and ESR;and a positive SARS-CoV- 2 test for recent infection by RT-PCR. Patient was treated with a locally available monoclonal antibody, tocilizumab, which was given on hospital day 43. Following infusion, she had lysis of fever and marked decrease in CRP, ferritin, IL-6, and ESR. Patient was discharged improved and without end-stage organ damage. Conclusion(s): Immunomodulators target hyperinflammation seen in MIS-A. There may be a role for the use of tocilizumab via blockage of IL-6. MIS-A remains a topic for research, particularly its disease characteristics, management, and relation to a dysregulated immune system.

Thrombotic Thrombocytopenic Purpura (TTP) secondary to Covid-19 infection in a patient with Systemic Lupus Erythematosus (SLE)

Background: Covid-19 infection has caused a global pandemic in the recent years and although initially it was considered mainly a respiratory ailment it has proven over time to cause a constellation of complications across various systems such as hematological, immune, cardiovascular, gastrointestinal, and neurological. Method(s): We report a case of a lupus patient with Covid-19 infection who presented initially with fever and gum bleeding with a negative dengue serology and negative HIV serology. Result(s): A 45-year- old lady with a 30-year history of SLE was admitted to our hospital with Covid 19 infection. She had relatively stable disease over the past few years but was admitted to the hospital with complaints of fever, gum bleeding and shortness of breath with no chest x-ray changes. Her oxygen saturations were 95% under room air and her vital signs were stable. Laboratory examinations revealed raised white cell count (11.63) with neutrophilia and elevated C-reactive protein (2.84mg/dl). Her platelet count was low at 113 when compared to her baseline of 549. An urgent peripheral blood film showed an incidental finding of Stomato-ovalocytosis with mild anaemia however there was no features of haemolysis. She was initially treated as acquired Immune thrombocytopenia provoked by Covid-19 infection and was started on IV hydrocortisone. She had a lack of response as evident of a further decline in her platelet counts and the following day, she developed rapid decline in her renal function wherein her creatinine increased from 83 to 207. An urgent ultrasound doppler of the kidneys to rule out acute renal vein thrombosis was organised however it showed normal patent renal vessels. Peripheral blood films were repeated which showed minimal schistocytes and the diagnosis was clinched with the Adamst13 activity levels being less than 0.2%. She was started on 20g IVIG per day with plasma exchange however succumbed to the illness. Conclusion(s): The diagnosis of TTP classically involves the recognition of the pentad of fever, microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure, and neurological abnormalities however 60% of patients do not fulfil the pentad. It is essential to recognize that Covid-19 is an acquired cause of TTP, and a high index of suspicion must be maintained for early treatment institution.

Post-COVID-19 elective surgery and transformation: exploring the role of ambulatory spinals in the high-risk patient population

At Whipps Cross Hospital, multi-morbid (high-risk) patients undergoing urological surgery are routinely listed on the surgical inpatient pathway. The 'Getting it right first time' [1] review of anaesthesia recommended day-case surgery as the default for suitable procedures, to help with waiting lists as well as to provide patients with a safe environment. To improve patient choice and postoperative outcomes, an ambulatory spinal pathway was piloted. Methods An earlier scoping exercise identified a pool of urology high-risk patients who could potentially benefit from an ambulatory spinal pathway. Based on this, prilocaine use for ambulatory spinal anaesthetic was provisionally approved by the drugs and therapeutic committee. A pilot ambulatory pathway was put in place, which helped identify suitable patients. The pilot pathway was limited to a select group of anaesthetists to minimise variations. Postoperatively, patients were followed up at 3 and 24 h and assessed for postoperative nausea, vomiting, pain, mobilisation, neurological symptoms and cognitive impairment. Results The total number of patients was 19. Mean ASA was 2.9. Average age was 74 years. The mean dose of hyperbaric prilocaine 2% used was 2.9 ml, 21% of cases utilised additional intrathecal additives. Regarding intra-operative analgesia, only paracetamol was used in 15% of cases. There were no conversions to general anaesthetic. The most common procedure was a cystoscopy with or without biopsy (42%). With comorbidities, diabetes mellitus was the most common (58%), followed by cardiac disease (53%) and respiratory disease (42%). At 3 h, 100% of patients were eating and all sensation had returned, 0% had cognitive impairment, 47% were sitting out and 42% mobilising. Sixteen per cent had hypotension and 5% had pain at rest. At 24 h, 0% had cognitive impairment, 50% had required analgesia and 84% were mobilising. All patients reported they would have a spinal anaesthetic again in the future. Discussion With an ageing population, who have multiple comorbidities, there is huge benefit regarding providing the choice of a spinal anaesthetic rather than general anaesthetic, which allows patients to go home the same day. This will not only provide financial savings to the service provider but also help clear the backlog of surgeries due to the COVID-19 pandemic and enhance patient recovery.

Incorporation of a smart sock with the virtual immersive test for postural stability

Purpose of Study: Assessment of an individual's postural stability serves as an indirect measure for both physiological and biomechanical stresses placed on an individual. More recently, some individuals after COVID-19 (SARS-CoV-2) infection have been identified with neurological complaints (Post-Acute Sequelae of Covid - PASC). These individuals can also be predisposed to decreased postural stability and an increased risk for falls. The purpose of the project was to incorporate two different wearable technology (virtual reality (VR) based virtual immersive sensorimotor test - VIST and pressure senor-based smart sock) to assess postural stability among healthy and individuals with PASC to quantify the overall status of the postural control system. Methods Used: All methods were conducted based on the University's Institutional Review Board (IRB# 21-296) with informed consent. A total of 12 males and females (six healthy and six with self-reported complaints of PASC) have completed the study so far. All participants were tested using the VIST, while standing on a force platform and wearing the smart sock simultaneously. The (VIST uses a VR headset and proprietary software to test an individual's integrated sensory, motor, and cognitive processes through eight unique tests (smooth pursuits, saccades, convergence, peripheral vision, object discrimination, gaze stability, head-eye coordination, cervical neuromotor control). Center of pressure (COP) data from force platform and pressure sensor data from the smart socks were used to calculate anterior-posterior and medial-lateral postural sway variables. These postural sway variables were analyzed using an independent samples t-test between the healthy and PASC groups at an alpha set at 0.05. Summary of Results: Significant differences (p < 0.05) between healthy and individuals with PASC with anteriorposterior and medial-lateral postural sway variables derived from COP measures, with individuals with PASC exhibiting significantly greater postural sway compared to healthy individuals in all eight tests of the VIST. The measures from the smart sock, while not statistically significant, exhibited the same findings of increased postural sway in individuals with PASC compared to healthy individuals. Conclusion(s): Findings from the current analysis revealed that individuals with PASC demonstrated significantly worse postural control compared to the healthy, when challenged with various sensorimotor tests in VIST, suggesting that postural control is compromised due to PASC. While not statistically significant due to a lower sample size, the measures from smart sock also indicated the same findings of the COP measures, suggesting a promising use of wearable technology in postural control assessments. In addition to other neurological signs and symptoms of PASC, assessment of postural stability using the VIST can provide more detailed clinical measures for diagnosis, treatment, and prognosis assessments. Copyright © 2023 Southern Society for Clinical Investigation.

Multisystem inflammatory syndrome associated with COVID-19 in children: Risk factors of severe life-threatening course of the disease

Background/Purpose: Multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19 infection is a life-threatening condition, required intensive care. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. Method(s): The retrospective study included 166 children (99 male, 67 female), aged from 4 months to 17 years (median 8.2 years), who met the WHO criteria for MIS-C. The criterion of severity was the fact of the ICU admission. The analysis of the obtained data was performed using the STATISTICA software package, version 10.0 (StatSoft Inc., USA). Result(s): To assess the factors associated with the severe course of MIS-C, patients were divided into two groups: those who were hospitalized in the ICU (n = 84;50.6%), and those who did not (n = 82;49.4%). Patients with a more severe course of MIS-C were significantly older. They had a high frequency of signs such as rash, edema, hepatomegaly, splenomegaly, neurological and respiratory symptoms. Hypotension/shock and myocardial damage were much more common in patients hospitalized in the ICU. Among the laboratory changes there were significant differences in the levels of hemoglobin, leukocytes and platelets, CRP, creatinine, troponin and D-dimer. The presence of macrophage activation syndrome was higher in patients, admitted in the ICU. Children, required intensive care required high dose corticosteroids and IVIG more often (table 1). FIGURE: 1) The first symptoms of progeria in infancy: scleroderma-like changes in the skin of the lower extremities and stiffness of knee joints at the age of 2 months. 2) Girl at the age of 3 years 5 months. Almost total alopecia with the absence of eyebrows and eyelashes. Pronounced venous pattern in the forehead, nasal bridge and nasolabial triangle. Conclusion(s): MIS-C is potentially a severe life-threatening condition, in which more than half (50.6%) of patients needed the ICU admission. The main factors determining the severity of MIS-C were: cardiovascular, resiratory and central nervous system disorders. It has been found that factors such as hepatomegaly, splenomegaly, D-dimer >2568 ng/ml, troponin >10 pg/ml, make it possible to identify a group of patients with high risk of severe MIS-C who may potentially need hospitalization in the ICU.

Catastrophic Antiphospholipid Crisis Triggered by Anticoagulant Switch

Case report - Introduction: The COVID-19 pandemic led to drastic changes for some patients on warfarin for venous thromboembolic (VTE) disease and atrial fibrillation. Warfarin monitoring necessitates frequent interaction with healthcare workers, which is sufficiently risky for COVID-19 transmission. As a result, selected patients were swapped over to novel oral anticoagulants (NOACs). Our patient was changed without investigating for antiphospholipid syndrome (APLS);it later transpired he was triple antibody positive. He presented in a crisis and we describe his narrative. Patients on warfarin due to presumed unprovoked venous thromboembolic disease should not be swapped to NOACs without completing, or checking, previous antiphospholipid antibody testing. Case report - Case description: A 73-year-old gentleman presented locally in August 2020 with erythema over the anterolateral surface of his left leg. He was initially treated with antibiotics for presumed cellulitis. Within a few days this lesion became necrotic and rapidly spread. At this point, he was transferred to a tertiary rheumatology centre. Within days to weeks, he developed several necrotic lesions affecting his trunk and limbs, with facial sparing noted. Approximately 30-35% of his whole-body surface became involved. He soon developed an oxygen requirement, with CTPA demonstrating lymphocytic interstitial pneumonitis without evidence of pulmonary emboli (PE). Throughout his admission, he had several other pathologies such as hyponatraemia that required level 2 care and severe noninfectious diarrhoea. Skin biopsy identified thrombotic vasculopathy. Serology confirmed triple positive antiphospholipid antibody status and a dsDNA titre of>400 iU/mL. This was the first-time serology had been undertaken despite a history of three deep vein thrombosis (DVT) episodes and two PE incidents. He had no history of SLE symptoms. His initial management for vasculitis secondary to APLS at the point of limited necrosis consisted of IV methylprednisolone followed by rituximab and PO prednisolone. While there was some delay in the progression of his disease, new areas of necrosis arose, leading to the patient receiving cyclophosphamide. Low molecular weight heparin was used for anticoagulation. This gentleman later developed proteinuria and neurological symptoms, fulfilling the criteria for catastrophic antiphospholipid syndrome. He received plasma exchange, without an improvement. He developed complications from his disease and treatment, including poor wound healing. It became apparent his condition would not improve and active treatments were stopped. He passed away 6 weeks after initial presentation. Prior to his admission to hospital, his warfarin was swapped to a NOAC. This is thought to have been the trigger behind catastrophic thrombosis. Case report - Discussion: After excluding other conditions such as necrotising fasciitis, this gentleman was rapidly started on IV methylprednisolone to halt any further progression. This is because glucocorticoids have the greatest evidence base for managing this poorly understood acute disease manifestation. After this failed to manage his condition, he was given a further immunosuppressive agent in the form of rituximab. This was used after his serology confirmed triple antibody status. It was hoped this would stop any further immunological mediated disease progression. Oral prednisolone was started at 40mg at this stage and kept under review with a tapering schedule. Cyclophosphamide was given within a few days of rituximab, with hope of a quicker onset of action. A careful MDT decision was made on these drug choices, particularly regarding their combined use and appreciating their side effect profiles. Cyclophosphamide has evidence behind its use, especially for those with APLS associated with lupus. While he did not develop any infections related to treatment, his condition progressed. Case reports suggest that plasma exchange can be useful in the management of catastrophic antiphospholipid syndrome, so the team recommen ed this. Consent at this stage became tricky due to his altered mental status, but it was felt he did demonstrate capacity for this specific decision. As his condition did not improve after this level of immunosuppression, the team reached the decision that no other treatments would likely change the outcome. He remained on oral steroids for the remainder of his admission. The other management facet of APLS crises pertains to anticoagulation. Low molecular weight heparin was recommended by the haematologists. His NOAC was stopped after the diagnosis was confirmed. Warfarin was restarted later in his admission given he had been well on this for years. Case report - Key learning points: This fascinating case exemplifies the importance of completing an antiphospholipid antibody screen for patients who present with unprovoked venous thromboembolic disease. NOACs are commonly used anticoagulant medications. Several case reports have demonstrated that patients with antiphospholipid syndrome experience breakthrough thromboembolic events when treated with NOACs. The highest risk is associated with history of arterial thrombosis and those with triple positive antibody status. Three clinical trials have either been completed or are in the process of investigating whether NOACs sufficiently prevent thromboembolic disease in these patients. The TRAPS study compared rivaroxaban to warfarin in those with triple antibody positive antiphospholipid syndrome. The study was terminated early given that higher adverse events were observed in the rivaroxaban arm (19%, n11/59) versus warfarinised patients (3%, n2/61). The RAPS study found no difference in thromboembolic risk and results from the ASTRO-APS study looking into apixaban are awaited. There is insufficient evidence to suggest that NOACs prevent VTE in a similar fashion to warfarin, so many still advocate the use of warfarin. The optimal immune management of this acute complication is not well elucidated, with a shortfall in mechanistic pathological understanding. The conference will generate discussion on this subject matter in detail. During the COVID-19 pandemic, it has been observed for patients to change anticoagulation from warfarin to NOACs. Given NOACs do not require monitoring, this medication change reduces the number of interactions patients have with healthcare services. We postulate this change triggered the crisis in our patient, where we suggest continuation of warfarin would have been ideal. This is due to the history of several unprovoked thromboembolic events without a prior antiphospholipid screen being completed. Dissemination of learning points from this case are imperative to ensure decision-making encompasses patients who may have undiagnosed antiphospholipid syndrome.

Neurological manifestations in pediatric patients with COVID-19: A case series

In this case series of two male and one female patient with an age range of 2-12 years, only one patient had a history of neurological disorder and underwent ventriculoperitoneal shunt for a medulloblastoma, which describes coronavirus disease-associated neurological manifestations in pediatric patients, among which seizures and sensory disturbances are noticeable. In order to describe the various clinical and neurological manifestations that appeared earlier or developed over the course of illness, a series of cases of pediatric patients with coronavirus disease was documented. Copyright © 2022, Indian Association of Biomedical Scientists. All rights reserved.