Clinical Improvement Following Delayed Initiation of Immunotherapy in a Case of LGI1 Antibody Encephalitis Presenting with Faciobrachial Dystonic Seizures Following COVID-19 Vaccination

Objective To demonstrate a case of suspected post-vaccine autoimmune encephalitis associated with leucine-rich glioma-inactivated protein (LGI1) antibodies with significant clinical improvement after initiation of immunotherapy nearly a year after symptom onset. Background Although the autoimmune encephalitides have overlap in presentation, some have unique manifestations (such as orofacial dyskinesias seen with NMDA encephalitis). These unique associations can serve as a clinical marker of response to treatment and even allow for earlier initiation of immunotherapy while awaiting results from antibody testing. LGI1 encephalitis characteristically presents with faciobrachial dystonic seizures (FBDS) that are refractory to anti-seizure medications (ASMs) but responsive to immunotherapy. Design/Methods Case report Results A previously healthy and highly independent 89-year-old woman developed what she described as abnormal posturing and spasms of the right shoulder two to three weeks after receiving the J&J COVID-19 vaccine. The abnormal movements progressed to involve the right side of her face and were refractory to multiple ASMs. EEG captured multiple events without epileptiform correlate. Several months later she developed paranoia, delusions, and hallucinations. Autoimmune encephalopathy panel returned positive for the LGI1-antibody around nine months after the onset of FBDS. Upon our initial exam, she had a fluctuating level of arousal, impaired recall of recent events, and was tangential in conversation. There were frequent, brief, repetitive, dystonic movements of the right side of the face consistent with FBDS. Admission was arranged for immunotherapy (intravenous methylprednisolone and intravenous immunoglobulin). Upon follow-up four weeks later, there was significant improvement in arousal and concentration with resolution of FBDS and delusions. Conclusions This case highlights a classic case of LGI1 encephalitis after vaccination presenting with FBDS and progressive cognitive changes. Despite immunotherapy being delayed, there was marked clinical improvement. It is important to recognize this entity and that it typically has a favorable outcome.

Affordances and Constraints of Online Museum Experiences for At-Home Science Engagement During the COVID-19 Pandemic

Online museum experiences, or OMEs, expand access to museums beyond physical buildings. With limited visitation during the COVID-19 pandemic, many museums increased OME offerings, including those marketed toward families. However, as most OMEs are developed for K-12 audiences, we have yet to understand how OMEs support-or fail to support-families' engagement with science. To investigate how OMEs facilitated or constrained families' engagement with at-home science learning, we conducted semi-structured interviews with parents and used quantitative discourse analysis to identify emergent affordances and constraints. These findings can inform the design of OMEs that effectively support families' at-home engagement with science. © ISLS.

Epitope Profiling Reveals the Antibody Immune Response Difference Between COVID‐19 Infected and Vaccinated

Antibodies play an important part in combating SARS‐CoV‐2 infection whether generated by the infection or vaccination. However, the many epitopes generated by infection have not been fully investigated with only a few epitopes known and these being mostly limited to the S protein’s receptor binding domain (RBD) and the N‐terminal domain which limits vaccine and drug design 1‐4. The difference between epitopes generated by infection and vaccination has also not been studied. To address this, we employed a SARS‐CoV‐2 proteome microarray to screen for linear epitopes recognized by antibodies present in COVID‐19 patients and individuals vaccinated with the Pfizer‐BioNTech mRNA COVID‐19 Vaccine. The proteome microarray consisted of S, N, and E proteins, as well as spotting peptides that were 15 amino acids in length with overlaps of 5‐amino acids, covering the entire SARS‐CoV‐2 proteome (MN908947.3) (Figure 1). Blood samples were incubated onto the arrays followed by an incubation of fluorescent secondary anti‐human antibodies. Fluorescent intensity data generated and normalized using the Z‐score method and then further analyzed for significance by parametric one‐way ANOVA with Dunnett's post hoc test (COVID‐19 cohort) and repeated measure ANOVAs with Dunnett's post hoc tests (vaccinated cohort). The full‐length S protein showed a significant increase in COVID‐19 patients at around 20‐23 days after symptom onset and vaccinated individuals over all time points in both IgM and IgG antibodies (Figure 2A). Linear mapping of the IgM epitopes revealed a degree of overlap between infected and vaccinated individuals (22.2%;6/27 total) with both having epitopes in the RBD and fusion peptide (FP) (Figure 2B). Structural mapping on 3D models of the S protein showed that all epitopes where on the surface of the protein and that COVID‐19 generated epitopes have a different pattern than those generated by vaccination (Figure 2C). An Epitope identified in this study with future prospects is epitope S481‐495 from COIVD‐19 patients that partially overlapped the binding site of two neutralizing antibodies previously isolated from COVID‐19 patients, S2H135 and F2B‐2F61, and contacted amino acids that interact with ACE2 receptor6,7. One epitope of note from the vaccinated individuals is epitope S811‐825 which mapped adjacent to the fusion‐peptide proximal region. These epitopes may be helpful in future vaccine and antibody therapy development. 1 Ju, B. et al. Nature 584, 115‐119. 2 Robbiani, D. F. et al. Nature 584, 437‐442. 3 Seydoux, E. et al. bioRxiv. 4 Wu, Y. et al. Science 368, 1274‐1278. 5 Piccoli, L. et al. Cell 183, 1024‐1042 e1021. 6 Casalino, L. et al. ACS Cent Sci 6, 1722‐1734. 7 Wang, Q. et al. Cell 181, 894‐904 e899.

SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites.

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and aligned with reported neutralizing antibody binding sites. Similar LPE overlap occurred after infection and vaccination, with LPE clusters specific to each stimulus, where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function. Vaccine-specific LPEs tended to map to sites known or likely to be affected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein. Mapping LPEs to regions of known functional importance in this manner may accelerate vaccine evaluation and discovery of targets for site-specific therapeutic interventions.

Managing Severe Hypoxic Respiratory Failure in COVID-19.

Purpose of Review: Adult respiratory distress syndrome is a life-threatening complication from severe COVID-19 infection resulting in severe hypoxic respiratory failure. Strategies at improving oxygenation have evolved over the course of the pandemic. Recent Findings: Although non-invasive respiratory support reduces the need for intubation, a significant number of patients with COVID-19 progress to invasive mechanical ventilation. Once intubated, a lung protective ventilation strategy should be employed that limits tidal volumes to 6 ml/kg of predicted body weight and employs sufficient positive end-expiratory pressure to maximize oxygen delivery while minimizing the fraction of inspired oxygen. Intermittent prone positioning is effective at improving survival, and there is a growing body of evidence that it can be safely performed in spontaneously breathing patients to reduce the need for invasive mechanical ventilation. Inhaled pulmonary vasodilators have not been shown to improve survival or cost-effectiveness in COVID-19 and should be used selectively. Summary: Finally, the best outcomes are likely achieved at centers with experience at severe ARDS management and protocols for escalation of care.

The Years They've Taken: Systemic Oppression, Black Bodies, and the Materiality of Grief

Lane and Perry conversation regarding their practice and friendship is presented. This discussion deepens their inquiries into Blackness, grief, mourning, vengeance, humor, and the physicality of survival. Taking place seven months into COVID times, they talk about how to create meaning out of the uprising for racial justice while managing their own grief as it both contracts and expands during a protracted, global pandemic whose end feels like a receding horizon.

Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention.

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.

SARS-CoV-2 breakthrough infection in a fully vaccinated hemodialysis patient

Introduction: End-stage kidney disease (ESKD) is associated with immunosuppression manifesting as both increased infection rates & impaired vaccine immunoresponsiveness. Nonetheless, COVID-19 vaccines have proven highly effective in dialysis-dependent ESKD patients, with reported seroconversion rates as high as ∼96%. Herein, we describe a case of breakthrough SARS-CoV-2 infection in a fullyvaccinated hemodialysis patient. Case Description: A 69 year-old white male with dialysis-dependent ESKD presented for routine rural in-center hemodialysis with a new intermittent nonproductive cough following known COVID-19 exposure. He tested positive for COVID-19 via both rapid antigen testing & RT-PCR despite full mRNA-1273/Moderna SARS-CoV-2 vaccination ∼2 mo prior, & was admitted for inpatient management pending availability of isolated outpatient dialysis. He was afebrile, normoxemic, & clinically stable at presentation & throughout his subsequent hospital course. Following 10 d of uneventful isolation, during which he received thrice-weekly hemodialysis but no COVID-19-specific therapies, he resumed maintenance outpatient dialysis. Of note, he was current on all recommended vaccinations for dialysis patients, but had required multiple courses of hepatitis B vaccination for a documented history of impaired serocoversion. The patient ultimately developed both anti-nucleocapsid IgM & anti-spike IgG antibodies directed against SARS-CoV-2, & viral genome sequencing revealed a novel SARS-CoV-2 variant of interest (B.1.526). Discussion: While breakthrough COVID-19 is rare -reported in <0.001% of the fully vacciniated U.S. population as of 20 Apr 2021 -incidence rates may be higher in specific immunosuppressed subgroups such as ESKD patients. This case illustrates the potential for fully-vaccinated ESKD patients to contract COVID-19, particularly following known exposure(s) or in the setting of viral variants. It is also consistent with accumulating anecdotal clinical experience suggesting that breakthrough infections are generally milder phenotypically than primary infections in vaccine-naïve individuals. As such, high levels of suspicion may be required for identification & proper isolation. Constrained local resources in rural settings may also require different risk mitigation & management strategies for in-center hemodialysis patients with breakthrough COVID-19.

BOugie or stylet in patients UnderGoing Intubation Emergently (BOUGIE): protocol and statistical analysis plan for a randomised clinical trial.

INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation. METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021. ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).

Donor to recipient transmission of SARS-CoV-2 by lung transplantation despite negative donor upper respiratory tract testing.

We describe a case of proven transmission of SARS-CoV-2 from lung donor to recipient. The donor had no clinical history or findings suggestive of infection with SARS-CoV-2 and tested negative by reverse transcriptase polymerase chain reaction (RT-PCR) on a nasopharyngeal (NP) swab obtained within 48 h of procurement. Lower respiratory tract testing was not performed. The recipient developed fever, hypotension, and pulmonary infiltrates on posttransplant day (PTD) 3, and RT-PCR testing for SARS-CoV-2 on an NP swab specimen was non-reactive, but positive on bronchoalveolar lavage (BAL) fluid. One thoracic surgeon present during the transplantation procedure developed COVID-19. Sequence analysis of isolates from donor BAL fluid (obtained at procurement), the recipient, and the infected thoracic surgeon proved donor origin of recipient and health-care worker (HCW) infection. No other organs were procured from this donor. Transplant centers and organ procurement organizations should perform SARS-CoV-2 testing of lower respiratory tract specimens from potential lung donors, and consider enhanced personal protective equipment for HCWs involved in lung procurement and transplantation.