Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient.

Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patient with hypogammaglobulinemia. Following mAb treatment, the patient did not clear the infection. During viral persistence, SARS-CoV-2 acquired three novel spike mutations. Neutralization and mouse protection analyses demonstrate a complete viral escape from REGN-COV at the expense of ACE-2 binding. Final clearance of the virus occurred upon reduction of the immunosuppressive regimen and total IgG substitution. Serology suggests that the development of highly neutralizing IgM rather than IgG substitution aids clearance. Our findings emphasise that selection pressure by mAbs on SARS-CoV-2 can lead to development of escape variants in immunocompromised patients. Thus, modification of immunosuppressive therapy, if possible, might be preferable to control and clearance of the viral infection.

Researching COVID to enhance recovery (RECOVER) autopsy study protocol: Rationale, objectives, and design (preprint)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Tissue Pathology Study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. Methods: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Casual inference methods will be employed to investigate associations between risk factors and pathologic outcomes. Discussion: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

A panel discussion of the COVID-19 crisis with

This article presents a panel discussion of COVID-19 crisis with Marilyn Lewis, Amy Krentzman, Andrea Kepler, Wendy Grab, and Marya Gwadz. The focus of the panel discussion is on the effect of the COVID-19 pandemic on various aspects of one's life. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness.

BACKGROUND: Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE: We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS: Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION: Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

Background: The ISCHEMIA trial compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes over a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy (INV) added to guideline-directed medical therapy or a conservative strategy (CON). Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and non-cardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models and Bayesian methods. Undetermined deaths were classified as cardiovascular as pre-specified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23 % women, 16% Hispanic, 4% Black, 42% diabetes, and median EF 0.60. A total of 557 deaths accrued over a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 non-cardiovascular deaths and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate 12.7% in INV, 13.4% in CON; adjusted hazard ratio (HR)=1.00, 95% CI: 0.85-1.18). There was a lower 7-year rate cardiovascular mortality (6.4% vs. 8.6%, adjusted HR=0.78, 95% CI: 0.63-0.96) with an initial invasive strategy but a higher 7-year rate of non-cardiovascular mortality (5.6% vs. 4.4%, adjusted HR=1.44, 95% CI: 1.08-1.91) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of non-cardiovascular mortality with an initial invasive strategy over a median follow-up of 5.7 years. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04894877; https://clinicaltrials.gov/ct2/show/NCT04894877.

You Do Not Have to Get through This Alone: Interpersonal Emotion Regulation and Psychosocial Resources during the COVID-19 Pandemic across Four Countries.

While experiencing the unpredictable events of the COVID-19 pandemic, we are likely to turn to people in order to regulate our emotions. In this research, we investigate how this interpersonal emotion regulation is connected to affective symptoms, above and beyond intrapersonal emotion regulation. Furthermore, we explore whether perceived psychosocial resources moderate these associations, i.e., if individuals reporting healthier social connections benefit differently from interpersonal emotion regulation. N = 1401 participants from the USA, UK, Germany, and Switzerland completed an online survey that included text samples. Affective symptoms (depression, adjustment disorder, fear of COVID-19) were examined based on self-reported as well as language-based indicators. As psychosocial resources, we examined social support, loneliness, attachment style, and trust. We defined latent variables for adaptive and maladaptive interpersonal emotion regulation and analyzed how they were associated with affective symptoms controlling for intrapersonal emotion regulation. Further, we analyzed how they interacted with psychosocial resources. Maladaptive interpersonal emotion regulation strategies were associated with affective symptoms. With lower psychosocial resources, the associations between interpersonal emotion regulation and depressive symptoms were more pronounced. The results highlight that maladaptive interpersonal emotion regulation is associated with worse mental health. These effects are not buffered by more psychosocial resources and are stronger for people with low psychosocial resources.

A Special Case of Acute Myocarditis with Left Ventricular Thrombus

Introduction. Acute myocarditis is a potential life-threatening disease and left ventricular thrombus could be a complication. Nowadays, myocarditis has been observed after SARS-CoV-2 vaccination. We report the case of a young adult female with left ventricular thrombus secondary to COVID19 mRNA vaccine-related acute myocarditis. Case report A 33-year-old afro-descendant female was admitted to the ED with dyspnea, heart-pounding and chest pain. The EKG showed sinus tachycardia with diffuse changes in repolarization. The lab tests showed: TnHS 8437 ng/mL, C-reactive protein 3,8 mg/dL, normal white blood cell count, NTproBNP 3800 pg/mL, GOT 171 UI/l, GPT 57 UI/l. She received the first dose of mRNA SARS-CoV-2 vaccine 21 days earlier. The PCR swab test for SARS-CoV-2 was negative. Clinical examination revealed HR 110 bpm, BP 105/75 mmHg, normal lung sounds, tachycardic heart sounds. Transthoracic echocardiogram showed EF 25%, massive apical adherent thrombus and mild diffuse pericardial effusion. Serological analysis for viral and bacterial infection were negative. Coronary angiography, cardiac- MRI, myocardial biopsy were not performed because of patient refuse and claustrophobia. LMWH 8000 UI bid, Ibuprofen 600 mg tid and Colchicine 0,5 mg/die were administered. The patient was discharged after 14 days with no symptoms, no residual thrombus and total EF recovery. The alleged adverse event was reported to the National Pharmacovigilance Network. Conclusions Myocarditis is a potential consequence of both COVID-19 and its mRNA vaccines. Post-vaccine myocarditis is usually self-limiting with a low rate of consequences.

Risk factors for COVID-19 infection in a longitudinal statewide seroepidemiology cohort (preprint)

Background: Virginia is a large state in the USA, yet it remains unclear what percentage of the population has had natural COVID-19 infection and whether risk factors for infection have changed over time.  Methods: Using a longitudinal cohort, from December 2021-July 2021 we performed follow up serology and a questionnaire on 784 individuals from across Virginia who had previously participated in a statewide COVID-19 seroepidemiology study in 2020. Children were also invited to participate and an additional 62 children also completed the study. Serology was performed using Roche nucleocapsid and spike serological assays. Results: The majority of participants were white (78.6%), over 50 years old (60.9%), and reported having received COVID-19 vaccine (93.4%). 28.6% had evidence of prior COVID-19 infection (nucleocapsid positive). Approximately 25-53% of COVID-19 infections were asymptomatic. Infection rates were lower in individuals >60 years old and were higher in Blacks and Hispanics. Infection rates were also higher in those without health insurance, in those with greater numbers of household children, and in those that reported a close contact or having undergone quarantine for COVID-19. Participants from Southwest Virginia had lower seropositivity (16.2%, 95% CI 6.5, 26.0) than other geographic regions. Boosted vaccinees had lower infection rates than non-boosted vaccinees. Frequenting indoor bars trended towards being a significant risk factor for infection, while frequently wearing an N95 mask trended towards protection. Infection rates were higher in children than adults (56.5% vs. 28.6%). Infection in the parent was a risk factor for child infection. Spike antibody levels declined with time since last vaccination, particularly in those that were vaccinated but not previously infected.  Conclusions: In this longitudinal statewide cohort we observed a lower than expected COVID-19 infection rate as of August 2022. Boosted vaccinees had lower infection rates. Children had higher infection rates and infections tracked within households. Previously identified demographic risk factors for infection tended to persist. Even after the omicron peak, a large number of Virginians remain uninfected with COVID-19, underscoring the need for ongoing vaccination strategies.

Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients.

BACKGROUND: Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. METHODS: We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. RESULTS: A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. CONCLUSIONS: In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

Estimation of age-stratified contact rates during the COVID-19 pandemic using a novel inference algorithm.

Well parameterized epidemiological models including accurate representation of contacts are fundamental to controlling epidemics. However, age-stratified contacts are typically estimated from pre-pandemic/peace-time surveys, even though interventions and public response likely alter contacts. Here, we fit age-stratified models, including re-estimation of relative contact rates between age classes, to public data describing the 2020-2021 COVID-19 outbreak in England. This data includes age-stratified population size, cases, deaths, hospital admissions and results from the Coronavirus Infection Survey (almost 9000 observations in all). Fitting stochastic compartmental models to such detailed data is extremely challenging, especially considering the large number of model parameters being estimated (over 150). An efficient new inference algorithm ABC-MBP combining existing approximate Bayesian computation (ABC) methodology with model-based proposals (MBPs) is applied. Modified contact rates are inferred alongside time-varying reproduction numbers that quantify changes in overall transmission due to pandemic response, and age-stratified proportions of asymptomatic cases, hospitalization rates and deaths. These inferences are robust to a range of assumptions including the values of parameters that cannot be estimated from available data. ABC-MBP is shown to enable reliable joint analysis of complex epidemiological data yielding consistent parametrization of dynamic transmission models that can inform data-driven public health policy and interventions. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Clinical and genomic signatures of SARS-CoV-2 Delta breakthrough infections in New York.

BACKGROUND: In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. METHODS: We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. FINDINGS: We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. INTERPRETATION: We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. FUNDING: The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

Generating 3D Spheres and 2D Air-Liquid Interface Cultures of Human Induced Pluripotent Stem Cell-Derived Type 2 Alveolar Epithelial Cells.

In the lung, the alveolar epithelium is a physical barrier from environmental stimuli and plays an essential role in homeostasis and disease. Type 2 alveolar epithelial cells (AT2s) are the facultative progenitors of the distal lung epithelium. Dysfunction and injury of AT2s can result from and contribute to various lung diseases. Improved understanding of AT2 biology is, thus, critical for understanding lung biology and disease; however, primary human AT2s are generally difficult to isolate and limited in supply. To overcome these limitations, human induced pluripotent stem cell (iPSC)-derived type 2 alveolar epithelial cells (iAT2s) can be generated through a directed differentiation protocol that recapitulates in vivo lung development. iAT2s grow in feeder-free conditions, share a transcriptomic program with human adult primary AT2s, and execute key functions of AT2s such as production, packaging, and secretion of surfactant. This protocol details the methods for maintaining self-renewing iAT2s through serial passaging in three-dimensional (3D) culture or adapting iAT2s to air-liquid interface (ALI) culture. A single-cell suspension of iAT2s is generated before plating in 3D solubilized basement membrane matrix (hereafter referred to as "matrix"), where they self-assemble into monolayered epithelial spheres. iAT2s in 3D culture can be serially dissociated into single-cell suspensions to be passaged or plated in 2D ALI culture. In ALI culture, iAT2s form a polarized monolayer with the apical surface exposed to air, making this platform readily amenable to environmental exposures. Hence, this protocol generates an inexhaustible supply of iAT2s, producing upwards of 1 x 1030 cells per input cell over 15 passages while maintaining the AT2 program indicated by SFTPCtdTomato expression. The resulting cells represent a reproducible and relevant platform that can be applied to study genetic mutations, model environmental exposures, or screen drugs.

Severe neurotoxicity of oral ivermectin: a systematic review of case and case series reports

Background and importanceIvermectin is a broad-spectrum antiparasitic. It was tested to treat COVID-19 but no benefit was found through large studies. Severe encephalopathy occurrence is known in patients treated with ivermectin and coinfected by a large number of Loa loa microfilariae but there is a growing concern due to severe encephalopathy reports in other contexts.Aim and objectivesAssess the evidence about severe neurological toxicity cases after ivermectin use.Material and methodsFollowing the PRISMA recommendations for systematic reviews, a search combining terms associated with ‘ivermectin’ and ‘drug toxicity’ was conducted using the MEDLINE and LILACS databases for all relevant English- and Spanish-language articles from inception through 30 September 2021. Cases and case–control reports were included. We excluded articles not mentioning at least minimal information on ‘ivermectin’ or ‘neurotoxicity’ in a first screening phase. In a subsequent selection phase, articles were excluded if they reported data on paediatric or pregnant patients, intoxications, non-oral route administration or animal data. The outcome of interest was cases of severe neurotoxicity (SN) in adult/adolescent patients (>11 years) treated with ivermectin. Data were synthesised narratively.Results266 articles were assessed and 17 met the inclusion criteria. 6 cases and 11 cases series reports in patients treated for strongyloidiasis, onchocerciasis, loiasis and scabies infections reported SN occurrence such as consciousness disorders, seizure or convulsion, encephalopathy and coma. SN not only was associated with Onchocerciasis treatment in Loa loa coinfected patients. Chandler RE reported 28 SN cases after ivermectin use outside the Onchocerciasis indication and Nzolo D et al reported cases of SN even with low blood levels of Loa loa microfilaria. 2 studies associated SN with the presence of ABCB1 mutation. Baudou E et al reported the case of patient with two human ABCB1 mutations who suffered SN andBourguinat C et al showed homozygotic haplotypes associated with alterations in drug disposition in 2 cases.Conclusion and relevanceAlthough SN has traditionally been reported after extensive Loa loa infections this occurs in other contexts. SN after ivermectin use must be detected early to avoid fatal consequences. Authors related this toxicity with human ABCB1 nonsense mutations that allow ivermectin penetration into the central nervous system. This could be a future field of research.References and/or acknowledgementsConflict of interestNo conflict of interest

A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

OBJECTIVES: We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN: Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING: Five U.S. medical centers. PATIENTS: Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS: Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS: Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

Self-focused and other-focused health concerns as predictors of the uptake of Corona contact tracing apps: Empirical study

Background: Corona contact tracing apps are a novel and promising measure to reduce the spread of COVID-19. They can help to balance the need to maintain normal life and economic activities as much as possible while still avoiding exponentially growing case numbers. However, a majority of citizens need to be willing to install such an app for it to be effective. Hence, knowledge about drivers for app uptake is crucial. Objective: This study aimed to add to our understanding of underlying psychological factors motivating app uptake. More specifically, we investigated the role of concern for one's own health and concern to unknowingly infect others. Methods: A two-wave survey with 346 German-speaking participants from Switzerland and Germany was conducted. We measured the uptake of two decentralized contact tracing apps officially launched by governments (Corona-Warn-App, Germany;SwissCovid, Switzerland), as well as concerns regarding COVID-19 and control variables. Results: Controlling for demographic variables and general attitudes toward the government and the pandemic, logistic regression analysis showed a significant effect of self-focused concerns (odds ratio [OR] 1.64, P = .002). Meanwhile, concern of unknowingly infecting others did not contribute significantly to the prediction of app uptake over and above concern for one's own health (OR 1.01, P = .92). Longitudinal analyses replicated this pattern and showed no support for the possibility that app uptake provokes changes in levels of concern. Testing for a curvilinear relationship, there was no evidence that "too much" concern leads to defensive reactions and reduces app uptake. Conclusions: As one of the first studies to assess the installation of already launched corona tracing apps, this study extends our knowledge of the motivational landscape of app uptake. Based on this, practical implications for communication strategies and app design are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Zoster Eye Disease Study: Rationale and Design.

PURPOSE: The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS: ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS: Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS: ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.

Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study.

BACKGROUND AND OBJECTIVE: Little is known about trajectories of recovery 12 months after hospitalization for severe COVID-19. METHODS: We conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test. RESULTS: Twelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index <100 (64%), t-MoCA ≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%), or poor sleep (10%). Twelve-month mRS scores did not differ significantly among those with (n = 113) or without (n = 129) neurologic complications during hospitalization after adjusting for age, sex, race, pre-COVID-19 mRS, and intubation status (adjusted OR 1.4, 95% CI 0.8-2.5), although those with neurologic complications had higher fatigue scores (T score 47 vs 44; p = 0.037). Significant improvements in outcome trajectories from 6 to 12 months were observed in t-MoCA scores (56% improved, median difference 1 point; p = 0.002) and Neuro-QoL anxiety scores (45% improved; p = 0.003). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients. DISCUSSION: At 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

Patient preferences using telehealth during the COVID-19 pandemic in four Victorian tertiary hospital services.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has had a major impact on healthcare services with many changes to telehealth care delivery. More information is needed about the patient perspective of telehealth in hospital services and the potential costs and benefits for patients. AIM: To measure patients' evaluation of telehealth, preferences for telehealth versus in-person appointments, and potential cost savings by patient characteristics. METHODS: A cross-sectional online survey (including patient and appointment characteristics, telehealth evaluation, preferences for care and costs) of adult patients using video telehealth in four metropolitan tertiary hospital services in Melbourne, Victoria. RESULTS: A total of 1045 patients (median age 44 years; interquartile range 29-59) participated with an overall response rate of 9.2%. For 98.7% patients, telehealth was convenient, 96.4% stated that it saved time, 95.9% found telehealth acceptable to receive care and 97.0% found that telehealth improved their access to care. Most (62.6%) preferred in-person consultations, although 86.9% agreed that telehealth was equivalent to an in-person consultation. Those in regional and rural areas were less likely to prefer in-person consultations. Patients attending for medical reasons were less likely to prefer in-person consultation compared with patients with surgical reasons. Patient preference to telehealth was independent of level of education, appointment type, self-rated health status and socio economic status. Patients saved an average of A$120.9 (standard deviation A$93.0) per appointment, with greater cost savings for patients from low and middle socio economic areas and regional or rural areas. CONCLUSION: Telehealth video consultations were largely evaluated positively with most patients considering the service to be as good as in-person. Understanding patient preference is critical to consider when implementing telehealth as mainstream across hospital health services.

'We are not going to shut down, because we cannot postpone pregnancy': a mixed-methods study of the provision of maternal healthcare in six referral maternity wards in four sub-Saharan African countries during the COVID-19 pandemic.

INTRODUCTION: Referral hospitals in sub-Saharan Africa are located in crowded urban areas, which were often epicentres of the COVID-19 pandemic. This paper prospectively assesses how maternal healthcare was provided in six referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the COVID-19 pandemic. METHODS: Mixed-methods design using three data sources: (1) qualitative data from repeated rounds of semi-structured interviews conducted between July 2020 and February 2021 with 22 maternity skilled heath personnel (SHP) on perceptions of care provision; (2) quantitative monthly routine data on caesarean section and labour induction from March 2019 to February 2021; and (3) timeline data of COVID-19 epidemiology, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on timeline analysis, and triangulated during reporting. RESULTS: We identified three periods: first wave, slow period and second wave. The first wave was challenging for SHP given little knowledge about COVID-19, lack of infection prevention and control training, and difficulties reaching workplace. Challenges that persisted beyond the first wave were shortage of personal protective equipment and no rapid testing for women suspected with COVID-19. We noted no change in the proportion of caesarean sections during the pandemic, and a small increase in the proportion of labour inductions. All hospitals arranged isolation areas for women suspected/confirmed with COVID-19 and three hospitals provided care to women with suspected/confirmed COVID-19. Breastfeeding was not discouraged and newborns were not separated from mothers confirmed with COVID-19. Care provision was maintained through dedication of SHP, support from hospital management and remote communication between SHP. CONCLUSION: Routine maternal care provision was maintained in referral hospitals, despite first wave challenges. Referral hospitals and SHP contributed to guideline development for pregnant women suspected/confirmed with COVID-19. Maternity SHP, women and pregnancy must always be included in priority setting when responding to health system shocks, including outbreaks.