Long COVID: Is there a kidney link?

Metabolic causes such as altered bioenergetics and amino acid metabolism may play a major role in Long COVID. Renal-metabolic regulation is an integral part of these pathways but has not been systematically or routinely investigated in Long COVID. Here we discuss the biochemistry of renal tubular injury as it may contribute to Long COVID symptoms. We propose three potential mechanisms that could be involved in Long COVID namely creatine phosphate metabolism, un-reclaimed glomerular filtrate and COVID specific proximal tubule cells (PTC) injury-a tryptophan paradigm. This approach is intended to allow for improved diagnostics and therapy for the long-haul sufferers.

SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed to be essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found that human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system. IMPORTANCE SARS-CoV-2 is the third lethal respiratory coronavirus, after MERS-CoV and SARS-CoV, to emerge this century, causing millions of deaths worldwide. Other common coronaviruses such as HCoV-OC43 cause less severe respiratory disease. Thus, it is imperative to understand the similarities and differences among these viruses in how each interacts with host cells. We focused here on the inositol-requiring enzyme 1α (IRE1α) pathway, part of the host unfolded protein response to virus-induced stress. We found that while MERS-CoV and HCoV-OC43 fully activate the IRE1α kinase and RNase activities, SARS-CoV-2 only partially activates IRE1α, promoting its kinase activity but not RNase activity. Based on IRE1α-dependent gene expression changes during infection, we propose that SARS-CoV-2 prevents IRE1α RNase activation as a strategy to limit detection by the host immune system.

Mental Health Implications for Aviators from COVID-19

Mental Health Implications for Aviators from COVID-19 Objective The authors present aeromedical implications from COVID-19 disruptions on the civil aviation sector, consider mental health impacts on pilots, and discuss possible helpful responses to support pilot mental health. Methods A multiple database review investigated articles from January 2002 to May 2021 on severe commercial aviation disruptions impacting pilot mental health and on pilot mental health coping or treatment. Fifteen papers were identified. Results During the COVID-19 pandemic, airline flights were severely reduced. By January 2021, airlines shed thousands of jobs and 24 airlines no longer existed. General population surveys found 13% of individuals had “serious distress” from the pandemic. In two aviation focused surveys, 40-66% of pilots agreed or strongly agreed that their mental health worsened since the COVID-19 pandemic. Compared to past Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) patients, more COVID-19 patients have mental health symptoms in the acute phase of illness;while about 10% of COVID-19 patients appear to have chronic or “long haul” symptoms. Mental Health treatment and coping strategies found helpful to pilots are discussed. Conclusions Pilots remain at risk for mental health symptoms and illness due to the COVID-19 pandemic. For those who develop severe distress or mental illness from the effects of the pandemic (or COVID-19 infection), early treatment with psychotherapy and/or approved medications may be warranted. This may decrease the likelihood of persistent physical or cognitive or mental health symptoms that would delay a return to flying status.

SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells (preprint)

Despite the efficacy of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 5 million individuals worldwide and continues to spread in countries where the vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed essential for viral replication. We examined the activation status and requirement of the master UPR sensor IRE1 kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and the murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1 as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1 whereby it autophosphorylates, but its RNase fails to splice XBP1. Moreover, IRE1 was dispensable for optimal replication in human cells for all coronaviruses tested. Our findings demonstrate that IRE1 activation status differs upon infection with distinct betacoronaviruses and is not essential for efficient replication of any of them. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1 through an unknown mechanism, perhaps as a strategy to eliminate detection by the host immune system.

From 5Vs to 6Cs: Operationalizing Epidemic Data Management with COVID-19 Surveillance

The COVID-19 pandemic brought to the forefront an unprecedented need for experts, as well as citizens, to visualize spatio-temporal disease surveillance data. Web application dashboards were quickly developed to fill t his g ap, b ut a ll of these dashboards supported a particular niche view of the pandemic (ie, current status or specific r egions). I n t his paper, we describe our work developing our COVID-19 Surveillance Dashboard, which offers a unique view of the pandemic while also allowing users to focus on the details that interest them. From the beginning, our goal was to provide a simple visual tool for comparing, organizing, and tracking near-real-time surveillance data as the pandemic progresses. In developing this dashboard, we also identified 6 key metrics which we propose as a standard for the design and evaluation of real-time epidemic science dashboards. Our dashboard was one of the first released to the public, and continues to be actively visited. Our own group uses it to support federal, state and local public health authorities, and it is used by individuals worldwide to track the evolution of the COVID-19 pandemic, build their own dashboards, and support their organizations as they plan their responses to the pandemic. © 2020 IEEE.

CLINICAL ORAL ABSTRACTS: Comparison of clinical outcomes among patients who did and did not have screening ultrasound or pelvic exam before obtaining medication abortion via direct-to-patient telemedicine and mail

Until recently, standard guidelines for provision of medication abortion (MA) required an ultrasound or pelvic exam be done prior to treatment to confirm intrauterine pregnancy and that the gestational age is within the recommended timeframe for outpatient MA. However, requiring these tests can introduce financial and logistical obstacles for patients. During the COVID-pandemic, use of "no test medication abortion" (NTMA) became more common, including in the TelAbortion study, a multicenter trial that provides MA by direct-to-patient telemedicine and mail. We compared clinical outcomes among study patients who had NTMA or who had an ultrasound or pelvic exam prior to MA. This prospective, observational study examined the association between use of screening ultrasound or pelvic exam and the occurrence of selected clinical events after MA. We included all participants in the TelAbortion study who were enrolled from March 25 to September 15, 2020 and who received services from a participating site that provided at least 2 NTMAs during the analysis period. The primary outcome was procedure abortion or ongoing pregnancy after MA. Other outcomes included a composite outcome of hospitalization and/or blood transfusion, ongoing pregnancy after MA, diagnosis of ectopic pregnancy after shipment of abortion medications, and receipt of clinical care after abortion medications were mailed. We compared outcomes for the 2 groups by calculating adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) using a logistic regression model with inverse probability weighting according to the propensity score and incorporating generalized estimating equations to adjust for clustering by study site. Propensity score weighting was done to increase comparability of the study groups with respect to age, race/ethnicity, prior pregnancies (any versus none), patient residence ≥150 miles from the study site, gestational age by date of last menstrual period, and whether patient used insurance to pay for the abortion service. We included 5 of the 9 participating TelAbortion sites. We analyzed outcomes among 384 TelAbortion patients, including 278 who had NTMA and 106 who had a screening ultrasound or pelvic exam before shipment of abortion medications. A procedure abortion or ongoing pregnancy after MA was reported for 16/278 (5.8%) NTMA patients compared to 2/106 (1.9%) patients who had screening ultrasound or pelvic exam (aOR = 3.23, 95% CI: 0.58–17.97). There were no diagnoses of ectopic pregnancy in either study group. Hospitalization and/or blood transfusion occurred in 2/276 (0.7%) and 1/106 (0.9%) of patients who had NTMA and screening ultrasound or pelvic exam, respectively (aOR = 1.13, 95% CI: 0.48–2.65). Ongoing pregnancy after MA was detected in 4/278 (1.4%) and 2/106 (1.9%) of patients who had NTMA and screening ultrasound or pelvic exam, respectively (aOR = 0.76, 95% CI: 0.08–7.16). More NTMA patients had unplanned clinical encounters after shipment of abortion medication (33/276, 12.0%) compared to patients who had screening ultrasound or pelvic exam (6/106, 5.7%, aOR = 2.91, 95% CI: 1.72–4.91). Of 264 patients who answered questions related to satisfaction, all 183 NTMA patients and 81 patients who had a screening ultrasound or pelvic exam reported being satisfied or very satisfied with the MA service. Individuals who obtain NTMA may be more likely to have a procedure abortion or ongoing pregnancy and have unplanned clinical encounters following MA compared to individuals who obtain a screening ultrasound or pelvic exam. However, NTMA was not associated with an increased risk of ongoing pregnancy or of hospitalization and/or blood transfusion. Moreover, more than 94% of NTMA patients had complete abortion without a procedural intervention. NTMA could increase access to MA without serious consequences for patient safety or satisfaction. [ABSTRACT FROM AUTHOR] Copyright of Contraception is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

CLINICAL ORAL ABSTRACTS: Safety and efficacy of no-test medication abortion: A retrospective multi-site study

Introduction The COVID-19 pandemic brought new attention to medication abortion because it does not require direct physical contact between patient and clinical staff. No-test approaches for medication abortion preserve the usual standard of care, except that they replace the in-person ultrasound or physical exam before the abortion with other evidence-based methods to assess the patient's duration of pregnancy and screen for ectopic pregnancy. Early in the pandemic, a no-test sample protocol was published to offer guidance for clinical practice. However, little has been published on the safety and efficacy outcomes of no-test approaches. Method Through webinars and personal contacts, we invited US-based clinics that had adopted the no-test medication abortion protocol to join the study. A no-test medication abortion was defined as not having a preabortion ultrasound or physical exam. Participating clinics abstracted data from medical records of all patients who received a no-test medication abortion and entered them into a REDCap database. We conducted descriptive analyses of the clinic protocols and the patient sample. We also developed a multilevel, multivariable model that accounted for clustering at the clinic-level to estimate the adjusted odds of medication abortion failure and adverse events. Results We included 11 clinics, 4 of which contributed some data from the TelAbortion Study. Clinics shared data on 791 patients served from Jan. 1 to Dec. 31, 2020. Among all patients, 58.1% received mifepristone in person and 41.9% received it by mail. At mifepristone provision, patients’ pregnancy durations ranged from 27 to 74 days;36.4% were <=42 days, 45.3% were 43 to 56 days, 16.4% were 57 to 70 days, and 1.9% were >71 days. We received at least some follow-up data for 626 patients (79.1%) and excluded 14 patients who did not take mifepristone. Of the remaining 612 patients, 5 (0.8%) experienced serious adverse events defined as hospital admission, abdominal surgery and blood transfusion. One patient had a confirmed ectopic pregnancy and was admitted to a hospital for salpingectomy 9 days after provision of mifepristone (included as a serious adverse event). Abortion outcome data were available for 394 patients (64.4%). Overall, 94.7% (95% CI: 92.0% to 96.7%) of patients had a complete abortion with <1600 mcg of misoprostol, without an aspiration, procedure, or more mifepristone and misoprostol. 2 patients had suspected or confirmed ongoing pregnancies. Outcomes were similar for those who received medications in-person and those who received them by mail. Conclusions No-test medication abortion with either in-person pick up or mailing of medications is effective and safe, with outcomes similar to rates found in the published literature. Moreover, omitting tests reduce COVID-19 risk and conform with FDA REMS requirements when combined with in-person pick up. Follow up rates (64.4%) with the NTMA approach were similar to other medication abortion protocols. Combining no-test medication abortion protocols with mailing of medications to patients would support public health efforts for those who want to avoid a clinic visit.

The perception of patient safety in an alternate site of care for elective surgery during the first wave of the novel coronavirus pandemic in the United Kingdom: a survey of 158 patients.

BACKGROUND: We undertook a prospective qualitative survey to ascertain the perceptions and experience of National Health Service patients in the United Kingdom who underwent planned or elective procedures and surgery at alternate 'clean' hospital sites during the coronavirus disease 2019 (COVID-19) pandemic. These alternate 'clean' hospital sites were independent hospitals running active staff and patient testing programmes for COVID-19 and which did not admit or treat patients suffering with COVID-19. METHODS: A prospective survey was undertaken to include patients at least 30 days after a planned surgery or procedure conducted at a 'clean' alternate hospital site during the COVID-19 pandemic. The study was conducted using structured interviews undertaken by trained assessors. A 20% sample group of patients were randomly selected to participate in this study. Qualitative data related to confidence, safety and perceptions of safety were collected. RESULTS: Ninety-five patients (60%) reported that they had prior worries or concerns about undergoing an elective procedure during the COVID-19 pandemic. A total of 47 patients (30%) had delayed their surgery at least once because of these concerns. A total of 150 patients (95%) felt that the precautions in place to protect their safety in the setting of an alternate 'clean' hospital site were well thought out and proportionate. Patients reported high levels of confidence in the measures undertaken. Separation of patient pathways using the independent sector and patient testing were identified by patients as having the greatest impact on their perception of safety. CONCLUSIONS: Patient confidence will be key to ensuring uptake of planned and elective procedures and surgery during the COVID-19 pandemic. Perceptions of safety will be key to this confidence and efforts to demonstrably enhance safety are well received by patients. In particular, patients felt that a dedicated programme of patient testing and separation of patient pathways provided the greatest levels of confidence in the safety of their treatment.