Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome.

Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)-induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

Care of the postcoronavirus disease 2019 patient.

PURPOSE OF REVIEW: In under a year, coronavirus disease 2019 (COVID-19) has taken the lives of hundreds of thousands of Americans, leaving millions of survivors in its wake. The enormous number of people who survived acute illness but continue to have symptoms has highlighted the need for standardized evaluation of the post-COVID-19 patient. This review, based on the current literature and our experience, aims to guide the care of patients who have survived COVID-19. RECENT FINDINGS: The literature on this topic is rapidly expanding and covers both pulmonary and nonpulmonary complications of COVID-19. Pulmonary complications include dyspnea with normoxia, organizing pneumonia and pulmonary fibrosis. Nonpulmonary complications include neurologic, cardiac, and thromboembolic disease. Special consideration should be taken for COVID-19 survivors of intensive care. SUMMARY: The current review outlines the major clinical findings in post-COVID-19 patients and provides a guidelines to the evaluation and management of prolonged symptoms.

Cross-functionalities of Bacillus deacetylases involved in bacillithiol biosynthesis and bacillithiol-S-conjugate detoxification pathways.

BshB, a key enzyme in bacillithiol biosynthesis, hydrolyses the acetyl group from N-acetylglucosamine malate to generate glucosamine malate. In Bacillus anthracis, BA1557 has been identified as the N-acetylglucosamine malate deacetylase (BshB); however, a high content of bacillithiol (~70%) was still observed in the B. anthracis ∆BA1557 strain. Genomic analysis led to the proposal that another deacetylase could exhibit cross-functionality in bacillithiol biosynthesis. In the present study, BA1557, its paralogue BA3888 and orthologous Bacillus cereus enzymes BC1534 and BC3461 have been characterized for their deacetylase activity towards N-acetylglucosamine malate, thus providing biochemical evidence for this proposal. In addition, the involvement of deacetylase enzymes is also expected in bacillithiol-detoxifying pathways through formation of S-mercapturic adducts. The kinetic analysis of bacillithiol-S-bimane conjugate favours the involvement of BA3888 as the B. anthracis bacillithiol-S-conjugate amidase (Bca). The high degree of specificity of this group of enzymes for its physiological substrate, along with their similar pH-activity profile and Zn²âº-dependent catalytic acid-base reaction provides further evidence for their cross-functionalities.

Social Networks as a Key Health Determinant in Acute Illness Recovery: A Lesson from the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic highlighted the importance of considering social determinants of health in health outcomes. Within this spectrum of determinants, social networks garnered attention as the pandemic highlighted the negative effects of social isolation in the context of social distancing measures. Postpandemic, examining the role social networks play in COVID-19 recovery can help guide patient care and shape future health policies. This study aimed to investigate the relationship between social networks and self-rated health change, as well as physical function, in patients recovering from COVID-19 pneumonia. METHODS: This was a retrospective cohort study utilizing clinical data from 2 New York City hospitals and a 9-month follow-up survey of COVID-19 pneumonia survivors. We evaluated a composite Social Network Score from the 6-item Lubben Social Network Scale and its association with 2 outcomes: 1) self-rated health change and 2) physical function. RESULTS: A total of 208 patients were included in this study. A 1-point increase in the Social Network Score was associated with greater odds of both same or improved self-rated health change (odds ratio [OR] 1.07, 95% CI 1.02-1.12, P = .01), as well as unimpaired physical function (OR 1.08, 95% CI 1.03-1.14, P < .01). CONCLUSION: This study emphasized the importance of social networks as a social determinant of health among patients recovering from COVID-19 hospitalization. Targeted interventions to enhance social networks may benefit not only COVID-19 patients but also individuals recovering from other acute illnesses.

Post-Intensive Care Unit Syndrome in a Cohort of COVID-19 Survivors in New York City.

Rationale: The coronavirus disease (COVID-19) pandemic has led to a dramatic increase in the number of survivors of critical illness. These survivors are at increased risk for physical, psychological, and cognitive impairments known collectively as post-intensive care syndrome (PICS). Little is known about the prevalence of PICS in COVID-19 survivors. Objectives: To report the prevalence of physical, psychological, and cognitive impairment among COVID-19 intensive care unit (ICU) survivors receiving follow-up care in an ICU recovery clinic, to assess for associations between PICS and ICU-related factors, and to compare the cohort of ICU survivors who attended a post-ICU clinic with a cohort of ICU survivors who did not. Methods: We performed a retrospective cohort study of COVID-19 ICU survivors admitted from March to May 2020 who were subsequently seen in a post-ICU recovery clinic in New York City. We abstracted medical chart data on available clinical screening instruments for physical, psychological, and cognitive impairment. Associations between these outcomes and care-related variables were tested. Baseline characteristics and in-hospital treatments of the post-ICU clinic cohort were compared with those of COVID-19 ICU survivors from the same institution who were not seen in the post-ICU clinic. Results: Eighty-seven COVID-19 ICU survivors were seen in our post-ICU recovery clinic. The median age was 62 years, and 74% were male. The median length of hospitalization was 51 days, and the median length of ICU stay was 22 days. At the post-ICU follow-up visit, 29%, 21%, and 13% of patients reported clinically significant levels of depressive symptoms, anxiety, and post-traumatic stress disorder symptoms, respectively. Twenty-five percent had cognitive impairment. The overall prevalence of PICS was 90%. There were no associations between length of ICU stay, delirium, and exposure to benzodiazepines, steroids, or systemic paralytics with positive screening results for physical, psychological, or cognitive impairment. Baseline characteristics and ICU-related factors were similar in the cohort of COVID-19 ICU survivors who attended the ICU recovery clinic and those who did not. Conclusions: PICS is common in COVID-19 survivors. We did not find any association with length of ICU stay or the use of benzodiazepines, steroids, or paralytics.