Serological response to vaccination in post-acute sequelae of COVID.

BACKGROUND: Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. METHODS: We prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. We used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. RESULTS: Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. CONCLUSION: We found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.

Comparison of clinical characteristics and outcomes of critically ill adults with SARS-CoV-2 infection during Delta and Omicron variant predominance periods: a single-hospital retrospective cohort study.

INTRODUCTION: Initial reports suggest the B.1.1.529 (Omicron) variant of SARS-CoV-2 causes less severe disease compared with the B.1.617.2 (Delta) variant, though more widespread vaccination contributed to these findings. Little is known about clinical characteristics and outcomes of patients with SARS-CoV-2 infection requiring intensive care during periods of Delta and Omicron variant predominance. AIM: To examine and compare characteristics of critically ill adults with SARS-CoV-2 infection during periods of Delta and Omicron variant predominance. METHODS: We conducted a retrospective cohort study of critically ill adults with SARS-CoV-2 infection at one academic hospital in Los Angeles during Delta (15 July 2021-23 September 2021) and Omicron (21 December 2021-27 January 2022) predominance. Patient characteristics were compared between Delta-period and Omicron-period hospitalisations, overall and stratified by vaccination status. RESULTS: 79 adults required intensive care during the Delta predominance period and 116 during the Omicron predominance period. We found similar proportions of intensive care unit admissions occurring in fully vaccinated patients between the two periods, despite Los Angeles County data revealing an almost 60% increase in the proportion of SARS-CoV-2 hospitalisations occurring in fully vaccinated persons. There was no difference in the need for invasive mechanical ventilation (IMV). Among those who required IMV, the median duration of IMV was shorter overall (Delta=18 days; Omicron=8 days; p=0.006) and among unvaccinated persons (Delta=19 days; Omicron=8.5 days; p=0.018). Among unvaccinated persons, the median intensive care unit length of stay was shorter (Delta=12 days; Omicron=5 days; p=0.037) during Omicron predominance. There was no difference in the proportion of patients who died while hospitalised. CONCLUSIONS: In this single-hospital study, critically ill patients with SARS-CoV-2 infection experienced less severe respiratory disease during Omicron predominance, likely due to reduced variant-specific virulence. Vaccination likely reduced development of critical illness in adults with SARS-CoV-2 infection during Omicron predominance.

Perception of interdisciplinary collaboration between ICU nurses and resident physicians during the COVID-19 pandemic.

Multidisciplinary collaboration is the hallmark of quality critical care. Prior studies have shown that nurses and physicians have different perceptions on communication and collaboration in the ICU. The Covid-19 pandemic has served to both strain and strengthen relationships between nurses and resident physicians in the ICU. This study used a survey-based approach sought to identify the similarities and differences between perception of collaboration between ICU nurses and resident physicians taking care of patients during the pandemic, and to identify whether they felt that the pandemic impacted the collaborative spirit of critical care. Although findings from this study suggest that overall residents and nurses perceive collaboration similarly, the COVID-19 pandemic may be differentially affecting the interdisciplinary dynamics of the ICU.

An International Virtual COVID-19 Critical Care Training Forum for Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in redeployment of non-critical care-trained providers to intensive care units across the world. Concurrently, traditional venues for delivery of medical education faced major disruptions. The need for a virtual forum to fill knowledge gaps for healthcare workers caring for patients with coronavirus disease (COVID-19) was apparent in the early stages of the pandemic. Objective: The weekly, open-access COVID-19 Critical Care Training Forum (CCCTF) organized by the American Thoracic Society (ATS) provided a global audience access to timely content relevant to their learning needs. The goals of the forum were threefold: to aid healthcare providers in assessment and treatment of patients with COVID-19, to reduce provider anxiety, and to disseminate best practices. Methods: The first 13 ATS CCCTF sessions streamed live from April to July 2020. Structured debriefs followed each session and participant feedback was evaluated in planning of subsequent sessions. A second set of 14 sessions streamed from August to November 2020. Content experts were recruited from academic institutions across the United States. Results: As of July 2020, the ATS CCCTF had 2,494 live participants and 7,687 downloads for a total of 10,181 views. The majority of participants had both completed training (58.6%) and trained in critical care (53.8%). Physicians made up a majority (82.2%) of the audience that spanned the globe (61% were international attendees). Conclusion: We describe the rapid and successful implementation of an open-access medical education forum to address training and knowledge gaps among healthcare personnel caring for patients with COVID-19.

Endotracheal Application of Ultraviolet A Light in Critically Ill Patients with Severe Acute Respiratory Syndrome Coronavirus 2: A First-in-Human Study.

INTRODUCTION: Our previous preclinical experiments show that under specific and monitored conditions, ultraviolet A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. The goal of this study was to evaluate the safety and effects of narrow-band UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Newly intubated, mechanically ventilated adults with SARS-CoV-2 infection and an endotracheal tube size of at least 7.50 mm were eligible for inclusion in the study. Subjects were treated with UVA for 20 min daily for 5 days and followed for 30 days. RESULTS: Five subjects were enrolled (mean age 56.60 years, three male). At baseline, all subjects scored 9/10 on the World Health Organization (WHO) clinical severity scale (10 = death), with predicted mortality ranging from 21% to 95%. Average endotracheal viral load significantly reduced from baseline to day 5 (- 2.41 log; range - 1.16 to - 4.54; Friedman p = 0.002) and day 6 (- 3.20; range - 1.20 to - 6.77; Friedman p < 0.001). There were no treatment-emergent adverse events, with no changes in oxygenation or hemodynamics during the 20-min treatments. One subject died 17 days after enrollment due to intracranial hemorrhagic complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, clinical improvement correlated with reduction of viral load (Spearman's rho = 1, p < 0.001). CONCLUSIONS: In this first-in-human study, endotracheal narrow-band UVA therapy, under specific and monitored settings, appears to be safe and associated with a reduction in respiratory SARS-CoV-2 viral burden over the treatment period. UVA therapy may provide a novel approach in the fight against COVID-19. CLINICAL TRIAL NUMBER: NCT04572399.

Creation of a dedicated line team for critically ill patients with COVID-19: A multidisciplinary approach to maximize resource utilization during the COVID-19 pandemic.

BACKGROUND: Pandemics create challenges for medical centers, which call for innovative adaptations to care for patients during the unusually high census, to distribute stress and work hours among providers, to reduce the likelihood of transmission to health care workers, and to maximize resource utilization. METHODS: We describe a multidisciplinary vascular access team's development to improve frontline providers' workflow by placing central venous and arterial catheters. Herein we describe the development, organization, and processes resulting in the rapid formation and deployment of this team, reporting on notable clinical issues encountered, which might serve as a basis for future quality improvement and investigation. We describe a retrospective, single-center descriptive study in a large, quaternary academic medical center in a major city. The COVID-19 vascular access team included physicians with specialized experience in placing invasive catheters and whose usual clinical schedule had been lessened through deferment of elective cases. The target population included patients with confirmed or suspected COVID-19 in the medical ICU (MICU) needing invasive catheter placement. The line team placed all invasive catheters on patients in the MICU with suspected or confirmed COVID-19. RESULTS AND CONCLUSIONS: Primary data collected were the number and type of catheters placed, time of team member exposure to potentially infected patients, and any complications over the first three weeks. Secondary outcomes pertained to workflow enhancement and quality improvement. 145 invasive catheters were placed on 67 patients. Of these 67 patients, 90% received arterial catheters, 64% central venous catheters, and 25% hemodialysis catheters. None of the central venous catheterizations or hemodialysis catheters were associated with early complications. Arterial line malfunction due to thrombosis was the most frequent complication. Division of labor through specialized expert procedural teams is feasible during a pandemic and offloads frontline providers while potentially conferring safety benefits.

Pre-existing traits associated with Covid-19 illness severity.

IMPORTANCE: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear. OBJECTIVE: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection. DESIGN: Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation. SETTING: A large, multihospital healthcare system in Southern California. PARTICIPANTS: All patients with confirmed Covid-19 infection (N = 442). RESULTS: Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile. CONCLUSIONS AND RELEVANCE: In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.