Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19.

BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). METHODS: In this phase I/II/III, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus. RESULTS: 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met: in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% CI, -0.51 to -0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation (death/MV) from day 6-29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2-74.0). No safety concerns were noted. CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.

Post-Intensive Care Syndrome Among Survivors in a Safety Net Hospital in South Bronx: A Comparison of Patients With and Without Coronavirus Disease 2019.

Comparison of post-intensive care syndrome between critically ill survivors with or without coronavirus disease 2019 (CovP and CovN, respectively) showed that fewer CovP were able to return to work full time at >1 year and none at <1 year after discharge and that the majority of CovP survivors were able to work part time during both evaluation periods compared to CovN.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial.

BACKGROUND: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19. METHODS: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 received intravenous sarilumab 400 mg or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation (MV). The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. RESULTS: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving MV (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving MV) at day 22 was 43.2% for sarilumab and 35.5% for placebo (risk difference, +7.5%; 95% confidence interval [CI], -7.4 to 21.3; P =.3261), a relative risk improvement of 21.7%. In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio for death for sarilumab vs placebo was 0.76 (95% CI, .51 to 1.13) overall and 0.49 (95% CI, .25 to .94) in patients receiving corticosteroids at baseline. CONCLUSIONS: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids. CLINICAL TRIALS REGISTRATION: NCT04315298.

Healthcare worker trauma and related mental health outcomes during the COVID-19 outbreak in New York City.

Healthcare workers (HCWs) faced a range of stressors during the coronavirus (COVID-19) pandemic, contributing to psychological stress. We use a psychological trauma framework to characterize the mental health burden for clinical and non-clinical healthcare worker occupations during the COVID-19 pandemic. The objective was to measure and characterize risk factors for trauma and anxiety-related mental health problems among HCWs at a public hospital in the epicenter of the COVID-19 pandemic in New York City (NYC). This study reports findings from a cross-sectional survey of NYC HCWs shortly after the initial 2020 infection surge. Over 800 hospital employees completed the survey that assessed professional quality of life indicators (compassion satisfaction [CS], burnout [BO], secondary traumatic stress [STS]), Coronavirus Anxiety (CS), Obsession with Coronavirus (OC), and PTSD symptoms. The survey also assessed pandemic-related work and life circumstances such as "do you have a family member or friend who tested positive for COVID". Relatively small percentages of HCWs endorsed probable Coronavirus Anxiety (6%), PTSD (13%), and Coronavirus Obsession (21%). We observed higher proportions of Burnout (29%), Moderate or High Secondary Traumatic Stress (45%), and High Compassion Satisfaction (52%). Adjusted regression models showed important implications for prior behavioral/emotional health concerns among HCWs, providing care for a patient that died from COVID-19, and other characteristics. This study supports prior studies documenting the mental health consequences for the healthcare workforce during the COVID-19 pandemic. This study builds on that base by including non-clinical staff in the sample and assessing pandemic life-stressors such as caring for sick family members.

Role of a Chest X-ray Severity Score in a Multivariable Predictive Model for Mortality in Patients with COVID-19: A Single-Center, Retrospective Study.

Predicting the mortality risk of patients with Coronavirus Disease 2019 (COVID-19) can be valuable in allocating limited medical resources in the setting of outbreaks. This study assessed the role of a chest X-ray (CXR) scoring system in a multivariable model in predicting the mortality of COVID-19 patients by performing a single-center, retrospective, observational study including consecutive patients admitted with a confirmed diagnosis of COVID-19 and an initial CXR. The CXR severity score was calculated by three radiologists with 12 to 15 years of experience in thoracic imaging, based on the extent of lung involvement and density of lung opacities. Logistic regression analysis was used to identify independent predictive factors for mortality to create a predictive model. A validation dataset was used to calculate its predictive value as the AUROC. A total of 628 patients (58.1% male) were included in this study. Age (p < 0.001), sepsis (p < 0.001), S/F ratio (p < 0.001), need for mechanical ventilation (p < 0.001), and the CXR severity score (p = 0.005) were found to be independent predictive factors for mortality. We used these variables to develop a predictive model with an AUROC of 0.926 (0.891, 0.962), which was significantly higher than that of the WHO COVID severity classification, 0.853 (0.798, 0.909) (one-tailed p-value = 0.028), showing that our model can accurately predict mortality of hospitalized COVID-19 patients.

Renal recovery after acute kidney injury in a minority population of hospitalized COVID-19 patients: A retrospective cohort study.

ABSTRACT: This study aimed to characterize survivors of Coronavirus disease 2019 (COVID-19) infection and acute kidney injury (AKI) that recover their renal function or progress to acute kidney disease (AKD) on discharge; and determine factors associated with progression to AKD during hospital stay.One thousand seventy four patients with COVID-19 infection were followed up until discharge/death. The incidence of AKI was 59.7%. Two hundred and sixty-six patients were discharged alive and included in the analysis, 71.8% had renal recovery (RR) while 28.2% were discharged with AKD. The AKD subset has higher rate of chronic kidney disease (CKD) ≥3 (33.4% vs 14.1%, P = .001), congestive heart failure (18.7% vs 5.8%, P = .001), use of non-invasive mechanical ventilation (10.7% vs 3.7%, P = .026) and vasopressors (25.3% vs 12.0%, P = .007). Of 19 patients in the AKI survivor cohort who received renal replacement therapy, 1 had RR while 18 progressed to AKD on discharge. Predictors to progression to AKD were CKD ≥3 (Odds Ratio [OR]: 3.23, 95% confidence interval [CI] 1.59-6.56, P = .001), congestive heart failure (OR: 4.59, 95% CI 1.76-11.78, P = .002), AKI on admission (OR: 2.71, 95% CI, 1.14-6.46, P = .025), and ongoing diarrhea (OR: 3.19, 95% CI, 1.02-9.96, P = .025).This study demonstrates a higher proportion of RR among survivors of COVID-19 infection in our minority predominant cohort. Early identification and appropriate management of patients at-risk to progress to AKD could improve outcomes, reduce long term sequalae of CKD/end stage renal disease, and have a major impact on health outcome and financial strain on healthcare system.

Impact of Local and Demographic Factors on Early COVID-19 Vaccine Hesitancy among Health Care Workers in New York City Public Hospitals.

Despite the development of several effective vaccines, SARS-CoV-2 continues to spread, causing serious illness among the unvaccinated. Healthcare professionals are trusted sources of information about vaccination, and therefore understanding the attitudes and beliefs of healthcare professionals regarding the vaccines is of utmost importance. We conducted a survey-based study to understand the factors affecting COVID-19 vaccine attitudes among health care professionals in NYC Health and Hospitals, at a time when the vaccine was new, and received 3759 responses. Machine learning and chi-square analyses were applied to determine the factors most predictive of vaccine hesitancy. Demographic factors, education, role at the hospital, perceptions of the pandemic itself, and location of work and residence were all found to significantly contribute to vaccine attitudes. Location of residence was examined for both borough and neighborhood, and was found to have a significant impact on vaccine receptivity. Interestingly, this borough-level data did not correspond to the number or severity of cases in the respective boroughs, indicating that local social or other influences likely have a substantial impact. Local and demographic factors should be strongly considered when preparing pro-vaccine messages or campaigns.

THE ROLE OF NONINVASIVE VENTILATION AND HIGH-FLOW NASAL CANNULA IN CRITICAL COVID-19 PNEUMONIA

139 (29.1%) underwent delaying intubation with HFNC/NIV with a median time to intubation of 2.9 (IQR,0.78-6.16) days, longer compared with the non-intervention group, 0.42 (IQR, 0.11-2.0) days. Kaplan Meier analysis was conducted to determine survival rate and Cox Proportional Hazard regression to determine mortality risk associated with delaying intubation. B Introduction/Hypothesis: b We aimed to determine the mortality risk associated with delaying intubation with High Flow Nasal Cannula (HFNC) and Non-invasive ventilation (NIV) in the setting of critical COVID-19 pneumonia patients that required mechanical ventilation. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins 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 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 . (Copyright applies to all s.)

Longitudinal humoral antibody response to SARS-CoV-2 infection among healthcare workers in a New York City hospital.

OBJECTIVE: Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs). DESIGN: A prospective longitudinal study. SETTING: This study was conducted in a New York City public hospital in the South Bronx, New York. PARTICIPANTS: HCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study. PRIMARY OUTCOME MEASURE: Evaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay. RESULTS: Anti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177-8812)) than in asymptomatic positive subjects (5803 (2825-11 920)). Marginally higher titres (2382 (1494-3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753-2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001). CONCLUSIONS: Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points.

Effect of parenteral nutrition in oxygen escalation/de-escalation in SARS-CoV-2 infected patients who are pre-intubation: A multicenter, observational study.

BACKGROUND & AIMS: SARS-CoV-2 infection includes a variety of gastrointestinal manifestations along with the usual viral symptoms of malaise and myalgias. The objective of this study was to determine if intravenous parenteral nutrition (PN) affected the risk of intubation in SARS-CoV-2 patients who were dependent on non-invasive ventilation. METHODS: Retrospective, multicenter case-control study which analyzed oxygen requirements for 1974 adults with SARS-CoV-2, who were admitted to the local public hospital system between March 1 and May 17, 2020. Relevant baseline biomarkers were studied over 5 days. The main outcome was an escalation or de-escalation of oxygen requirements relative to the exposure of PN. RESULTS: 111 patients received PN while on non-invasive ventilation. Patients who received PN had a significantly lower odds (p < 0.001) of oxygen escalation in comparison to their control group counterparts (OR = 0.804, 95% CI 0.720, 0.899) when matched for age, body mass index, Charlson comorbidity index, and gender. CONCLUSION: Initiating PN in the setting of non-invasive ventilation of SARS-CoV-2 infected patients was significantly associated with a lower odds of oxygen escalation. PN does not independently exacerbate oxygen requirements in SARS-CoV-2 infected pre-intubated patients.

Longitudinal analysis of severe acute respiratory syndrome coronavirus 2 seroprevalence using multiple serology platforms.

Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests are based on the full-length spike (S), the receptor-binding domain (RBD), or the nucleoprotein (NP) as substrates. Here, we used samples from healthcare workers (HCWs) to perform a longitudinal analysis of the antibody responses using a research-grade RBD and spike-based enzyme-linked immunosorbent assay (ELISA), a commercial RBD and spike-based ELISA, and a commercial NP-based chemiluminescent microparticle immunoassay. Seroprevalence ranged around 28% early during the pandemic and a good correlation was observed between RBD and spike-based ELISAs. Modest correlations were observed between NP and both RBD and spike-based assays. The antibody levels in HCWs declined over time; however, the overall seroprevalence measured by RBD and spike-based assays remained unchanged, while the seroprevalence of NP-reactive antibodies significantly declined. Moreover, RBD and spike-based assays effectively detected seroconversion in vaccinees. Overall, our results consolidate the strength of different serological assays to assess the magnitude and duration of antibodies to SARS-CoV-2.

Knowledge, Attitudes and Perceptions of COVID-19 Vaccination among Healthcare Workers of an Inner-City Hospital in New York.

Introduction: New York City is one of the areas most affected by the COVID-19 pandemic in the United States. Healthcare workers are among those at high risk of contracting the virus, and a vital source of information and trust in vaccines to the community. Methods: This study was conducted about attitudes towards COVID-19 vaccination among healthcare workers at a public hospital in New York City during the beginning of COVID-19 vaccination. 428 hospital employees responded. Results: Several factors were significantly associated with vaccine attitudes, including demographics such as gender (p = 0.002), age (p = 0.005), race (p < 0.001) and home location (p < 0.001), role within the hospital (p < 0.001), knowledge about the virus (p < 0.001) and confidence in and expectations about personal protective equipment and behaviors (p < 0.001). Structural equation modeling revealed that the most predictive factors were prior vaccine attitudes and concern with the speed of testing and approval of the vaccines (p < 0.001). Multivariate analysis reinforced these, while also identifying perceived personal risk as significant (p = 0.033). Conclusions: Several modifiable factors that reflect confidence in science, scientific knowledge, personal risk perception, experience and medical authority are correlated with vaccine attitudes, indicating that a holistic educational approach to improve trust in science is likely to be effective in long-term reduction in vaccine hesitancy.

Empiric use of anticoagulation in hospitalized patients with COVID-19: a propensity score-matched study of risks and benefits.

BACKGROUND: Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. METHODS: We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. RESULTS: The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345-0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110-1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114-3.729, p = 0.016). CONCLUSION: Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

SARS-CoV-2 seroprevalence among health care workers in a New York City hospital: A cross-sectional analysis during the COVID-19 pandemic.

BACKGROUND: New York City (NYC) has endured the greatest burden of COVID-19 infections in the US. Health inequities in South Bronx predisposed this community to a large number of infectious cases, hospitalizations, and mortality. Health care workers (HCWs) are at a high risk of exposure to the infection. This study aims to assess seroprevalence and the associated characteristics of consenting HCWs from an NYC public hospital. METHODS: This cross-sectional study includes serum samples for qualitative SARS-CoV-2 antibody testing with nasopharyngeal swabs for SARS-CoV-2; PCR and completion of an online survey capturing demographics, COVID-19 symptoms during the preceding months on duty, details of healthcare and community exposure, and travel history were collected from consenting participants in May 2020. Participants' risk of exposure to COVID-19 infection in the hospital and in the community was defined based on CDC guidelines. Travel history to high-risk areas was also considered an additional risk. The Odds Ratio with bivariable and multivariable logistic regression was used to assess characteristics associated with seroprevalence. RESULTS: A total of 500 HCW were tested, 137 (27%) tested positive for the SARS-CoV-2 antibody. Symptomatic participants had a 75% rate of seroconversion compared to those without symptoms. Subjects with anosmia and ageusia had increased odds of seroconversion in comparison to those without these symptoms. Community exposure was 34% among those who had positive antibodies. CONCLUSION: Seroprevalence among HCWs was high compared to the community at the epicenter of the pandemic. Further studies to evaluate sustained adaptive immunity in this high-risk group will guide our response to a future surge.

Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.