Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

OUTCOMES OF COVID-19 PATIENTS: ARE HISPANICS AT GREATER RISK?

Unadjusted mortality was higher in Whites than Hispanics (17.1% versus 10.7%;p< 0.001), however, after adjusting for confounding variables, in-hospital mortality was no different for Whites in comparison to Hispanics (HR 0.96, 95% CI 0.76-1.21, p=0.73). We compared in hospital mortality, use of intensive care unit services (rates of mechanical ventilation, vasopressor use and renal replacement therapy) between non-Hispanic whites with non-White/Black Hispanic. B Conclusions: b Hispanics as compared to Whites with COVID-19 require higher rates of ICU admission but have a similar mortality. [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.)

IS UNCONTROLLED DIABETES PRIOR TO HOSPITALIZATION A RISK FACTOR FOR WORSE OUTCOMES IN COVID-19?

B Conclusions: b Poorly controlled diabetes as judged by higher HbA1c had less severe COVID infection on admission, however, it was not associated with higher severity of COVID19 during the admission. The probability of in-hospital mortality and rate of readmissions decreased with increasing levels of HbA1c. B Introduction: b Diabetes is a known risk factor for COVID19 infection. [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.)

TOCILIZUMAB IN COVID-19 PATIENTS REQUIRING INVASIVE MECHANICAL VENTILATION: WHO BENEFITS MOST?

B Methods: b We identified primary admissions of all adult COVID19 patients on invasive mechanical ventilation (IMV) in EMR with positive COVID19 test results. B Introduction: b In severe Covid 19 infection, cytokine storm possibly plays a role in development of worsening of symptoms and possibly worse outcomes. [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.)

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial.

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration: ClinicalTrials.gov Identifier: NCT04364737.

Outcomes of Covid 19 patients-Are Hispanics at greater risk?

Disparities in outcomes exist in outcomes of coronavirus disease-19 (COVID-19). Little is known about other ethnic minorities in United States. We included all COVID-19 positive adult patients (≥18 years) hospitalized between March 1, 2020 and February 5th 2021. We compared in hospital mortality, use of intensive care unit services and inflammatory markers between non-Hispanic whites with non-White/Black Hispanic. Multivariable Cox proportional Hazard models were used to adjust for differences between the two groups. There were 4059 hospital admissions with COVID-19 in the study period. Of the 3288 White, 789 (24%) required intensive care unit (ICU) admission in comparison to 187 (24.3%) of the 770 Hispanics. Unadjusted mortality was higher in Whites than Hispanics (17.1% vs. 10.7%; p < 0.001). After adjusting for confounding variables, in-hospital mortality was not statistically different for Whites in comparison to Hispanics (hazard ratio [HR]: 0.96, 95% confidence interval [CI]: 0.76-1.21, p = 0.73). The adjusted rates of ICU transfers were significantly higher in Hispanics (HR: 1.34, 95% CI: 1.11-1.61, p = 0.002). Hispanics had significantly higher C-reactive protein, lactate dehydrogenase, and fibrinogen when compared to Whites. Hispanics as compared to Whites with COVID-19 require higher rates of ICU admission but have a similar mortality. Hispanics as compared to Whites with COVID-19 require higher rates of ICU admission but have a similar mortality.

Do high-dose corticosteroids improve outcomes in hospitalized COVID-19 patients?

Coronavirus disease 2019 (COVID-19) is characterized by dysregulated hyperimmune response and steroids have been shown to decrease mortality. However, whether higher dosing of steroids results in better outcomes has been debated. This was a retrospective observation of COVID-19 admissions between March 1, 2020, and March 10, 2021. Adult patients (≥18 years) who received more than 10 mg daily methylprednisolone equivalent dosing (MED) within the first 14 days were included. We excluded patients who were discharged or died within 7 days of admission. We compared the standard dose of steroids (<40 mg MED) versus the high dose of steroids (>40 mg MED). Inverse probability weighted regression adjustment (IPWRA) was used to examine whether higher dose steroids resulted in improved outcomes. The outcomes studied were in-hospital mortality, rate of acute kidney injury (AKI) requiring hemodialysis, invasive mechanical ventilation (IMV), hospital-associated infections (HAI), and readmissions. Of the 1379 patients meeting study criteria, 506 received less than 40 mg of MED (median dose 30 mg MED) and 873 received more than or equal to 40 mg of MED (median dose 78 mg MED). Unadjusted in-hospital mortality was higher in patients who received high-dose corticosteroids (40.7% vs. 18.6%, p < 0.001). On IPWRA, the use of high-dose corticosteroids was associated with higher odds of death (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.45-3.14, p < 0.001) but not with the development of HAI, readmissions, or requirement of IMV. High-dose corticosteroids were associated with lower rates of AKI requiring hemodialysis (OR 0.33; 95% CI 0.18-0.63). In COVID-19, corticosteroids more than or equal to 40 mg MED were associated with higher in-hospital mortality.

Incidence of Venous Thromboembolism and Effect of Anticoagulant Dosing in Hospitalized COVID-19 Patients.

Background: Coronavirus disease 2019 (COVID-19) is characterized by coagulopathy and thrombotic events. We examined factors associated with development of venous thromboembolism (VTE) in COVID-19 and to discern if higher dose of anticoagulation was beneficial in these patients. Methods: This study involves an observational study of prospectively collected data in the setting of a large community hospital in a rural setting in Northeast Georgia with COVID-19 between March 1, 2020 and February 5, 2021. Anticoagulation dose (none, standard, intermediate, and therapeutic dosages) was studied in adult patients (≥ 18 years). We constructed multivariable logistic regression model to examine the association of clinical characteristics with VTE. To examine the effect of dose of anticoagulation in preventing VTE, we used inverse probability weighted regression adjustment. Results: Of the 4,645 patients with COVID-19, 251 (5.4%) patients were found to have VTE. Of these, 91 had pulmonary embolism, 148 had deep venous thrombosis (DVT) and 12 had both. A total of 129 of VTE cases were diagnosed at admission. Of all admissions, 12.9% did not receive any DVT prophylaxis, 70.4% received prophylactic dose, 1.3% received intermediate dose and 15.5% received therapeutic dose. Male gender (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.0 - 2.4, P = 0.04) and Black race (OR: 2.0, 95% CI: 1.2 - 3.4, P = 0.01), along with higher levels of lactate dehydrogenase (LDH) and D-dimer were associated with higher odds of developing VTE. Patients receiving steroids had lower rates of VTE (3.9% vs. 8.3%, P < 0.001). Use of intermediate or therapeutic anticoagulation was not associated with lower odds of developing VTE. However, patients on therapeutic anticoagulation had lower odds of in hospital mortality when compared to standard dose (OR: 0.47, 95% CI: 0.27 - 0.80, P = 0.006). Conclusions: In COVID-19, D-dimer and LDH can be useful in predicting VTE. Steroids appear to have some protective role in development of VTE. Therapeutic anticoagulation did not result in lower rates of VTE but was associated with in-hospital mortality.

Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.

Vaccinations are widely credited with reducing death rates from COVID-19, but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation, and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose-regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared with that of non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2-infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity, and gender compared with that from non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression with existing therapeutics might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.

Does ABO Blood Groups Affect Outcomes in Hospitalized COVID-19 Patients?

BACKGROUND: Blood group type A has been associated with increased susceptibility for coronavirus disease 2019 (COVID-19) infection when compared to group O. The aim of our study was to examine outcomes in hospitalized COVID-19 patients among blood groups A and O. METHODS: This is an observational study. Kruskal-Wallis and Chi-square tests were used to compare continuous and categorical variables. Multivariable logistic regression models were used to examine association of blood groups with rates of mortality and severity of disease. All adult patients (> 18 years) admitted with COVID-19 infection between March 1, 2020 and March 10, 2021 at a large community hospital in Northeast Georgia were included. We compared mortality, severity of disease (use of mechanical ventilation, vasopressor, and acute renal failure), rates of venous thromboembolism and inflammatory markers between the blood groups. We used multivariable logistic regression model to adjust for demographical and clinical characteristics, use of COVID-19 medications and severity. RESULTS: A total of 3,563 of 5,204 admitted patients had information on blood groups. Of these, 1,301 (36.5%) were group A, 377 (10.6 %) were group B, 133 (3.7%) were group AB and 1,752 (49.2%) were group O. On adjusted analysis, there were no significant differences in rates of intensive care unit (ICU) admissions, mechanical ventilation, vasopressors, acute renal failure, venous thromboembolism and readmission rate between the blood groups A and O. In-hospital mortality was also not statistically different among the blood groups A and O (17.5% vs. 20.1%; P = 0.07). On adjusted analysis, in-hospital mortality was not lower in blood groups O (odds ratio (OR): 1.06; 95% confidence interval (CI): 0.80 - 1.40, P = 0.70). CONCLUSIONS: Once hospitalized with COVID-19 infection, blood groups A and O are not associated with increased severity or in-hospital mortality.

Extracorporeal Membrane Oxygenation with Right Ventricular Assist Device for COVID-19 ARDS.

BACKGROUND: Right ventricular failure is an underrecognized consequence of COVID-19 pneumonia. Those with severe disease are treated with extracorporeal membrane oxygenation (ECMO) but with poor outcomes. Concomitant right ventricular assist device (RVAD) may be beneficial. METHODS: A retrospective analysis of intensive care unit patients admitted with COVID-19 ARDS (Acute Respiratory Distress Syndrome) was performed. Nonintubated patients, those with acute kidney injury, and age > 75 were excluded. Patients who underwent RVAD/ECMO support were compared with those managed via invasive mechanical ventilation (IMV) alone. The primary outcome was in-hospital mortality. Secondary outcomes included 30-d mortality, acute kidney injury, length of ICU stay, and duration of mechanical ventilation. RESULTS: A total of 145 patients were admitted to the ICU with COVID-19. Thirty-nine patients met inclusion criteria. Of these, 21 received IMV, and 18 received RVAD/ECMO. In-hospital (52.4 versus 11.1%, P = 0.008) and 30-d mortality (42.9 versus 5.6%, P= 0.011) were significantly lower in patients treated with RVAD/ECMO. Acute kidney injury occurred in 15 (71.4%) patients in the IMV group and zero RVAD/ECMO patients (P< 0.001). ICU (11.5 versus 21 d, P= 0.067) and hospital (14 versus 25.5 d, P = 0.054) length of stay were not significantly different. There were no RVAD/ECMO device complications. The duration of mechanical ventilation was not significantly different (10 versus 5 d, P = 0.44). CONCLUSIONS: RVAD support at the time of ECMO initiation resulted in the no secondary end-organ damage and higher in-hospital and 30-d survival versus IMV in specially selected patients with severe COVID-19 ARDS. Management of severe COVID-19 ARDS should prioritize right ventricular support.

Predictors and outcomes of healthcare-associated infections in COVID-19 patients.

INTRODUCTION: Healthcare-associated infections (HAI) after viral illnesses are important sources of morbidity and mortality. This has not been extensively studied in hospitalized COVID-19 patients. METHODS: This study included all COVID-19-positive adult patients (≥18 years) hospitalized between 01 March and 05 August 2020 at the current institution. The Centers for Disease Control and Prevention definition of HAI in the acute care setting was used. The outcomes that were studied were rates and types of infections and in-hospital mortality. Several multivariable logistic regression models were constructed to examine characteristics associated with development of HAI. RESULTS: Fifty-nine (3.7%) of 1565 patients developed 140 separate HAIs from 73 different organisms: 23 were Gram-positive, 39 were Gram-negative and 11 were fungal. Patients who developed HAI did not have higher odds of death (OR 0.85, 95% CI 0.40-1.81, p = 0.69). HAIs were associated with the use of tocilizumab (OR 5.04, 95% CI 2.4-10.6, p < 0.001), steroids (OR 3.8, 95% CI 1.4-10, p = 0.007), hydroxychloroquine (OR 3.0, 95% CI 1.0-8.8, p = 0.05), and acute kidney injury requiring hemodialysis (OR 3.7, 95% CI 1.1-12.8, p = 0.04). CONCLUSIONS: HAI were common in hospitalized Covid-19 patients. Tocilizumab and steroids were associated with increased risk of HAIs.