COVID-19 mortality may be reduced among fully vaccinated solid organ transplant recipients.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality from COVID-19 due to their immunosuppressed state and reduced immunogenicity from COVID-19 mRNA vaccines. This investigation examined the association between COVID-19 mRNA vaccination status and mortality among SOT recipients diagnosed with COVID-19. METHODS & FINDINGS: A retrospective, registry-based chart review was conducted investigating COVID-19 mortality among immunosuppressed solid organ transplant (SOT) recipients in a large metropolitan healthcare system in Houston, Texas, USA. Electronic health record data was collected from consecutive SOT recipients who received a diagnostic SARS-CoV-2 test between March 1, 2020, and October 1, 2021. The primary exposure was COVID-19 vaccination status at time of COVID-19 diagnosis. Patients were considered 'fully vaccinated' at fourteen days after completing their vaccine course. COVID-19 mortality within 60 days and intensive care unit admission within 30 days were primary and secondary endpoints, respectively. Among 646 SOT recipients who were diagnosed with COVID-19 at Houston Methodist Hospital between March 2020, and October 2021, 70 (10.8%) expired from COVID-19 within 60 days. Transplanted organs included 63 (9.8%) heart, 355 (55.0%) kidney, 108 (16.7%) liver, 70 (10.8%) lung, and 50 (7.7%) multi-organ. Increasing age was a risk factor for COVID-19 mortality, while vaccination within 180 days of COVID-19 diagnosis was protective in Cox proportional hazard models with hazard ratio 1.04 (95% CI: 1.01-1.06) and 0.31 (0.11-0.90), respectively). These findings were confirmed in the propensity score matched cohort between vaccinated and unvaccinated patients. CONCLUSIONS: This investigation found COVID-19 mortality may be significantly reduced among immunosuppressed SOT recipients within 6 months following vaccination. These findings can inform vaccination policies targeting immunosuppressed populations worldwide.

Characteristics and Outcomes of DKA Admissions Before and During COVID-Pandemic

Background: COVID-increases risk of DKA and poor outcomes in patients with diabetes. Methods: A retrospective review was conducted of 4,959 DKA admissions from 1/1/2019-12/31/2021 at our hospital system. EHR data was collected on consecutive admissions coded with DKA for clinical characteristics, hospital outcomes of length of stay (LOS) , 30day readmission (30d RADM) and mortality. Data was analyzed for differences stratified by year 20vs. 2020 and 2021, and by COVID-infection. Results: Compared to 2019, patients in 2020 were older, more Hispanic and had CHF. Compared to 2019, patients in 2021 had less HTN and kidney disease but similar rates of CHF;Table 1. Mortality and LOS were higher for 2020 and 2021 while 30d RADM was lower;Table 2. Conclusion: Despite advancements in COVID-treatments, DKA patients have progressively poorer outcomes.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Health System Strategy to Safely Provide Surgical Care During the Covid-19 Pandemic

Houston Methodist’s policies designed to avoid the spread of severe acute respiratory syndrome coronavirus 2 during hospital-based surgeries or procedures led to a postintervention nosocomial Covid-19 infection rate of 0.1% during the first 19 months of the pandemic. Preoperative polymerase chain reaction testing was found to be particularly effective. Summary During the initial onset of the Covid-19 pandemic, there was little information regarding how to deliver surgical care safely. Houston Methodist, an eight-hospital system with a flagship academic medical center (Texas Medical Center), adopted and implemented policies that were driven by science and expert opinion, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction preoperative testing to decrease patient risk of Covid-19 diagnosis postintervention. In examining outcomes of the policies during the first 19 months of the pandemic, the authors discovered from a retrospective cohort study of 141,439 patients that the policies — especially SARS-CoV-2 preoperative testing — were effective in reducing postintervention Covid-19 disease, with an overall rate of 0.6%. Analysis of patients who had Covid-19 after intervention found that most had contracted the disease from community sources, which led to a nosocomial Covid-19 rate of 0.1%. Effective policy implementation was associated with successful delivery of safe surgical care during the pandemic.

Risk Factors Associated With an Impaired Antibody Response in Kidney Transplant Recipients Following 2 Doses of the SARS-CoV-2 mRNA Vaccine.

BACKGROUND: Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. METHODS: We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. RESULTS: KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. CONCLUSIONS: The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.

Risk factors for severity of COVID-19 in hospital patients age 18-29 years.

BACKGROUND: Since February 2020, over 2.5 million Texans have been diagnosed with COVID-19, and 20% are young adults at risk for SARS-CoV-2 exposure at work, academic, and social settings. This study investigated demographic and clinical risk factors for severe disease and readmission among young adults 18-29 years old, who were diagnosed at a hospital encounter in Houston, Texas, USA. METHODS AND FINDINGS: A retrospective registry-based chart review was conducted investigating demographic and clinical risk factors for severe COVID-19 among patients aged 18-29 with positive SARS-CoV-2 tests within a large metropolitan healthcare system in Houston, Texas, USA. In the cohort of 1,853 young adult patients diagnosed with COVID-19 infection at a hospital encounter, including 226 pregnant women, 1,438 (78%) scored 0 on the Charlson Comorbidity Index, and 833 (45%) were obese (≥30 kg/m2). Within 30 days of their diagnostic encounter, 316 (17%) patients were diagnosed with pneumonia, 148 (8%) received other severe disease diagnoses, and 268 (14%) returned to the hospital after being discharged home. In multivariable logistic regression analyses, increasing age (adjusted odds ratio [aOR] 1.1, 95% confidence interval [CI] 1.1-1.2, p<0.001), male gender (aOR 1.8, 95% CI 1.2-2.7, p = 0.002), Hispanic ethnicity (aOR 1.9, 95% CI 1.2-3.1, p = 0.01), obesity (3.1, 95% CI 1.9-5.1, p<0.001), asthma history (aOR 2.3, 95% CI 1.3-4.0, p = 0.003), congestive heart failure (aOR 6.0, 95% CI 1.5-25.1, p = 0.01), cerebrovascular disease (aOR 4.9, 95% CI 1.7-14.7, p = 0.004), and diabetes (aOR 3.4, 95% CI 1.9-6.2, p<0.001) were predictive of severe disease diagnoses within 30 days. Non-Hispanic Black race (aOR 1.6, 95% CI 1.0-2.4, p = 0.04), obesity (aOR 1.7, 95% CI 1.0-2.9, p = 0.046), asthma history (aOR 1.7, 95% CI 1.0-2.7, p = 0.03), myocardial infarction history (aOR 6.2, 95% CI 1.7-23.3, p = 0.01), and household exposure (aOR 1.5, 95% CI 1.1-2.2, p = 0.02) were predictive of 30-day readmission. CONCLUSIONS: This investigation demonstrated the significant risk of severe disease and readmission among young adult populations, especially marginalized communities and people with comorbidities, including obesity, asthma, cardiovascular disease, and diabetes. Health authorities must emphasize COVID-19 awareness and prevention in young adults and continue investigating risk factors for severe disease, readmission and long-term sequalae.

Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG.

Coronavirus disease 2019 (COVID-19) convalescent plasma has emerged as a promising therapy and has been granted Emergency Use Authorization by the US Food and Drug Administration for hospitalized COVID-19 patients. We recently reported results from interim analysis of a propensity score-matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high-titer anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We herein present results from a 60-day follow-up of a cohort of 351 transfused hospitalized patients. Prospective determination of enzyme-linked immunosorbent assay anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff ratio of 24.0 for transfused units, a value far exceeding the recent US Food and Drug Administration-required cutoff of 12.0 for designation of high-titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours after hospitalization for transfusing COVID-19 patients with high-titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high-titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.

Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present herein the results of an interim analysis of 316 patients enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain IgG titer convalescent plasma is efficacious in early-disease patients.

Clinical Outcomes Following Tocilizumab Administration in Mechanically Ventilated Coronavirus Disease 2019 Patients.

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.