Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Coronavirus disease 2019 (COVID-19) excess mortality outcomes associated with pandemic effects study (COPES): A systematic review and meta-analysis.

Background and aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times. Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain. Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256].

Non-COVID outcomes associated with the coronavirus disease-2019 (COVID-19) pandemic effects study (COPES): A systematic review and meta-analysis.

BACKGROUND: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. METHODS: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. RESULTS: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty). CONCLUSIONS: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020201256 (Sept 2, 2020).

Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.