SARS-CoV-2 coinfection with additional respiratory virus does not predict severe disease: a retrospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) claimed over 4 million lives by July 2021 and continues to pose a serious public health threat. OBJECTIVES: Our retrospective study utilized respiratory pathogen panel (RPP) results in patients with SARS-CoV-2 to determine if coinfection (i.e. SARS-CoV-2 positivity with an additional respiratory virus) was associated with more severe presentation and outcomes. METHODS: All patients with negative influenza/respiratory syncytial virus testing who underwent RPP testing within 7 days of a positive SARS-CoV-2 test at a large, academic medical centre in New York were examined. Patients positive for SARS-CoV-2 with a negative RPP were compared with patients positive for SARS-CoV-2 and positive for a virus by RPP in terms of biomarkers, oxygen requirements and severe COVID-19 outcome, as defined by mechanical ventilation or death within 30 days. RESULTS: Of the 306 SARS-CoV-2-positive patients with RPP testing, 14 (4.6%) were positive for a non-influenza virus (coinfected). Compared with the coinfected group, patients positive for SARS-CoV-2 with a negative RPP had higher inflammatory markers and were significantly more likely to be admitted (P = 0.01). Severe COVID-19 outcome occurred in 111 (36.3%) patients in the SARS-CoV-2-only group and 3 (21.4%) patients in the coinfected group (P = 0.24). CONCLUSIONS: Patients infected with SARS-CoV-2 along with a non-influenza respiratory virus had less severe disease on presentation and were more likely to be admitted-but did not have more severe outcomes-than those infected with SARS-CoV-2 alone.

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

The Effect of Vitamin D Supplementation on Severe COVID-19 Outcomes in Patients With Vitamin D Insufficiency

Introduction: Coronavirus Disease 2019 (COVID-19) deaths have surpassed one million worldwide with limited treatment modalities, and physicians are relying on alternative methods, such as Vitamin D supplementation, to prevent or halt disease progression without direct evidence. Research has proven that vitamin D supplementation can prevent inflammation based on its role in innate immune response;however, there have been limited studies regarding vitamin D supplementation in COVID-19. We aimed to determine whether vitamin D supplementation in vitamin D insufficient patients was associated with fewer severe COVID-19 outcomes, defined as mechanical ventilation or death. Methods: Retrospective study that analyzed data from all adult patients admitted to our tertiary care center between March 2020 and July 2020 with a positive RT-PCR for SARS CoV-2 and a serum 25-hydroxyvitamin D (25[OH]D) level measured within 90 days prior to the index admission. Patients with 25(OH)D &lt;30 ng/mL were considered vitamin D insufficient and patients ordered for least one weekly dose of ≥1,000 units of ergocalciferol or cholecalciferol were considered supplemented. Supplemented vitamin D insufficient patients were compared to non-supplemented vitamin D insufficient patients in terms of severe COVID-19 disease as defined by mechanical ventilation or death. Results: 129 COVID-19 patients with a vitamin D level &lt;30 ng/mL were identified, with a median vitamin D level of 21.4 ng/mL. A total of 43 patients (33.3%) had severe COVID-19 outcomes. 65 (50.4%) patients with vitamin D insufficiency were supplemented and 64 (49.6%) were not supplemented. Vitamin D supplementation with ≥1,000 units (OR 0.6, 95% CI 0.28 - 1.40;p=0.25), ≥5,000 units (OR 0.5, 95% CI 0.26 - 1.23;p=0.15), or ≥50,000 units (OR 1.0, 95% CI 0.42–2.20, p=0.92) weekly had no statistically significant effect on severe COVID-19 outcomes. The odds of severe COVID-19 outcomes in supplemented patients were non-significantly reduced at lower cutoff values for vitamin D insufficiency (&lt;20 ng/mL and &lt;12 ng/mL) for all supplementation amounts. Conclusion: Vitamin D supplementation in patients with vitamin D insufficiency did not significantly reduce severe COVID-19 outcomes;however, vitamin D supplementation was associated with non-statistically significant reduced odds of severe COVID-19 outcomes at lower cutoff values of vitamin D level. These results demonstrate that Vitamin D supplementation may have a protective effect against severe COVID-19 outcomes in patients with lower baseline levels of vitamin D.

ABO blood type association with SARS-CoV-2 infection mortality: A single-center population in New York City.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a variable clinical course with significant mortality. Early reports suggested higher rates of SARS-CoV-2 infection in patients with type A blood and enrichment of type A individuals among COVID-19 mortalities. STUDY DESIGN AND METHODS: The study includes all patients hospitalized or with an emergency department (ED) visit who were tested for SARS-CoV-2 between March 10, 2020 and June 8, 2020 and had a positive test result by nucleic acid test (NAT) performed on a nasopharyngeal swab specimen. A total of 4968 patients met the study inclusion criteria, with a subsequent 23.1% (n = 1146/4968) all-cause mortality rate in the study cohort. To estimate overall risk by ABO type and account for the competing risks of in-hospital mortality and discharge, we calculated the cumulative incidence function (CIF) for each event. Cause-specific hazard ratios (csHRs) for in-hospital mortality and discharge were analyzed using multivariable Cox proportional hazards models. RESULTS: Type A blood was associated with the increased cause-specific hazard of death among COVID-19 patients compared to type O (HR = 1.17, 1.02-1.33, p = .02) and type B (HR = 1.32,1.10-1.58, p = .003). CONCLUSIONS: Our study shows that ABO histo-blood group type is associated with the risk of in-hospital death in COVID-19 patients, warranting additional inquiry. Elucidating the mechanism behind this association may reveal insights into the susceptibility and/or immunity to SARS-CoV-2.

A Case-Control Study of Prone Positioning in Awake and Nonintubated Hospitalized Coronavirus Disease 2019 Patients.

To determine the association between prone positioning in nonintubated patients with coronavirus disease 2019 and frequency of invasive mechanical ventilation or inhospital mortality. DESIGN: A nested case-matched control analysis. SETTING: Three hospital sites in Bronx, NY. PATIENTS: Adult coronavirus disease 2019 patients admitted between March 1, 2020, and April 1, 2020. We excluded patients with do-not-intubate orders. Cases were defined by invasive mechanical ventilation or inhospital mortality. Each case was matched with two controls based on age, gender, admission date, and hospital length of stay greater than index time of matched case via risk-set sampling. The presence of nonintubated proning was identified from provider documentation. INTERVENTION: Nonintubated proning documented prior to invasive mechanical ventilation or inhospital mortality for cases or prior to corresponding index time for matched controls. MEASUREMENTS AND MAIN RESULTS: We included 600 patients, 41 (6.8%) underwent nonintubated proning. Cases had lower Spo2/Fio2 ratios prior to invasive mechanical ventilation or inhospital mortality compared with controls (case median, 97 [interquartile range, 90-290] vs control median, 404 [interquartile range, 296-452]). Although most providers (58.5%) documented immediate improvement in oxygenation status after initiating nonintubated proning, there was no difference in worst Spo2/Fio2 ratios before and after nonintubated proning in both case and control (case median Spo2/Fio2 ratio difference, 3 [interquartile range, -3 to 8] vs control median Spo2/Fio2 ratio difference, 0 [interquartile range, -3 to 50]). In the univariate analysis, patients who underwent nonintubated proning were 2.57 times more likely to require invasive mechanical ventilation or experience inhospital mortality (hazard ratio, 2.57; 95% CI, 1.17-5.64; p = 0.02). Following adjustment for patient level differences, we found no association between nonintubated proning and invasive mechanical ventilation or inhospital mortality (adjusted hazard ratio, 0.92; 95% CI, 0.34-2.45; p = 0.86). CONCLUSIONS: There was no significant association with reduced risk of invasive mechanical ventilation or inhospital mortality after adjusting for baseline severity of illness and oxygenation status.