Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients.

AIM: Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. METHODS AND RESULTS: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. CONCLUSIONS: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Long-term exposure to PM10 above WHO guidelines exacerbates COVID-19 severity and mortality.

BACKGROUND: Age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. OBJECTIVES: We aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. METHODS: A retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. RESULTS: We found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32-2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94-4.40), followed by PM10 (2.37, 95% CI 1.71-3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. DISCUSSION: These results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health.

Analysis of Oxygen Blood Saturation/Respiratory Rate Index, NEWS2, CURB65, and quick Sequential Organ Failure Assessment Scores to Assess Prognosis in Patients with Mild Coronavirus Disease 2019.

BACKGROUND: Hospital bed saturation has been one of the problems to solve during the SARS-CoV-2 pandemic. However, not every patient who is admitted requires close monitoring or specific therapeutics. Mild cases could be managed in the outpatient setting. OBJECTIVE: Our study aimed to analyze the accuracy of the oxygen saturation/respiratory rate (sat/RR) index, NEWS2, CURB65, and quick Sequential Organ Failure Assessment (qSOFA) scores to predict supplemental oxygen requirement and prolonged hospital stay in patients with mild coronavirus disease 2019 (COVID-19). METHODS: A prospective cohort study in an academic medical center. We compared the values of these scores according to the occurrence or not of each outcome. When differences between groups were statistically significant, the discriminatory capacity of the score for that outcome was analyzed. RESULTS: We included 271 patients. Of them, 11.07% required supplemental oxygen, showing significantly higher values of NEWS2 score and qSOFA score, and lower values of Sat/RR index. About 38% presented prolonged hospital stay, with significantly higher values of NEWS2 score and lower values of sat/RR index. The ROC curve area under the curve (AUC) of sat/RR index to discriminate the requirement of supplemental oxygen was 0.72 (CI 95% 0.61-0.84). The ROC curve of NEWS2 and qSOFA for the same outcome was 0.75 (95% [95% CI 0.65-0.85]) and 0.66 (95% CI 0.57-0.76), respectively. The ability of the Sat/RR index to discriminate the requirement of prolonged hospitalization showed an AUC of 0.67 (95% [95% CI 0.60- 0.73]). The NEWS2 score showed an AUC of 0.63 (CI 95% 0.56-0.70) for the same outcome. CONCLUSIONS: sat/RR index and NEWS2 score have a good capacity to discriminate patients at risk of clinical worsening, being the Sat/RR index simpler and easier to calculate.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Low HDL and high triglycerides predict COVID-19 severity.

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.