Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Achieving end-to-end success in the clinic: Pfizer's learnings on R&D productivity.

Over the past decade, Pfizer has focused efforts to improve its research and development (R&D) productivity. By the end of 2020, Pfizer had achieved an industry-leading clinical success rate of 21%, a tenfold increase from 2% in 2010 and well above the industry benchmark of ∼11%. The company had also maintained the quality of innovation, because 75% of its approvals between 2016 and 2020 had at least one expedited regulatory designation (e.g., Breakthrough Therapy). Pfizer's Signs of Clinical Activity (SOCA) paradigm enabled better decision-making and, along with other drivers (biology and modality), contributed to this productivity improvement. These laid a strong foundation for the rapid and effective development of the Coronavirus 2019 (COVID-19) vaccine with BioNTech, as well as the antiviral candidate Paxlovid™, under the company's 'lightspeed' paradigm.

Estimated impact of novel coronavirus-19 and transplant center inactivity on end-stage renal disease-related patient mortality in the United States.

To predict whether the COVID-19 pandemic and transplant center responses could have resulted in preventable deaths, we analyzed registry information of the US end-stage renal disease (ESRD) patient population awaiting kidney transplantation. Data were from the Organ Procurement and Transplantation Network (OPTN), the US Centers for Disease Control and Prevention, and the United States Renal Data System. Based on 2019 OPTN reports, annualized reduction in kidney transplantation of 25%-100% could result in excess deaths of wait-listed (deceased donor) transplant candidates from 84 to 337 and living donor candidate excess deaths from 35 to 141 (total 119-478 potentially preventable deaths of transplant candidates). Changes in transplant activity due to COVID-19 varied with some centers shutting down while others simply heeded known or suspected pandemic risks. Understanding potential excess mortality for ESRD transplant candidates when circumstances compel curtailment of transplant activity may inform policy and procedural aspects of organ transplant systems allowing ways to best inform patients and families as to potential risks in shuttering organ transplant activity. Considering that more than 700 000 Americans have ESRD with 100 000 awaiting a kidney transplant, our highest annual estimate of 478 excess total deaths from postponing kidney transplantation seems modest.

Emergency general surgery utilization and disparities during COVID-19: an interrupted time-series analysis.

OBJECTIVE: We aimed to compare general surgery emergency (GSE) volume, demographics and disease severity before and during COVID-19. BACKGROUND: Presentations to the emergency department (ED) for GSEs fell during the early COVID-19 pandemic. Barriers to accessing care may be heightened, especially for vulnerable populations, and patients delaying care raises public health concerns. METHODS: We included adult patients with ED presentations for potential GSEs at a single quaternary-care hospital from January 2018 to August 2020. To compare GSE volumes in total and by subgroup, an interrupted time-series analysis was performed using the March shelter-in-place order as the start of the COVID-19 period. Bivariate analysis was used to compare demographics and disease severity. RESULTS: 3255 patients (28/week) presented with potential GSEs before COVID-19, while 546 (23/week) presented during COVID-19. When shelter-in-place started, presentations fell by 8.7/week (31%) from the previous week (p<0.001), driven by decreases in peritonitis (ß=-2.76, p=0.017) and gallbladder disease (ß=-2.91, p=0.016). During COVID-19, patients were younger (54 vs 57, p=0.001), more often privately insured (44% vs 38%, p=0.044), and fewer required interpreters (12% vs 15%, p<0.001). Fewer patients presented with sepsis during the pandemic (15% vs 20%, p=0.009) and the average severity of illness decreased (p<0.001). Length of stay was shorter during the COVID-19 period (3.91 vs 5.50 days, p<0.001). CONCLUSIONS: GSE volumes and severity fell during the pandemic. Patients presenting during the pandemic were less likely to be elderly, publicly insured and have limited English proficiency, potentially exacerbating underlying health disparities and highlighting the need to improve care access for these patients. LEVEL OF EVIDENCE: III.

Consensus-based perioperative protocols during the COVID-19 pandemic.

OBJECTIVE: During the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints. METHODS: A multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion. RESULTS: Overall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery. CONCLUSIONS: Urgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.

Treatment of immunocompromised COVID-19 patients with convalescent plasma.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.

Is It Safe to Perform Lung Surgery During the Coronavirus Pandemic?

BACKGROUND:  Coronavirus disease (COVID-19) patients are rapidly growing in our community. Patients with compromised lungs and older age are supposedly at high risk of poor outcomes with COVID-19. We aimed to evaluate the COVID-19 impact on lung surgery during this pandemic at our hospital. METHODOLOGY: This is a retrospective study of all lung surgery patients at our hospital in Boca Raton over three months (February to April 2020). All patients who remained for at least one-day inpatient post-lung surgery were assessed to see if they had an increased incidence of coronavirus infection during the hospital stay or at the follow-up office visit. RESULTS: A total of 44 patients underwent thoracic surgery. It was found that there was no incidence of coronavirus infection in these patients. CONCLUSION: With adequate precautions, older patients can undergo lung surgery during this pandemic. There was no incidence of COVID-19 found among the patients during the hospital stay or at the first follow-up in the office. Also, the postoperative course was not adversely affected.

COVID-19 and Abdominal Transplant: A Stepwise Approach to Practice During Pandemic Conditions.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease has transformed innumerable aspects of medical practice, particularly in the field of transplantation. MAIN BODY: Here we describe a single-center approach to creating a generalizable, comprehensive, and graduated set of recommendations to respond in stepwise fashion to the challenges posed by these conditions, and the underlying principles guiding such decisions. CONCLUSIONS: Creation of a stepwise plan will allow transplant centers to respond in a dynamic fashion to the ongoing challenges posed by the COVID-19 pandemic.