Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial.

The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN50), and compared and combined markers in multivariable analyses. LV-MN50 was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.

The COVID-19 Pandemic Unmasked the Challenges Faced by Early-Stage Faculty in Infectious Diseases: A Call to Action.

The COVID-19 pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for Infectious Diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, women faculty, underrepresented in medicine and science faculty, and particularly ESF experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.

Effects of race on the outcome of COVID-19 in hospitalized patients.

BACKGROUND AND AIMS: Recent reports indicate that African Americans have higher mortality rates from SARS-CoV-2 coronavirus disease 19 (COVID-19) compared to Caucasians, with more marked differences in the Midwest region of the US. This study was performed to study differences in COVID-19 related mortality and hospital length of stay (LOS) between African Americans and Caucasians in Midwest setting, and identify factors associated with mortality and LOS. METHODS: Data were collected from the electronic health records (EHR) of patients admitted to hospitals in Midwest region of the US. EHR of 471 COVID-19 patients were reviewed. RESULTS: Approximately 63% were African Americans and 34% Caucasians. One hundred sixteen variables were tested. There was no significant difference in hospital mortality between African Americans and Caucasians (OR 1, 95% CI 0.48-1.94). Older age, Chronic kidney disease, mental status change, mechanical ventilation, vasopressor support, high neutrophil count, elevated AST and ALT, high lung involvement severity score and elevated CRP were associated with mortality in a univariate analysis (P < 0.05). Multivariable modeling indicated that mechanical ventilation was the only factor that predicted mortality (OR 6, 95% CI: 2.94-12.48). The LOS did not differ in African Americans and Caucasians. The use of oxygen via high flow nasal cannula (Survival Estimate 1.6, 95% CI: 1.20-2.26), low estimated glomerular filtration rate (Survival Estimate 1.4, 95% CI: 1.05-1.82) and mechanical ventilation (Survival Estimate 3.5, 95% CI: 2.72-4.37) were predictors of LOS. CONCLUSION: This study performed in Midwest setting in the US showed that race did not affect in-hospital mortality and LOS. Our analysis demonstrated new predictors of LOS.

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. RESULTS: The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. CONCLUSIONS: The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Rapid establishment of a COVID-19 convalescent plasma program in a regional health care delivery network.

BACKGROUND: COVID-19 convalescent plasma (CCP) represents an appealing approach to the treatment of patients with infections due to SARS-CoV-2. We endeavored to quickly establish a sustainable CCP transfusion program for a regional network of health care facilities. STUDY DESIGN AND METHODS: A regional collaborative group was activated to address the issues necessary to implementing a CCP transfusion program and making the program sustainable. A wide range of health care providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology (IT) specialists were required to make the program a success. RESULTS: The CCP implementation team initially consisted of four members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, six major implementation "themes" were addressed: (a) registration of individual hospitals and principal investigators with a national investigational new drug research protocol; (b) collaboration with a regional blood donor center; (c) targeted recruitment of convalesced donors; (d) IT issues related to all aspects of CCP ordering, distribution, and transfusion; (e) prioritization of patients to receive CCP; and (f) evaluation of CCP products including antibody characteristics and patient response to therapy. CONCLUSION: Within 4 weeks of initiation, CCP was successfully transfused at multiple hospitals in our regional health care delivery system. A program infrastructure was established that will make this program sustainable into the future. This approach has broader implications for the success of multi-institutional programs requiring rapid implementation.