COVID-19 Adult, Childhood, and Adolescent Vaccination Coverage Among Military and Civilian Families, United States.

INTRODUCTION: The COVID-19 pandemic affected the lives of military members and their families, with over 400,000 cases among U.S. military members since the start of the pandemic. The objective of this study is to examine and compare COVID-19 vaccination coverage of military members (active duty and Reserve/National Guard) and their family members (spouses, children, and adolescents) to that of their civilian counterparts using a large, nationally representative study. METHODS: Data from March 2 to May 9, 2022, of the Household Pulse Survey were analyzed for this study (n = 207,758). COVID-19 vaccination status (≥1 dose) was assessed for military members and their spouses, civilians, and children (aged 5 to 11 and 12 to 17 years) from both military and civilian families. Differences between military members, spouses, and their children compared to civilian adults and children were assessed using chi-squared and t-tests. Multivariable logistic regression was used to examine the association between military status and COVID-19 vaccination after controlling for sociodemographic characteristics. Reasons for not getting vaccinated for adults and children from military and civilian families were assessed. RESULTS: Compared to civilian adults and adjusted for sociodemographic characteristics, military members were more likely to be vaccinated (adjusted prevalence ratio = 1.07, 95% CI: 1.01-1.13). Vaccination coverage between active duty and civilian adults differed by subgroups. For example, among military members, COVID-19 vaccination coverage decreased with increasing age, from 87.5% among those aged 18 to 39 years to 56.0% among those aged ≥55 years. In contrast, among civilian adults, vaccination coverage increased with increasing age, from 78.5% among those aged 18 to 39 years to 91.2% among those aged ≥55 years. Military members were also less likely to be vaccinated than their civilian counterparts if they were Hispanic (68.5% vs. 85.2%), had a Bachelor's degree or higher (87.5% vs. 93.8%), or had $100,000 or more in annual household income (76.7% vs. 92.6%). Military members who had anxiety or depression (70.1%) were less likely to be vaccinated compared to civilian adults (84.4%). Military spouses (74.4%) were less likely to be vaccinated than civilian adults (84.7%). Children and adolescents who were homeschooled (35.1%) or had no preventive checkups in the past year (32.4%) were less likely to be vaccinated than their respective counterparts (52.5% and 54.0%, respectively). Military adults compared to civilian adults were more likely to report lack of trust in the government (47.5% vs. 35.2%) and, for children/adolescents, the belief that the vaccine is not needed (42.1% vs. 28.1%) as reasons for non-vaccination. CONCLUSIONS: Despite vaccine mandates and the high vaccination coverage found among the majority of military members, disparities exist in some subgroups. Educational interventions and increased communication from trusted leaders, such as medical providers and commanders, could increase confidence in vaccines among military families. Ensuring access to vaccines, empowering healthcare providers to recommend vaccines, and reminding parents of missed vaccinations or preventive checkups can help improve vaccination coverage. Achieving high vaccination among military members and their families is essential in protecting those in the forefront of the pandemic response and promoting the safety and security of the nation.

Recombinant Protein Micelles to Block Transduction by SARS-CoV-2 Pseudovirus.

The continuing emergence of variants of the SARS-CoV-2 virus requires the development of modular molecular therapies. Here, we engineered a recombinant amphiphilic protein, oleosin, to spontaneously self-assemble into multivalent micellar nanostructures which can block the Spike S1 protein of SARS-CoV-2 pseudoviruses (PVs). Short recombinant proteins like oleosin can be formulated more easily than antibodies and can be functionalized with precision through genetic engineering. We cloned S1-binding mini-protein genes called LCBx, previously designed by David Baker's laboratory (UW Seattle), to the N-terminus of oleosin, expressing Oleo-LCBx proteins in E. coli. These proteins largely formed 10-100 nm micelles as verified by dynamic light scattering. Two proteins, Oleo-LCB1 and Oleo-LCB3, were seen to completely and irreversibly block transduction by both wild-type and delta variant PVs into 293T-hsACE2 cells at 10 µM. Presented in multivalent micelles, these proteins reduced transduction by PVs down to a functional protein concentration of 5 nM. Additionally, Oleo-LCB1 micelles outperformed corresponding synthetic LCB1 mini-proteins in reducing transduction by PVs. Tunable aqueous solubility of recombinant oleosin allowed incorporation of peptides/mini-proteins at high concentrations within micelles, thus enhancing drug loading. To validate the potential multifunctionality of the micelles, we showed that certain combinations of Oleo-LCB1 and Oleo-LCB3 performed much better than the individual proteins at the same concentration. These micelles, which we showed to be non-toxic to human cells, are thus a promising step toward the design of modular, multifunctional therapeutics that could bind to and inactivate multiple receptors and proteins necessary for the infection of the SARS-CoV-2 virus.

SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Impact of Coronavirus Disease 2019 Restrictions on Retinal Detachment: A Multicenter Experience.

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Self-reported COVID-19 vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and United Kingdom.

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.

Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies.

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.

Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies (preprint)

Coronavirus disease 2019 (COVID-19) infection results in high mortality rates in patients with hematologic malignancies. Persistent and/or recurrent COVID-19 has not yet been demonstrated in this population. We identified patients with B-cell lymphomas as having a particularly high risk for persistent SARS-CoV-2 positivity. Subsequent analysis of patients with lymphoid malignancies and COVID-19 identified discrete risk factors for severity of primary infection as compared to disease chronicity. Active therapy and diminished T-cell counts were key drivers of acute mortality in lymphoma patients with COVID-19 infection. Conversely, B-cell depleting therapy was the primary driver of re-hospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. Statement of SignificanceWe establish persistent symptomatic COVID-19 infection as a novel clinical syndrome in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.

Microbiologic characterization and antibacterial use in hospitalized adults with COVID-19 infection

Background: Coronavirus disease 2019 (CoVID-19) admissions, oft complicated by an uncertain trajectory, lent to treatment influenced by supposition. Respiratory bacterial co-infection frequently was invoked. The purpose of this study was to determine the respiratory pathogen distribution and antibiotic prescribing patterns in hospitalized patients with CoVID-19. Methods: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ICD-10 code and/or positive polymerase chain reaction (PCR) hospitalized between March 1 and May 31, 2020 were included. Antibiotic utilization (patient days of therapy-pDOT) was collected for the institution during this period and two years prior. Respiratory microbiologic cultures were reviewed to examine the frequency of co-infection on presentation, categorized as within 3 calendar days from admission or afterward. The relationship of antibiotic utilization to positive cultures was also categorized. Results: Of the 7,969 encounters, 829 were ICD-10 coded and/or confirmed SARS-CoV-2 PCR positive and 196 (23.6%) had positive respiratory cultures. 89.8% of patients had endotracheal samples, the rest were isolated from sputum or bronchoalveolar lavage (17.4% and 6.6%, respectively). Patients were more likely to isolate commensal respiratory flora (108 versus 78 patients within the first 3 days of presentation. Notable isolates such as Staphylococcus aureus and Pseudomonas aeruginosa, were more often isolated after 3 days of hospitalization. While the CoVID-19 average hospital census was only 14.7% of the total, antibiotic utilization, (pDOT/1000) was 2.3 times higher, 831.9 versus 368.3 across the institution. During similar periods in 2018 and 2019, days of therapy overall were lower. For CoVID-19 infected patients, the frequency of antibiotic initiation was 73.2%. The length of therapy was on average 8 days with a high rate of observed restarts. Conclusion: Bacterial co-infection in an acute viral process is generally low. In this examination of CoVID-19 infected patients, the rate of any positive respiratory culture was 23.6%. A disproportionate effect on the volume of antibiotics and total days of therapy prompted an interest in early stewardship efforts and education. (Table Presented).

Systems serology detects functionally distinct coronavirus antibody features in children and elderly.

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

Development and validation of a predictive model for critical illness in adult patients requiring hospitalization for COVID-19.

BACKGROUND: Identifying factors that can predict severe disease in patients needing hospitalization for COVID-19 is crucial for early recognition of patients at greatest risk. OBJECTIVE: (1) Identify factors predicting intensive care unit (ICU) transfer and (2) develop a simple calculator for clinicians managing patients hospitalized with COVID-19. METHODS: A total of 2,685 patients with laboratory-confirmed COVID-19 admitted to a large metropolitan health system in Georgia, USA between March and July 2020 were included in the study. Seventy-five percent of patients were included in the training dataset (admitted March 1 to July 10). Through multivariable logistic regression, we developed a prediction model (probability score) for ICU transfer. Then, we validated the model by estimating its performance accuracy (area under the curve [AUC]) using data from the remaining 25% of patients (admitted July 11 to July 31). RESULTS: We included 2,014 and 671 patients in the training and validation datasets, respectively. Diabetes mellitus, coronary artery disease, chronic kidney disease, serum C-reactive protein, and serum lactate dehydrogenase were identified as significant risk factors for ICU transfer, and a prediction model was developed. The AUC was 0.752 for the training dataset and 0.769 for the validation dataset. We developed a free, web-based calculator to facilitate use of the prediction model (https://icucovid19.shinyapps.io/ICUCOVID19/). CONCLUSION: Our validated, simple, and accessible prediction model and web-based calculator for ICU transfer may be useful in assisting healthcare providers in identifying hospitalized patients with COVID-19 who are at high risk for clinical deterioration. Triage of such patients for early aggressive treatment can impact clinical outcomes for this potentially deadly disease.

Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19.

Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

Distinct systems serology features in children, elderly and COVID patients (preprint)

SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.