Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

INTRODUCTION: Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS: We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS: At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001). CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

Digital and virtual strategies to advance community stakeholder engagement in research during COVID-19 pandemic.

Despite the adversity presented by COVID-19 pandemic, it also pushed for experimenting with innovative strategies for community engagement. The Community Research Advisory Council (C-RAC) at Johns Hopkins University (JHU), is an initiative to promote community engagement in research. COVID-19 rendered it impossible for C-RAC to conduct its meetings all of which have historically been in person. We describe the experience of advancing the work of the C-RAC during COVID-19 using digital and virtual strategies. Since March 2020, C-RAC transitioned from in person to virtual meetings. The needs assessment was conducted among C-RAC members, and individualized solutions provided for a successful virtual engagement. The usual working schedule was altered to respond to COVID-19 and promote community engaged research. Attendance to C-RAC meetings before and after the transition to virtual operation increased from 69% to 76% among C-RAC members from the community. In addition, the C-RAC launched new initiatives and in eighteen months since January 2020, it conducted 50 highly rated research reviews for 20 research teams. The experience of the C-RAC demonstrates that when community needs are assessed and addressed, and technical support is provided, digital strategies can lead to greater community collaborations.

Corrigendum: Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients.

[This corrects the article DOI: 10.3389/fimmu.2022.878812.].

Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients.

Introduction: There is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients. Methods: A prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed. Results: Patients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors (p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection (p< 0.001), and than patients who required oxygen therapy (p< 0.05), and had 5-fold higher IgG1 titers than RF non-survivors (p< 0.001) and those who needed oxygen therapy (p< 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission (p< 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived (p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036). Conclusions: We demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection.

Responding to the Disproportionate Impact of COVID-19 Among Latinx Patients in Baltimore: The JHM Latinx Anchor Strategy.

Latinx immigrants have been profoundly impacted by COVID-19. As the Johns Hopkins Health System faced a surge in admissions of limited English proficiency patients with COVID-19, it became evident that an institutional strategy to address the needs of this patient population was needed. The Johns Hopkins Medicine (JHM) Latinx Anchor Strategy was established in April 2020 with diverse stakeholder engagement to identify the most urgent community needs and develop timely solutions. The JHM Latinx Anchor Strategy provided a platform for information sharing to promote equitable access to resources for Latinxs with limited English proficiency who were impacted by COVID-19. Leveraging institutional, community, and government resources and expertise, the JHM Latinx Anchor Strategy helped establish interventions to improve access to COVID-19 testing and care for low-income immigrants without a primary care doctor and helped mitigate economic vulnerability through the distribution of food for 2,677 individuals and cash to 446 families and 95 individuals (May to August 2020). Expanded linguistic and culturally competent communication through webinars and livestream events reached more than 10,000 community members and partners. Over 7,500 limited English proficiency patients received linguistically congruent direct patient services through the Esperanza Center bilingual hotline, community testing resulting efforts, and inpatient consultations. The first stage of the JHM Latinx Anchor Strategy relied heavily on volunteer efforts. Funding for a sustainable response will be required to address ongoing COVID-19 needs, including expansion of the bilingual/bicultural healthcare workforce, expanded access to primary care, and investments in population health strategies addressing social determinants of health.

Developing Breast Imaging Services in Low-Resource Settings

Breast cancer is the leading cause of cancer death for women worldwide, and its incidence continues to increase, particularly in low- and middle-income countries (LMICs).3 There is relatively higher mortality from breast cancer in LMICs compared to high-income countries (HICs), which may be due to differences in tumor biology, limited awareness about breast cancer on the part of patients or healthcare providers, and lack of access to screening, diagnostic, and treatment services.1,5-8 Without structured screening programs or easily accessible imaging and intervention, breast cancer in LMICs is more commonly diagnosed at a late stage (stage III or IV) compared to HICs.3 While early-stage breast cancer is largely curable with appropriate surgical, oncologic, and radiation therapy, late-stage breast cancer has a much higher morbidity and mortality rate.4,9 Furthermore, late-stage breast cancer requires more advanced therapies, which are difficult to come by in the low-resource setting. The Breast Health Global Initiative (BHGI) and the National Comprehensive Cancer Network (NCCN) have published comprehensive guidelines suggesting how resources should be allocated toward various aspects of breast cancer care depending on resource availability.12,13 We also adhere to a phased implementation approach to build capacity gradually without overwhelming our partners.14 Our first step of program planning, therefore, is always a thorough assessment of our target population and the local availability of screening, diagnostic services (imaging, tissue sampling, and pathology) and treatment. [...]we plan with an eye toward sustainability to ensure our interventions lead to lasting improvement. There is also evidence that ultrasound may be a useful screening tool in areas where mammography is unfeasible.17 In the United States, RAD-AID launched a longitudinal collaboration with the Black Women's Health Imperative (BWHI), National Alliance of Hispanic Health, and Hologic Inc.'s Project Health Equality to bring awareness to and address long-standing healthcare disparities that affect women of color.18 In this initiative, we collaborate with and support primary care centers that are already serving medically underserved women of color as well as tertiary centers interested in improving access to specialty care for women who need it most.

Towards Control and Oversight of SARS-CoV-2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors.

The development of versatile and sensitive biotools to quantify specific SARS-CoV-2 immunoglobulins in SARS-CoV-2 infected and non-infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in-house expressed recombinant spike (S) proteins is reported. Amperometric interrogation of captured N- and S-specific circulating total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), subsequently labelled with HRP-conjugated secondary antibodies, was performed at disposable single or multiplexed (8×) screen-printed electrodes using the HQ/HRP/H2 O2 system. The obtained results using N and in-house expressed S ectodomains of five SARS-CoV-2 variants of concern (including the latest Delta and Omicron) allow identification of vulnerable populations from those with natural or acquired immunity, monitoring of infection, evaluation of vaccine efficiency, and even identification of the variant responsible for the infection.

Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.

Centralized registry for COVID-19 research recruitment: Design, development, implementation, and preliminary results.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has had substantial global morbidity and mortality. Clinical research related to prevention, diagnosis, and treatment of COVID-19 is a top priority. Effective and efficient recruitment is challenging even without added constraints of a global pandemic. Recruitment registries offer a potential solution to slow or difficult recruitment. OBJECTIVES: The purpose of this paper is to describe the design and implementation of a digital research recruitment registry to optimize awareness and participant enrollment for COVID-19-related research in Baltimore and to report preliminary results. METHODS: Planning began in March 2020, and the registry launched in July 2020. The primary recruitment mechanisms include electronic medical record data, postcards distributed at testing sites, and digital advertising campaigns. Following consent in a Research Electronic Data Capture survey, participants answer questions related to COVID-19 exposure, testing, and willingness to participate in research. Branching logic presents participants with studies they might be eligible for. RESULTS: As of March 24, 2021, 9010 participants have enrolled, and 64.2% are female, 80.6% are White, 9.4% are Black or African American, and 6% are Hispanic or Latino. Phone outreach has had the highest response rate (13.1%), followed by email (11.9%), text (11.4%), and patient portal message (9.4%). Eleven study teams have utilized the registry, and 4596 matches have been made between study teams and interested volunteers. CONCLUSION: Effective and efficient recruitment strategies are more important now than ever due to the time-limited nature of COVID-19 research. Pilot efforts have been successful in connecting interested participants with recruiting study teams.

The Impact of Immunosuppression and Autoimmune Disease on Severe Outcomes in Patients Hospitalized with COVID-19.

Immunosuppression (IS) and autoimmune disease (AD) are prevalent in patients with severe coronavirus disease 2019 (COVID-19), but their impact on its clinical course is unknown. We investigated relationships between IS, AD, and outcomes in patients hospitalized with COVID-19. Data on consecutive admissions for COVID-19 were extracted retrospectively from medical records. Patients were assigned to one of four cohorts, according to whether or not they had an AD (AD and NAD) or were immunosuppressed (IS and NIS). The primary endpoint was development of severe acute respiratory distress syndrome (ARDS); secondary endpoints included death, and a composite of mechanical ventilation (MV) or death. A total of 789 patients were included: 569 (72.1%) male, 76 (9.6%) with an AD, and 63 (8.0%) with IS. Relative to the NIS-NAD cohort, patients in the IS-AD cohort had a significantly reduced risk of severe ARDS (adjusted hazard ratio [aHR] 0.42; 95% confidence interval [CI] 0.23-0.80; p = 0.008). No significant relationships between IS or AD status and either death or the composite of MV and death were identified, although a trend towards higher mortality was identified in the IS-NAD cohort (aHR vs NIS-NAD 1.71; 95% CI 0.94-3.12; p = 0.081). Patients in this cohort also had higher median serum levels of interleukin-6 compared with IS-AD patients (98.2 vs 21.6 pg/mL; p = 0.0328) and NIS-NAD patients (29.1 pg/mL; p = 0.0057). In conclusion, among patients hospitalized with COVID-19, those receiving immunosuppressive treatment for an AD may have a reduced risk of developing severe ARDS.