Clinical Evaluation of the Abbott Alinity SARS-CoV-2 Spike-Specific Quantitative IgG and IgM Assays among Infected, Recovered, and Vaccinated Groups.

The coronavirus disease 19 (COVID-19) pandemic continues to impose a significant burden on global health infrastructure. While identification and containment of new cases remain important, laboratories must now pivot and consider an assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in the setting of the recent availability of multiple COVID-19 vaccines. Here, we have utilized the latest Abbott Alinity semiquantitative IgM and quantitative IgG spike protein (SP) serology assays (IgMSP and IgGSP) in combination with Abbott Alinity IgG nucleocapsid (NC) antibody test (IgGNC) to assess antibody responses in a cohort of 1,236 unique participants comprised of naive, SARS-CoV-2-infected, and vaccinated (including both naive and recovered) individuals. The IgMSP and IgGSP assays were highly specific (100%) with no cross-reactivity to archived samples collected prior to the emergence of SARS-CoV-2, including those from individuals with seasonal coronavirus infections. Clinical sensitivity was 96% after 15 days for both IgMSP and IgGSP assays individually. When considered together, the sensitivity was 100%. A combination of NC- and SP-specific serologic assays clearly differentiated naive, SARS-CoV-2-infected, and vaccine-related immune responses. Vaccination resulted in a significant increase in IgGSP and IgMSP values, with a major rise in IgGSP following the booster (second) dose in the naive group. In contrast, SARS-CoV-2-recovered individuals had several-fold higher IgGSP responses than naive following the primary dose, with a comparatively dampened response following the booster. This work illustrates the strong clinical performance of these new serological assays and their utility in evaluating and distinguishing serological responses to infection and vaccination.

Post-acute sequelae of COVID-19 and longitudinal antibody levels in a community-based cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases. METHODS: The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18-89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021. RESULTS: Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire- 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8-10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6-7 months post-vaccination in cases were similar to that of controls. CONCLUSIONS: More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination.

Multidisciplinary care for patients with HCC: a systematic review and meta-analysis.

BACKGROUND: Given the complexity of managing HCC, professional society guidelines advocate multidisciplinary care (MDC) for patients with HCC. However, implementation of MDC programs requires a significant investment of time and resources. We conducted a systematic review and meta-analysis to enumerate potential benefits of MDC for patients with HCC. METHODS: We conducted a search of the PubMed/MEDLINE and EMBASE databases and national conference abstracts to identify studies published after January 2005 that reported early-stage presentation, treatment receipt, or overall survival among patients with HCC, stratified by MDC status. We calculated pooled risk ratios and HRs for clinical outcomes according to MDC receipt using the DerSimonian and Laird method for random effects models. RESULTS: We identified 12 studies (n = 15,365 patients with HCC) with outcomes stratified by MDC status. MDC was associated with improved overall survival (HR = 0.63, 95% CI: 0.45-0.88); however, its association with curative treatment receipt was not statistically significant (risk ratio = 1.60, 95% CI: 0.89-2.89) and pooled estimates were limited by high heterogeneity (I2 > 90% for both). Studies (n = 3) were discordant regarding an association between MDC and time-to-treatment initiation. MDC was associated with early-stage HCC (risk ratio = 1.60, 95% CI: 1.12-2.29), suggesting possible referral bias contributing to improved outcomes. Limitations of studies also included risk of residual confounding, loss to follow-up, and data preceding the availability of immune checkpoint inhibitors. CONCLUSION: MDC for patients with HCC is associated with improved overall survival, underscoring the likely benefit of managing patients with HCC in a multidisciplinary care setting.

Population-based correlates of COVID-19 infection: An analysis from the DFW COVID-19 prevalence study.

BACKGROUND: COVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population. METHODS: The DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18-89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data. RESULTS: Of 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings. CONCLUSION: Over 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence.

Stromal Hedgehog pathway activation by IHH suppresses lung adenocarcinoma growth and metastasis by limiting reactive oxygen species.

Activation of the Hedgehog (Hh) signaling pathway by mutations within its components drives the growth of several cancers. However, the role of Hh pathway activation in lung cancers has been controversial. Here, we demonstrate that the canonical Hh signaling pathway is activated in lung stroma by Hh ligands secreted from transformed lung epithelia. Genetic deletion of Shh, the primary Hh ligand expressed in the lung, in KrasG12D/+;Trp53fl/fl autochthonous murine lung adenocarcinoma had no effect on survival. Early abrogation of the pathway by an anti-SHH/IHH antibody 5E1 led to significantly worse survival with increased tumor and metastatic burden. Loss of IHH, another Hh ligand, by in vivo CRISPR led to more aggressive tumor growth suggesting that IHH, rather than SHH, activates the pathway in stroma to drive its tumor suppressive effects-a novel role for IHH in the lung. Tumors from mice treated with 5E1 had decreased blood vessel density and increased DNA damage suggestive of reactive oxygen species (ROS) activity. Treatment of KrasG12D/+;Trp53fl/fl mice with 5E1 and N-acetylcysteine, as a ROS scavenger, decreased tumor DNA damage, inhibited tumor growth and prolonged mouse survival. Thus, IHH induces stromal activation of the canonical Hh signaling pathway to suppress tumor growth and metastases, in part, by limiting ROS activity.