COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort.

The recommended COVID-19 booster vaccine uptake is low. At-home lateral flow assay (LFA) antigen tests are widely accepted for detecting infection during the pandemic. Here, we present the feasibility and potential benefits of using LFA-based antibody tests as a means for individuals to detect inadequate immunity and make informed decisions about COVID-19 booster immunization. In a health care provider cohort, we investigated the changes in the breadth and depth of humoral and T cell immune responses following mRNA vaccination and boosting in LFA-positive and LFA-negative antibody groups. We show that negative LFA antibody tests closely reflect the lack of functional humoral immunity observed in a battery of sophisticated immune assays, while positive results do not necessarily reflect adequate immunity. After booster vaccination, both groups gain depth and breadth of systemic antibodies against evolving SARS-CoV-2 and related viruses. Our findings show that LFA-based antibody tests can alert individuals about inadequate immunity against COVID-19, thereby increasing booster shots and promoting herd immunity.

Let Us Just Ask People What They Think: Community Perceptions and Recommendations about Coronavirus Vaccination.

Introduction: Despite widespread efforts to promote coronavirus disease 2019 vaccination in the United States, a significant segment of the population is still unvaccinated or incompletely vaccinated. Objective: The objective of this study was to understand attitudes toward the vaccine in patients presenting to an urban emergency department. Methods: We used a qualitative analysis and semistructured interviews with a convenience sample of patients presenting to an urban emergency department from January 18, 2021, to March 14, 2021. Our final sample consisted of 32 people. Results: We found that people trusted their own medical providers rather than popular or political figures. Critiques of the vaccination program highlighted difficulties in navigation and perceptions of inequity. Conclusions: Equitable distribution strategies and honest messaging may facilitate acceptance of the coronavirus disease 2019 vaccine. Trustworthy sources for vaccine knowledge should be used to target populations in which vaccine hesitancy is a persistent concern.

Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.

Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity. One Sentence Summary: SARS-CoV-2 point-of-care antibody tests are valuable and easy-to-access tools to inform inadequate humoral immunity and to support informed decision-making regarding the current and future booster vaccination.

Diagnostic accuracy of novel mRNA blood biomarkers of infection to predict outcomes in emergency department patients with undifferentiated abdominal pain.

Abdominal pain represents greater than 20% of US Emergency Department (ED) visits due to a wide range of illnesses. There are currently no reliable blood biomarkers to predict serious outcomes in patients with abdominal pain. Our previous studies have identified three mRNA transcripts related to innate immune activation: alkaline phosphatase (ALPL), interleukin-8 receptor-ß (IL8RB), and defensin-1 (DEFA1) as promising candidates to detect an intra-abdominal infection. The objective of this study was to evaluate the accuracy of these mRNA biomarkers to predict likely infection, hospitalization and surgery in Emergency Department patients with undifferentiated abdominal pain. We prospectively enrolled Emergency Department patients with undifferentiated abdominal pain who received an abdominal CT scan as part of their evaluation. Clinical outcomes were abstracted from the CT scan and medical records. mRNA biomarker levels were calculated independent of the clinical outcomes and their accuracy was assessed to predict infectious diagnoses, surgery and hospital admission. 89 patients were enrolled; 21 underwent surgery; 47 underwent hospital admission; and, no deaths were observed within 30 days. In identifying which cases were likely infectious, mRNA biomarkers' AUC values were: ALPL, 0.83; DEFA1 0.51; IL8RB, 0.74; and ALPL + IL8RB, 0.79. In predicting which Emergency Department patients would receive surgery, the AUC values were: ALPL, 0.75; DEFA1, 0.58; IL8RB, 0.75; and ALPL + IL8RB, 0.76. In predicting hospital admission, the AUC values were: ALPL, 0.78; DEFA1, 0.52; IL8RB, 0.74; and, ALPL + IL8RB, 0.77. For predicting surgery, ALPL + IL8RB's positive likelihood ratio (LR) was 3.97; negative LR (NLR) was 0.70. For predicting hospital admission, the same marker's positive LR was 2.80 with an NLR of 0.45. Where the primary cause for admission was a potentially infectious disorder, 33 of 34 cases (97%) had positive RNA scores. In a pragmatic, prospective diagnostic accuracy trial in Emergency Department patients with undifferentiated abdominal pain, mRNA biomarkers showed good accuracy to identify patients with potential infection, as well as those needing surgery or hospital admission.

A randomized control trial of a multiplex gastrointestinal PCR panel versus usual testing to assess antibiotics use for patients with infectious diarrhea in the emergency department.

OBJECTIVE: This study analyzed physician treating behavior through the use of a multiplex gastrointestinal polymerase chain reaction (GI PCR) test compared with usual testing in emergency department (ED) patients with suspected acute infectious diarrhea to assess differences in antibiotic management. METHODS: A prospective, single-center, randomized control trial was designed to investigate antibiotic use in ED patients with moderate to severe suspected infectious diarrhea, comparing those who received GI PCR to those who received usual testing. ED patients with signs of dehydration, inflammation, or persistent symptoms were randomized to either the experimental arm (GI PCR) or the control arm (usual testing or no testing). RESULTS: A total of 74 patients met study criteria and were randomized to either the experimental GI PCR arm (n = 38) or to the control arm (n = 36). Participants in the GI PCR arm received antibiotics in 87% of bacterial or protozoal diarrheal infections (13/15) whereas those in the control arm received antibiotics in 46% of bacterial or protozoal infections (6/13) (P value 0.042) with 2-proportion difference 0.41 (95% confidence interval 0.07 and 0.68). CONCLUSIONS: ED use of multiplex GI PCR led to an increase in antibiotic use for bacterial and protozoal causes of infectious diarrhea compared to usual testing. This increase in antibiotics appears to be appropriate given patients' moderate to severe symptoms and a definitive identification of a likely bacterial or protozoal cause of symptoms. Results should be interpreted with caution because of the small sample size.

Factors associated with clinical severity in emergency department patients presenting with symptomatic SARS-CoV-2 infection.

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic emergency department patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a cohort study of symptomatic patients presenting to a single emergency department (ED) with laboratory-confirmed SARS-CoV-2 infection from March 7-August 9, 2020. We collected patient-level information regarding demographics, insurance status, comorbidities, level of care, and mortality using a structured chart review. We compared characteristics of patients categorized by (1) home discharge, (2) general hospital ward admission, and (3) intensive care unit (ICU) admission or death within 30 days of the index visit. Univariate and multivariable logistic regression analyses were performed to report odds ratios (OR) and 95% confidence intervals (95% CI) between hospital admission versus ED discharge home and between ICU care versus general hospital ward admission. RESULTS: In total, 994 patients who presented to the ED with symptoms were included in the analysis with 551 (55.4%) patients discharged home, 314 (31.6%) patients admitted to the general hospital ward, and 129 (13.0%) admitted to the ICU or dying. Patients requiring admission were more likely to be Black or to have public insurance (Medicaid and/or Medicare). Patients who were admitted to the ICU or dying were more likely aged ≥ 65 years or male. In multivariable logistic regression, old age, public insurance, diabetes, hypertension, obesity, heart failure, and hyperlipidemia were independent predictors of hospital admission. When comparing those who needed ICU care versus general hospital ward admission in univariate logistic regression, patients with Medicaid (OR 2.4, 95% CI 1.2-4.6), Medicare (OR 4.2, 95% CI 2.1-8.4), Medicaid and Medicare (OR 4.3, 95% CI 2.4-7.7), history of chronic obstructive pulmonary disease (OR 2.2, 95% CI 1.2-4.2), hypertension (OR 1.7, 95% CI 1.1-2.7), and heart failure (OR 2.6, 95% CI 1.4-4.7) were more likely to be admitted into the ICU or die; Black (OR 1.1, 95% CI 0.4-2.9) and Hispanic/Latino (OR 1.0, 95% CI 0.6-1.8) patients were less likely to be admitted into the ICU; however, the associations were not statistically significant. In multivariable logistic regression, old age, male sex, public insurance, and heart failure were independent predictors of ICU care/death. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among Black patients may be attributable, in part, to low socioeconomic status and chronic health conditions.

Factors associated with clinical severity in Emergency Department patients presenting with symptomatic SARS-CoV-2 infection.

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic Emergency Department (ED) patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a retrospective case-series of symptomatic patients presenting to a single ED with laboratory-confirmed SARS-CoV-2 infection from March 12-August 9, 2020. We collected patient-level information regarding demographics, public insurance status (Medicare or Medicaid), comorbidities, level of care, and mortality using a structured chart review. We compared demographics and comorbidities of patients who were (1) able to convalesce at home, (2) required admission to general medical service, (3) required admission to intensive care unit (ICU), or (4) died within 30 days of the index visit. Multivariable logistic regression analyses were performed to report adjusted odds ratios (aOR) and the associated 95% confidence intervals (95% CI) with hospital admission versus ED discharge home. RESULTS: In total, 993 patients who presented to the ED with symptoms were included in the analysis with 370 (37.3%) patients requiring hospital admission and 70 (7.1%) patients requiring ICU care. Patients requiring admission were more likely to be Black or African American, to be Hispanic or Latino, or to have public insurance (either Medicaid or Medicare.) On multivariable logistic regression analysis comparing which patients required hospital admission, African-American race (aOR 1.4, 95% CI 0.7-2.8) and Hispanic ethnicity (aOR 1.1, 95% CI 0.5-2.0) were not associated with need for admission but, public insurance (Medicaid: aOR 3.4, 95% CI 2.2-5.4; Medicare: aOR 2.6, 95% CI 1.2-5.3; Medicaid and Medicare: aOR 3.6 95% CI 2.1-6.2) and the presence of hypertension (aOR 1.8, 95% CI 1.2-2.7), diabetes (aOR 1.6, 95% CI 1.1-2.5), obesity (aOR 1.7, 95% CI 1.1-2.5), heart failure (aOR 3.9, 95% CI 1.4-11.2), and hyperlipidemia (aOR 1.8, 95% CI 1.2-2.9) were identified as independent predictors of hospital admission. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among African Americans and Hispanics are likely to be closely related to low socioeconomic status and chronic health conditions and do not reflect an independent predisposition to disease severity.