Effectiveness of Monoclonal Antibody Therapy for Preventing COVID-19 Hospitalization and Mortality in a Statewide Population.

BACKGROUND: Monoclonal antibody (MAB) treatments for COVID-19 received Emergency Use Authorization in the United States. METHODS: We used surveillance data from Rhode Island to conduct a retrospective, statewide cohort study to estimate the effectiveness of MABs for preventing hospitalization and death during periods when Alpha and Delta variants were predominant. RESULTS: From 1/17/2021-10/26/2021, 285 long-term congregate care (LTCC) residents and 3,113 non-congregate patients met our eligibility criteria and received MAB; they were matched to 285 and 6,226 controls, respectively. Among LTCC residents, 8.8% (25/285) of patients who received MAB were hospitalized or died compared to 25.3% (72/285) of those who did not receive MAB (adjusted difference=16.7%, 95% confidence interval CI=11.0-22.3%). Among non-congregate patients, 4.5% (140/3,113) of patients who received MAB were hospitalized or died compared to 11.8% (737/6,226) of those who did not receive MAB (adjusted difference=7.2%, 95% CI=6.0-8.4%). CONCLUSIONS: Administration of MABs led to an absolute reduction in hospitalization or death during periods when Alpha and Delta variants were predominant.

A randomized trial of acceptance-based behavioral therapy to improve mental health outcomes for LGBTQ+ persons: Study protocol.

BACKGROUND: During the COVID-19 pandemic, public health measures limited social interactions as an effective and protective intervention for all. For many, however, this social isolation exacerbated mental health symptoms. People who identify as lesbian, gay, bisexual, transgender, and queer (LGBTQ+) were already at elevated risk of anxiety and depression, relative to cisgender and heterosexual populations, and pandemic-related social isolation likely heightened these disparities. In our prior work with sexual and gender minorities, we developed and established feasibility and acceptability of a novel acceptance-based behavioral therapy (ABBT) intervention for HIV treatment. ABBT showed promise in improving social support and reducing mental health symptoms. In the current study, we investigate the efficacy of ABBT, compared to a treatment-as-usual control condition, in a full-scale randomized controlled trial to improve social support for LGBTQ+ persons living with anxiety and depression. METHODS: Two hundred forty LGBTQ+ adults with anxiety and/or depressive symptoms will be recruited and equally randomized to receive: (a) the ABBT intervention, consisting of two 30-40 min sessions plus treatment-as-usual (TAU), or (b) TAU only. Primary outcomes are interviewer-assessed anxiety and depressive symptoms. Secondary outcomes are self-reported anxiety and depressive symptoms. Experiential avoidance and social support are hypothesized mediators and presence of an anxiety and/or depressive disorder is a hypothesized moderator. CONCLUSIONS: ABBT represents a novel, identify-affirming real-world approach to promoting social support as a means of improving mental health among individuals who identify as LGBTQ+. This study will contribute actionable data establishing the impact, mediational mechanisms, and effect modifiers of ABBT. CLINICALTRIALS: govregistration: NCT05540067.

Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers

We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.

BNT162b2 and mRNA-1273 Vaccine Effectiveness against SARS-CoV-2 and Variants in the Urban Underserved Population.

The real world COVID-19 vaccine effectiveness among the urban underserved Hispanic/Latino populations is unknown. We evaluated the mRNA vaccine effectiveness in preventing SARS-CoV-2 infections at a major federally qualified health center in Providence, Rhode Island, and a total of 38,602 patients were included. Time period was used as the SARS-CoV-2 variant proxy. Compared to the unvaccinated group, the adjusted vaccine effectiveness for 2 doses of BNT162b2 and mRNA-1273 were 94.6% and 97.5% respectively against the alpha variant/wild type, which dropped to 64.8% and 65.0% respectively against the delta variant and 31.6% and 25.6% respectively against the omicron variant. However, once received the booster dose (3rd dose) of BNT162b2 and mRNA-1273, the vaccine effectiveness against the omicron variant improved to 79.9% and 71.2% respectively. Improving the COVID-19 vaccine education and encouraging to receive a booster dose may help further reduce the burden of SARS-CoV-2 infection in this population.

Pre-exposure Prophylaxis Discontinuation During the COVID-19 Pandemic Among Men Who Have Sex With Men in a Multisite Clinical Cohort in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to put strain on health systems in the United States, leading to significant shifts in the delivery of routine clinical services, including those offering HIV pre-exposure prophylaxis (PrEP). We aimed to assess whether individuals discontinued PrEP use at higher rates during the COVID-19 pandemic and the extent to which disruptions to usual clinical care were mitigated through telehealth. METHODS: Using data from an ongoing prospective cohort of men who have sex with men (MSM) newly initiating PrEP in 3 mid-sized cities (n = 195), we calculated the rate of first-time discontinuation of PrEP use in the period before the COVID-19 pandemic and during the COVID-19 pandemic and compared these rates using incidence rate ratios (IRRs). Furthermore, we compared the characteristics of patients who discontinued PrEP use during these periods with those who continued to use PrEP during both periods. RESULTS: Rates of PrEP discontinuation before the COVID pandemic and during the COVID-19 pandemic were comparable [4.29 vs. 5.20 discontinuations per 100 person-months; IRR: 1.95; 95% confidence interval (CI): 0.83 to 1.77]. Although no significant differences in the PrEP discontinuation rate were observed in the overall population, the rate of PrEP discontinuation increased by almost 3-fold among participants aged 18-24 year old (IRR: 2.78; 95% CI: 1.48 to 5.23) and by 29% among participants covered by public insurance plans at enrollment (IRR: 1.29; 95% CI: 1.03 to 5.09). Those who continued to use PrEP were more likely to have had a follow-up clinical visit by telehealth in the early months of the pandemic (45% vs. 17%). CONCLUSIONS: In this study, rates of PrEP discontinuation were largely unchanged with the onset of the COVID-19 pandemic. The use of telehealth likely helped retain patients in PrEP care and should continue to be offered in the future.

Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 Among Previously Infected Healthcare Personnel and First Responders.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus testing among first responders and healthcare personnel who participated in a May 2020-August 2020 serosurvey that assessed spike protein antibodies provided an opportunity to assess reinfection. METHODS: Serology survey data were merged with virus testing results from Rhode Island (1 March 2020-17 February 2021) and New York City (10 March 2020-14 December 2020). Participants with a positive virus test ≥14 days before their serology test were included. Reinfection was defined as a second positive SARS-CoV-2 test ≥90 days after the first positive test. The association between serostatus and reinfection was assessed with a proportional hazards model. RESULTS: Among 1572 previously infected persons, 40 (2.5%) were reinfected. Reinfection differed by serostatus: 8.4% among seronegative vs 1.9% among seropositive participants (P < .0001). Most reinfections occurred among Rhode Island nursing home and corrections personnel (n = 30) who were most frequently tested (mean 30.3 tests vs 4.6 for other Rhode Island and 2.3 for New York City participants). The adjusted hazard ratio (aHR) for reinfection in seropositive vs seronegative persons was 0.41 (95% confidence interval [CI], .20-.81). Exposure to a household member with coronavirus disease 2019 (COVID-19) before the serosurvey was also protective (aHR, 0.34; 95% CI, .13-.89). CONCLUSIONS: Reinfections were uncommon among previously infected persons over a 9-month period that preceded widespread variant circulation. Seropositivity decreased reinfection risk. Lower reinfection risk associated with exposure to a household member with COVID-19 may reflect subsequently reduced household transmission.

Effectiveness Associated With Vaccination After COVID-19 Recovery in Preventing Reinfection.

Importance: The benefit of vaccination for preventing reinfection among individuals who have been previously infected with SARS-CoV-2 is largely unknown. Objective: To obtain population-based estimates of the probability of SARS-CoV-2 reinfection and the effectiveness associated with vaccination after recovery from COVID-19. Design, Setting, and Participants: This cohort study used Rhode Island statewide surveillance data from March 1, 2020, to December 9, 2021, on COVID-19 vaccinations, laboratory-confirmed cases, hospitalizations, and fatalities to conduct a population-based, retrospective study during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. Participants included Rhode Island residents aged 12 years and older who were previously diagnosed with COVID-19 and unvaccinated at the time of first infection, stratified into 3 subpopulations: long-term congregate care (LTCC) residents, LTCC employees, and the general population (ie, individuals not associated with congregate settings). Data were analyzed from October 2021 to January 2022. Exposures: Completion of the primary vaccination series, defined as 14 days after the second dose of an mRNA vaccine or 1 dose of vector virus vaccine. Main Outcomes and Measures: The main outcome was SARS-CoV-2 reinfection, defined as a laboratory-confirmed positive result on a polymerase chain reaction (PCR) or antigen test at least 90 days after the first laboratory-confirmed positive result on a PCR or antigen test. Results: Overall, 3124 LTCC residents (median [IQR] age, 81 [71-89]; 1675 [53.6%] females), 2877 LTCC employees (median [IQR] age, 41 [30-53]; 2186 [76.0%] females), and 94 516 members of the general population (median [IQR] age, 35 [24-52] years; 45 030 [47.6%] females) met eligibility criteria. Probability of reinfection at 9 months for those who remained unvaccinated after recovery from prior COVID-19 was 13.0% (95% CI, 12.0%-14.0%) among LTCC residents, 10.0% (95% CI, 8.8%-11.5%) among LTCC employees, and 1.9% (95% CI, 1.8%-2.0%) among the general population. Completion of the primary vaccination series after infection was associated with 49% (95% CI, 27%-65%) protection among LTCC residents, 47% (95% CI, 19%-65%) protection among LTCC employees, and 62% (95% CI, 56%-68%) protection in the general population against reinfection, adjusting for potential sociodemographic and clinical confounders and temporal variation in infection rates. Conclusions and Relevance: These findings suggest that risk of SARS-CoV-2 reinfection after recovery from COVID-19 was relatively high among individuals who remained unvaccinated. Vaccination after recovery from COVID-19 was associated with reducing risk of reinfection by approximately half.

Projected Effects of Disruptions to Human Immunodeficiency Virus (HIV) Prevention Services During the Coronavirus Disease 2019 Pandemic Among Black/African American Men Who Have Sex With Men in an Ending the HIV Epidemic Priority Jurisdiction.

Background: Disruptions in access to in-person human immunodeficiency virus (HIV) preventive care during the coronavirus disease 2019 (COVID-19) pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. Methods: We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men in Mississippi over 5 years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new pre-exposure prophylaxis (PrEP) starts, and HIV incidence. Results: We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. Conclusions: Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately after the disruption period.

Projected Effects of Disruptions to HIV Prevention Services During the COVID-19 Pandemic Among Black/African American Men Who Have Sex with Men in an Ending the HIV Epidemic Priority Jurisdiction

Disruptions in access to in-person HIV preventive care during the COVID-19 pandemic may have a negative impact on our progress towards the Ending the HIV Epidemic goals in the United States. We used an agent-based model to simulate HIV transmission among Black/African American men who have sex with men (MSM) in Mississippi over five years to estimate how different reductions in access affected the number of undiagnosed HIV cases, new PrEP starts, and HIV incidence. We found that each additional 25% decrease in HIV testing and PrEP initiation was associated with decrease of 20% in the number of cases diagnosed and 23% in the number of new PrEP starts, leading to a 15% increase in HIV incidence from 2020 to 2022. Unmet need for HIV testing and PrEP prescriptions during the COVID-19 pandemic may temporarily increase HIV incidence in the years immediately following the disruption period.

Statewide evaluation of COVID-19 vaccine hesitancy in Rhode Island.

BACKGROUND: Vaccines are effective in preventing Coronavirus Disease 2019 (COVID-19). Vaccine hesitancy defined as delay of acceptance or refusal of the vaccine is a major barrier to effective implementation. METHODS: Participants were recruited statewide through an English and Spanish social media marketing campaign conducted by a local news station during a one-month period as vaccines were becoming available in Rhode Island (from December 21, 2020 to January 22, 2021). Participants completed an online survey about COVID-19 vaccines and vaccine hesitancy with constructs and items adopted from the Health Belief Model. RESULTS: A total of 2,007 individuals completed the survey. Eight percent (n = 161) reported vaccine hesitancy. The sample had a median age of 58 years (interquartile range [IQR]: 45, 67), were majority female (78%), White (96%), Non-Hispanic (94%), employed (58%), and reported an annual individual income of $50,000 (59%). COVID-19 vaccine hesitancy was associated with attitudes and behaviors related to COVID-19. A one unit increase in concern about COVID-19 was associated with a 69% (Adjusted Odds Ratio: 0.31, 95% CI: 0.26-0.37) decrease in vaccine hesitancy. A one-level increase in the likelihood of getting influenza vaccine was associated with a 55% (AOR: 0.45 95% CI: 0.41-0.50) decrease in vaccine hesitancy. CONCLUSIONS: COVID-19 vaccine hesitancy was relatively low in a state-wide survey in Rhode Island. Future research is needed to better understand and tailor messaging related to vaccine hesitancy.

How Comorbidities Affect Hospitalization from Influenza in the Pediatric Population.

Influenza is a contagious respiratory illness and can lead to hospitalization and even death. Understanding how comorbidities affect the severity of influenza can help clinical management. The aim of this study is to offer more information about comorbidities that might be associated with the severity of influenza in children. We used a statewide network in Rhode Island, USA, to extract data for laboratory-confirmed influenza cases among children 19 years old or younger. We identified 1169 lab-confirmed influenza cases. The most common comorbidities were asthma (17.1%), neurodevelopmental disorders (10.3%), gastrointestinal disorders (7.6%), atopic dermatitis (7%), and endocrine and metabolic diseases (6.8%). Interestingly, 80.8% (63 out of 78) of children who had an influenza-related hospital admission had at least one comorbidity, and among hospitalized children with influenza, the most common comorbidities were neurological diseases (28.2%, 22/78), gastrointestinal disorders (25.6%, 20/78), endocrine and metabolic diseases (24.4%, 19/78), and neurodevelopmental disorders (23.1%, 18/78). Children with endocrine or metabolic diseases were 8.23 times more likely to be admitted to the hospital, and children with neurological disorders were 6.35 times more likely to be admitted (OR: 8.23, 95% CI: 4.42-15.32 and OR: 6.35, 95% CI: 3.60-11.24, respectively). In summary, we identified specific comorbidities associated with influenza hospitalization and length of hospital stay, and these groups should be prioritized for public health interventions.

Statewide Evaluation of SARS-CoV-2 Diagnoses and Sexual Orientation and Gender Identity.

OBJECTIVE: Understanding and identifying disparities in COVID-19 testing outcomes can help allocate resources to where they are most needed. The objective of this study was to estimate the association between lesbian, gay, bisexual, transgender, and queer (LGBTQ+) identity and SARS-CoV-2 test positivity. METHODS: Data were from the Rhode Island SARS-CoV-2 surveillance database and included tests scheduled from June 8, 2020, through January 15, 2021. We used multivariable generalized estimating equations accounting for repeat testing to estimate the odds of receiving a positive test result for SARS-CoV-2 by LGBTQ+ identity and race/ethnicity, adjusting for sociodemographic and temporal confounders. RESULTS: In multivariable analysis of 232 025 tests, LGBTQ+ people had lower odds of receiving a positive test result than cisgender heterosexual people (5.4% vs 8.7%; adjusted odds ratio [aOR] = 0.63; 95% CI, 0.59-0.68). Compared with cisgender heterosexual White people, LGBTQ+ White people were significantly less likely (aOR = 0.67; 95% CI, 0.61-0.73) and cisgender heterosexual people of color were significantly more likely (aOR = 1.71; 95% CI, 1.64-1.78) to receive a positive test result. LGBTQ+ people of color had similar test positivity (aOR = 0.90; 95% CI, 0.79-1.02) as cisgender heterosexual White people. People in sexual minority groups were significantly less likely than heterosexual people to receive a positive test result, but we found no significant differences in test results among cisgender, transgender, and gender nonconforming people. CONCLUSIONS: LGBTQ+ people may be less likely than heterosexual people to receive a positive test result for SARS-CoV-2, potentially related to protective health practices and greater social isolation. Addressing racial and ethnic disparities among both LGBTQ+ people and cisgender heterosexual people should be a priority of the public health workforce.

Impact of the COVID-19 pandemic on HIV testing rates across four geographically diverse urban centres in the United States: An observational study.

BACKGROUND: Non-emergent clinical services were limited or suspended during the early stages of the coronavirus disease 2019 (COVID-19) pandemic in the United States (U.S.). This could adversely impact epidemics of public health importance, such as HIV, and access to testing, which is a cornerstone of prevention efforts. METHODS: In this observational study, we collected HIV testing and positivity rate clinical data from four geographically diverse U.S. healthcare systems in New Orleans, Louisiana; Minneapolis, Minnesota; Providence, Rhode Island; and, Seattle, Washington. Data from 2019 to 2020 were examined to assess changes in HIV testing in community-based, emergency department, and outpatient settings. Poisson regression was used to explore trends in HIV testing through phases of the COVID-19 pandemic. FINDINGS: In outpatient settings, there was a 68-97% reduction in the number of HIV tests per week during each state's stay-at-home order period, compared to during the pre-stay-at-home order period in early 2020. HIV testing remained reduced 11-54% after states transitioned to advisory phases. The HIV positivity rate increased slightly at outpatient settings, except in New Orleans where it fell. INTERPRETATION: We found a concerning trend of substantially decreased HIV testing across four geographically diverse sites. These findings suggest that new HIV infections within the U.S. may be undiagnosed and not yet linked to clinical care and services, as a consequence of the COVID-19 pandemic. Thus, augmented efforts to identify patients and link them to HIV services will be needed as healthcare settings return to full operation. FUNDING: U.S. National Institute of Mental Health.

Evaluation of the Treatment Efficacy and Safety of Remdesivir for COVID-19: a Meta-analysis.

Remdesivir is one of few FDA-approved treatments for severe cases of Coronavirus Disease 2019 (COVID-19). To better assess its efficacy and safety, we conducted a meta-analysis to systematically identify and synthesize existing findings. We conducted a comprehensive literature search among six electronic databases and unpublished studies. Random-effects meta-analyses were performed to summarize the risk ratio (RR) and rate estimates from eligible studies. Funnel plots, the Egger test, and the trim and fill analysis were used to detect publication bias. Thirteen eligible studies were included in this meta-analysis, giving a pooled sample size of 10,002 COVID-19 hospitalized patients (5068 administered remdesivir; 4934 control). Among patients on remdesivir, we synthesized mortality (15%, 95% confidence interval [CI]: 9%, 22%), clinical improvement (64%, 95% CI: 51%, 78%), recovery (70%, 95% CI: 57%, 83%), hospital discharge (74%, 95% CI: 60%, 87%), serious adverse effect (SAE) (21%, 95% CI:13%, 29%), and Grade 3 or 4 adverse effect (AE) (30%, 95% CI: 12%, 48%). Patients on remdesivir were 17% (RR: 0.83, 95% CI: 0.65, 1.06) less likely to die than those within the control group. Additionally, remdesivir had favorable outcomes in terms of clinical improvement, recovery, and hospital discharge. Lastly, non-mechanically ventilated patients had better overall clinical outcomes than mechanically ventilated patients. Remdesivir shows a moderate-favorable treatment efficacy among hospitalized COVID-19 patients with disproportionate impact among non-mechanically ventilated patients; however, a substantial proportion of COVID-19 patients may suffer from SAE or Grade 3 or 4 AE during the treatment course. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-021-01014-y.

Duration of Viral Nucleic Acid Shedding and Early Reinfection With Severe Respiratory Syndrome Coronavirus 2 in Healthcare Workers and First Responders.

We estimated the distributions of duration of SARS-CoV-2 nucleic acid shedding and time to reinfection among 137 persons with at least 2 positive nucleic acid amplification test (NAAT) results from March to September 2020. We analyzed gaps of varying length between subsequent positive and negative NAAT results and estimated a mean duration of nucleic acid shedding of 30.1 days (95% confidence interval [CI], 26.3-34.5). Mean time to reinfection was 89.1 days (95% CI, 75.3-103.5). Together, these indicate that a 90-day period between positive NAAT results can reliably define reinfection in immunocompetent persons although reinfection can occur at shorter intervals.

Low Seroprevalence of SARS-CoV-2 in Rhode Island blood donors during may 2020 as determined using multiple serological assay formats.

BACKGROUND: Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. METHODS: We measured the percentage of severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). To estimate seroprevalence, we utilized the Bayesian statistical method to adjust for sensitivity and specificity of the commercial tests used. RESULTS: We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April-May of 2020. Daily new case rates peaked in RI in late April 2020. We found HTSAs and LFAs were positively correlated with ELISA assays to detect antibodies specific to SARS-CoV-2 in blood donors. CONCLUSIONS: These data imply that seroconversion, and thus infection, is likely not widespread within this population. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.