Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden. METHODS: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens. RESULTS: Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59). CONCLUSIONS: The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

Effectiveness of BNT162b2 Vaccine for Preventing COVID-19-Related Hospitalizations: A Test-Negative Case-Control Study.

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021-January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.8%) were enrolled, and 1571 (64.5%) were included in the BNT162b2 analysis. The median age was 58 years (IQR, 44-68), 889 (56.6%) were female, 1034 (65.8%) were African American, 359 (22.9%) were White, 56 (3.6%) were Hispanic ethnicity, 645 (41.1%) were SARS-CoV-2-positive, 412 (26.2%) were vaccinated with a primary series, and 273 (17.4%) had received ≥1 booster of BNT162b2. The overall adjusted VE of the BNT162b2 primary series was 58.5% (95% CI 46.0, 68.1), while the adjusted VE of ≥1 booster was 78.9% (95% CI 70.0, 85.1). The adjusted overall VE of primary series for African American/Black individuals was 64.0% (95% CI 49.9, 74.1) and 82.7% (95% CI 71.9, 89.4) in those who received ≥1 booster. When analysis was limited to the period of Omicron predominance, overall VE of the primary series decreased with widened confidence intervals (24.5%, 95% CI -4.5, 45.4%), while VE of ≥1 booster was maintained at 60.9% (95% CI 42.0, 73.6). BNT162b2 primary series and booster vaccination provided protection against COVID-19-associated ARI hospitalization among a predominantly African American population.

Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

BACKGROUND: Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. METHODS: We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). RESULTS: Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). CONCLUSIONS: Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.

BK polyomavirus associated progressive multifocal leukoencephalopathy in a person living with HIV.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the white matter central nervous system occurring in immunocompromised patients particularly those with T cell deficiency such as in HIV, haematological and solid organ malignancies and those taking immunomodulatory medications. PML is caused by JC virus however in rare cases BK virus has been isolated in the cerebral spinal fluid of patients presenting with PML. In this case we describe a 49 year old man who presented to the emergency department with a 2 week history of progressive right sided weakness and dysarthria. His background history included HIV diagnosed in 2005, he had not engaged with care in the past 2 years and had not been taking anti-retroviral therapy (ART). Other past medical history included untreated hepatitis C. His CD4 count was 90 (11%) cells/mm3 on admission and his HIV viral load VL) was 141,000 copies/ml. Magnetic resonance imaging(MRI) showed a hypointense lesion on T1, hyperintense on T2 and FLAIR without diffusion restriction and without mass effect. A lumbar puncture was performed which confirmed JC virus was positive (PCR <50 copies/ml) and also revealed BK virus was positive (PCR 46,511 copies/ml). The patient was commenced on tenofovir alafenamide fumarate/emtricitabine/darunavir/cobicistat in combination with dolutegravir 50mg twice daily. On day 40 post commencement of ART the patient was readmitted with worsening of his right arm weakness and dysarthria. A repeat MRI was performed which showed the hyperdense lesion on T2 and FLAIR appeared slightly larger with some slight enhancement with gadolinium contrast but no other features suggesting PML immune reconstitution inflammatory syndrome (IRIS). The CD4 count had increased to 141(17%) and HIV VL had decreased to 85 copies/ml. A clinical diagnosis of PML IRIS was made and the patient was commenced on prednisolone 30mg BD which lead to an initial improvement in symptoms. Interestingly in this case, both JC virus and BK virus were detected in the CSF of this patient with the level of JC virus being too low to quantify. BK virus was not detectable on peripheral serum sampling suggesting that BK virus is replicating in the CNS independent of other body sites. There have been 5 case reports in the literature of BK virus as the cause of PML. Testing for BK virus should be considered in patients presenting with signs and symptoms of PML and encephalitis particularly when no other cause is found.