ABSTRACT
Background. The burden of Respiratory Syncytial Virus (RSV)-associated hospitalization in adults is incompletely understood. The COVID-19 pandemic has resulted in multiple public health measures (e.g., social distancing, handwashing, masking) to decrease SARS-CoV-2 transmission, which could impact RSV-associated hospitalizations. We sought to compare RSV-associated hospitalizations from 2 pre- and one mid-COVID-19 winter viral respiratory seasons. Methods. We conducted an IRB-approved prospective surveillance at two Atlanta-area hospitals during the winter respiratory viral seasons from Oct 2018-Apr 2021 for adults ≥ 50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region surrounding Atlanta, Georgia. Those with symptoms > 14 days were excluded. Standard of care test results were included. Asymptomatic adults ≥ 50 years of age were enrolled as controls in Seasons 1 and 2. Nasopharyngeal swabs from cases and controls were tested for RSV using BioFireR FilmArrayR Respiratory Viral Panel (RVP). We compared the demographic features and outcomes of RSV+ cases and controls. Results. RSV was detected in 71/2,728 (2.6%) hospitalized adults with ARI, CHF, or COPD and 4/466 (0.9%) controls. In Season 1, RSV occurred in 5.9% (35/596 patients), in Season 2 3.6% (35/970 patients), but in only 0.09% (1/1,162 patients) in Season 3 (P < 0.001 for both seasons). RSV detection in Season 3 was similar to RSV detection among controls during Seasons 1 and 2 (P=0.6). Median age of cases and controls was 67 years (Table 1). Of cases with RSV 11% were admitted to the ICU and two required mechanical ventilation. The majority of hospitalized patients were discharged home (95.8%) with a median length of hospitalization of three days (IQR 2-7). Conclusion. Over 3 seasons, RSV was detected in 2.6% of adults admitted to the hospital with ARI, CHF or COPD. The rate of RSV dramatically declined during the 2020-21 winter respiratory viral season, likely due to public health measures implemented in response to COVID-19.
ABSTRACT
Background. A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses. Methods. Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses. Results. Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization. Conclusion. COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden.
ABSTRACT
Background. Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods. From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eightcounty region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results. During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Conclusion. Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations.
ABSTRACT
Purpose/Objective(s): Low-dose radiotherapy (LD-RT) is a well-established treatment for multiple human inflammatory conditions. Whole-lung LD-RT may be effective in COVID-19-related pneumonia. Materials/Methods: Patients hospitalized with COVID-19-related pneumonia receiving supportive care, glucocorticosteroids, and/or remdesivir were administered LD-RT treatment of 0.5 or 1.5 Gy to the bilateral lungs on a prospective, combined phase I/II, multi-site, single-institution trial. Patients were followed for 28 days or until discharge and compared to controls blindly matched by age, comorbidity, duration of symptoms, and disease severity. Eligible patients were confirmed by SARS-CoV-2 positive PCR, unable to wean from oxygen at enrollment, and had radiographic consolidations. Patients were enrolled into 5 cohorts stratified by treatment variables and severity of illness: LD-RT alone vs. LD-RT with concurrent drug therapies, non-intubated vs. intubated status, and low (1.5 Gy) vs. lower (0.5 Gy) radiation dose. Qualitative aims were to establish safety and explore efficacy. Quantitative endpoints were continuous, categorical, and time-to-event, and included clinical recovery, intubation, radiographic changes, and biomarker responses. Intubation endpoints are reported for all cohorts using the log-rank test and Kaplan-Meier method. Results: Outcomes of 80 patients were available for analysis at study closure. In total, 40 of 70 planned patients (57% trial enrollment) received whole-lung LD-RT between April 24 and December 7, 2020 and were compared to 40 matched controls. Cohorts 1&2: Ten non-intubated patients received 1.5 Gy without concurrent COVID-directed drug therapies (10 of 10 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 40% in controls compared to 10% following LD-RT (P = 0.11). Cohort 3: One intubated patient received 1.5 Gy (1 of 20 planned, 5% cohort enrollment). Cohort 4: Twenty separate non-intubated patients received 1.5 Gy with concurrent dexamethasone/remdesivir (20 of 20 planned, 100% cohort enrollment) and were compared to matched controls. Intubation rates were 32% in controls compared to 14% following LD-RT (P = 0.09). Cohort 5: Nine patients received 0.5 Gy with concurrent drug therapies (9 of 20 planned, 45% cohort enrollment) and were compared to matched controls. Zero controls required intubation compared to 11% following LD-RT (P = 0.32). Among all non-intubated patients and matched controls combined (n = 78), mechanical ventilation was required in 28% of controls compared to 12% following LD-RT (reduced 57%, P = 0.05). The trial was prematurely closed due to observed reproducibility of efficacy. A randomized trial is now ongoing. Conclusion: In the first, prospective, phase I/II trial of radiotherapy for COVID-19-related pneumonia, a single treatment of whole-lung LD-RT reduced intubation rates by 57% compared to controls in patients receiving supportive care with or without drug therapies (P = 0.05).
ABSTRACT
Purpose : Coronavirus disease (COVID-19) has escalated to a global pandemic with increasing reports of ophthalmic disease. We report ophthalmic observations of hospitalized COVID-19 patients and correlate retinal disease findings with clinical and laboratory data. Methods : Retrospective review of COVID-19 patients who underwent ophthalmic exam during hospitalization within Emory Healthcare between April-July 2020. Results : Thirty-seven patients were examined with 23 (62%) females and a mean age of 54 years. 35 patients were admitted to the ICU. Ophthalmic manifestations included conjunctival injection in 12 eyes (17%), chemosis in 8 (11%) and retinopathy in 20 eyes (27%) with bilateral retinopathy in 6 patients (16%). No difference in baseline comorbidities or COVID-19 complication development was observed between patients with and without retinopathy. However, patients with retinopathy required ICU care for 1 week longer than those without retinopathy (27.6 vs 19.9 days p=0.19). The mean sequential organ failure assessment score at ICU admission was 6.18. All patients with retinopathy required both mechanical ventilation and vasopressors, while in patients without retinopathy, 15 (65%) and 12 (52%) required mechanical ventilation and vasopressors respectively (p=0.015, p=0.002). 6 patients with retinopathy required extracorporal membrane oxygenation compared to 1 without retinopathy (p=0.0070). While the mean peak D-Dimer was elevated at 18477, in the entire cohort, the peak D-Dimer was higher in patients with retinopathy (28,971 vs 12,575, p=0.0298). The fibrinogen nadir during hospitalization was on average 338 for the entire cohort, and reduced in patients with retinopathy (262 vs 381, p=0.029). Peak D-dimer analyses with a threshold of 16,508 showed an odds ratio of 16.7 (95% CI 3.11-89.3) for retinopathy. Fibrinogen nadir with a threshold of 367 showed odds ratio of 0.06 (95% CI 0.01-0.53) with 0.75 concordance. Conclusions : Retinopathy was the most common ophthalmic manifestation in a critically ill COVID-19 population, exceeding 25% of patients. Elevated D-dimers and a lower fibrinogen nadir in patients with retinopathy suggest a pathogenic relationship between coagulation pathways and retinal microangiopathy.
ABSTRACT
Vaccines are an essential component of pandemic preparedness but can be limited due to challenges in production and logistical implementation. While vaccine candidates were rapidly developed against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), immunization campaigns remain an obstacle to achieving herd immunity. Dissolvable microneedle patches are advantageous for many possible reasons: improved immunogenicity;dose-sparing effects;expected low manufacturing cost;elimination of sharps;reduction of vaccine wastage;no need for reconstitution;simplified supply chain, with reduction of cold chain supply through increased thermostability;ease of use, reducing the need for healthcare providers;and greater acceptability compared to traditional hypodermic injections. When applied to coronavirus disease 2019 (COVID-19) and future pandemic outbreaks, microneedle patches have great potential to improve vaccination globally and save many lives.
ABSTRACT
Background: Sensitive and specific SARS-CoV-2 antibody diagnostics are urgently needed to estimate the seroprevalence of SARS-CoV-2 infection in both the general population and special risk groups. Moreover, validated serologic assays are critical to understanding immunity to SARS-CoV-2 infection over time and identifying correlates of protection. Methods: An enzyme-linked immunosorbent assay (ELISA) protocol to detect antibodies (IgG) that bind the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was validated and ROC curve analysis performed by testing a large panel of pre-pandemic sera (n=162) and convalescent sera from RT-PCR-confirmed COVID-19 cases (n=60). We then applied this test in two cohorts: 1) Healthcare personnel (HCP) that were enrolled in a longitudinal surveillance cohort just after peak local transmission and 2) Mildly ill patients being tested for SARS-CoV-2 infection by RT-PCR from NP swabs in an ambulatory testing clinic. Results: ROC curve analysis yielded an AUC of 0.9953, with a sensitivity and specificity at 91.67% and 99.38% at the optimal OD normalization threshold of 0.20. In 240 HCP surveilled at enrollment, 5.83% had positive IgG results. Of 19 symptomatic patients who presented to the ambulatory clinic, 5/19 had a positive PCR. In convalescence (13-74 days post symptom onset), 3 of those 5 were positive for IgG. Conclusion: We demonstrated high sensitivity and specificity of the SARS-CoV-2 RBD ELISA. This simple assay is an efficient way to track seroconversion and duration of antibody responses to SARS-CoV-2 for different populations, particularly since RBD-binding antibodies have been shown to correlate with neutralization activity and may be useful to determine protective immunity following natural infection or vaccination. Ongoing work will assess variation in magnitude, character and duration of antibody responses in key populations and seek to maximize deployability of large-scale SARS-CoV-2 serology. (Table Presented).