From pandemic to endemic: Divergence of COVID-19 positive-tests and hospitalization numbers from SARS-CoV-2 RNA levels in wastewater of Rochester, Minnesota.

Traditionally, public health surveillance relied on individual-level data but recently wastewater-based epidemiology (WBE) for the detection of infectious diseases including COVID-19 became a valuable tool in the public health arsenal. Here, we use WBE to follow the course of the COVID-19 pandemic in Rochester, Minnesota (population 121,395 at the 2020 census), from February 2021 to December 2022. We monitored the impact of SARS-CoV-2 infections on public health by comparing three sets of data: quantitative measurements of viral RNA in wastewater as an unbiased reporter of virus level in the community, positive results of viral RNA or antigen tests from nasal swabs reflecting community reporting, and hospitalization data. From February 2021 to August 2022 viral RNA levels in wastewater were closely correlated with the oscillating course of COVID-19 case and hospitalization numbers. However, from September 2022 cases remained low and hospitalization numbers dropped, whereas viral RNA levels in wastewater continued to oscillate. The low reported cases may reflect virulence reduction combined with abated inclination to report, and the divergence of virus levels in wastewater from reported cases may reflect COVID-19 shifting from pandemic to endemic. WBE, which also detects asymptomatic infections, can provide an early warning of impending cases, and offers crucial insights during pandemic waves and in the transition to the endemic phase.

Hybrid Immunity Provides Protective Advantage Over Vaccination or Prior Remote Coronavirus Disease 2019 Alone.

Background: The protective efficacy of prior coronavirus disease 2019 (COVID-19) with or without vaccination remains unknown. This study sought to understand if 2 or more messenger RNA (mRNA) vaccine doses provide additional protection in patients with prior infection, or if infection alone provides comparable protection. Methods: We conducted a retrospective cohort study of the risk of COVID-19 from 16 December 2020 through 15 March 2022, among vaccinated and unvaccinated patients of all ages with and without prior infection. A Simon-Makuch hazard plot illustrated the incidence of COVID-19 between groups. Multivariable Cox proportional hazards regression was used to examine the association of demographics, prior infection, and vaccination status with new infection. Results: Among 101 941 individuals with at least 1 COVID-19 polymerase chain reaction test prior to 15 March 2022, 72 361 (71.0%) received mRNA vaccination and 5957 (5.8%) were previously infected. The cumulative incidence of COVID-19 was substantially higher throughout the study period for those previously uninfected and unvaccinated, and lowest for those previously infected and vaccinated. After accounting for age, sex, and the interaction between vaccination and prior infection, a reduction in reinfection risk was noted during the Omicron and pre-Omicron phases of 26% (95% confidence interval [CI], 8%-41%; P = .0065) to 36% (95% CI, 10%-54%; P = .0108), respectively, among previously infected and vaccinated individuals, compared to previously infected subjects without vaccination. Conclusions: Vaccination was associated with lower risk of COVID-19, including in those with prior infection. Vaccination should be encouraged for all including those with prior infection, especially as new variants emerge and variant-specific booster vaccines become available.

Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis.

Background: Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Results: Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15-0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48-3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Conclusions: Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.

Incidence of Respiratory Syncytial Virus Infection in Older Adults Before and During the COVID-19 Pandemic.

Importance: Little is known about the burden and outcomes of respiratory syncytial virus (RSV)-positive acute respiratory infection (ARI) in community-dwelling older adults. Objective: To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants: This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure: RSV-positive and -negative ARI. Main Outcomes and Measures: RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results: In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, -16.7 [95% CI, -31.8 to -1.8]; fatigue, -8.4 [95% CI, -14.3 to -2.4]; and difficulty in social functioning, -11.9 [95% CI, -19.8 to -4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: -4.0 [95% CI, -8.5 to -1.3]; difficulty in social functioning, -5.8 [95% CI, -10.3 to -1.3]; and limitation due to emotional problem, -7.0 [95% CI, -12.7 to -1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, -4.4 [95% CI, -7.3 to -1.5]; difficulty in social functioning, -5.2 [95% CI, -8.7 to -1.7] and limitation due to emotional problem, -5.7 [95% CI, -10.7 to -0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance: In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Impact of a change in universal gloving protocol on rates of central line-related bloodstream infection, Clostridioides difficile, and vancomycin-resistant Enterococcus.

In this retrospective cohort of adult hematology-oncology and transplant patients, discontinuation of universal gloving did not result in significant changes in rates of central line-associated bloodstream infection, Clostridioides difficile infection, or vancomycin-resistant Enterococcus colonization. Active surveillance and subsequent isolation may be a viable alternative strategy to universal precautions.

Rates of Asymptomatic COVID-19 Infection and Associated Factors in Olmsted County, Minnesota, in the Prevaccination Era.

Objective: To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the prevaccination era. Patients and Methods: We screened first responders (n=191) and Olmsted County employees (n=564) for antibodies to SARS-CoV-2 from November 1, 2020 to February 28, 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all polymerase chain reaction (PCR)-confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, abstracted symptom information, estimated rates of asymptomatic infection and examined related factors. Results: Twenty (10.5%; 95% CI, 6.9%-15.6%) first responders and 38 (6.7%; 95% CI, 5.0%-9.1%) county employees had positive antibodies; an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4 of 20 (20%; 95% CI, 3.0%-37.0%) first responders and 10 of 39 (26%; 95% CI, 12.6%-40.0%) county employees were asymptomatic. Of 6020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385; 95% CI, 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age (0-18 years [odds ratio {OR}, 2.3; 95% CI, 1.7-3.1] and >65 years [OR, 1.40; 95% CI, 1.0-2.0] compared with ages 19-44 years), body mass index (overweight [OR, 0.58; 95% CI, 0.44-0.77] or obese [OR, 0.48; 95% CI, 0.57-0.62] compared with normal or underweight) and tests after November 20, 2020 ([OR, 1.35; 95% CI, 1.13-1.71] compared with prior dates). Conclusion: Asymptomatic rates in Olmsted County before COVID-19 vaccine rollout ranged from 6% to 25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection.

Monkeypox 2022: Gearing Up for Another Potential Public Health Crisis.

Monkeypox virus, a member of the Orthopoxvirus genus, was first identified as the etiology of monkeypox in 1970 in the Democratic Republic of Congo and remains endemic in regions of Central and West Africa. Following the most recent outbreak of monkeypox in multiple countries throughout Europe and North America, the infection has been declared a public health emergency by the Centers for Disease Control and Prevention. Within this report, we aim to provide clinicians with a focused overview of the epidemiology, clinical manifestation, diagnosis, and approaches to treat and prevent monkeypox infection amidst the global outbreak.

Clinical Characteristics and Outcomes of Patients With SARS-CoV-2 Reinfection.

Objective: To examine the clinical characteristics, risk of hospitalization, and mortality of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Patients and Methods: We retrospectively reviewed all patients with SARS-CoV-2 reinfection at all Mayo Clinic sites between May 23, 2020, and June 30, 2021 (the period before the emergence of the Delta variant in the United States). The reinfection was defined as a positive SARS-CoV-2 test more than or equal to 90 days after initial infection or 45-89 days after with symptomatic second episode. Vaccination status was classified as fully vaccinated, first dose, and unvaccinated. Comparative analysis of baseline characteristics and comorbidities was performed by hospitalization and vaccination status. The survival analysis of the hospitalized patients was performed using Cox proportional hazard regression. Results: Among the 554 patients reinfected with SARS-CoV-2, 59 (10.6%) were pediatric, and 495 (89.4%) were adults. The median age was 13.9 years (interquartile range, 8.5-16.5 years) for the pediatric and 50.2 years (interquartile range, 28.4-65.6 years) for the adult population. Among the adult patients, the majority were unvaccinated (83.4%, n=413), and the duration to reinfection from initial infection was the longest in the fully vaccinated group (P<.001). Forty-two (75%) out of 56 patients were seropositive within 7 days of reinfection. In hospitalized adult patients, Charlson Comorbidity Index was an independent risk factor for mortality (adjusted hazard ratio, 0.35; 95% CI, 0.19-0.51). Conclusion: In this study, most adult patients with SARS-CoV-2 reinfection were unvaccinated. Furthermore, the duration to reinfection was longest in fully vaccinated individuals. Seropositivity was common among adult patients.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Real-World Incidence of Breakthrough Coronavirus Disease 2019 Hospitalization After Vaccination vs Natural Infection in a Large, Local, Empaneled Primary Care Population Using Time-to-Event Analysis.

We followed 106 349 primary care patients for 22 385 3099 person-days across 21 calendar months and documented 69 breakthrough coronavirus disease 2019 (COVID-19) hospitalizations: 65/102,613 (0.06%) among those fully vaccinated, 3/11 047 (0.03%) among those previously infected, and 1/7,313 (0.01%) among those with both statuses. These data give providers real-world context regarding breakthrough COVID-19 hospitalization risk.

Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy.

Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.

Quantifying the Importance of COVID-19 Vaccination to Our Future Outlook.

Predictive models have played a critical role in local, national, and international response to the COVID-19 pandemic. In the United States, health care systems and governmental agencies have relied on several models, such as the Institute for Health Metrics and Evaluation, Youyang Gu (YYG), Massachusetts Institute of Technology, and Centers for Disease Control and Prevention ensemble, to predict short- and long-term trends in disease activity. The Mayo Clinic Bayesian SIR model, recently made publicly available, has informed Mayo Clinic practice leadership at all sites across the United States and has been shared with Minnesota governmental leadership to help inform critical decisions during the past year. One key to the accuracy of the Mayo Clinic model is its ability to adapt to the constantly changing dynamics of the pandemic and uncertainties of human behavior, such as changes in the rate of contact among the population over time and by geographic location and now new virus variants. The Mayo Clinic model can also be used to forecast COVID-19 trends in different hypothetical worlds in which no vaccine is available, vaccinations are no longer being accepted from this point forward, and 75% of the population is already vaccinated. Surveys indicate that half of American adults are hesitant to receive a COVID-19 vaccine, and lack of understanding of the benefits of vaccination is an important barrier to use. The focus of this paper is to illustrate the stark contrast between these 3 scenarios and to demonstrate, mathematically, the benefit of high vaccine uptake on the future course of the pandemic.

Prevalence of SARS-CoV-2 Antibodies in a Multistate Academic Medical Center.

OBJECTIVE: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel. METHODS: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research. RESULTS: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group. CONCLUSION: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.

Providing safe care for patients in the coronavirus disease 2019 (COVID-19) era: A case series evaluating risk for hospital-associated COVID-19.

OBJECTIVE: We evaluated the risk of patients contracting coronavirus disease 2019 (COVID-19) during their hospital stay to inform the safety of hospitalization for a non-COVID-19 indication during this pandemic. METHODS: A case series of adult patients hospitalized for 2 or more nights from May 15 to June 15, 2020 at large tertiary-care hospital in the midwestern United States was reviewed. All patients were screened at admission with the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test. Selected adult patients were also tested by IgG serology. After dismissal, patients with negative serology and PCR at admission were asked to undergo repeat serologic testing at 14-21 days after discharge. The primary outcome was healthcare-associated COVID-19 defined as a new positive SARS-CoV-2 PCR test on or after day 4 of hospital stay or within 7 days of hospital dismissal, or seroconversion in patients previously established as seronegative. RESULTS: Of the 2,068 eligible adult patients, 1,778 (86.0%) completed admission PCR testing, while 1,339 (64.7%) also completed admission serology testing. Of the 1,310 (97.8%) who were both PCR and seronegative, 445 (34.0%) repeated postdischarge serology testing. No healthcare-associated COVID-19 cases were detected during the study period. Of 1,310 eligible PCR and seronegative adults, no patients tested PCR positive during hospital admission (95% confidence interval [CI], 0.0%-0.3%). Of the 445 (34.0%) who completed postdischarge serology testing, no patients seroconverted (0.0%; 95% CI, 0.0%-0.9%). CONCLUSION: We found low likelihood of hospital-associated COVID-19 with strict adherence to universal masking, physical distancing, and hand hygiene along with limited visitors and screening of admissions with PCR.

Deployment of an Interdisciplinary Predictive Analytics Task Force to Inform Hospital Operational Decision-Making During the COVID-19 Pandemic.

In March 2020, our institution developed an interdisciplinary predictive analytics task force to provide coronavirus disease 2019 (COVID-19) hospital census forecasting to help clinical leaders understand the potential impacts on hospital operations. As the situation unfolded into a pandemic, our task force provided predictive insights through a structured set of visualizations and key messages that have helped the practice to anticipate and react to changing operational needs and opportunities. The framework shared here for the deployment of a COVID-19 predictive analytics task force could be adapted for effective implementation at other institutions to provide evidence-based messaging for operational decision-making. For hospitals without such a structure, immediate consideration may be warranted in light of the devastating COVID-19 third-wave which has arrived for winter 2020-2021.