Diagnostic performance of multiplex lateral flow tests in ambulatory patients with acute respiratory illness.

We assessed the performance of three different multiplex lateral flow assays manufactured by SureScreen, Microprofit and Goldsite which provide results for influenza, respiratory syncytial virus (RSV) and SARS-CoV-2. Between 4 April and 20 October 2023, 1646 patients 6 months and older presenting to an outpatient department of a hospital in Hong Kong with ≥2 symptoms or signs of an acute respiratory illness were enrolled. The point estimates for all three multiplex tests had sensitivity >80% for influenza A and SARS-CoV-2 compared to PCR, and the tests manufactured by Microprofit and Goldsite had sensitivity >84% to detect RSV. Specificity was >97% for all three tests except for the SureScreen test which had specificity 86.2% (95% CI: 83.9% to 88.3%) for influenza A. Sensitivity was lower than reported by the manufacturers, resulting in a higher risk of false negatives. The three multiplex tests performed better in patients with high viral loads.

Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong.

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (Re) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.

Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals.

Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification. Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.

Within-host diversity of SARS-CoV-2 lineages and effect of vaccination.

Viral and host factors can shape SARS-CoV-2 within-host viral diversity and virus evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here we analysed deep sequencing data from 2,146 SARS-CoV-2 samples with different viral lineages to describe the patterns of within-host diversity in different conditions, including vaccine-breakthrough infections. Variant of Concern (VOC) Alpha, Delta, and Omicron samples were found to have higher within-host nucleotide diversity while being under weaker purifying selection at full genome level compared to non-VOC SARS-CoV-2 viruses. Breakthrough Delta and Omicron infections in Comirnaty and CoronaVac vaccinated individuals appeared to have higher within-host purifying selection at the full-genome and/or Spike gene levels. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 evolution. Our findings suggest that vaccination does not increase SARS-CoV-2 protein sequence space and may not facilitate emergence of more viral variants.

Natural Reassortment of Eurasian Avian-Like Swine H1N1 and Avian H9N2 Influenza Viruses in Pigs, China.

Several zoonotic influenza A viruses detected in humans contain genes derived from avian H9N2 subtypes. We uncovered a Eurasian avian-like H1N1 swine influenza virus with polymerase basic 1 and matrix gene segments derived from the H9N2 subtype, suggesting that H9N2 viruses are infecting pigs and reassorting with swine influenza viruses in China.

Recombinant BA.1/BA.2 SARS-CoV-2 Virus in Arriving Travelers, Hong Kong, February 2022.

We studied SARS-CoV-2 genomes from travelers arriving in Hong Kong during November 2021-February 2022. In addition to Omicron and Delta variants, we detected a BA.1/BA.2 recombinant with a breakpoint near the 5' end of the spike gene in 2 epidemiologically linked case-patients. Continued surveillance for SARS-CoV-2 recombinants is needed.

Genomic epidemiology of SARS-CoV-2 under an elimination strategy in Hong Kong.

Hong Kong employed a strategy of intermittent public health and social measures alongside increasingly stringent travel regulations to eliminate domestic SARS-CoV-2 transmission. By analyzing 1899 genome sequences (>18% of confirmed cases) from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases. Community outbreaks were caused by novel introductions rather than a resurgence of circulating strains. Thus, local outbreak prevention requires strong border control and community surveillance, especially during periods of less stringent social restriction. Non-adherence to prolonged preventative measures may explain sustained local transmission observed during wave four in late 2020 and early 2021. We also found that, due to a tight transmission bottleneck, transmission of low-frequency single nucleotide variants between hosts is rare.

Probable Transmission of SARS-CoV-2 Omicron Variant in Quarantine Hotel, Hong Kong, China, November 2021.

We report detection of severe acute respiratory syndrome coronavirus 2 Omicron variant (B.1.1.529) in an asymptomatic, fully vaccinated traveler in a quarantine hotel in Hong Kong, China. The Omicron variant was also detected in a fully vaccinated traveler staying in a room across the corridor from the index patient, suggesting transmission despite strict quarantine precautions.

Monitoring International Travelers Arriving in Hong Kong for Genomic Surveillance of SARS-CoV-2.

We sequenced ≈50% of coronavirus disease cases imported to Hong Kong during March-July 2021 and identified 70 cases caused by Delta variants of severe acute respiratory syndrome coronavirus 2. The genomic diversity detected in Hong Kong was similar to global diversity, suggesting travel hubs can play a substantial role in surveillance.

Air travel-related outbreak of multiple SARS-CoV-2 variants.

BACKGROUND: A large cluster of 59 cases were linked to a single flight with 146 passengers from New Delhi to Hong Kong in April 2021. This outbreak coincided with early reports of exponential pandemic growth in New Delhi, which reached a peak of > 400 000 newly confirmed cases on 7 May 2021. METHODS: Epidemiological information including date of symptom onset, date of positive-sample detection and travel and contact history for individual cases from this flight were collected. Whole genome sequencing was performed, and sequences were classified based on the dynamic Pango nomenclature system. Maximum-likelihood phylogenetic analysis compared sequences from this flight alongside other cases imported from India to Hong Kong on 26 flights between June 2020 and April 2021, as well as sequences from India or associated with India-related travel from February to April 2021 and 1217 reference sequences. RESULTS: Sequence analysis identified six lineages of SARS-CoV-2 belonging to two variants of concern (Alpha and Delta) and one variant of public health interest (Kappa) involved in this outbreak. Phylogenetic analysis confirmed at least three independent sub-lineages of Alpha with limited onward transmission, a superspreading event comprising 37 cases of Kappa and transmission of Delta to only one passenger. Additional analysis of another 26 flights from India to Hong Kong confirmed widespread circulation of all three variants in India since early March 2021. CONCLUSIONS: The broad spectrum of disease severity and long incubation period of SARS-CoV-2 pose a challenge for surveillance and control. As illustrated by this particular outbreak, opportunistic infections of SARS-CoV-2 can occur irrespective of variant lineage, and requiring a nucleic acid test within 72 hours of departure may be insufficient to prevent importation or in-flight transmission.

Genetic Diversity of SARS-CoV-2 among Travelers Arriving in Hong Kong.

We sequenced 10% of imported severe acute respiratory syndrome coronavirus 2 infections detected in travelers to Hong Kong and revealed the genomic diversity of regions of origin, including lineages not previously reported from those countries. Our results suggest that international or regional travel hubs might be useful surveillance sites to monitor sequence diversity.

SARS-CoV-2 under an elimination strategy in Hong Kong.

Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity. ONE SENTENCE SUMMARY: Out of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.

SARS-CoV-2 Superspread in Fitness Center, Hong Kong, China, March 2021.

To investigate a superspreading event at a fitness center in Hong Kong, China, we used genomic sequencing to analyze 102 reverse transcription PCR-confirmed cases of severe acute respiratory syndrome coronavirus 2 infection. Our finding highlights the risk for virus transmission in confined spaces with poor ventilation and limited public health interventions.

Introduction of ORF3a-Q57H SARS-CoV-2 Variant Causing Fourth Epidemic Wave of COVID-19, Hong Kong, China.

We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing truncation of ORF3b. This virus evades induction of cytokine, chemokine, and interferon-stimulated gene expression in primary human respiratory cells.

Diagnostic accuracy of lung ultrasound for SARS-CoV-2: a retrospective cohort study.

BACKGROUND: As medical infrastructures are strained by SARS-CoV-2, rapid and accurate screening tools are essential. In portions of the world, reverse transcription polymerase chain reaction (RT-PCR) testing remains slow and in limited supply, and computed tomography is expensive, inefficient, and involves exposure to ionizing radiation. Multiple studies evaluating the efficiency of lung point-of-care ultrasound (POCUS) have been published recently, but include relatively small cohorts and often focus on characteristics associated with severe illness rather than screening efficacy. This study utilizes a retrospective cohort to evaluate the test characteristics (sensitivity, specificity, likelihood ratios, predictive values) of lung POCUS in the diagnosis of SARS-CoV-2, and to determine lung score cutoffs that maximize performance for use as a screening tool. RESULTS: Lung POCUS examinations had sensitivity 86%, specificity 71.6%, NPV 81.7%, and PPV 77.7%. The Lung Ultrasound Score had an area under the curve of 0.84 (95% CI 0.78, 0.90). When including only complete examinations visualizing 12 lung fields, lung POCUS had sensitivity 90.9% and specificity 75.6%, with NPV 87.2% and PPV 82.0% and an area under the curve of 0.89 (95% CI 0.83, 0.96). Lung POCUS was less accurate in patients with a history of interstitial lung disease, severe emphysema, and heart failure. CONCLUSIONS: When applied in the appropriate patient population, lung POCUS is an inexpensive and reliable tool for rapid screening and diagnosis of SARS-CoV-2 in symptomatic patients with influenza-like illness. Adoption of lung POCUS screening for SARS-CoV-2 may identify patients who do not require additional testing and reduce the need for RT-PCR testing in resource-limited environments and during surge periods.

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy.

BACKGROUND: An elevated gamma gap (>4 g/dL), the difference between serum total protein and albumin, can trigger testing for chronic infections or monoclonal gammopathy, despite a lack of evidence supporting this clinical threshold. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2014, gamma gap was derived in three subpopulations based on availability of testing for human immunodeficiency virus (HIV; N = 25,680), hepatitis C (HCV; N = 45,134), and monoclonal gammopathy of unknown significance (MGUS; N = 6,118). Disease status was confirmed by HIV antibody and Western blot, HCV RNA test, or electrophoresis with immunofixation. Sensitivity, specificity, and likelihood ratios were calculated for different gamma gap thresholds. Area under the curve (AUC) was used to assess performance and cubic splines were used to characterize the relationship between the gamma gap and each disease. RESULTS: Mean gamma gaps of participants with HIV, HCV, or MGUS ranged from 3.4-3.8 g/dL. The AUC was 0.80 (95%CI: 0.75,0.85) for HIV, 0.74 (0.72,0.76) for HCV, and 0.64 (0.60,0.69) for MGUS. An elevated gamma gap of over 4 g/dL corresponded to sensitivities of 39.3%, 19.0%, and 15.4% and specificities of 98.4%, 97.8%, and 95.4% for HIV, HCV, and MGUS, respectively. A higher prevalence of all three diseases was observed at both low and high gamma gaps. DISCUSSION: An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.

Point-of-Care Ultrasound for Hospitalists: A Position Statement of the Society of Hospital Medicine.

Many hospitalists incorporate point-of-care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision-making processes surrounding POCUS program management.

Benefits to patients choosing preoperative weight loss in gastric bypass surgery: new results of a randomized trial.

BACKGROUND: Historically, preoperative weight loss has been encouraged for patients undergoing gastric bypass surgery to decrease liver mass, technically facilitating the procedure. In an earlier prospective randomized trial investigating effects of preoperative weight loss on patients' clinical outcomes, we reported no differences in postoperative complications or weight-loss profiles at 6-month followup. This article demonstrates results of the same study, with 1-year followup. STUDY DESIGN: One hundred consecutive patients in an 18-month period preparing to undergo gastric bypass surgery at Stanford University Medical Center were selected. Fifty patients were randomly assigned to lose 10% or more of their excess body weight preoperatively, and 50 patients were assigned to no preoperative weight-loss requirements. After 1 year, patient demographics and data on postoperative complications, cure or improvement of comorbidities, and differences in weight-loss profiles were collected. RESULTS: At 1 year, the 2 groups had similar preoperative demographics and body mass indexes (BMIs). Patients in the weight-loss group, on average, lost 8.2% of their excess body weight preoperatively compared with the nonweight-loss group, which gained 1.1% (p = 0.007). After a year, the patients in both arms of the study showed no difference in weight, BMI, excess weight-loss, and number of remaining comorbidites. But when patients were divided according to those who had lost at least 5% of their excess body weight preoperatively, the 1-year results for excess weight-loss, weight, and BMI were much lower for the weight-loss group. CONCLUSIONS: Preoperative weight loss in patients undergoing gastric bypass surgery is safe and feasible. It should be encouraged, because it will markedly improve longterm weight loss.