Digital cough monitoring - A potential predictive acoustic biomarker of clinical outcomes in hospitalized COVID-19 patients.

PURPOSE: Recent developments in the field of artificial intelligence and acoustics have made it possible to objectively monitor cough in clinical and ambulatory settings. We hypothesized that time patterns of objectively measured cough in COVID-19 patients could predict clinical prognosis and help rapidly identify patients at high risk of intubation or death. METHODS: One hundred and twenty-three patients hospitalized with COVID-19 were enrolled at University of Florida Health Shands and the Centre Hospitalier de l'Université de Montréal. Patients' cough was continuously monitored digitally along with clinical severity of disease until hospital discharge, intubation, or death. The natural history of cough in hospitalized COVID-19 disease was described and logistic models fitted on cough time patterns were used to predict clinical outcomes. RESULTS: In both cohorts, higher early coughing rates were associated with more favorable clinical outcomes. The transitional cough rate, or maximum cough per hour rate predicting unfavorable outcomes, was 3·40 and the AUC for cough frequency as a predictor of unfavorable outcomes was 0·761. The initial 6 h (0·792) and 24 h (0·719) post-enrolment observation periods confirmed this association and showed similar predictive value. INTERPRETATION: Digital cough monitoring could be used as a prognosis biomarker to predict unfavorable clinical outcomes in COVID-19 disease. With early sampling periods showing good predictive value, this digital biomarker could be combined with clinical and paraclinical evaluation and is well adapted for triaging patients in overwhelmed or resources-limited health programs.

Persistence of SARS-CoV-2 omicron variant in children and utility of rapid antigen testing as an indicator of culturable virus (preprint)

We screened 65 longitudinally-collected nasal swab samples from 31 children aged 0-16 years who were positive for SARS-CoV-2 omicron BA.1. By day 7 after onset of symptoms 48% of children remained positive by rapid antigen test. In a sample subset we found 100% correlation between antigen test results and virus culture.

Severe Acute Respiratory Syndrome Coronavirus 2 Delta Vaccine Breakthrough Transmissibility in Alachua County, Florida.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. METHODS: Between October 2020 and July 2021, we sequenced 4439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral RNA burden and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals. RESULTS: The majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about 3 months (104 ±â€…57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, 3 of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad viral RNA copy number values during acute infection (interquartile range, 1.2-8.64 Log copies/mL), on average 38% lower than matched unvaccinated patients (3.29-10.81 Log copies/mL, P < .00001). Nevertheless, 49% to 50% of all breakthroughs, and 56% to 60% of Delta-infected breakthroughs exhibited viral RNA levels above the transmissibility threshold (4 Log copies/mL) irrespective of time after vaccination. CONCLUSIONS: Delta infection transmissibility and general viral RNA quantification patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should specifically address whether extra vaccine doses curb breakthrough contribution to epidemic spread.

Low-frequency variants in mildly symptomatic vaccine breakthrough infections presents a doubled-edged sword.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) has raised questions regarding vaccine protection against SARS-CoV-2 infection, transmission, and ongoing virus evolution. Twenty-three mildly symptomatic "vaccination breakthrough" infections were identified as early as January 2021 in Alachua County, Florida, among individuals fully vaccinated with either the BNT162b2 (Pfizer) or the Ad26 (Janssen/J&J) vaccines. SARS-CoV-2 genomes were successfully generated for 11 of the vaccine breakthroughs, and 878 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These 11 individuals were characterized by infection with VOCs, but also low-frequency variants present within the surrounding population. Low-frequency mutations were observed, which have been more recently identified as mutations of interest owing to their location within targeted immune epitopes (P812L) and association with increased replicative capacity (L18F). We present these results to posit the nature of the efficacy of vaccines in reducing symptoms as both a blessing and a curse-as vaccination becomes more widespread and self-motivated testing reduced owing to the absence of severe symptoms, we face the challenge of early recognition of novel mutations of potential concern. This case study highlights the critical need for continued testing and monitoring of infection and transmission among individuals regardless of vaccination status.

SARS-CoV-2 infections in infants in Haiti 2020-2021; evidence from a serological cohort (preprint)

Between February 2019 and March 2021, 388 dried blood spot samples were obtained from 257 children <30 months of age who were part of a longitudinal maternal/infant cohort in Haiti. Among the children followed, 16.7% became seropositive; sampling date was the only covariate associated with the hazard of seroconversion.

SARS-CoV-2 Delta vaccine breakthrough transmissibility in Alachua, Florida (preprint)

BackgroundSARS-CoV-2 Delta variant has caused a dramatic resurgence in infections in the United Sates, raising questions regarding potential transmissibility among vaccinated individuals. MethodsBetween October 2020 and July 2021, we sequenced 4,439 SARS-CoV-2 full genomes, 23% of all known infections in Alachua County, Florida, including 109 vaccine breakthrough cases. Univariate and multivariate regression analyses were conducted to evaluate associations between viral load (VL) level and patient characteristics. Contact tracing and phylogenetic analysis were used to investigate direct transmissions involving vaccinated individuals. ResultsThe majority of breakthrough sequences with lineage assignment were classified as Delta variants (74.6%) and occurred, on average, about three months (104 {+/-} 57.5 days) after full vaccination, at the same time (June-July 2021) of Delta variant exponential spread within the county. Six Delta variant transmission pairs between fully vaccinated individuals were identified through contact tracing, three of which were confirmed by phylogenetic analysis. Delta breakthroughs exhibited broad VL values during acute infection (IQR 1.2 - 8.64 Log copies/ml), on average 38% lower than matched unvaccinated patients (3.29 - 10.81 Log copies/ml, p<0.00001). Nevertheless, 49-50% of all breakthroughs, and 56-60% of Delta-infected breakthroughs exhibited VL above the transmissibility threshold (4 Log copies/ml) irrespective of time post vaccination. ConclusionsDelta infection transmissibility and general VL patterns in vaccinated individuals suggest limited levels of sterilizing immunity that need to be considered by public health policies. In particular, ongoing evaluation of vaccine boosters should address whether extra vaccine doses might curb breakthrough contribution to epidemic spread.

SARS-CoV-2 infection of BNT162b2(mRNA)-vaccinated individuals is not restricted to variants of concern or high-risk exposure environments (preprint)

The emergence of SARS-CoV-2 variants of concern (VOC) has raised questions regarding the extent of protection of currently implemented vaccines. Ten "vaccination breakthrough" infections were identified in Alachua County, Florida, among individuals fully vaccinated with the BNT162b2 mRNA vaccine as a result of social or household transmission. Eight individuals presented mild symptoms in the absence of infection with other common respiratory viruses, confirmed using viral genetic sequencing. SARS-CoV-2 genomes were successfully generated for five of the vaccine breakthroughs and 399 individuals in the surrounding area and were included for reference-based phylogenetic investigation. These five individuals were characterized by infection with both VOCs and low-frequency variants present within the surrounding population. Mutations in the Spike protein were consistent with their respective circulating lineages, with the exception of a viable, low-frequency (approximately 1%) B.1.1.7 mutation, which we describe as a mutation of potential concern. The findings indicate that in cases of limited vaccine protection, infection is not restricted to VOCs or high-risk settings, highlighting the critical need for continued testing and monitoring of infection among individuals regardless of vaccination status.

Emergence of porcine delta-coronavirus pathogenic infections among children in Haiti through independent zoonoses and convergent evolution (preprint)

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, coronavirus emergence in our species has been associated with zoonotic transmissions from animal reservoirs 1,2 , underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae – Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus , – human infections reported to date have been limited to alpha- and betacoronaviruses 3 . We identify, for the first time, porcine deltacoronavirus (PDCoV) strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the nsp15 and the spike glycoprotein genes by convergent evolution. In particular, structural analysis predicts that one of the changes in the Spike S1 subunit, which contains the receptor-binding domain, may affect protein’s flexibility and binding to the host cell receptor. Our findings not only underscore the ability of deltacoronaviruses to adapt and potentially lead to human-to-human transmission, but also raise questions about the role of such transmissions in development of pre-existing immunity to other coronaviruses, such as SARS-CoV-2.

Isolation of SARS-CoV-2 from the air in a car driven by a COVID patient with mild illness (preprint)

ABSTRACT We used a Sioutas personal cascade impactor sampler (PCIS) to screen for SARS-CoV-2 in a car driven by a COVID-19 patient. SARS-CoV-2 was detectable at all PCIS stages by PCR and was cultured from the section of the sampler collecting particles in the 0.25 to 0.50 □μm size range.

Earliest Detection to Date of SARS-CoV-2 in Florida: Identification Together With Influenza Virus on the Main Entry Door of a University Building, February 2020 (preprint)

BackgroundQuestions persist about patterns of initial dissemination of SARS-CoV-2 in the United States in early 2020.MethodsIn February and March, 2020, environmental surface swab samples were collected from the handle of the main entry door of a major university building in Florida, as part of a pilot surveillance project screening for influenza. Samples were taken at the end of regular classroom hours, between the dates of February 1-5 and February 19-March 4, 2020. ResultsInfluenza H1N1pdm09 was isolated from the door handle on four of the 19 days sampled.  Both SARS-CoV-2 and influenza virus were detected in the sample collected on February 21, 2020. Based on sequence analysis, the Florida SARS-CoV-2 strain (designated UF-11) was identical to strains being identified in Washington state during the same time period, while the earliest similar sequences were sampled in China/Hubei between Dec 30th 2019 and Jan 5th 2020. The first human case of COVID-19 was not officially reported in Florida until March 1st. In an analysis of sequences from COVID-19 patients in this region of Florida, there was only limited evidence of subsequent dissemination of the UF-11 strain.  Identical or highly similar strains, possibly related through a common transmission chain, were detected with increasing frequency in Washington state between end of February and beginning of March. ConclusionsOur data provide further documentation of the rapid early spread of SARS-CoV-2, and underscore the likelihood that closely related strains were cryptically circulating in multiple U.S. communities before the first “official” cases were recognized.

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients (preprint)

BackgroundThere currently is substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols. MethodsAir samples were collected in the room of two COVID-19 patients, one of whom had an active respiratory infection with a nasopharyngeal (NP) swab positive for SARS-CoV-2 by RT-qPCR. By using VIVAS air samplers that operate on a gentle water-vapor condensation principle, material was collected from room air and subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and of virus isolated in cell culture from air sampling and from a NP swab from a newly admitted patient in the room were sequenced. FindingsViable virus was isolated from air samples collected 2 to 4.8m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the NP swab from the patient with an active infection. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. InterpretationPatients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus. FundingPartly funded by Grant No. 2030844 from the National Science Foundation and by award 1R43ES030649 from the National Institute of Environmental Health Sciences of the National Institutes of Health, and by funds made available by the University of Florida Emerging Pathogens Institute and the Office of the Dean, University of Florida College of Medicine. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVarious studies report detection of SARS-CoV-2 in material collected by air samplers positioned in clinics and in some public spaces. For those studies, detection of SARS-CoV-2 has been by indirect means; instead of virus isolation, the presence of the virus in material collected by air samplers has been through RT-PCR detection of SARS-CoV-2 RNA. However, questions have been raised about the clinical significance of detection of SARS-CoV-2 RNA, particularly as airborne viruses are often inactivated by exposure to UV light, drying, and other environmental conditions, and inactivated SARS-CoV-2 cannot cause COVID-19. Added value of this studyOur virus isolation work provides direct evidence that SARS-CoV-2 in aerosols can be viable and thus pose a risk for transmission of the virus. Furthermore, we show a clear progression of virus-induced cytopathic effects in cell culture, and demonstrate that the recovered virus can be serially propagated. Moreover, we demonstrate an essential link: the viruses we isolated in material collected in four air sampling runs and the virus in a newly admitted symptomatic patient in the room were identical. These findings strengthen the notion that airborne transmission of viable SARS-CoV-2 is likely and plays a critical role in the spread of COVID-19. Implications of all the available evidenceScientific information on the mode of transmission should guide best practices Current best practices for limiting the spread of COVID-19. Transmission secondary to aerosols, without the need for an aerosol-generating procedure, especially in closed spaces and gatherings, has been epidemiologically linked to exposures and outbreaks. For aerosol-based transmission, measures such as physical distancing by 6 feet would not be helpful in an indoor setting and would provide a false-sense of security. With the current surges of cases, to help stem the COVID-19 pandemic, clear guidance on control measures against SARS-CoV-2 aerosols are needed.