COVID-19 subphenotypes at hospital admission are associated with mortality: a cross-sectional study.

BACKGROUND: We have an incomplete understanding of COVID-19 characteristics at hospital presentation and whether underlying subphenotypes are associated with clinical outcomes and therapeutic responses. METHODS: For this cross-sectional study, we extracted electronic health data from adults hospitalized between 1 March and 30 August 2020 with a PCR-confirmed diagnosis of COVID-19 at five New York City Hospitals. We obtained clinical and laboratory data from the first 24 h of the patient's hospitalization. Treatment with tocilizumab and convalescent plasma was assessed over hospitalization. The primary outcome was mortality; secondary outcomes included intubation, intensive care unit (ICU) admission and length of stay (LOS). First, we employed latent class analysis (LCA) to identify COVID-19 subphenotypes on admission without consideration of outcomes and assigned each patient to a subphenotype. We then performed robust Poisson regression to examine associations between COVID-19 subphenotype assignment and outcome. We explored whether the COVID-19 subphenotypes had a differential response to tocilizumab and convalescent plasma therapies. RESULTS: A total of 4620 patients were included. LCA identified six subphenotypes, which were distinct by level of inflammation, clinical and laboratory derangements and ranged from a hypoinflammatory subphenotype with the fewest derangements to a hyperinflammatory with multiorgan dysfunction subphenotypes. Multivariable regression analyses found differences in risk for mortality, intubation, ICU admission and LOS, as compared to the hypoinflammatory subphenotype. For example, in multivariable analyses the moderate inflammation with fever subphenotype had 3.29 times the risk of mortality (95% CI 2.05, 5.28), while the hyperinflammatory with multiorgan failure subphenotype had 17.87 times the risk of mortality (95% CI 11.56, 27.63), as compared to the hypoinflammatory subphenotype. Exploratory analyses suggested that subphenotypes may differential respond to convalescent plasma or tocilizumab therapy. CONCLUSION: COVID-19 subphenotype at hospital admission may predict risk for mortality, ICU admission and intubation and differential response to treatment.KEY MESSAGEThis cross-sectional study of COVID patients admitted to the Mount Sinai Health System, identified six distinct COVID subphenotypes on admission. Subphenotypes correlated with ICU admission, intubation, mortality and differential response to treatment.

Prenatal and Postnatal Household Air Pollution Exposure and Infant Growth Trajectories: Evidence from a Rural Ghanaian Pregnancy Cohort.

BACKGROUND: The exposure-response association between prenatal and postnatal household air pollution (HAP) and infant growth trajectories is unknown. OBJECTIVES: To evaluate associations between prenatal and postnatal HAP exposure and stove interventions on growth trajectories over the first year of life. METHODS: The Ghana Randomized Air Pollution and Health Study enrolled n=1,414 pregnant women at ≤24wk gestation from Kintampo, Ghana, and randomized them to liquefied petroleum gas (LPG), improved biomass, or open fire (control) stoves. We quantified HAP exposure by repeated, personal prenatal and postnatal carbon monoxide (CO) and, in a subset, fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] assessments. Length, weight, mid-upper arm circumference (MUAC) and head circumference (HC) were measured at birth, 3, 6, 9, and 12 months; weight-for-age, length-for-age (LAZ), and weight-for-length z (WLZ)-scores were calculated. For each anthropometric measure, we employed latent class growth analysis to generate growth trajectories over the first year of life and assigned each child to a trajectory group. We then employed ordinal logistic regression to determine associations between HAP exposures and growth trajectory assignments. Associations with stove intervention arm were also considered. RESULTS: Of the 1,306 live births, 1,144 had valid CO data and anthropometric variables measured at least once. Prenatal HAP exposure increased risk for lower length [CO odds ratio (OR)= 1.17, 95% CI: 1.01, 1.35 per 1-ppm increase; PM2.5 OR= 1.07, 95% CI: 1.02, 1.13 per 10-µg/m3 increase], lower LAZ z-score (CO OR= 1.15, 95% CI: 1.01, 1.32 per 1-ppm increase) and stunting (CO OR= 1.25, 95% CI: 1.08, 1.45) trajectories. Postnatal HAP exposure increased risk for smaller HC (CO OR= 1.09, 95% CI: 1.04, 1.13 per 1-ppm increase), smaller MUAC and lower WLZ-score (PM2.5 OR= 1.07, 95% CI: 1.00, 1.14 and OR= 1.09, 95% CI: 1.01, 1.19 per 10-µg/m3 increase, respectively) trajectories. Infants in the LPG arm had decreased odds of having smaller HC and MUAC trajectories as compared with those in the open fire stove arm (OR= 0.58, 95% CI: 0.37, 0.92 and OR= 0.45, 95% CI: 0.22, 0.90, respectively). DISCUSSION: Higher early life HAP exposure (during pregnancy and through the first year of life) was associated with poorer infant growth trajectories among children in rural Ghana. A cleaner-burning stove intervention may have improved some growth trajectories. https://doi.org/10.1289/EHP8109.

Infant Nasopharyngeal Microbiota Subphenotypes and Early Childhood Lung Function: Evidence from a Rural Ghanaian Pregnancy Cohort.

Early life respiratory microbiota may increase risk for future pulmonary disease. Associations between respiratory microbiota and lung health in children from low- and middle-income countries are not well-described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) prospective pregnancy cohort in Kintampo, Ghana, we collected nasopharyngeal swabs in 112 asymptomatic children aged median 4.3 months (interquartile range (IQR) 2.9, 7.1) and analyzed 22 common bacterial and viral pathogens with MassTag polymerase chain reaction (PCR). We prospectively followed the cohort and measured lung function at age four years by impulse oscillometry. First, we employed latent class analysis (LCA) to identify nasopharyngeal microbiota (NPM) subphenotypes. Then, we used linear regression to analyze associations between subphenotype assignment and lung function. LCA suggest that a two-class model best described the infant NPM. We identified a higher diversity subphenotype (N = 38, 34%) with more pathogens (median 4; IQR 3.25, 4.75) and a lower diversity subphenotype (N = 74, 66%) with fewer pathogens (median 1; IQR 1, 2). In multivariable linear regression models, the less diverse NPM subphenotype had higher small airway resistance (R5-R20 ß = 17.9%, 95% CI 35.6, 0.23; p = 0.047) compared with the more diverse subphenotype. Further studies are required to understand the role of the microbiota in future lung health.

Erroneous Reporting of Deaths Attributed to Pneumonia and Influenza at 2 New York City Teaching Hospitals, 2013-2014.

OBJECTIVES: Cause-of-death information, reported by frontline clinicians after a patient's death, is an irreplaceable source of public health data. However, systematic bias in cause-of-death reporting can lead to over- or underestimation of deaths attributable to different causes. New York City consistently reports higher rates of deaths attributable to pneumonia and influenza than many other US cities and the country. We investigated systematic erroneous reporting as a possible explanation for this phenomenon. METHODS: We reviewed all deaths from 2 New York City hospitals during 2013-2014 in which pneumonia or influenza was reported as the underlying cause of death (n = 188), and we examined the association between erroneous reporting and multiple extrinsic factors that may influence cause-of-death reporting (patient demographic characteristics and medical comorbidities, time and hospital location of death, type of medical provider reporting the death, and availability of certain diagnostic information). RESULTS: Pneumonia was erroneously reported as the underlying cause of death in 163 (86.7%) reports. We identified heart disease and dementia as the more likely underlying cause of death in 21% and 17% of erroneously reported deaths attributable to pneumonia, respectively. We found no significant association between erroneous reporting and the multiple extrinsic factors examined. CONCLUSIONS: Our results underscore how erroneous reporting of 1 condition can lead to underreporting of other causes of death. Misapplication or misunderstanding of procedures by medical providers, rather than extrinsic factors influencing the reporting process, are key drivers of erroneous cause-of-death reporting.

Modulation sensitivity in the perceptual organization of speech.

In a spoken utterance, a talker expresses linguistic constituents in serial order. A listener resolves these linguistic properties in the rapidly fading auditory sample. Classic measures agree that auditory integration occurs at a fine temporal grain. In contrast, recent studies have proposed that sensory integration of speech occurs at a coarser grain, approximate to the syllable, on the basis of indirect and relatively insensitive perceptual measures. Evidence from cognitive neuroscience and behavioral primatology has also been adduced to support the claim of sensory integration at the pace of syllables. In the present investigation, we used direct performance measures of integration, applying an acoustic technique to isolate the contribution of short-term acoustic properties to the assay of modulation sensitivity. In corroborating the classic finding of a fine temporal grain of integration, these functional measures can inform theory and speculation in accounts of speech perception.

Estimating speech spectra for copy synthesis by linear prediction and by hand.

Linear prediction is a widely available technique for analyzing acoustic properties of speech, although this method is known to be error-prone. New tests assessed the adequacy of linear prediction estimates by using this method to derive synthesis parameters and testing the intelligibility of the synthetic speech that results. Matched sets of sine-wave sentences were created, one set using uncorrected linear prediction estimates of natural sentences, the other using estimates made by hand. Phoneme restrictions imposed on linguistic properties allowed comparisons between continuous and intermittent voicing, oral or nasal and fricative manner, and unrestricted phonemic variation. Intelligibility tests revealed uniformly good performance with sentences created by hand-estimation and a minimal decrease in intelligibility with estimation by linear prediction due to manner variation with continuous voicing. Poorer performance was observed when linear prediction estimates were used to produce synthetic versions of phonemically unrestricted sentences, but no similar decline was observed with synthetic sentences produced by hand estimation. The results show a substantial intelligibility cost of reliance on uncorrected linear prediction estimates when phonemic variation approaches natural incidence.

Auditory-phonetic projection and lexical structure in the recognition of sine-wave words.

Speech remains intelligible despite the elimination of canonical acoustic correlates of phonemes from the spectrum. A portion of this perceptual flexibility can be attributed to modulation sensitivity in the auditory-to-phonetic projection, although signal-independent properties of lexical neighborhoods also affect intelligibility in utterances composed of words. Three tests were conducted to estimate the effects of exposure to natural and sine-wave samples of speech in this kind of perceptual versatility. First, sine-wave versions of the easy and hard word sets were created, modeled on the speech samples of a single talker. The performance difference in recognition of easy and hard words was used to index the perceptual reliance on signal-independent properties of lexical contrasts. Second, several kinds of exposure produced familiarity with an aspect of sine-wave speech: (a) sine-wave sentences modeled on the same talker; (b) sine-wave sentences modeled on a different talker, to create familiarity with a sine-wave carrier; and (c) natural sentences spoken by the same talker, to create familiarity with the idiolect expressed in the sine-wave words. Recognition performance with both easy and hard sine-wave words improved after exposure only to sine-wave sentences modeled on the same talker. Third, a control test showed that signal-independent uncertainty is a plausible cause of differences in recognition of easy and hard sine-wave words. The conditions of beneficial exposure reveal the specificity of attention underlying versatility in speech perception.

Is desynchrony tolerance adaptable in the perceptual organization of speech?

Speech signal components that are desynchronized from the veridical temporal pattern lose intelligibility. In contrast, audiovisual presentations with large desynchrony in visible and audible speech streams are perceived without loss of integration. Under such conditions, the limit of desynchrony that permits audiovisual integration is also adaptable. A new project directly investigated the potential for adaptation to consistent desynchrony with unimodal auditory sine-wave speech. Listeners transcribed sentences that are highly intelligible, with veridical temporal properties. Desynchronized variants were created by leading or lagging the tone analog of the second formant relative to the rest of the tones composing the sentences, in 50-msec steps, ranging from 250-msec lead to 250-msec lag. In blocked trials, listeners only tolerated desynchronies <50 msec, and exhibited no gain in intelligibility to consistent desynchrony. Unimodal auditory and bimodal audiovisual forms of perceptual integration evidently exhibit different temporal characteristics, an indication of distinct perceptual functions.

AUDITORY-PHONETIC PROJECTION AND LEXICAL STRUCTURE IN THE RECOGNITION OF SINE-WAVE WORDS.

Speech remains intelligible despite the elimination of canonical acoustic correlates of phonemes from the spectrum. A portion of this perceptual flexibility can be attributed to modulation sensitivity in the auditory-to-phonetic projection, though signal-independent properties of lexical neighborhoods also affect intelligibility in utterances composed of words. Three tests were conducted to estimate the effects of exposure to natural and sine-wave samples of speech in this kind of perceptual versatility. First, sine-wave versions of the easy/hard word sets were created, modeled on the speech samples of a single talker. The performance difference in recognition of easy and hard words was used to index the perceptual reliance on signal-independent properties of lexical contrasts. Second, several kinds of exposure produced familiarity with an aspect of sine-wave speech: 1) sine-wave sentences modeled on the same talker; 2) sine-wave sentences modeled on a different talker, to create familiarity with a sine-wave carrier; and 3) natural sentences spoken by the same talker, to create familiarity with the idiolect expressed in the sine-wave words. Recognition performance with both easy and hard sine-wave words improved after exposure only to sine-wave sentences modeled on the same talker. Third, a control test showed that signal-independent uncertainty is a plausible cause of differences in recognition of easy and hard sine-wave words. The conditions of beneficial exposure reveal the specificity of attention underlying versatility in speech perception.