AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

BACKGROUND: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. METHODS: This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. FINDINGS: Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Strengthened Interficial Adhesive Fracture Energy by Young's Modulus Matching Degree Strategy in Carbon-Based HTM Free MAPbI3 Perovskite Solar Cell with Enhanced Mechanical Compatibility.

Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.

The pathogenesis of common Gjb2 mutations associated with human hereditary deafness in mice.

Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2+/35delG and Gjb2+/235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P) 28. A homozygous mutant mouse model, Gjb235delG/35delG, was then generated using enhanced tetraploid embryo complementation, demonstrating that GJB2 plays an indispensable role in mouse placenta development. These mice exhibited profound hearing loss similar to human patients at P14, i.e., soon after the onset of hearing. Mechanistic analyses showed that Gjb2 35delG disrupts the function and formation of intercellular gap junction channels of the cochlea rather than affecting the survival and function of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism of DFNB1A-related hereditary deafness and opens up a new avenue for investigating the treatment of this disease.

Comparative transcriptome analysis provides insights into the molecular mechanisms of high-frequency hearing differences between the sexes of Odorrana tormota.

BACKGROUND: Acoustic communication is important for the survival and reproduction of anurans and masking background noise is a critical factor for their effective acoustic communication. Males of the concave-eared frog (Odorrana tormota) have evolved an ultrasonic communication capacity to avoid masking by the widespread background noise of local fast-flowing streams, whereas females exhibit no ultrasonic sensitivity. However, the molecular mechanisms underlying the high-frequency hearing differences between the sexes of O. tormota are still poorly understood. RESULTS: In this study, we sequenced the brain transcriptomes of male and female O. tormota, and compared their differential gene expression. A total of 4,605 differentially expressed genes (DEGs) between the sexes of O. tormota were identified and eleven of them were related to auditory based on the annotation and enrichment analysis. Most of these DEGs in males showed a higher expression trend than females in both quantity and expression quantity. The highly expressed genes in males were relatively concentrated in neurogenesis, signal transduction, ion transport and energy metabolism, whereas the up-expressed genes in females were mainly related to the growth and development regulation of specific auditory cells. CONCLUSIONS: The transcriptome of male and female O. tormota has been sequenced and de novo assembled, which will provide gene reference for further genomic studies. In addition, this is the first research to reveal the molecular mechanisms of sex differences in ultrasonic hearing between the sexes of O. tormota and will provide new insights into the genetic basis of the auditory adaptation in amphibians during their transition from water to land.

A humanized murine model, demonstrating dominant progressive hearing loss caused by a novel KCNQ4 mutation (p.G228D) from a large Chinese family.

The pathogenic variants in KCNQ4 cause DFNA2 nonsyndromic hearing loss. However, the understanding of genotype-phenotype correlations between KCNQ4 and hearing is limited. Here, we identified a novel KCNQ4 mutation p.G228D from a Chinese family, including heterozygotes characterized by high-frequency hearing loss that is progressive across all frequencies and homozygotes with more severe hearing loss. We constructed a novel murine model with humanized homologous Kcnq4 mutation. The heterozygotes had mid-frequency and high-frequency hearing loss at 4 weeks, and moved toward all frequencies hearing loss at 12 weeks, while the homozygotes had severe-to-profound hearing loss at 8 weeks. The degeneration of outer hair cells (OHCs) was observed from basal to apical turn of cochlea. The reduced K+ currents and depolarized resting potentials were revealed in OHCs. Remarkably, we observed the loss of inner hair cells (IHCs) in the region corresponding to the frequency above 32 kHz at 8-12 weeks. The results suggest the degeneration of OHCs and IHCs may contribute to high-frequency hearing loss in DFNA2 over time. Our findings broaden the variants of KCNQ4 and provide a novel mouse model of progressive hearing loss, which contributes to an understanding of pathogenic mechanism and eventually treatment of DFNA2 progressive hearing loss.

Occurrence of Iodophenols in Aquatic Environments and the Deiodination of Organic Iodine with Ferrate(VI).

Toxic and odorous iodophenols are commonly identified as disinfection by-products (DBPs) in drinking water. Herein, ng/L levels of iodophenols were identified in river water, wastewater treatment plant effluent, and medical wastewater, with the simultaneous identification of µg/L to mg/L levels of iodide (I-) and total organic iodine (TOI). Oxidation experiment suggested that the I-, TOI, and iodophenols could be oxidized by ferrate [Fe(VI)], and more than 97% of TOI had been transformed into stable and nontoxic IO3-. Fe(VI) initially cleaved the C-I bond of iodophenols and led to the deiodination of iodophenols. The resulted I- was swiftly oxidized into HOI and IO3-, with the intermediate phenolic products be further oxidized into lower molecular weight products. The Gibbs free energy change (ΔG) of the overall reaction was negative, indicating that the deiodination of iodophenols by Fe(VI) was spontaneous. In the disinfection of iodine-containing river water, ng/L levels of iodophenols and chloro-iodophenols formed in the reaction with NaClO/NH2Cl, while Fe(VI) preoxidation was effective for inhibiting the formation of iodinated DBPs. Fe(VI) exhibited multiple functions for oxidizing organic iodine, abating their acute toxicity/cytotoxicity and controlling the formation of iodinated DBPs for the treatment of iodide/organic iodine-containing waters.

Facile Synthesis of Unsolvated Alkali Metal Octahydrotriborate Salts MB3 H8 (M=K, Rb, and Cs), Mechanisms of Formation, and the Crystal Structure of KB3 H8.

A facile synthesis of heavy alkali metal octahydrotriborates (MB3 H8 ; M=K, Rb, and Cs) has been developed. It is simply based on reactions of the pure alkali metals with THF⋅BH3 , does not require the use of electron carriers or the addition of other reaction media such as mercury, silica gel, or inert salts as for previous procedures, and delivers the desired products at room temperature in very high yields. However, no reactions were observed when pure Li or Na was used. The reaction mechanisms for the heavy alkali metals were investigated both experimentally and computationally. The low sublimation energies of K, Rb, and Cs were found to be key for initiation of the reactions. The syntheses can be carried out at room temperature because all of the elementary reaction steps have low energy barriers, whereas reactions of LiBH4 /NaBH4 with THF⋅BH3 have to be carried out under reflux. The high stability and solubility of KB3 H8 were examined, and a crystal structure thereof was obtained for the first time.

Ca(2+) and OH(-) release of ceramsites containing anorthite and gehlenite prepared from waste lime mud.

Lime mud is a kind of solid waste in the papermaking industry, which has been a source of serious environmental pollution. Ceramsites containing anorthite and gehlenite were prepared from lime mud and fly ash through the solid state reaction method at 1050°C. The objective of this study was to explore the efficiency of Ca(2+) and OH(-) release and assess the phosphorus and copper ion removal performance of the ceramsites via batch experiments, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show that Ca(2+) and OH(-) were released from the ceramsites due to the dissolution of anorthite, gehlenite and available lime. It is also concluded that gehlenite had stronger capacity for Ca(2+) and OH(-) release compared with anorthite. The Ca(2+) release could be fit well by the Avrami kinetic model. Increases of porosity, dosage and temperature were associated with increases in the concentrations of Ca(2+) and OH(-) released. Under different conditions, the ceramsites could maintain aqueous solutions in alkaline conditions (pH=9.3-10.9) and the release of Ca(2+) was not affected. The removal rates of phosphorus and copper ions were as high as 96.88% and 96.81%, respectively. The final pH values of both phosphorus and copper ions solutions changed slightly. The reuse of lime mud in the form of ceramsites is an effective strategy.

A base editor for the long-term restoration of auditory function in mice with recessive profound deafness.

A prevalent recessive mutation (c.2485C>T, p.Q829X) within the OTOF gene leads to profound prelingual hearing loss. Here we show that in Otof mice harbouring a mutation (c.2482C>T, p.Q828X) homozygous to human OTOF that faithfully mimics the hearing-loss phenotype, a base editor (consisting of the deaminase ABE7.10max and the Cas9 variant SpCas9-NG) packaged in adeno-associated viruses and injected into the inner ear of the mice via the round-window membrane effectively corrected the pathogenic mutation, with no apparent off-target effects. The treatment restored the levels of the otoferlin protein in 88% of the inner hair cells and stably rescued the auditory function of the mice to near-wild-type levels for over 1.5 years while improving synaptic exocytosis in the inner hair cells. We also show that an adenine base editor that targets the prevalent human OTOF mutation restored hearing in humanized mice to levels comparable to those of the wild-type counterparts. Base editors may be effective for the treatment of hereditary deafness.

Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

[Study on high-temperature phase change of tobermorite].

In the present paper, the high-temperature phase change of pure tobermorite was investigated by TGA/DSC, X-ray diffraction and infrared spectroscopy (IR) respectively. The DSC results showed that four interlayer water molecules were lost when they were heated at 300 degrees C. As the temperature increased to 724 degrees C, Si-O-H bonds were cleaved and dehydroxylation occurred. The XRD results showed that many diffraction peaks o f tobermorite disappeared and the crystal structure was broken and collapsed. Then tobermorite tends to be disordered and amorphous. When the calcination temperature increased to 861 degrees C, the disordered structure recombined to wollastonite, and the crystal structure became ordered and stable. Finally, the structure completely transformed to 2M-wollastonite at 1 000 degrees C. It should include the process of high-temperature phase change of tobermorite: tobermorite --> dehydration tobermorite --> dehydroxylation tobermorite --> wollastonite.

Molecular Phylogeny and Evolution of the Tuerkayana (Decapoda: Brachyura: Gecarcinidae) Genus Based on Whole Mitochondrial Genome Sequences.

Tuerkayana is of particular interest because it has been separated, in recent years, from Cardisoma and Discoplax but studies of its taxonomic status, especially from a whole mitochondrial genome perspective, have been lacking. In this study, the mitogenomes of four species (Tuerkayana magnum, Tuerkayana rotundum, Tuerkayana hirtipes, and Tuerkayana celeste) of Tuerkayana are sequenced and contrasted with other species in Brachyura for the first time. The phylogenetic tree of Brachyura, which includes 206 crab species (189 species of Brachyuran and 17 Anomura species) with a complete mitogenome, was constructed to evaluate the phylogenetic position of Tuerkayana and Gecarcinidae within Brachyuran, and explore the monophyly of Gecarcinidae. Furthermore, two single gene trees based on cox1 and 16SrRNA separately within interspecies of Gecarcinidae were reconstructed, providing molecular evidence for Tuerkayana and further clarifying the division of genera in Gecarcinidae. Based on the mitogenome dataset of 206 crabs, the branch-site model was utilized to explore selective pressure in individual codons with CodeML. The strong selective pressure shown in nad6 indicates that it may have played a significant role in the evolution of Gecarcinidae.

Degradation mechanism of BPA under VUV irradiation: efficiency contribution and DFT calculations.

Bisphenol A (BPA) is regarded as a hazardous pollutant that exists widely in aquatic environments, posing a severe threat to human health. In this study, a vacuum ultraviolet (VUV) lamp emitting a hybrid of 254 nm and 185 nm light was used to degrade BPA. Results indicated that photolysis via 254 nm wavelength accounted for 24.93% for BPA decay, while indirect oxidation was responsible for 52.27% of decay. Results confirmed that the degradation of BPA under VUV illumination mainly occurred via photo-excited degradation and ·OH electrophilic addition reactions based on average local ionization energy (ALIE) calculation and density functional theory (DFT) calculations. Therefore, only light with a wavelength of 254 nm was able to induce the first three excited states of BPA, forming the electron transition type of n → π* from O atom to a single benzene ring and π → π* in the single benzene ring. Indirect oxidation by ·OH occurred as it preferentially attacked the C6 atom in BPA ring A. Moreover, the energy required for photo-excited degradation was about twofold than that of ·OH electrophilic addition reactions.

Specific knockdown of Htra2 by CRISPR-CasRx prevents acquired sensorineural hearing loss in mice.

CasRx, a recently discovered member of the type VI CRISPR system with minimum size, offers a new approach for RNA manipulation with high efficiency and specificity in prokaryotes and eukaryotes. However, in vivo studies of functional recovery using the CasRx system have not been well characterized. Here, we sought to establish an adeno-associated virus (AAV)-CasRx-guide RNA (gRNA) system for the specific knockdown of Htra2 transcript to protect mice from aminoglycosides-induced hearing loss. For the study, we verified an optimized gRNA in vitro, which was packaged into a single AAV with CasRx, and injected the packaged AAV into mice with hearing loss induced by neomycin and auditory functions investigated by auditory brainstem response tests. Upon using the AAV-CasRx-gRNA system, we found the knockdown of Htra2 transcript led to less cochlear hair cell loss and improved auditory function, with low off-target and adverse side effects. Additionally, the decrease in Htra2 significantly inhibits mRNA expression of Casp3 and Casp9. In conclusion, the AAV-CasRx-gRNA-mediated knockdown of Htra2 transcript in mice has been proved effective and safe for preventing hearing loss induced by aminoglycosides and, thus, represents a promising genetic approach for the future clinical applications for treating non-inherited hearing loss.

Precise detection of CRISPR-Cas9 editing in hair cells in the treatment of autosomal dominant hearing loss.

Gene therapy would benefit from the effective editing of targeted cells with CRISPR-Cas9 tools. However, it is difficult to precisely assess the editing performance in vivo because the tissues contain many non-targeted cells, which is one of the major barriers to clinical translation. Here, in the Atoh1-GFP;Kcnq4 +/G229D mice, recapitulating a novel mutation we identified in a hereditary hearing loss pedigree, the high-efficiency editing of CRISPR-Cas9 in hair cells (34.10% on average) was precisely detected by sorting out labeled cells compared with only 1.45% efficiency in the whole cochlear tissue. After injection of the developed AAV_SaCas9-KKH_sgRNA agents, the Kcnq4 +/G229D mice showed significantly lower auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) thresholds, shorter ABR wave I latencies, higher ABR wave I amplitudes, increased number of surviving outer hair cells (OHCs), and more hyperpolarized resting membrane potentials of OHCs. These findings provide an innovative approach to accurately assess the underestimated editing efficiency of CRISPR-Cas9 in vivo and offer a promising strategy for the treatment of KCNQ4-related deafness.

Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing.

CRISPR/RfxCas13d (CasRx) editing system can specifically and precisely cleave single-strand RNAs, which is a promising treatment for various disorders by downregulation of related gene expression. Here, we tested this RNA-editing approach on Beethoven (Bth) mice, an animal model for human DFNA36 due to a point mutation in Tmc1. We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1Bth transcript by 90.8%, and the Tmc1 wild type transcript (Tmc1+) by 44.3%. We then injected a newly developed AAV vector (AAV-PHP.eB) based CasRx into the inner ears of neonatal Bth mice, and we found that Tmc1Bth was reduced by 70.2% in 2 weeks with few off-target effects in the whole transcriptome. Consistently, we found improved hair cell survival, rescued hair bundle degeneration, and reduced mechanoelectrical transduction current. Importantly, the hearing performance, measured in both ABR and DPOAE thresholds, was improved significantly in all ages over 8 weeks. We, therefore, have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss, paving way for its further application in many other hereditary diseases in hearing and beyond.

Rational Design on Chemical Regulation of Interfacial Microstress Engineering by Matching Young's Modulus in a CsPbBr3 Perovskite Film with Mechanical Compatibility toward Enhanced Photoelectric Conversion Efficiency.

Thermodynamically induced tensile stress in the perovskite film will lead to the formation of atomic vacancies, seriously destroying the photovoltaic efficiency stability of the perovskite solar cells (PSCs). Among them, cations and halide anions vacancies are unavoidable; these point vacancies are considered to be a major source of the ionic migration and perovskite degradation at the crystal boundary and surface of the perovskite films. Here, we use choline bromide to modify the perovskite film by occupying the atomic defects in the CsPbBr3 perovskite film. The results show that the zwitterion quaternary ammonium ions and bromide ions in choline bromide can simultaneously occupy the Cs+ cation and Br- anions vacancies in the perovskite film by the ionic bonding effect, for which the defect-state density on the surface of the perovskite film can be significantly reduced, leading to the effective enhancement of carrier lifetime. In addition, the residual stress at the crystal boundary can be effectively reduced by lowering the Young's modulus in the CsPbBr3 perovskite film. As a result, the optimized device achieves a photoelectric conversion efficiency (PCE) of 9.06% with an increase of 41.1% compared to the control device with a PCE of 6.42%. Most importantly, the newborn thermal stress due to thermal expansion during heat working conditions can be transferred from the polycrystalline perovskite to the carbon layer by the matched Young's modulus, thus resulting in improved stability perovskite film under environmental conditions. The work provides new insights for preparing high-quality perovskite films with low defect-state density and residual stress.

Application of vacuum-ultraviolet (VUV) for phenolic homologues removal in humic acid solution: Efficiency, pathway and DFT calculation.

Vacuum-ultraviolet (VUV) photo-initiated oxidation of phenolic homologues in simulative natural water were investigated, including phenol, o-dihydroxybenzene (ODB), m-dihydroxybenzene (MDB), p-dihydroxybenzene (PDB), paranitrophenol (PNP) and o-chlorophenol (OCP). Results showed the phenolic homologues removal rate reached at least 90% in pure water, which was dependent on temperature, pH, concentration of HA, and functional group of HA. Experimental results indicated that 0.2 mg/L HA might be a critical point. Additionally, the rate constant of the six phenolic homologues reduced by 76.85%, 77.81%, 71.91%, 79.15%, and 55.69%, respectively in the MDB solution, and 79.73%, 82.80%, 95.36%, 80.38%, and 92.64%, respectively in the benzoic acid (BA) solution, compared to the rate constant in pure water. Moreover, quantum chemistry calculation indicated that the variances between phenolic compounds in removal rate were attributed to the substituent on the benzene ring. And, to some extent, the carboxy group of HA was supposed to arose the suppression for phenolic homologues removal rate. Mechanism involved phenolic homologues degradation using vacuum-ultraviolet (VUV) was summarized, where it underwent the formation of quinone structures, ring opening, short-chain organic acid, even eventually the transformation into NO3- and Cl- of PNP and OCP.

COVID19: A Systematic Approach to Early Identification and Healthcare Worker Protection.

The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms "COVID-19," "2019-nCoV," "SARS-CoV-2," or "Novel Coronavirus Pneumonia." The main symptoms of COVID-19 are fever (83-98.6%), cough (59.4-82%), and fatigue (38.1-69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.

Approaching Otolaryngology Patients During the COVID-19 Pandemic.

Objective. To describe coronavirus disease 2019 (COVID-19) patient presentations requiring otolaryngology consultation and provide recommendations for protective measures based on the experience of ear, nose, and throat (ENT) departments in 4 Chinese hospitals during the COVID-19 pandemic. Study Design. Retrospective case series. Setting. Multicenter. Subjects and Methods. Twenty hospitalized COVID-19 patients requiring ENT consultation from 3 designated COVID-19 hospitals in Wuhan, Shanghai, and Shenzhen were identified. Data on demographics, comorbidities, COVID-19 symptoms and severity, consult reason, treatment, and personal protective equipment (PPE) use were collected and analyzed. Infection control strategies implemented for ENT outpatients and emergency room visits at the Eye and ENT Hospital of Fudan University were reported. Results. Median age was 63 years, 55% were male, and 95% were in severe or critical condition. Six tracheotomies were performed. Posttracheotomy outcomes were mixed (2 deaths, 2 patients comatose, all living patients still hospitalized). Other consults included epistaxis, pharyngitis, nasal congestion, hyposmia, rhinitis, otitis externa, dizziness, and tinnitus. At all hospitals, powered air-supply filter respirators (PAPRs) were used for tracheotomy or bleeding control. PAPR or N95-equivalent masks plus full protective clothing were used for other complaints. No inpatient ENT providers were infected. After implementation of infection control strategies for outpatient clinics, emergency visits, and surgeries, no providers were infected at the Eye and ENT Hospital of Fudan University. Conclusions and Relevance. COVID-19 patients require ENT consultation for many reasons, including tracheotomy. Otolaryngologists play an indispensable role in the treatment of COVID-19 patients but, due to their work, are at high risk of exposure. Appropriate protective strategies can prevent infection of otolaryngologists.