Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism.

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics-and an understanding of pathobiology and epizootiology of rabies in testament to One Health-before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable-occasional treatment-of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral-essentially 'one and done'. Exploiting mammalian social behaviors, future 'spreadable vaccines' might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Validation of extracorporeal membrane oxygenation mortality prediction and severity of illness scores in an international COVID-19 cohort.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a lifesaving support modality for severe respiratory failure, but its resource-intensive nature led to significant controversy surrounding its use during the COVID-19 pandemic. We report the performance of several ECMO mortality prediction and severity of illness scores at discriminating survival in a large COVID-19 V-V ECMO cohort. METHODS: We validated ECMOnet, PRESET (PREdiction of Survival on ECMO Therapy-Score), Roch, SOFA (Sequential Organ Failure Assessment), APACHE II (acute physiology and chronic health evaluation), 4C (Coronavirus Clinical Characterisation Consortium), and CURB-65 (Confusion, Urea nitrogen, Respiratory Rate, Blood Pressure, age >65 years) scores on the ISARIC (International Severe Acute Respiratory and emerging Infection Consortium) database. We report discrimination via Area Under the Receiver Operative Curve (AUROC) and Area under the Precision Recall Curve (AURPC) and calibration via Brier score. RESULTS: We included 1147 patients and scores were calculated on patients with sufficient variables. ECMO mortality scores had AUROC (0.58-0.62), AUPRC (0.62-0.74), and Brier score (0.286-0.303). Roch score had the highest accuracy (AUROC 0.62), precision (AUPRC 0.74) yet worst calibration (Brier score of 0.3) despite being calculated on the fewest patients (144). Severity of illness scores had AUROC (0.52-0.57), AURPC (0.59-0.64), and Brier Score (0.265-0.471). APACHE II had the highest accuracy (AUROC 0.58), precision (AUPRC 0.64), and best calibration (Brier score 0.26). CONCLUSION: Within a large international multicenter COVID-19 cohort, the evaluated ECMO mortality prediction and severity of illness scores demonstrated inconsistent discrimination and calibration highlighting the need for better clinically applicable decision support tools.

Development of Machine Learning Regression Model for COVID-19 Drug Target Prediction

There is a perennial need to identify novel, effective therapeutic agents to combat rising infections. Recently, prediction of therapeutic targets to decrease the impact of COVID-19 has posed an urgent challenge requiring innovative solutions. Successful identification of novel drug-target combinations may greatly facilitate drug development. To meet this need, we developed a COVID-19 drug target prediction model using machine learning approaches to quickly identify drug candidates for 18 COVID-19 protein targets. Specifically, we analyzed the performance of three prediction models to predict drug-target docking scores, which represents the strength of interactions between ligands and proteins. Docking scores were predicted for 300,457 molecules on 18 different COVID-19 related protein docking targets. Our proposed approach achieved a competitive performance with mathrm{R}-{2}=0.69,MAE=0.285, MSE=0.627. In addition, we identify chemical structures associated with stronger binding affinities across target binding sites. We believe our work could potentially save pharmaceutical companies significant resources, especially during the early stages of drug development. © 2022 IEEE.

Efficacy of a smartphone-based virtual companion to treat insomniac complaints in the general population: Sleep diary monitoring versus an internet autonomous intervention

Objectives/Introduction: Insomnia is the most prevalent sleep disorder worldwide and cognitive behavioural therapy is the front-line treatment. Digital health technologies have a role to play in screening and delivering interventions remotely and without the need for human intervention. The KANOPEE app, which provides a screening and behavioural intervention for insomnia symptoms through an interaction with a virtual agent, showed encouraging results in previous studies during and after the COVID-19 lockdown, but has not yet been evaluated in a controlled study. This study aims at comparing the benefits of KANOPEE, a smartphone application proposing repeated interactions with a virtual companion to screen and deliver personalized recommendations to deal with insomnia complaints;with another application proposing an electronic sleep diary and named "My Sleep Diary". The acceptance and potential benefits of these digital solutions are demonstrated in real-life settings (i.e., without soliciting human medical resources) and in the general population. Method(s): Subjects were included if they downloaded one of the apps between December 2020 and October 2021;and were of legal age. Both apps are available on downloading platforms in France and both groups were equivalent in terms of baseline characteristics. Primary outcome was Insomnia Severity Index (ISI) and secondary outcomes were Total Sleep Time (TST) and Sleep Efficiency (SE). Result(s): 535 users completed the 17-day intervention with KANOPEE and 489 users completed My Sleep Diary for 17 days. A differential effect was obtained for KANOPEE users compared to My Sleep Diary users regarding ISI score (interaction Time x Group: F [2,2014] = 16.9, p < 0.001) and TST (KANOPEE users gained 48 min of sleep after intervention, while My Sleep Diary users gained only 16 min of sleep). Patients with the most severe ISI score (>15) benefited the most from KANOPEE (interaction severity x Time: F [4,2014] = 26.3, p < 0.001). Conclusion(s): KANOPEE provides significantly greater benefits than an electronic sleep diary regarding reduction of insomnia complaints in a self-selected sample of the general population.

Circadian misalignment is associated with COVID-19 infection

Background: Circadian system contributes to the regulation of inflammatory processes, but the role of circadian misalignment as a risk factor for contracting Covid-19 has up to now been poorly studied. The aim of this study was to explore the relationship between circadian misalignment (chronic disturbance of the circadian system) and the risk of Covid-19 infection in a population of subjects suspected of contact or infection with SARS-CoV-2. Method(s): Cross-sectional single-center study conducted during a period without lockdown in winter 2021. Recruitment took place in a Covid-19 outpatient testing center. Subjects between 18 and 45 years old were included whether they were symptomatic or not, healthcare workers or not, in contact with a Covid-19 case or not. To determine social jetlag, a proxy of circadian misalignment, they were asked about their usual sleep-wake behaviors. Usual sleep duration and sleep-wake timing were explored on workdays and free days. Social jetlag was defined as at least 2 h shift of circadian alignment (defined as the difference between mid-sleep on workdays and mid-sleep on free days, midsleep as the median between bedtime and rise time). Result(s): One thousand fourteen subjects were included (sampling rate: 10.8%, 39% men, mean age 28 +/- 8) with 56 subjects positive for Covid-19 (positivity rate: 5.5%). Usual mean sleep duration was equivalent in both groups (7 h47 versus 7 h49, p = 0.733). Social jetlag greater than 2 h comprised 33.3% of subjects in the Covid-19 group versus 20.6% in the control group (p = 0.026). After adjustment on age, gender, BMI and work schedules, subjects presenting with social jetlag greater than 2 h had a 2.07-fold higher likelihood to test positive than subjects who had identical sleep-wake timing on workdays and free days (OR = 2.07, 95%CI = [1.12e3.80], p = 0.024). Conclusion(s): Circadian misalignment not only is present in subjects infected by Covid-19 but could also be responsible for a higher likelihood of being infected. The chronobiological impact on the immune system or a higher likelihood of being exposed to social contacts during nocturnal activities could explain our findings, which need to be confirmed in a future large cohort study. Regular sleep-wake timing could ultimately become a target for preventing Covid-19 infection.

CIRCADIAN MISALIGNMENT IS ASSOCIATED WITH COVID-19 INFECTION

Introduction: Sleep disturbances are frequently reported in patients infected by Covid-19, but the role of sleep-wake behaviors as a risk factor to contract Covid-19 has up to now poorly been studied. The aim of this study was to explore the relationship between usual sleep-wake behaviors and the risk of Covid-19 infection in a population of subjects suspect of contact or infection with SARS-CoV-2. Methods: Cross-sectionnal monocentric study set during a nonconfined period in winter 2021. Recruitment took place in a Covid-19 ambulatory screening platform. Subjects between 18 and 45 years old were included whether they were symptomatic or not, healthcare workers or not, in contact with a Covid-19 case or not. They were asked about their usual sleep-wake behaviors. Usual sleep duration and sleep timing were explored during workdays and free days. Circadian misalignment was defined as at least 2 hours shift of circadian alignment (defined as the difference between mid-sleep during workdays and mid-sleep during free days, mid sleep as the middle between bedtime and getting up time). Results: One thousand eighteen subjects were included in our study (acceptance rate: 10.8%, 39% of men, mean age of 28± 8). Habitual mean sleep duration was equivalent in both groups (7h47 vs 7h49, p=0.733). Circadian misalignment greater than 2 hours concerned 33% of subjects in the Covid-19 group versus 20% of the control group (p=0.026). After adjustment on age, gender, BMI and work schedules, subjects presenting a circadian misalignment superior to 2 hours had 2.07 more chances to be tested positive than subjects which respected on identical sleep-wake timing between workdays and free days (OR=2.07, 95%CI= [1.12-3.80], p=0.024). Conclusion: Altered sleep not only is present in subjects infected by Covid-19 but could be responsible of a higher change to be infected. Chronobiological impact on immune system and higher chances to be exposed to social contacts could explain our findings which deserve to be confirmed through a future large cohort study. Ultimately regular sleep-wake pattern could constitute a privileged prevention target to fight Covid-19 infection.

Rabies in the Tropics.

Purpose of Review: Rabies is an ancient yet still neglected tropical disease (NTD). This review focuses upon highlights of recent research and peer-reviewed communications on the underestimated tropical burden of disease and its management due to the complicated dynamics of virulent viral species, diverse mammalian reservoirs, and tens of millions of exposed humans and animals - and how laboratory-based surveillance at each level informs upon pathogen spread and risks of transmission, for targeted prevention and control. Recent Findings: While both human and rabies animal cases in enzootic areas over the past 5 years were reported to PAHO/WHO and OIE by member countries, still there is a huge gap between these "official" data and the need for enhanced surveillance efforts to meet global program goals. Summary: A review of the complex aspects of rabies perpetuation in human, domestic animal, and wildlife communities, coupled with a high fatality rate despite the existence of efficacious biologics (but no therapeutics), warrants the need for a One Health approach toward detection via improved laboratory-based surveillance, with focal management at the viral source. More effective methods to prevent the spread of rabies from enzootic to free zones are needed.

COVID-19 Vaccine Hesitancy and Determinants of Acceptance among Healthcare Workers, Academics and Tertiary Students in Nigeria.

The COVID-19 pandemic has resulted in millions of human deaths, prompting the rapid development and regulatory approval of several vaccines. Although Nigeria implemented a COVID-19 vaccination program on 15 March 2021, low vaccine acceptance remains a major challenge. To provide insight on factors associated with COVID-19 vaccine hesitancy (VH), we conducted a national survey among healthcare workers, academics, and tertiary students, between 1 September 2021 and 31 December 2021. We fitted a logistic regression model to the data and examined factors associated with VH to support targeted health awareness campaigns to address public concerns and improve vaccination rates on par with global efforts. A total of 1525 respondents took part in the survey, composed of healthcare-workers (24.5%, 373/1525), academics (26.9%, 410/1525), and students (48.7%, 742/1525). Only 29% (446/1525) of the respondents were vaccinated at the time of this study. Of the 446 vaccinated respondents, 35.7% (159/446), 61.4% (274/446) and 2.9% (13/446) had one, two and three or more doses, respectively. Reasons for VH included: difficulty in the vaccination request/registration protocols (21.3%, 633/1079); bad feelings towards the vaccines due to negative social media reports/rumours (21.3%, 633/1079); personal ideology/religious beliefs against vaccination (16.7%, 495/1079); and poor confidence that preventive measures were enough to protect against COVID-19 (11%, 323/1079). Some health concerns that deterred unvaccinated respondents were: innate immunity issues (27.7%, 345/1079); allergic reaction concerns (24.6%, 307/1079); and blood clot problems in women (21.4%, 266/1079). In the multivariable model, location of respondents/geopolitical zones, level of education, testing for COVID-19, occupation/job description and religion were significantly associated with VH. Findings from this study underscore the need for targeted awareness creation to increase COVID-19 vaccination coverage in Nigeria and elsewhere. Besides professionals, similar studies are recommended in the general population to develop appropriate public health interventions to improve COVID-19 vaccine uptake.

Spatiotemporal heterogeneity and determinants of canine rabies evidence at Local Government Area Level in Nigeria: Implications for rabies prevention and control

Canine rabies poses a significant risk to humans and animals in Nigeria. However, the lack of reliable tools to evaluate the performance of existing canine rabies control programs to inform public health policy decisions poses a severe obstacle. We obtained canine rabies surveillance data from the National Veterinary Research Institute (NVRI) and supplemented these data with rabies diagnoses reported in the published studies from Nigeria. To uncover contextual factors (i.e., environmental and sociodemographic) associated with canine rabies evidence at the Local Government Area (LGA) level, we classified LGAs in Nigeria into four categories based on evidence availability (i.e., LGAs with NVRI data or published studies, both, or no evidence). We described the geographical and temporal variation in coverage. We fitted a multinomial regression model to examine the association between LGA level canine rabies evidence and potential sociodemographic and ecological determinants of canine rabies evidence. The effective annual testing during the 19 years was less than one dog/100,000 Nigerian resident-year. Our results showed that 58% of Nigerian LGAs (450/774) had not been targeted by the existing national rabies surveillance or studies on rabies, including ten states capitals with high human populations. While 16% (122/774) of Nigerian LGAs concentrated in Taraba, Adamawa, and Abia had canine rabies evidence from published studies, none of these LGAs was represented in the NVRI rabies surveillance data. We also observed an increasing trend in rabies evidence over time towards the eastern part of Nigeria. Our multinomial regression model indicated that education level, poverty, population density, land use and temperature were significantly associated with canine rabies evidence at the LGA level. This study underscores the value of combining canine rabies evidence from different sources to better understand the current disease situation for targeted intervention. Highlights • This study shows the value of combining different evidence sources to advocate for public health interventions.• Educational level, poverty, population density, land use and temperature were determinants of evidence of canine rabies.• Such evidence demonstrates the need to expand Nigeria's rabies laboratory-based surveillance to support rabies prevention.

How should we measure intraocular pressure in the era of coronavirus disease 2019? Balancing infectious risk, cleaning requirements, and accuracy.

PURPOSE OF REVIEW: Accurate and precise measurement of intraocular pressure (IOP) is a vitally important component of the ophthalmic examination. There are multiple methods of tonometry, each of which has considerations in light of the ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. This review discusses these considerations and compares various tonometer methods with the gold standard of Goldmann applanation tonometry (GAT). RECENT FINDINGS: The SARS-CoV-2 virus may spread via droplets, microaerosols, or direct contact in the ophthalmology clinic. Tonometry poses a high risk of contamination. The accuracy and reliability of various methods of tonometry with single-use disposable equipment has been compared with Goldmann applanation tonometry. SUMMARY: Goldmann applanation tonometry with disposable applanation tips, Tono-pen, and iCare employ single use tips to decrease the risk of cross-contamination of infectious agents. Review of the literature demonstrates good correlation between these devices and GAT, although the published level of agreement between devices varies.

Sex-, Race- and Ethnicity-Based Differences in Thromboembolic Events Among Adults Hospitalized With COVID-19.

Background Patients hospitalized with COVID-19 have an increased risk of thromboembolic events. Whether sex, race or ethnicity impacts these events is unknown. We studied the association between sex, race, and ethnicity and venous and arterial thromboembolic events among adults hospitalized with COVID-19. Methods and Results We used the American Heart Association Cardiovascular Disease COVID-19 registry. Primary exposures were sex and race and ethnicity, as defined by the registry. Primary outcomes were venous thromboembolic events and arterial thromboembolic events. We used logistic regression for risk adjustment. We studied 21 528 adults hospitalized with COVID-19 across 107 centers (54.1% men; 38.1% non-Hispanic White, 25.4% Hispanic, 25.7% non-Hispanic Black, 0.5% Native American, 4.0% Asian, 0.4% Pacific Islander, and 5.9% other race and ethnicity). The rate of venous thromboembolic events was 3.7% and was more common in men (4.2%) than women (3.2%; P<0.001), and in non-Hispanic Black patients (4.9%) than other races and ethnicities (range, 1.3%-3.8%; P<0.001). The rate of arterial thromboembolic events was 3.9% and was more common in men (4.3%) than women (3.5%; P=0.002), and in non-Hispanic Black patients (5.0%) than other races and ethnicities (range, 2.3%-4.7%; P<0.001). Compared with men, women were less likely to experience venous thromboembolic events (adjusted odds ratio [OR], 0.71; 95% CI, 0.61-0.83) and arterial thromboembolic events (adjusted OR, 0.76; 95% CI, 0.66-0.89). Compared with non-Hispanic White patients, non-Hispanic Black patients had the highest likelihood of venous thromboembolic events (adjusted OR, 1.27; 95% CI, 1.04-1.54) and arterial thromboembolic events (adjusted OR, 1.35; 95% CI, 1.11-1.65). Conclusions Men and non-Hispanic Black adults hospitalized with COVID-19 are more likely to have venous and arterial thromboembolic events. These subgroups may represent at-risk patients more susceptible to thromboembolic COVID-19 complications.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

Factors associated with acceptance of a virtual companion providing screening and advices for sleep problems during COVID-19 crisis

The COVID-19 crisis has generated an increase of sleep problems in the general population. Digital technologies can help dealing with mental health repercussions of COVID-19 but their acceptance by the population need to be better understood. KANOPEE is a smartphone application providing interactions with a virtual companion to screen and deliver personalized advices to deal with sleep problems. In this study we tried to highlight the factors associated with acceptance of this app, among factors including user characteristics, perceived trustworthiness of the virtual companion and context of use. 3,479 users answered the acceptance questionnaires, with a very positive attitude towards the app. Results indicate that age, education, familiarity with technologies, trustworthiness of the virtual agent and length of interaction are significantly associated with acceptance of the app. To conclude, this study is one of the first to measure acceptance of a virtual companion providing support during the COVID-19 crisis, and provide avenues of research for design and evaluation of intelligent virtual agents for health. © 2021 ACM.

North American lower-extremity revascularization and amputation during COVID-19: Observations from the Vascular Quality Initiative.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic's impact on vascular procedural volumes and outcomes has not been fully characterized. METHODS: Volume and outcome data before (1/2019 - 2/2020), during (3/2020 - 4/2020), and following (5/2020 - 6/2020) the initial pandemic surge were obtained from the Vascular Quality Initiative (VQI). Volume changes were determined using interrupted Poisson time series regression. Adjusted mortality was estimated using multivariable logistic regression. RESULTS: The final cohort comprised 57,181 patients from 147 US and Canadian sites. Overall procedure volumes fell 35.2% (95% CI 31.9%, 38.4%, p < 0.001) during and 19.8% (95% CI 16.8%, 22.9%, p < 0.001) following the surge, compared with presurge months. Procedure volumes fell 71.1% for claudication (95% CI 55.6%, 86.4%, p < 0.001) and 15.9% for chronic limb-threatening ischemia (CLTI) (95% CI 11.9%, 19.8%, p < 0.001) but remained unchanged for acute limb ischemia (ALI) when comparing surge to presurge months. Adjusted mortality was significantly higher among those with claudication (0.5% vs 0.1%; OR 4.38 [95% CI 1.42, 13.5], p = 0.01) and ALI (6.4% vs 4.4%; OR 2.63 [95% CI 1.39, 4.98], p = 0.003) when comparing postsurge with presurge periods. CONCLUSION: The first North American COVID-19 pandemic surge was associated with a significant and sustained decline in both elective and nonelective lower-extremity vascular procedural volumes. When compared with presurge patients, in-hospital mortality increased for those with claudication and ALI following the surge.

Impact of the 1st and 2nd Wave of the COVID-19 Pandemic on Primary or Revision Total Hip and Knee Arthroplasty-A Cross-Sectional Single Center Study.

The aim of this study was to evaluate the number of primary and revision total joint arthroplasties (TJA/rTJA) in 2020 compared to 2019. Specifically, the first and the second waves of the COVID-19 pandemic were evaluated as well as the pre-operative COVID-19 test. A cross-sectional single-center study of our prospectively maintained institutional arthroplasty registry was performed. The first COVID-19 wave and the second COVID-19 wave led to a socioeconomic lockdown in 2020. Performed surgeries, cause of revision, age, gender, and American Society of Anesthesiologists-level were analyzed. Preoperative COVID-19 testing was evaluated and nationwide COVID-19 data were compared to other countries. In 2020, there was a decrease by 16.2% in primary and revision TJAs of the hip and knee compared to 2019. We observed a reduction of 15.8% in primary TJAs and a reduction of 18.6% on rTJAs in 2020 compared to 2019. There is an incline in total hip arthroplasties (THAs) and a decline in total knee arthroplasties (TKAs) comparing 2019 to 2020. During the first wave, there was a reduction in performed primary TJAs of 86%. During the second wave, no changes were observed. This is the first study quantifying the impact of the COVID-19 pandemic on primary and revision TJAs regarding the first and second wave.

Transcriptional and proteomic insights into the host response in fatal COVID-19 cases.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.