Persisting chemosensory dysfunction in COVID-19 - a cross-sectional population-based survey.

BACKGROUND: Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals. METHODOLOGY: Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin' Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia. RESULTS: Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD. CONCLUSION: Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.

Designing Spellcasters from Clinician Perspectives: A Customizable Gesture-Based Immersive Virtual Reality Game for Stroke Rehabilitation

Developing games is time-consuming and costly. Overly clinical therapy games run the risk of being boring, which defeats the purpose of using games to motivate healing in the first place [10, 23]. In this work, we adapt and repurpose an existing immersive virtual reality (iVR) game, Spellcasters, originally designed purely for entertainment for use as a stroke rehabilitation game-which is particularly relevant in the wake of COVID-19, where telehealth solutions are increasingly needed [4]. In preparation for participatory design sessions with stroke survivors, we collaborate with 14 medical professionals to ensure Spellcasters is safe and therapeutically valid for clinical adoption. We present our novel VR sandbox implementation that allows medical professionals to customize appropriate gestures and interactions for each patient's unique needs. Additionally, we share a co-designed companion app prototype based on clinicians' preferred data reporting mechanisms for telehealth. We discuss insights about adapting and repurposing entertainment games as serious games for health, features that clinicians value, and the potential broader impacts of applications like Spellcasters for stroke management.

GAN-based Face Reconstruction for Masked-Face

Facial recognition and identification which play an important role in human-computer interaction, secure authentication and criminal face recognition, are impeded by the advent of face masks due to COVID-19 pandemic. This is a challenging problem due to the following reasons: (i) masks cover quite a large part of the face even below the chin, (ii) it is not possible to collect and prepare a real paired-face images with and without mask object, (iii) face alterations and the presence of different masks is even more challenging. In this work, we propose a general framework that can be used to reconstruct the hidden part of face concealed by mask. We have employed GAN-based unpaired domain translation technique to translate masked face images from the source to the unmasked images in the destination domain. To this end, we also create a paired datasets of real face images and synthesized correspondence's with face-masks and use it towards training of our proposed GAN-based facial reconstruction system which can be used for facial identification and secure authentication in human-computer interaction. The obtained results demonstrate that our model outperforms other representative state-of-the-art face completion approaches both qualitatively and quantitatively. © 2022 Owner/Author.

The Gang's All Here: How People Used Games to cope with COVID19 Quarantine

In 2020, the rapid spread of COVID-19 forced many people to self-isolate, resulting in struggles with mental health [60], and an increase in gaming [3]. In this paper, we seek to examine how individuals used digital games during the quarantine. We conducted a two-tier qualitative study where we used a thematic analysis of tweets to derive questions for an online survey that we distributed. Results of thematic analysis of survey responses identified 15 themes. Some themes confirm previous works' findings, particularly how games are used to increase social connection or distract oneself from unpleasant situations. We also found new themes unique to the quarantine, such as interactions with non-player characters used as a surrogate for real-world interaction and using in-game routines as a substitute to real-world routines lost due to the pandemic. This work discusses the use of games during the pandemic and can be seeds for future studies.

Kidney injury molecule 1 is a receptor for SARS-CoV-2 in lung and kidney

Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first reported in Wuhan in 2019 and reached pandemic proportions. SARS-CoV-2-related respiratory failure and acute kidney injury (AKI) are major complications of infection. Kidney Injury Molecule-1 (KIM-1) is a scavenger receptor expressed by kidney epithelial cells and was previously reported to be a receptor for Hepatitis virus A. We hypothesized that KIM-1 is a receptor for SARS-CoV-2 and may play an important role in COVID-19 lung and kidney injury. Methods: Human lung and kidney autopsy samples were immunostained and analyzed. Liposomal nanoparticles displaying the SARS-CoV-2 spike protein on their surface (virosomes) were generated. Virosome uptake by A549 lung epithelial cells, mouse primary lung epithelial cells and human kidney tubuloids (3D structures of kidney epithelial cells) was evaluated in the presences or absence of anti-KIM-1 antibody or TW-37, a small molecule inhibitor of KIM-1-mediated endocytosis that we discovered. Protein-protein interaction characteristics between purified SARS-CoV-2 spike protein and purified KIM-1 were determined using microscale thermophoresis. HEK293 cells expressing human KIM-1 but not angiotensin-converting enzyme 2 (ACE2) were infected with live SARS-CoV-2 or pseudovirions expressing the SARS-CoV-2 spike protein. Results: KIM-1 was expressed in lung and kidney epithelial cells in COVID-19 patient autopsy samples. Human and mouse lung and kidney epithelial cells expressed KIM-1 and endocytosed spike-virosomes. Both anti-KIM-1 antibodies and TW-37 inhibited uptake. Enhanced KIM-1 expression by human kidney tubuloids increased virosome uptake. KIM-1 positive cells expressed less ACE2. Using microscale thermophoresis, the EC50 for interaction between KIM-1 and SARS-CoV-2 spike protein and the receptor binding domain were 56.2±28.8 nM and 9.95±3.10 nM, respectively. KIM-1-expressing HEK293 cells without ACE2 expression had increased susceptibility to infection by live SARS-CoV-2 and pseudovirions expressing spike when compared with control cells. Conclusions: KIM-1 is a receptor for SARS-CoV-2 in the lung and kidney and thus, KIM-1 inhibitors such as TW-37 can be potential therapeutics and/or prophylactic agents for COVID-19.

Kidney organoids represent a novel platform to study adaptive and innate immunity

Background: Human kidney organoids have been utilized as a model to study genetic kidney diseases and kidney development. Innate or adaptive immune responses in organoids are currently poorly defined. Kidney transplant rejection and activation of complement pathways are two common renal immune phenomena. SARS-CoV-2 virus, the pathogen of the recent pandemic, leads to complement pathway activation in human kidneys and can infect kidney organoids. Here, we investigated (i) the alloimmunogenicity of kidney organoids in a humanized mice model, and (ii) the responses to exogenous complement C5a and spike protein (S1) of SARS-CoV-2 in kidney organoids. Methods: Kidney organoids were generated from human embryonic stem cells using protocols developed in our laboratory, and transplanted under the kidney capsule in humanized (BLT) mice. Immunophenotype, mixed lymphocyte reaction, and intracellular cytokine staining were analyzed from grafts and mouse splenocytes collected after 30 days of transplantation. In other experiments organoids were treated with S1 protein and human recombinant C5a for 24 hours or 3 days respectively, followed by qPCR and immunofluorescence analysis. Results: Transplanted organoids were extensively infiltrated by lymphocytes. Graft CD8+ T cells demonstrated a switch from naïve to memory T cells. Splenocytes isolated from transplanted BLT mice showed increased IFN-γ and TNF-α. Splenocytes proliferated after exposure to 2D kidney organoids (MLR) for 72 hours ex vivo, and organoids were markedly injured as reflected by DNA damage (γ-H2AX) and cleaved caspase 3. Reflecting innate responses, robust interstitial fibrosis was found in nontransplanted organoids after direct activation of C5aR by exogenous C5a. We confirmed ACE2 expression on proximal tubules and parietal epithelium of glomeruli, consistent with human autopsy results. Non-transplanted organoids treated with S1 protein showed transcriptionally upregulated C5a1 receptors. Conclusions: Our results indicate the alloimmunogenicity of kidney organoids and the deleterious effects of C5a in kidney organoids. Human kidney organoids represent a novel platform to study renal immunology including adaptive and innate immunity and the inflammatory responses to coronavirus disease (COVID-19).

Kidney injury molecule 1 is a receptor for SARS-COV-2

Background: Acute kidney injury (AKI) is a common feature of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. Kidney Injury Molecule-1 (KIM-1) has been reported to be a receptor for Hepatitis A virus. KIM-1 is a scavenger receptor in kidney epithelial cells. We hypothesized that KIM-1 is a receptor for SARS-CoV-2 and may play an important role in COVID-19-associated AKI. Methods: Liposomal nanoparticles displaying the SARS-CoV-2 spike protein trimer (S1 and S2) on their surface (virosomes) were generated. We evaluated spike protein and virosome uptake by human KIM-1 expressing kidney epithelial cells and human kidney tubuloids, 3D structures of kidney epithelial cells. KIM-1-mediated uptake was compared to uptake by ACE2, a well-known receptor for SARS-CoV-2. Our recently discovered specific KIM-1 uptake inhibitor, JB-1 was tested for its ability to block virosomes uptake by KIM-1 expressing cells. KIM-1 expression was augmented in the tubuloids by infection with adenovirus vector carrying human KIM-1 cDNA to examine if the virosome uptake was enhanced. Protein-protein interaction characteristics between purified SARS-CoV-2 spike protein and S1 binding domain and purified KIM-1 were determined using microscale thermopheresis. Results: KIM-1 expression on kidney epithelial cells markedly enhanced virosome uptake, despite no change in ACE2 expression. This KIM-1 specific uptake was inhibited by JB-1. Human kidney tubuloids also endocytosed virosomes, and tubuloids with enhanced KIM-1 expression secondary to infection of KIM-1-adenovirus had increased uptake of virosomes. Using microscale thermopheresis the Kd for interaction between KIM-1 and SARS-CoV-2 spike protein and the receptor binding domain were 56.2+/-28.8 nM and 9.95+/-3.10 nM respectively. Conclusions: KIM-1 is a receptor for SARS-CoV-2. KIM-1 specific uptake of the SARS-CoV-2- virosomes suggests that KIM-1 confers efficient SARS-CoV-2 binding in kidney epithelial cells when these cells are expressing KIM-1. The KIM-1 dependent virosome uptake by 3D tubuloids indicates that this can be a valuable human cell model for studying SARS-CoV-2 interactions and testing for inhibitors. KIM-1 inhibitors, such as JB-1, can be potential therapeutics SARS-CoV-2 for COVID-19. Kidney tubular intraluminal and systemic circulating levels of KIM-1 ectodomain may be protective by acting as decoy receptor for the virus.