MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice. METHODS: Whole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8+ T cells. RESULTS: Our results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2Kd showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2Kb in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2Kb inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8+ T cells caused by SARS-CoV-2/BMA8 infection. CONCLUSIONS: Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.

Isolation of a Novel Bat Rhabdovirus with Evidence of Human Exposure in China.

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

Distinct core glycan and O-glycoform utilization of SARS-CoV-2 Omicron variant Spike protein RBD revealed by top-down mass spectrometry.

The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations particularly in the S receptor-binding domain (S-RBD) that significantly improve transmissibility and evasion of neutralizing antibodies. But exactly how the mutations in the Omicron variant enhance viral escape from immunological protection remains to be understood. The S-RBD remains the principal target for neutralizing antibodies and therapeutics, thus new structural insights into the Omicron S-RBD and characterization of the post-translational glycosylation changes can inform rational design of vaccines and therapeutics. Here we report the molecular variations and O-glycoform changes of the Omicron S-RBD variant as compared to wild-type (WA1/2020) and Delta (B.1.617.2) variants using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings reveal high resolution detail of Omicron O-glycoforms and their utilization to provide direct molecular evidence of proteoform alterations in the Omicron variant which could shed light on how this variant escapes immunological protection.

Distinct core glycan and O-glycoform utilization of SARS-CoV-2 Omicron variant Spike protein RBD revealed by top-down mass spectrometry† † Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2sc02132c

The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations particularly in the S receptor-binding domain (S-RBD) that significantly improve transmissibility and evasion of neutralizing antibodies. But exactly how the mutations in the Omicron variant enhance viral escape from immunological protection remains to be understood. The S-RBD remains the principal target for neutralizing antibodies and therapeutics, thus new structural insights into the Omicron S-RBD and characterization of the post-translational glycosylation changes can inform rational design of vaccines and therapeutics. Here we report the molecular variations and O-glycoform changes of the Omicron S-RBD variant as compared to wild-type (WA1/2020) and Delta (B.1.617.2) variants using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings reveal high resolution detail of Omicron O-glycoforms and their utilization to provide direct molecular evidence of proteoform alterations in the Omicron variant which could shed light on how this variant escapes immunological protection. Top-down mass spectrometry reveals O-glycoform structural changes in the SARS-CoV-2 Omicron variant. Resolving the mutations and post-translational alterations can inform strategies for designing variant-directed diagnostics and therapeutics.

Distinct Core Glycan and O-Glycoform Utilization of SARS-CoV-2 Omicron Variant Spike Protein RBD Revealed by Top-Down Mass Spectrometry.

The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations particularly in the S receptor-binding domain (S-RBD) that significantly improve transmissibility and evasion of neutralizing antibodies. But exactly how the mutations in the Omicron variant enhance viral escape from immunological protection remains to be understood. The S-RBD remains the principal target for neutralizing antibodies and therapeutics, thus new structural insights into the Omicron S-RBD and characterization of the post-translational glycosylation changes can inform rational design of vaccines and therapeutics. Here we report the molecular variations and O-glycoform changes of the Omicron S-RBD variant as compared to wild-type (WA1/2020) and Delta (B.1.617.2) variants using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings reveal high resolution detail of Omicron O-glycoforms and their utilization to provide direct molecular evidence of proteoform alterations in the Omicron variant which could shed light on how this variant escapes immunological protection.

Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries

IntroductionRegardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic.ObjectivesIn our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic.MethodsA multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail.ResultsAmong the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance.ConclusionsWe found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy.

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated genes. Then, mitochondrial antiviral signaling protein (MAVS) was identified as the target via which ORF10 suppresses the IFN-I signaling pathway, and MAVS was found to be degraded through the ORF10-induced autophagy pathway. Furthermore, overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced mitophagy. Mechanistically, ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X (NIX) and induced mitophagy through its interaction with both NIX and LC3B. Moreover, knockdown of NIX expression blocked mitophagy activation, MAVS degradation, and IFN-I signaling pathway inhibition by ORF10. Consistent with our observations, in the context of SARS-CoV-2 infection, ORF10 inhibited MAVS expression and facilitated viral replication. In brief, our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response; that is, ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX.

The Associations of Lymphocyte Ratio and Neutrophil Ratio on Liver Dysfunction in COVID-19 Patients.

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.

A novel SARS-CoV-2 related coronavirus with complex recombination isolated from bats in Yunnan province, China.

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.

Structural O-Glycoform Heterogeneity of the SARS-CoV-2 Spike Protein Receptor-Binding Domain Revealed by Top-Down Mass Spectrometry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes an extensively glycosylated surface spike (S) protein to mediate host cell entry, and the S protein glycosylation plays key roles in altering the viral binding/function and infectivity. However, the molecular structures and glycan heterogeneity of the new O-glycans found on the S protein regional-binding domain (S-RBD) remain cryptic because of the challenges in intact glycoform analysis by conventional bottom-up glycoproteomic approaches. Here, we report the complete structural elucidation of intact O-glycan proteoforms through a hybrid native and denaturing top-down mass spectrometry (MS) approach employing both trapped ion mobility spectrometry (TIMS) quadrupole time-of-flight and ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR)-MS. Native top-down TIMS-MS/MS separates the protein conformers of the S-RBD to reveal their gas-phase structural heterogeneity, and top-down FTICR-MS/MS provides in-depth glycoform analysis for unambiguous identification of the glycan structures and their glycosites. A total of eight O-glycoforms and their relative molecular abundance are structurally elucidated for the first time. These findings demonstrate that this hybrid top-down MS approach can provide a high-resolution proteoform-resolved mapping of diverse O-glycoforms of the S glycoprotein, which lays a strong molecular foundation to uncover the functional roles of their O-glycans. This proteoform-resolved approach can be applied to reveal the structural O-glycoform heterogeneity of emergent SARS-CoV-2 S-RBD variants as well as other O-glycoproteins in general.

Association between well-being and compliance with COVID-19 preventive measures by healthcare professionals: A cross-sectional study.

IMPORTANCE: Knowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness. OBJECTIVE: This survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals. DESIGN: Multi-national cross-sectional study was carried out using electronic surveys between May-June 2020. SETTING: Multi-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail. PARTICIPANTS: Participants ≥21 years working in healthcare and non-healthcare related professions. MAIN OUTCOME: Risk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP. RESULTS: HCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being. CONCLUSION AND RELEVANCE: While healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome.

BACKGROUND AND AIM: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. METHODS: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. RESULTS: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. CONCLUSION: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

IDDF2020-ABS-0205 The impact of the COVID-19 pandemic on irritable bowel syndrome

IDDF2020-ABS-0205 Table 1Comparison of demographic variables between respondents with and without IBS Non-IBS (n = 2024) IBS (n = 305) p Age 39.7 ± 12.9 40.1 ± 13.0 1.0 Gender 0.6 Male 727 (35.9) 119 (39.0) Female 1297 (64.1) 186 (61.0) Race 0.2 Bengali 31 (1.5) 2 (0.7) Caucasian 24 (1.2) 6 (2.0) Chinese 1148 (56.7) 188 (61.6) Filipino 45 (2.2) 2 (0.7) Indian 154 (7.6) 20 (6.6) Japanese 5 (0.2) 0 (0.0) Korean 131 (6.5) 28 (9.2) Malay 328 (16.2) 39 (12.8) Others 158 (7.8) 20 (6.6) Economic region 0.3 High 1156 (57.1) 183 (60.0) Upper-middle 457 (22.6) 74 (24.3) Middle/Low 411 (20.3) 48 (15.7) What is your highest education level? 0.8 No formal education/Primary school 9 (0.4) 0 (0.0) Secondary school 164 (8.1) 29 (9.5) Pre-university 258 (12.7) 44 (14.4) Tertiary – undergraduate/postgraduate degree 1593 (78.7) 232 (76.1) Employment 0.4 Full-time 1497 (74.0) 213 (69.8) Part-time 125 (6.2) 18 (5.9) Not working 402 (19.9) 74 (24.3) Housing 1.0 Dormitory 61 (3.0) 13 (4.3) Government housing with 2 or 3 rooms 306 (15.1) 37 (12.1) Government housing with more than 3 rooms 376 (18.6) 62 (20.3) Private apartment or condominium 601 (29.7) 89 (29.2) Private landed property 680 (33.6) 104 (34.1) Annual household Income per capita in USD (total household income/number of people in the household) 1.0 Less than $1000 259 (12.8) 37 (12.1) $1000 - $2000 274 (13.5) 46 (15.1) $2000 - $4000 375 (18.5) 49 (16.1) $4000 - $6000 211 (10.4) 29 (9.5) $6000 - $8000 138 (6.8) 24 (7.9) $8000 - $10000 173 (8.5) 23 (7.5) More than $10000 594 (29.3) 97 (31.8) Have you been diagnosed with COVID-19? 1.0 Yes 32 (1.6) 4 (1.3) No 1992 (98.4) 301 (98.7) Compliance 0.029 Yes 715 (35.3) 86 (28.2) No 1309 (64.7) 219 (71.8) Not flourishing 1025 (50.6) 207 (67.9) <0.01 Flourishing 999 (49.4) 98 (32.1) Well-being total scores 45.8 ± 14.6 40.5 ± 14.8 <0.01 Emotional well-being 10.3 ± 3.5 9.4 ± 3.6 <0.01 Social well-being 15.0 ± 6.1 12.8 ± 6.1 <0.01 Psychological well-being 20.4 ± 6.6 18.3 ± 6.7 <0.01 Abstract IDDF2020-ABS-0205 Table 2Comparison of demographic variables between respondents who reported no change and worsening in severity of IBSQuestion No change (n = 183) Worsen (n = 35) p Age 38.8 ± 12.2 40.1 ± 14.3 1.0 Gender 1.0 Male 71 (38.8) 14 (40.0) Female 112 (61.2) 21 (60.0) Economic region 0.1 High 110 (60.1) 28 (80.0) Upper-middle 44 (24.0) 6 (17.1) Middle/Low 29 (15.8) 1 (2.9) What is your highest education level? 1.0 Secondary school 18 (9.8) 4 (11.4) Pre-university 22 (12.0) 5 (14.3) Tertiary – undergraduate/postgraduate degree 143 (78.1) 26 (74.3) Employment 0.2 Full-time 132 (72.1) 26 (74.3) Part-time 7 (3.8) 4 (11.4) Not working 44 (24.0) 5 (14.3) Work from home 1.0 Yes 45 (32.1) 8 (26.7) No 95 (67.9) 22 (73.3) Compliance 1.0 Yes 54 (29.5) 10 (28.6) No 129 (70.5) 25 (71.4) Which of the following would you consider as main reason for compliance with social distancing measures? 0.034 Fear of getting COVID 19 90 (49.2) 11 (31.4) Fear of family members getting COVID 19 86 (47.0) 19 (54.3) Fear of fines/punitive measures 7 (3.8) 5 (14.3) Would you willingly participate in the contact tracing app? 1.0 Yes 143 (78.1) 27 (77.1) No 40 (21.9) 8 (22.9) For how long are you willing to practice social distancing behaviour to keep yourself and others safe? 0.016 As long as it takes 137 (74.9) 18 (51.4) For another 2–3 weeks 4 (2.2) 4 (11.4) For another 1 month 12 (6.6) 6 (17.1) For another 3 months 14 (7.7) 5 (14.3) For another 6 months 13 (7.1) 1 (2.9) I want social distancing to stop now 3 (1.6) 1 (2.9) Flourishing <0.01 Yes 64 (35.0) 3 (8.6) No 119 (65.0) 32 (91.4) Well-being total scores 40.5 ± 15.0 35.4 ± 13.3 0.1 Emotional well-being 9.5 ± 3.5 7.7 ± 3.6 0.014 Social well-being 12.7 ± 6.3 11.7 ± 4.7 0.8 Psychological well-being 18.3 ± 6.9 15.9 ± 6.5 0.1 Abstract IDDF2020-ABS-0205 Table 3Univariable and multivariable regression of factors associated with worsening in severity of IBS (with no change in severity of IBS group as reference)Question OR (95% CI) p AdjOR(95%CI) p Do you wash your hands before and after handing food?* Never (ref) 1.00 - - Seldom 0.0 (0.0) 1.0 - - 50% of the time 0.0 (0.0) 1.0 - - Most of the time 0.0 (0.0) 1.0 - - Always 0.0 (0.0) 1.0 - - Do you cover your mouth when you sneeze or cough?* Never (ref) 1.00 - - Seldom 0.0 (0.0) 1.0 - - 50% of the time 0.0 (0.0) 1.0 - - Most of the time 0.0 (0.0) 1.0 - - Always 0.0 (0.0) 1.0 - - Which of the following would you consider as main reason for compliance with social distancing measures? Fear of getting COVID 19 (ref) 1.00 1.00 Fear of family members getting COVID 19 1.8 (0.8 – 4.0) 0.1 2.0 (0.9 – 4.7) 0.1 Fear of fines/punitive measures 5.8 (1.6 – 21.6) <0.01 5.9 (1.4 – 25.6) 0.017 For how long are you willing to practice social distancing behaviour to keep yourself and others safe? As long as it takes (ref) 1.00 1.00 For another 2–3 weeks 7.6 (1.7 – 33.1) <0.01 6.0 (1.2 – 28.8) 0.026 For another 1 month 3.8 (1.3 – 11.4) 0.017 2.9 (0.9 – 9.0) 0.1 For another 3 months 2.7 (0.9 – 8.4) 0.1 3.1 (0.9 – 10.2) 0.1 For another 6 months 0.6 (0.1 – 4.7) 0.6 0.6 (0.1 – 4.7) 0.6 I want social distancing to stop now 2.5 (0.3 – 25.7) 0.4 1.3 (0.1 – 22.3) 0.9 Emotional well-being 0.9 (0.8 – 1.0) <0.01 0.9 (0.8 – 1.0) 0.042 Flourishing was excluded from analysis due to overlap with emotional well-being.*Excluded from multivariable analysis due to 0 respondents in reference categories for respondents with no change in control IBSConclusionsOur study showed differences in well-being and compliance to social distancing between IBS and non-IBS respondents, and these factors influence the worsening in severity of IBS. Further research will focus on how occupational stress and dietary changes may influence IBS symptoms

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

A Universal Screening Strategy for SARS-CoV-2 Infection in Intensive Care Units: Korean Experience in a Single Hospital

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols. This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP). MATERIALS AND METHODS: This prospective single-armed observational study was conducted in 2 ICUs of a single hospital. The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated. RESULTS: During the 7-week study period, no positive screening case was reported among a total of 142 patients. Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks. CONCLUSION: A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable.

Bacterial modification of the host glycosaminoglycan heparan sulfate modulates SARS-CoV-2 infectivity (preprint)

The human microbiota has a close relationship with human disease and it remodels components of the glycocalyx including heparan sulfate (HS). Studies of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike protein receptor binding domain suggest that infection requires binding to HS and angiotensin converting enzyme 2 (ACE2) in a codependent manner. Here, we show that commensal host bacterial communities can modify HS and thereby modulate SARS-CoV-2 spike protein binding and that these communities change with host age and sex. Common human-associated commensal bacteria whose genomes encode HS-modifying enzymes were identified. The prevalence of these bacteria and the expression of key microbial glycosidases in bronchoalveolar lavage fluid (BALF) was lower in adult COVID-19 patients than in healthy controls. The presence of HS-modifying bacteria decreased with age in two large survey datasets, FINRISK 2002 and American Gut, revealing one possible mechanism for the observed increase in COVID-19 susceptibility with age. In vitro, bacterial glycosidases from unpurified culture media supernatants fully blocked SARS-CoV-2 spike binding to human H1299 protein lung adenocarcinoma cells. HS-modifying bacteria in human microbial communities may regulate viral adhesion, and loss of these commensals could predispose individuals to infection. Understanding the impact of shifts in microbial community composition and bacterial lyases on SARS-CoV-2 infection may lead to new therapeutics and diagnosis of susceptibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/238444v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@14ff1ecorg.highwire.dtl.DTLVardef@193d84corg.highwire.dtl.DTLVardef@15d6f9eorg.highwire.dtl.DTLVardef@14b16c6_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract. Diagram of hypothesis for bacterial mediation of SARS-CoV-2 infection through heparan sulfate (HS).It is well known that host microbes groom the mucosa where they reside. Recent investigations have shown that HS, a major component of mucosal layers, is necessary for SARS-CoV-2 infection. In this study we examine the impact of microbial modification of HS on viral attachment. C_FIG