No genetic causal association between systemic lupus erythematosus and COVID-19.

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2.

BACKGROUND: The distribution of ACE2 and accessory proteases (ANAD17 and CTSL) in cardiovascular tissue and the host cell receptor binding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial to understanding the virus's cell invasion, which may play a significant role in determining the viral tropism and its clinical manifestations. METHODS: We conducted a comprehensive analysis of the cell type-specific expression of ACE2, ADAM17, and CTSL in myocardial tissue from 10 patients using RNA sequencing. Our study included a meta-analysis of 2 heart single-cell RNA-sequencing studies with a total of 90,024 cells from 250 heart samples of 10 individuals. We used co-expression analysis to locate specific cell types that SARS-CoV-2 may invade. RESULTS: Our results revealed cell-type specific associations between male gender and the expression levels of ACE2, ADAM17, and CTSL, including pericytes and fibroblasts. AGT, CALM3, PCSK5, NRP1, and LMAN were identified as potential accessory proteases that might facilitate viral invasion. Enrichment analysis highlighted the extracellular matrix interaction pathway, adherent plaque pathway, vascular smooth muscle contraction inflammatory response, and oxidative stress as potential immune pathways involved in viral infection, providing potential molecular targets for therapeutic intervention. We also found specific high expression of IFITM3 and AGT in pericytes and differences in the IFN-II signaling pathway and PAR signaling pathway in fibroblasts from different cardiovascular comorbidities. CONCLUSIONS: Our data indicated possible high-risk groups for COVID-19 and provided emerging avenues for future investigations of its pathogenesis. TRIAL REGISTRATION: (Not applicable).

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission.

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.

COVID-19 vaccination hesitancy and safety among adult people with epilepsy in eastern China.

OBJECTIVE: This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE). METHODS: We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed. RESULTS: A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37-0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55-0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06-4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75-129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57-337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination. CONCLUSION: Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE.

A phantom study of a protective trolley for neonatal radiographic imaging: new equipment to protect the operator from scatter radiation.

Chest radiography is commonly performed as a diagnostic tool of neonatal diseases. Contact-based radiation personal protective equipment (RPPE) has been widely used for radiation protection, but it does not provide full body protection and it is often shared between users, which has become a major concern during the coronavirus disease 2019 (COVID-19) pandemic. To address these issues, we developed a novel trolley to protect radiographers against X-ray radiation by reducing scatter radiation during neonatal radiographic examinations. We measured the scatter radiation doses from a standard neonatal chest radiograph to the radiosensitive organs using a phantom operator in three protection scenarios (trolley, radiation personal protective equipment [RPPE], no protection) and at three distances. The results showed that the scatter radiation surface doses were significantly reduced when using the trolley compared with RPPE and with no protection at a short distance (P<0.05 for both scenarios in all radiosensitive organs). The novel protective trolley provides a non-contact protective tool for radiographers against the hazard of scatter radiation during neonatal radiography examinations.

Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection.

Background: The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative. Methods: We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student's unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs' ability to identify breakthrough infected individuals in the vaccinated population. Results: The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population. Conclusion: Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.

Real-time detection of viruses in aerosols with weak light imaging based on Tesla discharge

The analysis and detection of nucleic acid and specific antigens and antibodies are the most basic technologies for virus monitoring. However, the potential window for applying these technologies exists within a late specific period in the early monitoring and control of unknown viruses, especially human and animal pathogenic viruses transmitted via aerosols, e.g., SARS-CoV-2 and its variants. This is because early, real-time, and convenient monitoring of unknown viruses in the air or exhaled gas cannot be directly achieved through existing technologies. Herein, we report a weak light spectral imaging technology based on Tesla discharge (termed T-DAI) that can quickly monitor for viruses in real time in simulated aerosols with 71% sensitivity and 76% specificity for aerosol virus concentrations exceeding approximately 2800 vp/μl. This technology realizes the rapid detection of low concentrations of viruses in aerosols and could provide an important means for predicting, screening, and monitoring unknown or pandemic pathogenic viruses in the air or exhaled breath of humans and animals. [ FROM AUTHOR] Copyright of Applied Physics Letters is the property of American Institute of Physics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: This study aimed to investigate the seroreactivity of Coronavirus disease 2019 (COVID-19) vaccination and its adverse events among systemic lupus erythematosus (SLE) patients, rheumatoid arthritis (RA) patients, and healthy controls (HCs). METHODS: A total of 60 SLE patients, 70 RA patients and 35 HCs, who received a complete inactivated COVID-19 vaccine (Vero cells) regimen, were recruited in the current study. Serum IgG and IgM antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2, and the self-reported vaccination-related adverse events among SLE patients, RA patients and HCs. The inactivated COVID-19 vaccines appeared to be well-tolerated and moderately immunogenic. In addition, case-only analysis indicated that in SLE patients, the disease manifestation of rash and anti-SSA autoantibody were associated with seroprevalence of IgG antibody against SARS-CoV-2, whereas the uses of ciclosporin and leflunomide had influence on the seroprevalence of IgM antibody against SARS-CoV-2. In RA patients, rheumatoid factor (RF) appeared to be associated with the seroprevalence of IgG antibody against SARS-CoV-2. CONCLUSION: Our study reveals that the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar among SLE, RA and HCs, suggesting that COVID-19 vaccine is safe and effective for SLE and RA patients to prevent from the pandemic of COVID-19.

Face Masks, Public Policies and Slowing the Spread of COVID-19: Evidence from Canada

We estimate the impact of mask mandates and other non-pharmaceutical interventions (NPI) on COVID-19 case growth in Canada, including regulations on businesses and gatherings, school closures, travel and self-isolation, and long-term care homes. We partially account for behavioral responses using Google mobility data. Our identification approach exploits variation in the timing of indoor face mask mandates staggered over two months in the 34 public health regions in Ontario, Canada's most populous province. We find that, in the first few weeks after implementation, mask mandates are associated with a reduction of 25 percent in the weekly number of new COVID-19 cases. Additional analysis with province-level data provides corroborating evidence. Counterfactual policy simulations suggest that mandating indoor masks nationwide in early July could have reduced the weekly number of new cases in Canada by 25 to 40 percent in mid-August, which translates into 700 to 1,100 fewer cases per week.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Face masks, public policies and slowing the spread of COVID-19: Evidence from Canada.

We estimate the impact of indoor face mask mandates and other non-pharmaceutical interventions (NPI) on COVID-19 case growth in Canada. Mask mandate introduction was staggered from mid-June to mid-August 2020 in the 34 public health regions in Ontario, Canada's largest province by population. Using this variation, we find that mask mandates are associated with a 22 percent weekly reduction in new COVID-19 cases, relative to the trend in absence of mandate. Province-level data provide corroborating evidence. We control for mobility behaviour using Google geo-location data and for lagged case totals and case growth as information variables. Our analysis of additional survey data shows that mask mandates led to an increase of about 27 percentage points in self-reported mask wearing in public. Counterfactual policy simulations suggest that adopting a nationwide mask mandate in June could have reduced the total number of diagnosed COVID-19 cases in Canada by over 50,000 over the period July-November 2020. Jointly, our results indicate that mandating mask wearing in indoor public places can be a powerful policy tool to slow the spread of COVID-19.

Development and application of an indirect enzyme-linked immunosorbent assay using recombinant S1 for serological testing of porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) causes severe infectious diseases in all ages of swine and leads to serious economic losses. Serologic tests are widely accepted and used to detect anti-PEDV antibodies that could indicate PEDV infection or vaccination. In this study, PEDV recombinant S1 protein (rS1) was expressed with the Bac-to-Bac system and purified by nickel-affinity chromatography. An indirect enzyme-linked immunosorbent assay based on rS1 (rS1-ELISA) was then developed and optimized by checkerboard assays with serial dilutions of antigen and serum. Serum samples from 453 domestic pigs and 42 vaccinated pigs were analyzed by the indirect fluorescent antibody (IFA) test and rS1-ELISA. Taking IFA as a gold standard, rS1-ELISA produced a high sensitivity (90.7%) and specificity (94.6%) by a receiver operating characteristic (ROC) curve. In addition, ROC analysis also revealed that rS1-ELISA was consistent with IFA (area under the curve 0.9583 +or- 0.0082). This rS1-ELISA was then applied to antibody detection in inactivated PEDV vaccinated pigs. The antibody could be detected 2-4 weeks after the first inoculation. These results indicated that the rS1-ELISA established in this study provides a promising and reliable tool for serologic detection of anti-PEDV IgG antibodies in infected or vaccinated pigs.

Epithelial cell-specific loss of function of Miz1 causes a spontaneous COPD-like phenotype and up-regulates Ace2 expression in mice.

Cigarette smoking, the leading cause of chronic obstructive pulmonary disease (COPD), has been implicated as a risk factor for severe disease in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we show that mice with lung epithelial cell-specific loss of function of Miz1, which we identified as a negative regulator of nuclear factor κB (NF-κB) signaling, spontaneously develop progressive age-related changes resembling COPD. Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2. Concomitant partial loss of NF-κB/RelA prevented the development of COPD-like phenotype in Miz1-deficient mice. Miz1 protein levels are reduced in the lungs from patients with COPD, and in the lungs of mice exposed to chronic cigarette smoke. Our data suggest that Miz1 down-regulation-induced sustained activation of NF-κB-dependent inflammation in the lung epithelium is sufficient to induce progressive lung and airway destruction that recapitulates features of COPD, with implications for COVID-19.

Real-time naive case fatality rates can reflect timeliness of case confirmation during pandemics.

An objective law was observed that naive case fatality rates (CFRs) of a disease will decrease early and then gradually increase infinitely near the true CFR as time went on during an outbreak. The normal growth of naive CFR was an inherent character rather than indicating the disease was becoming more severe. According to the law, by monitoring real-time naive CFRs, it can help outbreak-controllers know if there were many cases left unconfirmed or undiscovered in the outbreak. We reflected on the use of the naive CFR in the context of COVID-19 outbreaks. The results showed that Hubei Province of China, France and South Korea had cases that were not confirmed in a timely manner during the initial stages of the outbreak. Delayed case confirmations existed for long periods of time in France, Italy, the United Kingdom, the Netherlands and Spain. Monitoring of real-time naive CFRs could be helpful for decision-makers to identify under-reporting of cases during pandemics.

Non-optimal effectiveness of convalescent plasma transfusion and hydroxychloroquine in treating COVID-19: a case report.

BACKGROUND: Convalescent plasma (CP) transfusion was reported to be effective in treating critically ill patients with COVID-19, and hydroxychloroquine could potently inhibit SARS-CoV-2 in vitro. Herein, we reported a case receiving combination therapy with CP transfusion and hydroxychloroquine for the first time. CASE PRESENTATION: Laboratory findings showed high lactic acid level (2.1 mmol/L) and C-reactive protein (CRP, 48.8 mg/L), and low white blood cell count (1.96 × 109/L) in a 65-year-old Chinese man, who was diagnosed with severe COVID-19. CP was intravenously given twice, and hydroxychloroquine was orally administrated for a week (0.2 g, three times a day). The lactic acid and C-reactive protein levels remained high (2.1 mmol/L and 73.23 mg/L, respectively), while the arterial oxyhemoglobin saturation decreased to 86% with a low oxygenation index (OI, 76 mmHg) on day 4 after CP transfusion. His temperature returned to normal and the OI ascended above 300 on day 11. Moreover, the RNA test remained positive in throat swab, and computed tomography revealed severe pulmonary lesions on day 11 after admission. CONCLUSION: These findings suggested that the effectiveness of combination therapy with CP and hydroxychloroquine may be non-optimal, and specific therapy needs to be explored.

Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19.

Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.

Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19.

OBJECTIVES: To compare the clinical characteristics and the dynamics of viral load between imported and non-imported patients with COVID-19. DESIGN AND METHODS: Data from 51 laboratory-confirmed patients were retrospectively analyzed. RESULTS: The incubation period in the tertiary group was longer than that in the imported and secondary groups (both p < 0.05). Fever was the most common symptom at the onset of illness (73.33%, 58.82%, and 68.42%, respectively), and half of the patients had a low-grade temperature (<38.0 °C) with a short duration of fever (<7 days). CT scans showed that most patients in the three groups had bilateral pneumonia (80.00%, 76.47%, and 73.68%, respectively). Ct values detected in the tertiary patients were similar to those for the imported and secondary groups at the time of admission (both p > 0.05). For the tertiary group, the viral load was undetectable in half of the patients (52.63%) on day 7, and in all patients on day 14. For one third of the patients in the imported and secondary groups, the viral load remained positive on day 14 after the admission. CONCLUSIONS: COVID-19 can present as pneumonia with a low onset of symptoms, and the infectivity of SARS-CoV2 may gradually decrease in tertiary patients.