Pathogenesis and Management of Acute Necrotizing Encephalopathy.

INTRODUCTION: During the COVID-19 pandemic, many cases of acute necrotizing encephalopathy (ANE) secondary to COVID-19 have been reported. ANE is characterized by a rapid onset, a fulminant course, and low morbidity and fatality rates. Therefore, clinicians need to be vigilant for such disorders, especially during the influenza virus and COVID-19 epidemics. AREAS COVERED: The authors summarize the most recent studies on the clinical spectrum and treatment essentials of ANE to provide references for prompt diagnosis and improved treatment of this rare but fatal disease. EXPERT OPINION: ANE is a type of necrotizing lesion of the brain parenchyma. There are two major types of reported cases. One is isolated and sporadic ANE, which is primarily caused by viral infections, particularly influenza and HHV-6 virus. The other type is familial recurrent ANE, which is caused by RANBP2 gene mutations. ANE patients have rapid progression and a very poor prognosis, with acute brain dysfunction occurring within days of viral infection and requiring admission to the intensive care unit. Clinicians still need to investigate and find solutions for the problems of early detection and treatment of ANE.

Corrigendum: COVID-19 and sudden sensorineural hearing loss: a systematic review.

[This corrects the article DOI: 10.3389/fneur.2022.883749.].

Identification of Darunavir Derivatives for Inhibition of SARS-CoV-2 3CLpro.

The effective antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed around the world. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a pivotal role in virus replication; it also has become an important therapeutic target for the infection of SARS-CoV-2. In this work, we have identified Darunavir derivatives that inhibit the 3CLpro through a high-throughput screening method based on a fluorescence resonance energy transfer (FRET) assay in vitro. We found that the compounds 29# and 50# containing polyphenol and caffeine derivatives as the P2 ligand, respectively, exhibited favorable anti-3CLpro potency with EC50 values of 6.3 µM and 3.5 µM and were shown to bind to SARS-CoV-2 3CLpro in vitro. Moreover, we analyzed the binding mode of the DRV in the 3CLpro through molecular docking. Importantly, 29# and 50# exhibited a similar activity against the protease in Omicron variants. The inhibitory effect of compounds 29# and 50# on the SARS-CoV-2 3CLpro warrants that they are worth being the template to design functionally improved inhibitors for the treatment of COVID-19.

Direct Quantitation of SARS-CoV-2 Virus in Urban Ambient Air via a Continuous-Flow Electrochemical Bioassay.

Airborne SARS-CoV-2 virus surveillance faces challenges in complicated biomarker enrichment, interferences from various non-specific matters and extremely low viral load in the urban ambient air, leading to difficulties in detecting SARS-CoV-2 bioaerosols. This work reports a highly specific bioanalysis platform, with an exceptionally low limit-of-detection (≤1 copy m-3 ) and good analytical accordance with RT-qPCR, relying on surface-mediated electrochemical signaling and enzyme-assisted signal amplification, enabling gene and signal amplification for accurate identification and quantitation of low doses human coronavirus 229E (HCoV-229E) and SARS-CoV-2 viruses in urban ambient air. This work provides a laboratory test using cultivated coronavirus to simulate the airborne spread of SARS-CoV-2, and validate that the platform could reliably detect airborne coronavirus and reveal the transmission characteristics. This bioassay conducts the quantitation of real-world HCoV-229E and SARS-CoV-2 in airborne particulate matters collected from road-side and residential areas in Bern and Zurich (Switzerland) and Wuhan (China), with resultant concentrations verified by RT-qPCR.

Rapid screening of benzyl dodecyl dimethyl ammonium bromide co-metabolic degrading bacteria based on NIR hyperspectral imaging technology.

As a typical disinfectant, the use of benzyl dodecyl dimethyl ammonium bromide (BDAB) has dramatically increased since the emergence of SARS-CoV-2, posing a threat to environmental balance and human health. Screening BDAB co-metabolic degrading bacteria is required for efficient microbial degradation. Conventional methods for screening co-metabolic degrading bacteria are laborious and time-consuming, especially when the number of strains is large. This study aimed to develop a novel method for the rapid screening of BDAB co-metabolic degrading bacteria from the cultured solid medium using near-infrared hyperspectral imaging (NIR-HSI) technology. Based on NIR spectra, the concentration of BDAB in the solid medium can be well predicted by partial least squares regression (PLSR) models, non-destructively and rapidly, with Rc2 > 0.872 and Rcv2 > 0.870. The results show that the predicted BDAB concentrations decrease after degrading bacteria utilization, comparing with the regions where no degrading bacteria grew. The proposed method was applied to directly identify the BDAB co-metabolic degrading bacteria cultured on the solid medium, and two kinds of co-metabolic degrading bacteria RQR-1 and BDAB-1 were correctly identified. This method provides a high-efficiency method for screening BDAB co-metabolic degrading bacteria from a large number of bacteria.

Inhibitory activities of a sulfated oligo-porphyran from Pyropia yezoensis against SARS-CoV-2

COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-β-d-Gal-(1 → 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-l-Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibited the infection with an EC50 of 37.52 μg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Case report: Acute hepatitis in neonates with COVID-19 during the Omicron SARS-CoV-2 variant wave: a report of four cases.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), first emerging in December 2019 and continuously evolving, poses a considerable challenge worldwide. It was reported in the literature that neonates had mild upper respiratory symptoms and a better outcome after Omicron SARS-CoV-2 variant infection, but there was insufficient data about complications and prognosis. Case Presentation: In this paper, we present the clinical and laboratory characteristics of four COVID-19 neonate patients with acute hepatitis during the Omicron SARS-CoV-2 variant wave. All patients had a clear history of Omicron exposure and were infected via contact with confirmed caregivers. Low to moderate fever and respiratory symptoms were the primary clinical manifestations, and all patients had a normal liver function at the initial stage of the course. Then, the fever lasted 2 to 4 days, and it was noted that hepatic dysfunction might have occurred 5 to 8 days after the first onset of fever, mainly characterized by moderate ALT and AST elevation (>3 to 10-fold of upper limit). There were no abnormalities in bilirubin levels, blood ammonia, protein synthesis, lipid metabolism, and coagulation. All the patients received hepatoprotective therapy, and transaminase levels gradually decreased to the normal range after 2 to 3 weeks without other complications. Conclusions: This is the first case series about moderate to severe hepatitis in COVID-19 neonatal patients via horizontal transmission. Besides fever and respiratory symptoms, the clinical doctor should pay much attention to evaluating the risk of liver function injury after SARS-CoV-2 variants infection, which is usually asymptomatic and has a delayed onset.

Low molecular weight fucoidan attenuating pulmonary fibrosis by relieving inflammatory reaction and progression of epithelial-mesenchymal transition

Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti-epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found the expression of COL2A1, β-catenin, TGF-β, TNF-α and IL-6 were declined in mice lung tissue. Besides, the phosphorylation of PI3K and Akt were inhibited by LMWF. In addition, the progression of EMT induced by TGF-β1 was inhibited by LMWF through down-regulated both TGF-β/Smad and PI3K/AKT signaling pathways. These data indicate that unique LMWF can protect the lung from fibrosis by weakening the process of inflammation and EMT, and it is a promising therapeutic option for the treatment of PF.

Dynamic and classifier-based model SARS-CoV-2 Omicron spillover risk assessment in China

The coronavirus disease 2019 (COVID-19) continues to have a huge impact on health care and economic systems around the world. The first question to ponder is to understand the flow of COVID-19 in the spatial and temporal dimensions. We collected 7 Omicron clusters outbreaks in China since the outbreak of COVID-19 as of August 2022, selected outbreak cases from different Provinces and cities, and collected variable indicators that affect spillover outcomes, such as distance, migration index, PHSM index, daily reported cases number and so on. First, variables influencing spillover outcome events were assessed and analyzed retrospectively by constructing an infectious disease dynamics model and a classifier model, and secondly, the association between explanatory variables and spillover outcome events was constructed by fitting a logistics function. This study incorporates 7 influencing factors and classifies the spillover risk level into 3 levels. If different outbreak sites could be classified into different levels of spillover, it may reduce the pressure of epidemic prevention in some cities due to the lack of a uniform standard, which might be more conducive to achieving the goal of "dynamic zero".

Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase.

COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound, against SARS-CoV-2 infection in vitro. The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage. Mechanistically, the inhibition of viral replication by oridonin depends on the oxidation activity of α, ß-unsaturated carbonyl. Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity, but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations. In particular, oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants (BA.1 and BA.2), which highlights its potential as a pan-coronavirus antiviral agent. Overall, our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.

Moxibustion Treatment of COVID-19 and Rehabilitation Period of COVID-19: A Scoping Review.

Objective: The aim of this study is to provide a scoping review of the clinical literature on moxibustion therapy for the treatment of Coronavirus disease 2019 (COVID-19). Design: The PubMed, Embase, Cochrane Library, MEDLINE, CNKI, Wanfang, and VIP databases were searched from January 1, 2020, to August 31, 2022. Essential data were extracted from each article, and the data were displayed using tables and graphs. The study did not require IRB approval. Results: This scoping review included 14 research articles: 8 observational studies, 5 randomized controlled trials, and 1 nonrandomized clinical trial. All the studies were published by Chinese scholars. The findings revealed that moxibustion can contribute to reducing the symptoms of patients with COVID-19, improving inflammation and immune indicators, and shortening the time of nucleic acid negative conversion. Moxibustion confers curative effects on patients of all ages and degrees of illness. In addition, moxibustion can optimize the prognosis of patients in the rehabilitation period. The most commonly chosen acupoints are ST36, RN4, RN8, and RN12. No side effect was mentioned in the included studies. Conclusion: Moxibustion can produce a good effect in the treatment and rehabilitation of patients with COVID-19. It is safe, effective, simple, and noninvasive and should be included as standard care.

The effectiveness of COVID-19 vaccination against all-cause mortality in patients with type 2 diabetes mellitus: The observation during the initial period of the cancellation of the "Dynamic Zero Policy" in mainland China.

AIMS: This study aims to assess the effectiveness of COVID-19 vaccination against all-cause death in patients with type 2 diabetes mellitus (T2DM). METHODS: Subjects were patients with T2DM who were administered by general practitioner (GP). Use electronic exchange platform to obtain the information on COVID-19 vaccination, all-cause deaths and risk factors. Logistic regression models were used to calculate the odd ratio (OR) and 95% CI for the association between COVID-19 vaccination and mortality. The vaccine effectiveness (VE) was calculated as (1- adjusted OR) × 100%. RESULTS: A total of 26,916 subjects had 53.81%, 17.65%, and 23.43% coverage for the booster, full, and partial COVID-19 vaccination, reported 328 deaths and a mortality of 1.2%. The adjusted OR (95%CI) was 0.85(0.60-1.21) for those received partial vaccination, 0.31(0.22-0.43) for those received full vaccination, and 0.12(0.08-0.18) for those received booster vaccination, compared to the unvaccinated individuals. The VE (95%CI) was 88.00%(82.30-91.80) of booster vaccination, 69.30%(56.60-78.30) of full vaccination, and 17.60%(-17.10-42.00) of partial vaccination. CONCLUSION: COVID-19 vaccination could effectively prevent the all-cause death in patients with T2DM during the omicron variant outbreak period, after the cancellation of the "Dynamic Zero Policy" in mainland China.

The impact of the COVID-19 pandemic on nosocomial infections: a retrospective analysis in a tertiary maternal and child healthcare hospital.

Objective: The constant changes in the control strategies of the Corona Virus Disease 2019 (COVID-19) pandemic have greatly affected the prevention and control of nosocomial infections (NIs). This study assessed the impact of these control strategies on the surveillance of NIs in a regional maternity hospital during the COVID-19 pandemic. Methods: This retrospective study compared the observation indicators of nosocomial infections and their changing trends in the hospital before and during the COVID-19 pandemic. Results: In total, 2,56,092 patients were admitted to the hospital during the study. During the COVID-19 pandemic, the main drug-resistant bacteria in hospitals were Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis. The detection rate of S. agalactiae increased annually, while that of E. faecalis remained the same. The detection rate of multidrug-resistant bacteria decreased during the pandemic (16.86 vs. 11.42%), especially that of CRKP (carbapenem-resistant Klebsiella pneumoniae 13.14 vs. 4.39, P < 0.001). The incidence of nosocomial infections in the pediatric surgery department decreased significantly (OR: 2.031, 95% CI: 1.405-2.934, P < 0.001). Regarding the source of infection, a significant reduction was observed in respiratory infections, followed by gastrointestinal infections. In the routine monitoring of the ICU, the incidence of central line-associated bloodstream infection (CLABSI) decreased significantly (9.4/1,000 catheter days vs. 2.2/1,000 catheter days, P < 0.001). Conclusion: The incidence of nosocomial infections was lower than that before the COVID-19 pandemic. The prevention and control measures for the COVID-19 pandemic have reduced the number of nosocomial infections, especially respiratory, gastrointestinal, and catheter-related infections.

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.

BACKGROUND: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. METHODS: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. FINDINGS: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The 'beta variant' RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. INTERPRETATION: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. FUNDING: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Lockdown Sound Diaries

Infants and children with positive PCR test results have been forcefully separated from their parents—unless their parent(s) also test positive and can therefore accompany them to a quarantine facility. On 29 March 2022, a headless robotic dog, carrying an electronic loudspeaker on its back that broadcast a pre-recorded message, walked along an empty, sunny street inside a residential compound in Shanghai (Figures 1 and 2). The app specialises in promoting podcasts (播客) and fostering podcast communities, distinguishing itself from other audio apps such as Ximalaya.FM, which feature a wide variety of audio programs such as audio books, music, comic dialogues, and news briefs (McHugh 2022: 223–25;Xu and Morris 2021). [...]a sound diary contains many elements that are hard to communicate in a written form, such as changes in pitch and volume, laughter, background music, ambient sounds, and even equipment noises from phones or recorders—all of which are open to the aural and affective perceptions of podcasters and listeners.

Porcine Epidemic Diarrhea Virus Replication in Human Intestinal Cells Reveals Potential Susceptibility to Cross-Species Infection.

Various coronaviruses have emerged as a result of cross-species transmission among humans and domestic animals. Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea, vomiting, dehydration, and high mortality in neonatal piglets. Porcine small intestinal epithelial cells (IPEC-J2 cells) can be used as target cells for PEDV infection. However, the origin of PEDV in pigs, the host range, and cross-species infection of PEDV remain unclear. To determine whether PEDV has the ability to infect human cells in vitro, human small intestinal epithelial cells (FHs 74 Int cells) were inoculated with PEDV LJX and PEDV CV777 strains. The results indicated that PEDV LJX, but not PEDV CV777, could infect FHs 74 Int cells. Furthermore, we observed M gene mRNA transcripts and N protein expression in infected FHs 74 Int cells. A one-step growth curve showed that the highest viral titer of PEDV occurred at 12 h post infection. Viral particles in vacuoles were observed in FHs 74 Int cells at 24 h post infection. The results proved that human small intestinal epithelial cells are susceptible to PEDV infection, suggesting the possibility of cross-species transmission of PEDV.

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.