Quantifying the rebound of influenza epidemics after the adjustment of zero-COVID policy in China.

The coexistence of coronavirus disease 2019 (COVID-19) and seasonal influenza epidemics has become a potential threat to human health, particularly in China in the oncoming season. However, with the relaxation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, the rebound extent of the influenza activities is still poorly understood. In this study, we constructed a susceptible-vaccinated-infectious-recovered-susceptible (SVIRS) model to simulate influenza transmission and calibrated it using influenza surveillance data from 2018 to 2022. We projected the influenza transmission over the next 3 years using the SVIRS model. We observed that, in epidemiological year 2021-2022, the reproduction numbers of influenza in southern and northern China were reduced by 64.0 and 34.5%, respectively, compared with those before the pandemic. The percentage of people susceptible to influenza virus increased by 138.6 and 57.3% in southern and northern China by October 1, 2022, respectively. After relaxing NPIs, the potential accumulation of susceptibility to influenza infection may lead to a large-scale influenza outbreak in the year 2022-2023, the scale of which may be affected by the intensity of the NPIs. And later relaxation of NPIs in the year 2023 would not lead to much larger rebound of influenza activities in the year 2023-2024. To control the influenza epidemic to the prepandemic level after relaxing NPIs, the influenza vaccination rates in southern and northern China should increase to 53.8 and 33.8%, respectively. Vaccination for influenza should be advocated to reduce the potential reemergence of the influenza epidemic in the next few years.

Dysbiosis of oropharyngeal microbiome and antibiotic resistance in hospitalized COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing and multiple studies have elucidated its pathogenesis, however, the related- microbiome imbalance caused by SARS-CoV-2 is still not clear. In this study, we have comprehensively compared the microbiome composition and associated function alterations in the oropharyngeal swabs of healthy controls and coronavirus disease 2019 (COVID-19) patients with moderate or severe symptoms by metatranscriptomic sequencing. We did observe a reduced microbiome alpha-diversity but significant enrichment of opportunistic microorganisms in patients with COVID-19 compared with healthy controls, and the microbial homeostasis was rebuilt following the recovery of COVID-19 patients. Correspondingly, less functional genes in multiple biological processes and weakened metabolic pathways such as carbohydrate metabolism, energy metabolism were also observed in COVID-19 patients. We only found higher relative abundance of limited genera such as Lachnoanaerobaculum between severe patients and moderate patients while no worthy-noting microbiome diversity and function alteration were observed. Finally, we noticed that the co-occurrence of antibiotic resistance and virulence was closely related to the microbiome alteration caused by SRAS-CoV-2. Overall, our findings demonstrate that microbial dysbiosis may enhance the pathogenesis of SARS-CoV-2 and the antibiotics treatment should be critically considered.

The Environmental Stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on the Surfaces of Widely Used Transport Packaging Materials.

The increased transmissibility of SARS-CoV-2 variants of concern (VOCs) has raised questions regarding the environmental stability of these viruses. Although a prolonged survival time has been reported for SARS-CoV-2, how long new variants can persist on contaminated surfaces and how environmental factors affect the persistence time are not fully characterized. The present study provides a comprehensive assessment of the stability of Omicron variants BA.1 and BA.5, which are currently circulating strains, on the surfaces of widely used transport packaging materials. By monitoring viable virus detection over a 7-day period under different environmental conditions, it was found that the environmental stability of SARS-CoV-2 Omicron variants depended heavily on the surface type, temperature, and virus concentration. In addition, virus nucleic acid exhibited high stability on the material surface independent of whether viable virus was detected. These findings provide useful information for logistics practitioners and the general public to appropriately deal with transport items under different conditions to minimize the risk of epidemic transmission. IMPORTANCE This study shows the environmental stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on surfaces of widely used transport packaging materials. The findings demonstrate that the environmental stability of the SARS-CoV-2 Omicron variants varies based on material type. The viability of SARS-CoV-2 on material surfaces depends heavily on temperature and viral titer. Low temperatures and high viral titers promote virus survival. Moreover, in contrast to virus viability, virus nucleic acid exhibits high stability on the surfaces of widely used materials, making the detection of virus nucleic acid unsuitable for evaluating the risk of epidemic transmission.

Stable and durable antibody responses in SARS-recovered donors vaccinated with inactivated SARS-CoV-2 vaccine.

Whether the immune imprinting caused by severe acute respiratory syndrome coronavirus (SARS-CoV) affects the efficiency of SARS-CoV-2 vaccination has attracted global concern. Little is known about the dynamic changes of antibody response in SARS convalescents inoculated with three doses of inactivated SARS-CoV-2 vaccine although lack of cross-neutralizing antibody response to SARS-CoV-2 in SARS survivors has been reported. We longitudinally examined the neutralizing antibodies (nAbs) against SARS-CoV and SARS-CoV-2 as well as spikes binding IgA, IgG, IgM, IgG1, and IgG3 antibodies in 9 SARS-recovered donors and 21 SARS-naïve donors. Stably higher nAbs and spike antigens-specific IgA, IgG antibodies against SARS-CoV-2 were observed in SARS-recovered donors compared with SARS-naïve donors during the period with two doses of BBIBP-CorV vaccination. However, the third-dose BBIBP-CorV stimulated a sharply and shortly higher increase of nAbs in SARS-naïve donors than in SARS-recovered donors. It is worth noting that, regardless of prior SARS infection, the Omicron subvariants were found to subvert immune responses. Moreover, certain subvariants such as BA.2, BA.2.75, or BA.5 exhibited a high degree of immune evasion in SARS survivors. Interestingly, BBIBP-CorV recalled higher nAbs against SARS-CoV compared with SARS-CoV-2 in SARS-recovered donors. In SARS survivors, a single dose of inactivated SARS-CoV-2 vaccine provoked immune imprinting for the SARS antigen, providing protection against wild-type SARS-CoV-2, and the earlier variants of concern (VOCs) including Alpha, Beta, Gamma, and Delta but not against Omicron subvariants. As such, it is important to evaluate the type and dosage of SARS-CoV-2 vaccine for SARS survivors.

Pre-existing humoral immunity to low pathogenic human coronaviruses exhibits limited cross-reactive antibodies response against SARS-CoV-2 in children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes asymptomatic or mild symptoms, even rare hospitalization in children. A major concern is whether the pre-existing antibodies induced by low pathogenic human coronaviruses (LPH-CoVs) in children can cross-react with SARS-CoV-2. To address this unresolved question, we analyzed the pre-existing spike (S)-specific immunoglobin (Ig) G antibodies against LPH-CoVs and the cross-reactive antibodies against SARS-CoV-2 in 658 serum samples collected from children prior to SARS-CoV-2 outbreak. We found that the seroprevalence of these four LPH-CoVs reached 75.84%, and about 24.64% of the seropositive samples had cross-reactive IgG antibodies against the nucleocapsid, S, and receptor binding domain antigens of SARS-CoV-2. Additionally, the re-infections with different LPH-CoVs occurred frequently in children and tended to increase the cross-reactive antibodies against SARS-CoV-2. From the forty-nine serum samples with cross-reactive anti-S IgG antibodies against SARS-CoV-2, we found that seven samples with a median age of 1.4 years old had detected neutralizing activity for the wild-type or mutant SARS-CoV-2 S pseudotypes. Interestingly, all of the seven samples contained anti-S IgG antibodies against HCoV-OC43. Together, these data suggest that children's pre-existing antibodies to LPH-CoVs have limited cross-reactive neutralizing antibodies against SRAS-CoV-2.

Research progress on SARS-CoV-2

Since December 2019. the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, has spread rapidly to other provinces and cities in China, and worldwide. Severe acute respiratory syndrome (SARS)-CoV-2 belongs to the fi-coronavirus family, which is closely related to SARS-CoV and Middle East respiratory syndrome (MERS)-CoV, but quite different, especially in the spike protein. SARS-CoV-2 may he derived from bats according to sequence comparison. SARS-CoV-2 uses the same receptor, angiotensin converting enzyme II (ACE2), as SARS-CoV. The main transmission routes include droplets and close contacts. The lack of effective drugs and vaccine is a challenge for outbreak control.

Rational design of AAVrh10-vectored ACE2 functional domain to broadly block the cell entry of SARS-CoV-2 variants.

The frequently emerging SARS-CoV-2 variants have weakened the effectiveness of existing COVID-19 vaccines and neutralizing antibody therapy. Nevertheless, the infections of SARS-CoV-2 variants still depend on angiotensin-converting enzyme 2 (ACE2) receptor-mediated cell entry, and thus the soluble human ACE2 (shACE2) is a potential decoy for broadly blocking SARS-CoV-2 variants. In this study, we firstly generated the recombinant AAVrh10-vectored shACE2 constructs, a kind of adeno-associated virus (AAV) serotype with pulmonary tissue tropism, and then validated its inhibition capacity against SARS-CoV-2 infection. To further optimize the minimized ACE2 functional domain candidates, a comprehensive analysis was performed to clarify the interactions between the ACE2 orthologs from various species and the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein. Based on the key interface amino acids, we designed a series of truncated ACE2 orthologs, and then assessed their potential affinity to bind to SARS-CoV-2 variants RBD in silico. Of note, we found that the 24-83aa fragment of dog ACE2 (dACE224-83) had a higher affinity to the RBD of SARS-CoV-2 variants than that of human ACE2. Importantly, AAVrh10-vectored shACE2 or dACE224-83 constructs exhibited a broadly blockage breadth against SARS-CoV-2 prototype and variants in vitro and ex vivo. Collectively, these data highlighted a promising therapeutic strategy against SARS-CoV-2 variants.

Comparative global B cell receptor repertoire difference induced by SARS-CoV-2 infection or vaccination via single-cell V(D)J sequencing.

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

Vaccination strategy for preventing the spread of SARS-CoV-2 in the limited supply condition: A mathematical modeling study.

To mitigate SARS-CoV-2 transmission, vaccines have been urgently approved. With their limited availability, it is critical to distribute the vaccines reasonably. We simulated the SARS-CoV-2 transmission for 365 days over four intervention periods: free transmission, structural mitigation, personal mitigation, and vaccination. Sensitivity analyses were performed to obtain robust results. We further evaluated two proposed vaccination allocations, including one-dose-high-coverage and two-doses-low-coverage, when the supply was low. 33.35% (infection rate, 2.68 in 10 million people) and 40.54% (2.36) of confirmed cases could be avoided as the nonpharmaceutical interventions (NPIs) adherence rate rose from 50% to 70%. As the vaccination coverage reached 60% and 80%, the total infections could be reduced by 32.72% and 41.19%, compared to the number without vaccination. When the durations of immunity were 90 and 120 days, the infection rates were 2.67 and 2.38. As the asymptomatic infection rate rose from 30% to 50%, the infection rate increased 0.92 (SD, 0.16) times. Conditioned on 70% adherence rate, with the same amount of limited available vaccines, the 20% and 40% vaccination coverage of one-dose-high-coverage, the infection rates were 2.70 and 2.35; corresponding to the two-doses-low-coverage with 10% and 20% vaccination coverage, the infection rates were 3.22 and 2.92. Our results indicated as the duration of immunity prolonged, the second wave of SARS-CoV-2 would be delayed and the scale would be declined. On average, the total infections in two-doses-low-coverage was 1.48 times (SD, 0.24) as high as that in one-dose-high-coverage. It is crucial to encourage people in order to improve vaccination coverage and establish immune barriers. Particularly when the supply is limited, a wiser strategy to prevent SARS-CoV-2 is equally distributing doses to the same number of individuals. Besides vaccination, NPIs are equally critical to the prevention of widespread of SARS-CoV-2.

Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-ß production.

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.

Hypozincemia in COVID-19 Patients Correlates With Stronger Antibody Response.

Zinc ion as an enzyme cofactor exhibits antiviral and anti-inflammatory activity during infection, but circulating zinc ion level during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is unclear. This study aimed to evaluate serum zinc ion level in Coronavirus Disease 2019 (COVID-19) patients and healthy subjects, as well as its correlation with antibodies against SARS-CoV-2. 114 COVID-19 patients and 48 healthy subjects (38 healthy volunteers and 10 close contacts of patients with COVID-19) were included. Zinc ion concentration and levels of antibodies against SARS-CoV-2 Spike 1 + Spike 2 proteins, nucleocapsid protein, and receptor-binding domain in serum were measured. Results showed that the concentration of zinc ion in serum from COVID-19 patients [median: 6.4 nmol/mL (IQR 1.5 - 12.0 nmol/mL)] were significantly lower than that from the healthy subjects [median: 15.0 nmol/mL (IQR 11.9 - 18.8 nmol/mL)] (p < 0.001) and the difference remained significant after age stratification (p < 0.001) or when the patients were at the recovery stage (p < 0.001). Furthermore, COVID-19 patients with more severe hypozincemia showed higher levels of IgG against the receptor-binding domain of SARS-CoV-2 spike protein. Further studies to confirm the effect of zinc supplementation on improving the outcomes of COVID-19, including antibody response against SARS-CoV-2, are warranted.

Single-Cell Analysis Reveals the Immune Characteristics of Myeloid Cells and Memory T Cells in Recovered COVID-19 Patients With Different Severities.

Despite many studies on the immune characteristics of Coronavirus disease 2019 (COVID-19) patients in the progression stage, a detailed understanding of pertinent immune cells in recovered patients is lacking. We performed single-cell RNA sequencing on samples from recovered COVID-19 patients and healthy controls. We created a comprehensive immune landscape with more than 260,000 peripheral blood mononuclear cells (PBMCs) from 41 samples by integrating our dataset with previously reported datasets, which included samples collected between 27 and 47 days after symptom onset. According to our large-scale single-cell analysis, recovered patients, who had severe symptoms (severe/critical recovered), still exhibited peripheral immune disorders 1-2 months after symptom onset. Specifically, in these severe/critical recovered patients, human leukocyte antigen (HLA) class II and antigen processing pathways were downregulated in both CD14 monocytes and dendritic cells compared to healthy controls, while the proportion of CD14 monocytes increased. These may lead to the downregulation of T-cell differentiation pathways in memory T cells. However, in the mild/moderate recovered patients, the proportion of plasmacytoid dendritic cells increased compared to healthy controls, accompanied by the upregulation of HLA-DRA and HLA-DRB1 in both CD14 monocytes and dendritic cells. In addition, T-cell differentiation regulation and memory T cell-related genes FOS, JUN, CD69, CXCR4, and CD83 were upregulated in the mild/moderate recovered patients. Further, the immunoglobulin heavy chain V3-21 (IGHV3-21) gene segment was preferred in B-cell immune repertoires in severe/critical recovered patients. Collectively, we provide a large-scale single-cell atlas of the peripheral immune response in recovered COVID-19 patients.

SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1.

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

Different Transmission Dynamics of Coronavirus Disease 2019 (COVID-19) and Influenza Suggest the Relative Efficiency of Isolation/Quarantine and Social Distancing Against COVID-19 in China.

BACKGROUND: Nonpharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) are vital to reducing transmission risks. However, the relative efficiency of social distancing against COVID-19 remains controversial, since social distancing and isolation/quarantine were implemented almost at the same time in China. METHODS: In this study, surveillance data of COVID-19 and seasonal influenza in 2018-2020 were used to quantify the relative efficiency of NPIs against COVID-19 in China, since isolation/quarantine was not used for the influenza epidemics. Given that the relative age-dependent susceptibility to influenza and COVID-19 may vary, an age-structured susceptible/infected/recovered model was built to explore the efficiency of social distancing against COVID-19 under different population susceptibility scenarios. RESULTS: The mean effective reproductive number, Rt, of COVID-19 before NPIs was 2.12 (95% confidence interval [CI], 2.02-2.21). By 11 March 2020, the overall reduction in Rt of COVID-19 was 66.1% (95% CI, 60.1-71.2%). In the epidemiological year 2019-20, influenza transmissibility was reduced by 34.6% (95% CI, 31.3-38.2%) compared with transmissibility in epidemiological year 2018-19. Under the observed contact pattern changes in China, social distancing had similar efficiency against COVID-19 in 3 different scenarios. By assuming the same efficiency of social distancing against seasonal influenza and COVID-19 transmission, isolation/quarantine and social distancing could lead to 48.1% (95% CI, 35.4-58.1%) and 34.6% (95% CI, 31.3-38.2%) reductions of the transmissibility of COVID-19, respectively. CONCLUSIONS: Though isolation/quarantine is more effective than social distancing, given that the typical basic reproductive number of COVID-19 is 2-3, isolation/quarantine alone could not contain the COVID-19 pandemic effectively in China.

Meta-analysis of COVID-19 single-cell studies confirms eight key immune responses.

Several single-cell RNA sequencing (scRNA-seq) studies analyzing immune response to COVID-19 infection have been recently published. Most of these studies have small sample sizes, which limits the conclusions that can be made with high confidence. By re-analyzing these data in a standardized manner, we validated 8 of the 20 published results across multiple datasets. In particular, we found a consistent decrease in T-cells with increasing COVID-19 infection severity, upregulation of type I Interferon signal pathways, presence of expanded B-cell clones in COVID-19 patients but no consistent trend in T-cell clonal expansion. Overall, our results show that the conclusions drawn from scRNA-seq data analysis of small cohorts of COVID-19 patients need to be treated with some caution.

Comparison of influenza surveillance systems in Australia, China, Malaysia and expert recommendations for influenza control.

BACKGROUND: The Western Pacific Region (WPR) is exposed each year to seasonal influenza and is often the source of new influenza virus variants and novel pathogen emergence. National influenza surveillance systems play a critical role in detecting emerging viruses, monitoring influenza epidemics, improving public disease awareness and promoting pandemic preparedness, but vary widely across WPR countries. The aim of this study is to improve existing influenza surveillance systems by systematically comparing selected WPR influenza surveillance systems. METHODS: Three national influenza surveillance systems with different levels of development (Australia, China and Malaysia) were compared and their adherence to World Health Organization (WHO) guidance was evaluated using a structured framework previously tested in several European countries consisting of seven surveillance sub-systems, 19 comparable outcomes and five evaluation criteria. Based on the results, experts from the Asia-Pacific Alliance for the Control of Influenza (APACI) issued recommendations for the improvement of existing surveillance systems. RESULTS: Australia demonstrated the broadest scope of influenza surveillance followed by China and Malaysia. In Australia, surveillance tools covered all sub-systems. In China, surveillance did not cover non-medically attended respiratory events, primary care consultations, and excess mortality modelling. In Malaysia, surveillance consisted of primary care and hospital sentinel schemes. There were disparities between the countries across the 5 evaluation criteria, particularly regarding data granularity from health authorities, information on data representativeness, and data communication, especially the absence of publicly available influenza epidemiological reports in Malaysia. This dual approach describing the scope of surveillance and evaluating the adherence to WHO guidance enabled APACI experts to make a number of recommendations for each country that included but were not limited to introducing new surveillance tools, broadening the use of specific existing surveillance tools, collecting and sharing data on virus characteristics, developing immunization status registries, and improving public health communication. CONCLUSIONS: Influenza monitoring in Australia, China, and Malaysia could benefit from the expansion of existing surveillance sentinel schemes, the broadened use of laboratory confirmation and the introduction of excess-mortality modelling. The results from the evaluation can be used as a basis to support expert recommendations and to enhance influenza surveillance capabilities.

Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression.

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1ß, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the "cytokine storm" occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.

Synchronized nonpharmaceutical interventions for the control of COVID-19.

The world is experiencing an ongoing pandemic of coronavirus disease-2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In attempts to control the pandemic, a range of nonpharmaceutical interventions (NPIs) has been implemented worldwide. However, the effect of synchronized NPIs for the control of COVID-19 at temporal and spatial scales has not been well studied. Therefore, a meta-population model that incorporates essential nonlinear processes was constructed to uncover the transmission characteristics of SARS-CoV-2 and then assess the effectiveness of synchronized NPIs on COVID-19 dynamics in China. Regional synchronization of NPIs was observed in China, and it was found that a combination of synchronized NPIs (the travel restrictions, the social distancing and the infection isolation) prevented 93.7% of SARS-CoV-2 infections. The use of synchronized NPIs at the time of the Wuhan lockdown may have prevented as much as 38% of SARS-CoV-2 infections, compared with the unsynchronized scenario. The interconnectivity of the epicenter, the implementation time of synchronized NPIs, and the number of regions considered all affected the performance of synchronized NPIs. The results highlight the importance of using synchronized NPIs in high-risk regions for the control of COVID-19 and shed light on effective strategies for future pandemic responses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11071-021-06505-0.

New framework for recombination and adaptive evolution analysis with application to the novel coronavirus SARS-CoV-2.

The 2019 novel coronavirus (SARS-CoV-2) has spread rapidly worldwide and was declared a pandemic by the WHO in March 2020. The evolution of SARS-CoV-2, either in its natural reservoir or in the human population, is still unclear, but this knowledge is essential for effective prevention and control. We propose a new framework to systematically identify recombination events, excluding those due to noise and convergent evolution. We found that several recombination events occurred for SARS-CoV-2 before its transfer to humans, including a more recent recombination event in the receptor-binding domain. We also constructed a probabilistic mutation network to explore the diversity and evolution of SARS-CoV-2 after human infection. Clustering results show that the novel coronavirus has diverged into several clusters that cocirculate over time in various regions and that several mutations across the genome are fixed during transmission throughout the human population, including D614G in the S gene and two accompanied mutations in ORF1ab. Together, these findings suggest that SARS-CoV-2 experienced a complicated evolution process in the natural environment and point to its continuous adaptation to humans. The new framework proposed in this study can help our understanding of and response to other emerging pathogens.