Some properties of branching processes with random control functions and affected by viral infectivity in random environments.

In this paper, a model of branching processes with random control functions and affected by viral infectivity in independent and identically distributed random environments is established, and the Markov property of the model and a sufficient condition for the model to be certainly extinct under some conditions are discussed. Then, the limit properties of the model are studied. Under the normalization factor {Sn:n∈N}, the normalization processes {Wˆn:n∈N} are studied, and the sufficient conditions of {Wˆn:n∈N} a.s., L1 and L2 convergence are given; A sufficient condition and a necessary condition for convergence to a nondegenerate at zero random variable are obtained. Under the normalization factor {In:n∈N}, the normalization processes {W¯n:n∈N} are studied, and the sufficient conditions of {W¯n:n∈N} a.s., and L1 convergence are obtained.

[Evaluation of the dynamics of detection of viable SARS-CoV-2 (Coronaviridae: Betacoronavirus: Sarbecovirus) in biological samples obtained from patients with COVID-19 in a health care setting, as one of the indicators of the infectivity of the virus].

INTRODUCTION: The study of the mechanisms of transmission of the SARS-CoV-2 virus is the basis for building a strategy for anti-epidemic measures in the context of the COVID-19 pandemic. Understanding in what time frame a patient can spread SARS-CoV-2 is just as important as knowing the transmission mechanisms themselves. This information is necessary to develop effective measures to prevent infection by breaking the chains of transmission of the virus. The aim of the work is to identify the infectious SARS-CoV-2 virus in patient samples in the course of the disease and to determine the duration of virus shedding in patients with varying severity of COVID-19. MATERIALS AND METHODS: In patients included in the study, biomaterial (nasopharyngeal swabs) was subjected to analysis by quantitative RT-PCR and virological determination of infectivity of the virus. RESULTS: We have determined the timeframe of maintaining the infectivity of the virus in patients hospitalized with severe and moderate COVID-19. Based on the results of the study, we made an analysis of the relationship between the amount of detected SARS-CoV-2 RNA and the infectivity of the virus in vitro in patients with COVID-19. The median time of the infectious virus shedding was 8 days. In addition, a comparative analysis of different protocols for the detection of the viral RNA in relation to the identification of the infectious virus was carried out. CONCLUSION: The obtained data make it possible to assess the dynamics of SARS-CoV-2 detection and viral load in patients with COVID-19 and indicate the significance of these parameters for the subsequent spread of the virus and the organization of preventive measures.

Comparison of the Ct-values for genomic and subgenomic SARS-CoV-2 RNA reveals limited predictive value for the presence of replication competent virus.

SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19. In addition to the full length positive-sensed, single-stranded genomic RNA (gRNA), viral subgenomic RNAs (sgRNAs) that are required for expression of the 3' region of the genome are synthesized in virus-infected cells. However, whether these sgRNA-species might be used as a measure of active virus replication and to predict infectivity is still under debate. The commonly used methods to monitor and quantitate SARS-CoV-2 infections are based on RT-qPCR analysis and the detection of gRNA. The infectivity of a sample obtained from nasopharyngeal or throat swabs is associated with the viral load and inversely correlates with Ct-values, however, a cut-off value predicting the infectivity highly depends on the performance of the assay. Furthermore, gRNA derived Ct-values result from nucleic acid detection and do not necessarily correspond to active replicating virus. We established a multiplex RT-qPCR assay on the cobas 6800 omni utility channel concomitantly detecting SARS-CoV-2 gRNAOrf1a/b, sgRNAE,7a,N, and human RNaseP-mRNA used as human input control. We compared the target specific Ct-values with the viral culture frequency and performed ROC curve analysis to determine the assay sensitivity and specificity. We found no advantage in the prediction of viral culture when using sgRNA detection compared to gRNA only, since Ct-values for gRNA and sgRNA were highly correlated and gRNA offered a slightly more reliable predictive value. Single Ct-values alone only provide a very limited prediction for the presence of replication competent virus. Hence, careful consideration of the medical history including symptom onset has to be considered for risk stratification.

Importance of cycle threshold values in detection of severity and outcome in patients with severe acute respiratory syndrome coronavirus 2

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019. Cycle threshold (Ct) value of real-time reverse transcription polymerase chain reaction (RT-PCR) assay inversely correlated with viral load and can provide an indirect method of quantifying the number of copies of viral RNA in the sample is not reported clinically. Hence, this study was undertaken to compare the Ct values of patients tested positive for SARS CoV-2 by RT-PCR with severity of illness, duration of hospital stay, and mortality. Materials and Methods: A retrospective study was conducted over a period of 6 months in a tertiary care hospital in Bangalore. All patients tested positive for SARS CoV-2 by RT-PCR and admitted in our hospital were included in the study. Details of the patients on the duration of hospital stay, age, presence of comorbidities, intubation, and mortality were collected. Results: The study comprised of 80 patients, 48 (60%) males and 32 (40%) females. The mean age of the study population was 38.38 years. Majority of patients 41.25% had Ct value between 25 and 30. Patients with lower Ct values were significant associated with increased duration of hospital stay and infected more than one person in family indicating higher probability of transmission of infection. Mortality showed significant association with patients of more than 60 years' age. Interpretation and Conclusions: The study shows possible association between Ct values of SARS-CoV-2 RT-PCR assay with the duration of hospitalization, infectivity, and mortality. Mention of Ct value along with the positive report could potentially be used to guide patient care management, infection control, and occupational health decisions.

The latest research progress of novel coronavirus "Omicron sub-variant BA.5"

Since the outbreak of COVID-19, severe acute respiratory syndrome coronavirus 2 genome is still mutating, forming a variety of variants with strong transmission capacity, causing the spread of the epidemic worldwide, posing a serious threat to people's physical and mental health, and posing a major challenge to global public health. Omicron remains the main variant in several outbreaks worldwide, accounting for about 99% of the global genetic sequence. Recently, the World Health Organization announced that the subvariant of Omicron BA.5 has been found in more than 100 countries and regions around the world, causing the global epidemic rebound. However, there are few studies on the subvariant BA.5. This article reviews the latest research progress in epidemiology, infectivity, pathogenicity, vaccine and monoclonal antibody protection against Omicron subvariant BA.5, in order to provide reference for scientific prevention and control of Omicron subvariant BA.5.

Modifications in SARS-CoV-2 N Linker Region Regulate RNA Interactions and Phase Separation

The N protein of the SARS-CoV-2 virion is critical for viral genome packaging via RNA binding and regulation of viral transcription at the replication-transcription complex (RTC). The N protein can be divided into five main domains, and the central region is the linker, which is predicted to be primarily disordered and has not been heavily studied. The linker is Serine-Arginine Rich, which is phosphorylated at multiple sites by host kinases during infection, thereby promoting the N protein's role in viral transcription. Phosphorylation is a critical process for the regulation of many cellular processes and can provide recognition sites for binding complexes. In a study that examined the recognition of the SARS-CoV-2 N protein by the human 14-3-3 protein, the linker was found to contain critical phosphosites for 14-3-3 binding. The goals of this project are to determine the structure, dynamics, and RNA interactions of the Serine-Arginine Rich linker region. To accomplish this, we performed Nuclear Magnetic Resonance spectroscopy (NMR) experiments to analyze the structure of the linker region of the N protein and its ability to bind viral RNA. NMR confirms predictions that the linker is not entirely unstructured and it is able to bind RNA. The linker region of the N protein with phosphoserine incorporated at S188 was also examined via an NMR titration experiment with 1-1000 RNA. Compared to wild type, the incorporation of phosphorylation decreases binding. Other biophysical techniques such as Analytical Ultracentrifugation (AUC) and Multi-Angle Light Scattering (MALS) are used to identify the association state of the linker and the size of the resulting protein-RNA complex. We are currently working to biophysically characterize the structure, dynamics, and viral RNA binding ability of a mutation found in the Delta and Omicron variants: the R203M linker, which have been shown to enhance viral infectivity. This work was supported by the NSF EAGER grant NSF/ MCB 2034446 and URSA Engage. Support to facilities includes the Oregon State University NMR Facility funded in part by NIH, HEI Grant 1S10OD018518, and by the M. J. Murdock Charitable Trust grant # 2014162.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

PLASMA LIPIDS AND AMINO ACIDS LINKED TO LOW SARS-CoV-2 SUSCEPTIBILITY

Background: The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why a subset of unvaccinated individuals remain uninfected despite high-risk exposures. Method(s): We studied an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 ('nonsusceptible') from April to June 2020, who were compared against 'susceptible' individuals to SARS-CoV-2, including uninfected subjects who became infected during the follow-up, and hospitalized patients with different disease severity providing samples at early disease stages. We analyzed plasma samples using different mass spectrometry technique and obtained metabolites and lipids profiles. Result(s): We found that the metabolite profiles were predictive of the selected study groups and identified lipids profiles and metabolites linked to SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, we showed that non-susceptible individuals exhibited unique metabolomics and lipidomic patterns characterized by upregulation of most lipids -especially ceramides and sphingomyelin-and amino acids related to tricarboxylic acid cycle and mitochondrial metabolism, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. Lipids and metabolites pathways analysis revealed that metabolites related to energy production, mitochondrial and tissue dysfunction, and lipids involved in membrane structure and virus infectivity were key markers of SARS-CoV-2 susceptibility. Conclusion(s): Lipid and metabolic profiles differ in 'nonsusceptible' compared to individuals susceptible to SARS-CoV-2. Our study suggests that lipid profiles are relevant actors during SARS-CoV-2 pathogenesis and highlight certain lipids relevant to understand SARS-CoV-2 pathogenesis. (Figure Presented).

Surfactant Protein B Reduces Respiratory Viral Infectivity in Human Lungs

Purpose of Study: COVID pneumonia caused by SARS-CoV-2 can result in a depletion of surfactant & lung injury, which resembles neonatal respiratory distress syndrome. Exogenous surfactant has shown promise as a therapeutic option in intubated hospitalized patients. Our preliminary data in human lung organoids (LOs) with a deficiency of surfactant protein B (SP-B) showed an increased viral load compared to normal LOs. Single cell RNA sequencing (scRNAseq) revealed that SP-B-deficient cells showed increased viral entry genes (ACE2 receptor) & dysregulated inflammatory markers emanating from the lung cells themselves. Our objective was to determine: (1) cell-specific transcriptional differences between normal & SP-B deficient human lung cells after infection with SARS-CoV-2 and (2) a therapeutic role of SP-B protein & surfactant in COVID-19 pneumonia. Methods Used: We used normal and SP-B mutant (homozygous, frameshift, loss of function mutation p.Pro133GlnfsTer95, previously known as 121ins2) human induced pluripotent stem cells (hiPSC) and differentiated them into 3D proximal lung organoids. The organoids were infected with the delta variant of SARS-CoV-2 for 24 hours at an MOI of 1. Infected and uninfected organoids were fixed in trizol in triplicate and underwent processing for bulk RNA sequencing. We tested for differentially expressed genes using the program DEseq. We also plated normal iPSC derived lung organoids as a monolayer and pre-treated them with 1mg/ml of Poractant alfa or 5 uM of recombinant SP-B protein. The delta strain of SARS-CoV-2 was added to the 96 wells at an MOI of 0.1 for one hour with shaking, then an overlay with DMEM/CMC/FBS was added and left on for 23 hours. The plate was fixed and stained for nucleocapsid (NC) protein. Summary of Results: Bioinformatic analysis of the bulk RNA sequencing data showed an increase in the multiple cytokines and chemokines in the SP-B mutant LOs compared to control. We also saw differential gene expression patterns in the SP-B mutant LOs including a reduction in SFTPC, FOXA2, and NKX2-1 and an increase in IL1A, VEGFA, PPARG and SMAD3. In the exogenous surfactant experiments, there was a decrease in total expression of viral NC in the Poractant alfa & rSP-B-treated cells compared to SARS-CoV-2 infection alone (p<0.001). Conclusion(s): Surfactant modulates the viral load of SARS-CoV-2 infection in the human lung. Deficiency in SP-B results in the dysregulation of the lung epithelial inflammatory signaling pathways resulting in worsening infections.

Evaluation of Rapid Antigen Test as a Marker of SARS-CoV-2 Infectivity.

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 continues to spread globally. Reverse transcriptase polymerase chain reaction (RT-PCR), which is considered the gold standard for diagnosis, does not always indicate contagiousness. This study was planned to evaluate the performance of the rapid antigen test (RAT) with the duration of symptoms and the usefulness of these tests in determining the infectivity of patients by performing sub-genomic RT-PCR. Methodology This prospective, observational study was designed to compare the diagnostic value of the COVID-19 RAT (SD Biosensor, Korea) with COVID-19 RT-PCR (Thermo Fisher, USA) by serial testing of patients. To evaluate the infectivity of the virus, sub-genomic RT-PCR was performed on previous RAT and RT-PCR-positive samples. Results Of 200 patients, 102 were positive on both RT-PCR and RAT, with 87 patients serially followed and tested. The sensitivity and specificity of RAT were 92.73% and 93.33%, respectively, in symptomatic patients. The mean duration of RAT positivity was 9.1 days, and the mean duration of RT-PCR positivity was 12.6 days. Sub-genomic RT-PCR test was performed on samples that were reported to be positive by RAT, and 73/87 (83.9%) patients were found to be positive. RAT was positive in symptomatic patients whose duration of illness was less than 10 days or those with a cycle threshold value below 32. Conclusions Thus, RAT can be used as the marker of infectivity of SARS-CoV-2 in symptomatic patients, especially in healthcare workers.

Water bath is more efficient than hot air oven at thermal inactivation of coronavirus.

BACKGROUND: Thermal inactivation is a conventional and effective method of eliminating the infectivity of pathogens from specimens in clinical and biological laboratories, and reducing the risk of occupational exposure and environmental contamination. During the COVID-19 pandemic, specimens from patients and potentially infected individuals were heat treated and processed under BSL-2 conditions in a safe, cost-effective, and timely manner. The temperature and duration of heat treatment are optimized and standardized in the protocol according to the susceptibility of the pathogen and the impact on the integrity of the specimens, but the heating device is often undefined. Devices and medium transferring the thermal energy vary in heating rate, specific heat capacity, and conductivity, resulting in variations in efficiency and inactivation outcome that may compromise biosafety and downstream biological assays. METHODS: We evaluated the water bath and hot air oven in terms of pathogen inactivation efficiency, which are the most commonly used inactivation devices in hospitals and biological laboratories. By evaluating the temperature equilibrium and viral titer elimination under various conditions, we studied the devices and their inactivation outcomes under identical treatment protocol, and to analyzed the factors, such as energy conductivity, specific heat capacity, and heating rate, underlying the inactivation efficiencies. RESULTS: We compared thermal inactivation of coronavirus using different devices, and have found that the water bath was more efficient at reducing infectivity, with higher heat transfer and thermal equilibration than a forced hot air oven. In addition to the efficiency, the water bath showed relative consistency in temperature equilibration of samples of different volumes, reduced the need for prolonged heating, and eliminated the risk of pathogen spread by forced airflow. CONCLUSIONS: Our data support the proposal to define the heating device in the thermal inactivation protocol and in the specimen management policy.

Concern over global outbreak of acute severe hepatitis of unknown etiology in children

Acute severe hepatitis in children of unknown cause is a childhood liver disease of unknown etiology that emerged suddenly during the global pandemic of coronavirus disease 2019. Since it was reported in early April 2022, it has involved more than 20 countries around the world with about 450 cases, mainly in Europe and North America, and no similar case has been reported in China. The disease occurs mostly in children under 5 years of age and is characterized mainly by liver disease manifestations such as jaundice and elevated transaminases, with rare respiratory symptoms;a few cases develop into liver failure and need liver transplantation, and most cases have a good prognosis. The disease is currently considered to be caused by infection, but the exact pathogen remains unclear. Adenovirus is detected in blood in many cases, so the possibility of infection caused by adenovirus should be considered;and factors such as lack of trained immunity and persistent inflammatory in children with COVID-19 should also be considered. The disease is no evidence of interpersonal transmission, infectivity is low, but the possibility of a pandemic outbreak in countries with a high prevalence of COVID-2019 needs to be guarded against;hand hygiene and respiratory protection may reduce the risk of morbidity. This article provides an overview of the epidemiological and clinical features of the disease and analyzes its nature, etiology and transmission risk in order to provide updated awareness of its clinical diagnosis and treatment.

Transmission Model of COVID-19 Pandemic Based on Infectivity and Immunity

Objective Many mutant strains of SARS-CoV-2 have stronger infectivity and immune escape ability. The situation of epidemic evaluation, prevention and control is serious. The aim of the present paper is to track and predict the infectious transmission of COVID-19 through a theoretical model. Methods Based on the grid epidemic model, this paper discussed the relationship between the duration of infection and the effect of group immunity, and on this basis, established the theoretical model of infection transmission of COVID-19. The infectivity parameter A and the immune effect parameter B are introduced to predict the daily variation curve of infection. The parameter (Equation presented)can be used to quantitatively compare the comprehensive infectivity of each mutant, and we also test the conjecture that the infection parameters A and B are not related to regional factors. Results Through the theoretical model of infection transmission of COVID-19, the infectious time was accurately predicted. By analyzing the infectivity and electrical changes of mutant strains, the internal relationship between the infectivity of mutant strains and the electrical changes of mutant residues was pointed out. The parameter changes of mutants were analyzed, and the comprehensive infectivity of each mutant was quantitatively compared. We also verified the conjecture that parameters A and B are only related to the nature of the virus itself and the coexistence of the virus and the human body, but not related to the region where the disease occurs and evaluated and compared the epidemic prevention level of each outbreak region. Conclusion This paper established a theoretical model of infection transmission of COVID-19, which can predict the duration of the epidemic, the number of new infections per day, and evaluate the infectivity of the virus, immune escape ability, comprehensive infectivity, and regional epidemic prevention level. It can also give some suggestions on epidemic prevention countermeasures according to the possible parameter changes caused by virus variation. © 2022 Institute of Biophysics,Chinese Academy of Sciences. All rights reserved.

A novel isothermal digital amplification system and its application for absolute quantification of respiratory infectious virus

Herein, we establish a novel isothermal digital amplification system termed digital nicking and extension chain reaction system-based amplification (dNESBA) by utilizing the isothermal NESBA technique and the newly developed miniaturized fluorescence monitoring system (mFMS). dNESBA enables parallel isothermal NESBA reactions in more than 10,000 localized droplet microreactors and read the fluorescence signals rapidly in 150 s by mFMS. This system could identify the genomic RNA (gRNA) extracted from target respiratory syncytial virus A (RSV A) as low as 10 copies with remarkable specificity. The practical applicability of dNESBA was also successfully verified by reliably detecting the gRNA in the artificial sputum samples with excellent reproducibility and accuracy. Due to the intrinsic advantages of isothermal amplifying technique including the elimination of the requirement of thermocycling device and the enhanced portability of the miniaturized read-out equipment, the dNESBA technique equipped with mFMS could serve as a promising platform system to achieve point-of-care (POC) digital molecular diagnostics, enabling absolute and ultra-sensitive quantification of various infectious pathogens even in an early stage.Copyright © 2023

Effects of Temperature and Water Types on the Decay of Coronavirus: A Review

The analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) gene copy numbers in wastewater samples can provide quantitative information on Coronavirus Disease-19 (COVID-19) cases within a sewer catchment. However, many wastewater-based epidemiology (WBE) studies have neglected virus decay during the wastewater transportation process in sewers while back-calculating COVID-19 prevalence. Among various sewer condition parameters, wastewater temperature and dilution by fresh/saltwater infiltration may result in a significant change to the virus decay, in terms of both infectivity and Ribonucleic Acid (RNA). This paper reviewed the literature to identify and discuss the effects of temperature and water types (i.e., wastewater, freshwater, and seawater) on coronavirus decay based on the decay rate constants that were collected from published papers. To evaluate the importance of virus decay, a sensitivity analysis was then conducted with decay rates of SARS-CoV-2 RNA based on a WBE back-calculation equation. Finally, the decay rates of coronavirus in wastewater were also compared with those of other viruses to further understand the difference among virus species. The decay of SARS-CoV-2 RNA was found to be less impacted by temperature variation than viable coronaviruses. Nevertheless, WBE back-calculation was still sensitive to the RNA decay rates increased by warm wastewater (i.e., over 26 °C), which could lead to a two-times higher relative variance in estimated COVID-19 prevalence, considering the wastewater temperature variation between 4 and 37 °C in a sewer catchment with a 12-h hydraulic retention time. Comparatively, the sensitivity of the WBE estimation to the enveloped SARS-CoV-2 was greater than nonenveloped enteric viruses, which were less easily degradable in wastewater. In addition, wastewater dilution by stormwater inflow and accompanied cold weather might alleviate the decay of coronavirus infectivity, thus increasing the potential risk of COVID-19 transmission through wastewater. Overall, this paper aims to better understand the impact of in-sewer processes on coronavirus decay and its potential implications for WBE. The outcome could quantitatively inform WBE and improve awareness of the increased risk of COVID-19 infection via wastewater during heavy rainfall events. Given the identified scarcity of data available for coronavirus decay in salt water or with chemical additions, future research on the fate of SARS-CoV-2 subjected to chemical dosing for sewer or wastewater treatment plant operations is recommended. © 2023 by the authors.

Infectious viruses from transfected SARS-CoV-2 genomic RNA.

SARS-CoV-2 emerged at the end of 2019, and like other novel pathogens causing severe symptoms, WHO recommended heightened biosafety measures for laboratories working with the virus. The positive-stranded genomic RNA of coronaviruses has been known to be infectious since the 1970s, and overall, all experiments with the possibility of SARS-CoV-2 propagation are carried out in higher containment level laboratories. However, as SARS-CoV-2 RNA has been routinely handled in BSL-2 laboratories, the question of the true nature of RNA infectiousness has risen along with discussion of appropriate biosafety measures. Here, we studied the ability of native SARS-CoV-2 genomic RNA to produce infectious viruses when transfected into permissive cells and discussed the biosafety control measures related to these assays. In transfection assays large quantities of genomic vRNA of SARS-CoV-2 was required for a successful production of infectious viruses. However, the quantity of vRNA alone was not the only factor, and especially when the transfected RNA was derived from infected cells, even small amounts of genomic vRNA was enough for an infection. Virus replication was found to start rapidly after transfection, and infectious viruses were detected in the cell culture media at 24 h post-transfection. In addition, silica membrane-based kits were shown to be as good as traditional TRI-reagent based methods in extracting high-quality, 30 kb-long genomic vRNA. Taken together, our data indicates that all transfection experiments with samples containing genomic SARS-CoV-2 RNA should be categorized as a propagative work and the work should be conducted only in a higher containment BSL-3 laboratory.

In vivo effect of mouthwashes on viable viral load of SARS-CoV-2 in saliva: a pilot study.

Current data on the efficacy of antiseptic mouthwashes to reduce viral load are contradictory. Firstly, in vitro data indicate very strong virucidal effects that are not replicated in clinical studies. Secondly, most clinical studies identify a limited effect, do not include a control/placebo group, or do not evaluate viral viability in an infection model. In the current manuscript, we perform a double-blind, randomized clinical trial where salivary viral load was measured before and after the mouthwash, and where saliva samples were also cultured in an in vitro infection model of SARS-CoV-2 to evaluate the effect of mouthwashes on viral viability. Our data show a 90-99% reduction in SARS-CoV-2 salivary copies with one of the tested mouthwashes, although we show that the remaining viruses are mostly viable. In addition, our data suggest that the active ingredient concentration and the overall excipients' formulation can play an important role; and most importantly, they indicate that the effect is not immediate, being significant at 15 min and having maximum effectiveness after 1 h. Thus, we show that some oral mouthwashes can be useful in reducing viral transmission, although their efficacy must be improved through refined formulations or revised protocols.

Age-specific transmission dynamics under suppression control measures during SARS-CoV-2 Omicron BA.2 epidemic.

BACKGROUND: From March to June 2022, an Omicron BA.2 epidemic occurred in Shanghai. We aimed to better understand the transmission dynamics and identify age-specific transmission characteristics for the epidemic. METHODS: Data on COVID-19 cases were collected from the Shanghai Municipal Health Commission during the period from 20th February to 1st June. The effective reproductive number (Rt) and transmission distance between cases were calculated. An age-structured SEIR model with social contact patterns was developed to reconstruct the transmission dynamics and evaluate age-specific transmission characteristics. Least square method was used to calibrate the model. Basic reproduction number (R0) was estimated with next generation matrix. RESULTS: R0 of Omicron variant was 7.9 (95% CI: 7.4 to 8.4). With strict interventions, Rt had dropped quickly from 3.6 (95% CI: 2.7 to 4.7) on 4th March to below 1 on 18th April. The mean transmission distance of the Omicron epidemic in Shanghai was 13.4 km (95% CI: 11.1 to 15.8 km), which was threefold longer compared with that of epidemic caused by the wild-type virus in Wuhan, China. The model estimated that there would have been a total 870,845 (95% CI: 815,400 to 926,289) cases for the epidemic from 20th February to 15th June, and 27.7% (95% CI: 24.4% to 30.9%) cases would have been unascertained. People aged 50-59 years had the highest transmission risk 0.216 (95% CI: 0.210 to 0.222), and the highest secondary attack rate (47.62%, 95% CI: 38.71% to 56.53%). CONCLUSIONS: The Omicron variant spread more quickly and widely than other variants and resulted in about one third cases unascertained for the recent outbreak in Shanghai. Prioritizing isolation and screening of people aged 40-59 might suppress the epidemic more effectively. Routine surveillance among people aged 40-59 years could also provide insight into the stage of the epidemic and the timely detection of new variants. TRIAL REGISTRATION: We did not involve clinical trial.

Overview of SARS-CoV-2 and Possible Targets for the Management of COVID-19 Infections

COVID-19 is a respiratory infection caused by a newer strain of coronavirus known as SARS-CoV-2. The major problem of COVID-19 infections is the ARDS, followed by respiratory failure, organ failure, and even death with multiple organ dysfunction, including cardiovascular collapse. Moreover, it affects the old age population with co-morbid conditions. The deficiency of diet, micronutrients, and vitamins also plays a key role in diminishing the immune power, and increases the rate of viral infectivity. The possible reasons and management methods are discussed in this review. The management methods enhance the host immune system via multi-functional and multi-targeted actions. The global rate of COVID-19 outbreak necessitates the need to develop newer medicines. The drug discovery process is based on the exposure of viral proteins, genome sequence, replication mechanisms, pathophysiological mechanisms, and host cell components (as a target) reactions. This article highlights the overview of coronavirus components, the replications process, and possible targets for the management of coronavirus infections. It may lead to the rapid development of newer medicines for the treatment of coronavirus in-fections.Copyright © 2022 Bentham Science Publishers.

Proteomic determinants of disease, mortality and sequelae in COVID-19 patients requiring invasive mechanical ventilation

Introduction: The molecular mechanisms linked to the pathology of severe COVID-19 and its outcomes are poorly described. Aim(s): To analyze the proteomic profile of bronchial aspirates (BAS) samples from critically ill COVID-19 patients in order to identify factors associated with the disease and its prognosis. Method(s): Multicenter study including 74 critically ill non-COVID-19 and COVID-19 patients. BAS was obtained by bronchoaspiration after invasive mechanical ventilation (IMV) initiation. Proximity extension assay (PEA) technology was used for proteomic profiling. Random forest (RF) statistical models were used to predict the variable importance. Result(s): After adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-alpha showed differences between COVID-19 and non-COVID-19 patients. Reduced levels of ENTPD2 and PTN were observed in non-survivors, even after adjustment. AGR2, NQO2, IL-1alpha, OSM and TRAIL, were the top five strongest predictors for ICU mortality and were used to build a prediction model. PTN (HR=4.00) ENTPD2 (HR=2.14) and the prediction model (HR=6.25) were associated with higher risk of death. In survivors, FCRL1, NTF4 and THOP1 correlated with lung function (DLCO levels) 3-months after hospital discharge. Similar findings were observed for Flt3L and THOP1 and radiological features (TSS). The proteins identified are expressed in immune and non-immune lung cells. A poor control of viral infectivity and an inappropriate reparative response seems to be linked to the disease and fatal outcomes, respectively. Conclusion(s): In critically ill COVID-19 patients, specific proteomic profiles are associated with the pathology, mortality and lung sequelae.