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SARS-CoV-2 has infected more than 600 million people worldwide over the last 2.5 years. So far, there efficacy of many antiviral drugs against COVID-19 has been evaluated only in small studies conducted in different countries. Objective. To assess the efficacy of umifenovir in patients with COVID-19. Materials and methods. We performed systematic search of publications in the PubMed and Google Scholar databases. Sixteen studies with a total of 1,843 patients were included in the analysis. The following endpoints were evaluated: frequencies of negative PCR test on days 7 and 14;mortality in patients with mild, moderate, and severe disease;and frequency of fever resolution on day 7. Results. We found that patients receiving umifenovir demonstrated a significantly higher frequency of negative PCR test on day 7 than patients who received no causal therapy or other antiviral drugs (odds ratio (OR) 1.69, 95% confidence interval (CI): 1.09-2.62, p = 0.02, I2 = 13%). This difference was even more significant among patients with mild to moderate COVID-19 (OR: 2.03, 95% CI: 1.24-3.32, p = 0.005, I2 = 0%), as well as on day 14 (OR: 2.02, 95% CI: 1.35-3.94, p = 0.0007, I2 = 50%). We also observed a reduced risk of death in the studies that included only patients with mild and moderate disease (JR: 0.53, 95% CI: 0.33-0.83, p = 0.006, I2 = 0). Umifenovir therapy did not affect the frequency of fever resolution by day 7 (OR: 0.87, 95% CI: 0.49-1.56, p = 0.64, I2 = 0%). Conclusion. Umifenovir significantly accelerated virus elimination by days 7 and 14 among patients with mild to moderate COVID-19. Umifenovir also reduced the risk of death compared to other antiviral drugs.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Problem: COVID-19 placentitis is a rare complication of maternal SARS-CoV-2 respiratory infection associated with serious adverse obstetric outcomes, including intra-uterine death. The precise role of SARS-CoV-2 in COVID-19 placentitis is uncertain, as trophoblast infection is only observed in around one-half of the affected placenta. Method of Study: Through multi-omic spatial profiling, including Nanostring GeoMX digital spatial profiling and Lunaphore COMET multiplex IHC, we provide a deep characterization of the immunopathology of placentitis from obstetrically complicated maternal COVID-19 infection. Result(s):We show that SARS-CoV-2 infection of placental trophoblasts is associated with a distinct innate and adaptive immune cell infiltrate, florid cytokine expression and upregulation of viral restriction factors. Quantitative spatial analyses reveal a unique microenvironment surrounding virus-infected trophoblasts characterizedd by multiple immune evasion mechanisms, including immune checkpoint expression, cytotoxic T-cell exclusion, and interferon blunting. Placental viral loads inversely correlated with the duration of maternal infection consistent with progressive virus clearance, potentially explaining the absence of virus in some cases. Conclusion(s): Our results demonstrate a central role for placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis.
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Background & Aim: Despite the successful implementation of vaccines worldwide, COVID-19 remains a risk in patients with a compromised immune system. Emerging viral variants have also reduced the effectiveness of monoclonal antibody therapies in these patients. New treatment options are therefore required to improve clinical outcomes. Methods, Results & Conclusion(s): T cell immunotherapy has proven effective for the treatment of a number of refractory viral diseases in patients with a compromised immune system. We have now completed the manufacture of a bank of SARS-CoV-2 specific T cells and commenced an open-label phase I clinical trial at the Royal Brisbane and Women's Hospital, Australia. Patients enrolled in the study receive two doses of partially HLA-matched allogeneic T cells at a fortnightly interval. We have thus far recruited and treated three immune compromised patients with SARS-CoV-2 T cells. In two of the three patients treated thus far, the administration of T cell therapy was coincident with the clearance of viral load after 28 days. Viral clearance in these patients was also associated with an increase in circulating SARS-CoV-2 specific T cells. Our preliminary observations suggest that SARS-CoV-2 specific T cell therapy is well tolerated and has the potential to impact viral control in immune compromised patients.Copyright © 2023 International Society for Cell & Gene Therapy
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Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. The most common sites of metastatic breast cancer are bone, liver and lung. Respiratory viral infections inflict illnesses on countless people. The latest pandemic caused by the respiratory virus, SARS-CoV-2, has infected more than 600 million worldwide, with documented COVID-related death upward of 1 million in the United States alone. Respiratory viral infections result in increased inflammation with immune cell influx and expansion to facilitate viral clearance. Prior studies have shown that inflammation, including through neutrophils, can contribute to dormant cancer cells reawakening and outgrowth. Moreover, inhibition of IL6 has been shown to decrease breast cancer lung metastasis in mouse models. However, how respiratory viral infections contribute to breast cancer lung metastasis remains to be unraveled. Using MMTV/PyMT and MMTV/NEU mouse models of breast cancer lung metastasis and influenza A virus as a model respiratory virus, we demonstrated that acute influenza infection and the accompanying inflammation and immune cell influx awakens and dramatically increased proliferation and expansion of dormant disseminated cancer cells (DCC) in the lungs. Acute influenza infection leads to immune influx and expansion, including neutrophils and macrophages, with increased proportion of MHCII+ macrophages in early time points, and a sustained decrease in CD206+ macrophages starting 6 days post-infection until 28 days after the initial infection. Additionally, we observed a sustained accumulation of CD4+ T cells around expanding tumor cells for as long as 28 days after the infection. Notably, neutrophil depletion or IL6 knockout reversed the flu-induced dormant cell expansion in the lung. Finally, awakened DCC exhibited downregulation of vimentin immunoreactivity, suggesting a role for phenotypic plasticity in DCC outgrowth following viral infection. In conclusion, we show that respiratory viral infections awaken and increase proliferation of dormant breast cancer cells in the lung, and that depletion of neutrophils or blocking IL6 reverses influenza-induced dormant cell awakening and proliferation.
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Background: Omicron is the recently emerged highly transmissible severe acute respiratory syndrome coronavirus 2 variant that has caused a dramatic increase in coronavirus disease-2019 infection cases worldwide. This study was to investigate the association between demographic and laboratory findings, and the duration of Omicron viral clearance. Methods: Approximately 278 Omicron cases at the Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine were retrospectively analyzed between August 11 and August 31, 2022. Demographic and laboratory data were also collected. The association between demographics, laboratory findings, and duration of Omicron viral clearance was analyzed using Pearson correlation analysis and univariate and multivariate logistic regression. Results: Univariate logistic regression analyses showed that a prolonged viral clearance time was significantly associated with older age and lower immunoglobulin (Ig) G and platelet (PLT) levels. Using multinomial logistic regression analyses, direct bilirubin, IgG, activated partial thromboplastin time (APTT), and PLT were independent factors for longer viral shedding duration. The model combining direct bilirubin, IgG, APTT, and PLT identifies patients infected with Omicron whose viral clearance time was ≥7 days with 62.7% sensitivity and 83.4% specificity. Conclusion: These findings suggest that direct bilirubin, IgG, PLT, and APTT are significant risk factors for a longer viral shedding duration in patients infected with Omicron. Measuring levels of direct bilirubin, IgG, PLT, and APTT is advantageous to identify patients infected with Omicron with longer viral shedding duration.
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COVID-19 , Immunoglobulin G , Humans , SARS-CoV-2 , Partial Thromboplastin Time , Retrospective Studies , China , BilirubinABSTRACT
HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.
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Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Nasal Sprays , SARS-CoV-2 , Cohort Studies , Propensity Score , Immunoglobulin MABSTRACT
Background: Oseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19. Methods: This multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance. Results: A total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: -0.84, 95%CI: (-1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: -0.27, 95% CI: [-0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality. Conclusion: Oseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.
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Koutsakos et al. have recently published an article showing that SARS-CoV-2 breakthrough infection results in robust naïve and memory T cell activation, and the activity of CD8 T cells strongly correlates with viral clearance.
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Background: A 5-day course of nirmatrelvir-ritonavir (N/R) can significantly reduce the hospitalization and death rates and the duration of infectiousness in high-risk SARS-CoV-2 patients. However, in a fraction of treated individuals virus rebounds following an initial recovery after treatment. The mechanism driving rebound is not well understood. We hypothesize that treatment with N/R near the time of symptom onset halts the depletion of target cells, but does not fully eliminate the virus, and thus can lead to viral rebound. Method(s): Previously, we and others have developed viral dynamic models and successfully used them to fit data on SARS-CoV-2 infection. Here we expand these models and incorporate N/R pharmacokinetic and pharmacodynamic effects and an adaptive immune response. Result(s): We fit this model to the data presented in Charness et al., NEJM (2022) where longitudinal quantitative PCR data is available for 3 individuals who experienced viral rebounds after taking N/R. We found that the model fit the data well. By varying model parameters from their best-fit values, we show the occurrence of viral rebound is sensitive to model parameters, and the time treatment is initiated, which may explain why only a fraction of individuals rebound. Finally, the model with its best-fit parameter values was used to test the therapeutic effects of treatment extended to 10 days or a second 5-day course of N/R initiated one day after symptoms reoccur. Conclusion(s): Our model fits predicted that virus is not fully eliminated during N/R treatment and supported our initial hypothesis that at the end of treatment target cells are available to allow viral resurgence. Simulating the effect of starting treatment later, we find the probability of viral rebound occurring decreases, suggesting that delaying treatment may be a strategy to reduce viral rebound. However, N/R treatment accelerates viral clearance and hence potentially can reduce viral transmission. Thus, delaying treatment may have a detrimental effect on public health and could also have impact on the severity of disease in the high-risk patients for whom N/R is recommended. Increasing treatment from 5 to 10 days continues to preserve target cells and thus may still allow viral rebound if viable virus is present at the end of treatment and sufficient adaptive immunity has not developed. Simulating giving a second course of treatment one day after symptoms reappear, did not prevent rebound.
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Background: Evolution evidence of Coronavirus disease 2019 (COVID-19) and viral clearance time remains limited in tropical settings. Understanding this is crucial for public health control measures at community-level. We evaluated the viral dynamics of SARS-CoV-2 infection and factors associated with positivity duration in COVID-19 cases in Cameroon. Method(s): We conducted a prospective cohort-study of SARS-CoV-2 positive cases from the first to third wave (March 2020-October 2021) in Yaounde- Cameroon. RT-PCR was performed on nasopharyngeal swabs. SARS-CoV-2 positivity duration was evaluated from the first to last positive test before a negative result. Epi-info V.7.0 was used for data analyses with p< 0.05 considered statistically significant Results: A total of 282 participants were enrolled. The mean age was 41+/-14 years, with male predominant (62.1%). We had 15.6% symptomatic cases and cough most common (59.09%). The overall median positivity duration was 15[IQR: 9-23] days with 15[ IQR: 13-16] in the first, 17[ IQR: 11-26] in the second and 8[ IQR: 4-12] in the third wave (p= 0.007). Positivity duration was significantly higher in males (16 versus 14 days, p=0.03) and people aged >40 years (15 versus 14 days, p=0.02). Positivity duration was not affected by presence or absence of symptoms (p=0.80). No significant correlation was found with viral load (r=0.03;p=0.61). Considering baseline (24.7+/-7.2Ct) and last viral load (29.3+/-5.9 Ct), the DELTACt (4.6+/-1.3) and positivity duration (15 days) revealed a kinetic in viral decay of 0.3+/-0.087 Ct/day. Conclusion(s): A median positivity duration of 15 days is in accordance with viral clearance around 2 weeks for optimal confinement at community-level. Men and/or the elderly stand at higher risk of prolonged infection. Given the viral decay (0.3 Ct daily), we suggest personalized confinement periods. The variability of positivity duration according to phases could be function of strains which could be a factor of positivity duration.
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Background: Immunocompromised persons are disproportionately affected by severe SARS-CoV-2 infection, but immune compromise is heterogenous, which may impact viral dynamics. We hypothesized that higher degrees of compromised immunity are associated with higher viral shedding and slower viral clearance in the absence of COVID-19 therapeutics. Method(s): Participants enrolled in ACTIV-2/A5401, a platform trial for COVID-19 therapeutics in non-hospitalized adults within 10 days of symptom onset, received either an active treatment or placebo between 8/2020 and 7/2021. Participants were categorized based on the extent of immunosuppression into none, mild, moderate and severe categories at enrollment (day 0). Longitudinal anterior nasal (AN) and plasma SARS-CoV-2 levels were measured with a quantitative PCR assay. Regression models assessed associations between immunocompromise severity and viral levels (VL) at day 0, and longitudinally among those on placebo with quantifiable RNA at day 0. Multivariate analyses adjusted for demographics and symptom duration and vaccination status at day 0. Result(s): Immunocompromised (mild 383, moderate 159, severe 35) and immunocompetent (1956) participants had comparable symptom durations at day 0 (median 6 days) and most were unvaccinated (~95%). AN VL at day 0 was higher in the moderate/severe group compared to the immunocompetent group (adjusted difference in means: 0.47 log10 copies/mL, 95% CI 0.12, 0.83). While AN VL decayed at similar rates among all groups from day 0 to 3, there was a trend towards higher cumulative AN VLs across the 28-day follow-up in the moderate/severe group compared to immunocompetent group (adjusted fold difference in VL AUC 1.63, 95%CI 0.95, 2.77). The mild group showed no differences in day 0 VL or AUC compared to the immunocompetent group. The frequency of detectable plasma SARS-CoV-2 RNA was similar at day 0 across all groups (overall 21%), but there appeared to be a higher proportion of immunocompromised participants with detectable plasma viral RNA at day 7 (moderate/severe 2/23 [9%], mild 5/44 [11%]) compared to the immunocompetent group (8/282, 3%). Conclusion(s): Before emergence of Omicron and widespread vaccination, moderate/severe immunocompromised status was associated with higher nasal viral levels at study enrollment and showed a trend towards higher cumulative AN viral load, and all immunocompromised groups appeared to have more persistent plasma viremia during follow-up.
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Background: Polymorphonuclear neutrophils (PMNs) recruited to the airway lumen in cystic fibrosis (CF) undergo a rapid transcriptional program, resulting in exocytosis of granules and inhibition of bacterial killing. As a result, chronic infection, feed-forward inflammation, and structural tissue damage occur. Because CF airway PMNs are also highly pinocytic, we hypothesized that we could deliver protein- and ribonucleic acid (RNA)-based therapies to modulate their function to benefit patients. We elected to use extracellular vesicles (EVs) as a delivery vector because they are highly customizable, and airway PMNs have previously been shown by our group to process and use their cargo efficiently [1]. Furthermore, our prior work on CF airway PMNs [2] led to identification of the long noncoding RNA MALAT1, the transcription factor Ehf, and the histone deacetylase/long-chain fatty deacylase HDAC11 as potential targets to modulate CF airway PMN dysfunction. Method(s): H441 human club epithelial cells were chosen for EV production because they efficiently communicate with lung-recruited primary human PMNs [1]. Relevant constructs were cloned into an expression plasmid downstream of a constitutive cytomegalovirus or U6 promoter with an additional puromycin selection cassette. EVs were generated in serumdepleted media and purified by differential centrifugation. Quality and concentration of EVs was determined by electron microscopy and nanoparticle tracking analysis and cargo content by western blot (protein) or qualitative reverse transcription polymerase chain reaction (RNA). Enhanced green fluorescent protein and messenger ribonucleic acid (mRNA) were used as controls. To test delivery to primary human PMNs, generated EVs were applied in the apical fluid of an airway transmigration model [2]. PMN activation was assessed by flow cytometry, and bacterial (PA01 and Staphylococcus aureus 8325-4) killing and viral (influenza Avirus [IAV] H1N1/PR/8/34;SARS-CoV-2/Washington) clearance assays were conducted. Result(s): To package protein, we used EV-loading motifs such as the tetraspanin CD63, Basp1 amino acids 1-9, and the palmitoylation signal of Lyn kinase. To load mRNA, a C'D box motif recognized by the RNA-binding protein L7Ae was included in the 3' untranslated region of the expressed RNA, and CD63-L7Ae was co-expressed. Airway-recruited PMNs treated with EVs containing small interfering RNAs against MALAT1 or HDAC11 showed greater ability to clear bacteria. Conversely, PMNs treated with constructs encasing MALAT1 or HDAC11 efficiently cleared IAV and SARSCoV- 2. PMNs expressing Ehf showed greater clearance of bacteria and viruses. Conclusion(s): Our findings suggest mutually exclusive roles of MALAT-1 and HDAC11 in regulating bacterial and viral clearance by airway-recruited PMNs. Expression of Ehf in airway PMNs may be a pathogen-agnostic approach to enhancing clearance by airway-recruited PMNs. Overall, our study brings proof-of-concept data for therapeutic RNA/protein transfer to airway-recruited PMNs in CF and other lung diseases and for use of EVs as a promising method for cargo delivery to these cells. It is our expectation that, by treating the immune compartment of CF airway disease, pathogentherapies, such as antibiotics will be more effective, and epithelial-targeted therapies, such as CFTR modulators, will have greater penetrance into the cell types of interest.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. These cases occurred mostly in patients who were asymptomatic and showed negative results from PCR and serology tests for SARS-CoV-2. We hypothesized that chilblain patients are predisposed to mount a robust innate immunity against the virus, which clinically manifests as chilblains and promotes early viral clearance, thereby preventing pulmonary disease and precluding adaptive responses. By profiling skin lesions in the early stage following chilblain onset, we uncover a transient IRF7-dependent type I interferon (IFN) signature that is driven by the acral infiltration of systemically activated plasmacytoid dendritic cells (pDCs). Patients' peripheral blood mononuclear cells (PBMCs) demonstrate increased production of IFNalpha when exposed to SARS-CoV-2 and influenza A, but not herpes simplex virus 1 (HSV-1), indicating a heightened ability to detect RNA -but not DNA- viruses. Further investigations revealed enhanced responsiveness of pDCs in chilblain patients to the RNA sensor TLR7, but not the DNA sensor TLR9. Collectively, our study establishes a two-step model for the immunopathology of SARS-CoV-2-related chilblains: enhanced TLR7 immunity in pDCs, likely triggered by SARS-CoV-2 exposure at the mucosal site, leads to prompt viral clearance, which explains the lack of infection markers in most cases. Subsequently, systemic spread of activated pDCs and infiltration of the toes in response to mechanical stress or acral coldness, may result in IFN-mediated tissue damage with development of chilblains.Copyright © 2023
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OBJECTIVES: We sought to identify the predictors of delayed viral clearance in patients with cancer with asymptomatic COVID-19 when the SARS-CoV-2 Omicron variants prevailed in Hong Kong. METHODS: All patients with cancer who were attending radiation therapy for head and neck malignancies or systemic anticancer therapy saved their deep throat saliva or nasopharyngeal swabs at least twice weekly for SARS-CoV-2 screening between January 1 and April 30, 2022. The multivariate analyses identified predictors of delayed viral clearance (or slow recovery), defined as >21 days for the cycle threshold values rising to ≥30 or undetectable in two consecutive samples saved within 72 hours. Three machine learning algorithms evaluated the prediction performance of the predictors. RESULTS: A total of 200 (15%) of 1309 patients tested positive for SARS-CoV-2. Age >65 years (P = 0.036), male sex (P = 0.003), high Charlson comorbidity index (P = 0.042), lung cancer (P = 0.018), immune checkpoint inhibitor (P = 0.036), and receipt of one or no dose of COVID-19 vaccine (P = 0.003) were significant predictors. The three machine learning algorithms revealed that the mean ± SD area-under-the-curve values predicting delayed viral clearance with the cut-off cycle threshold value ≥30 was 0.72 ± 0.11. CONCLUSION: We identified subgroups with delayed viral clearance that may benefit from targeted interventions.
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COVID-19 , Lung Neoplasms , Humans , Male , Aged , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 VaccinesABSTRACT
A transient inline spiking system is a promising tool for evaluating the performance of a virus filter in continuous operation. For better implementation of the system, we performed a systematic analysis to understand the residence time distribution (RTD) of inert tracers in the system. We aimed to understand the RTD of a salt spike, not retained onto or within the membrane pore, to focus on its mixing and spreading within the processing units. A concentrated NaCl solution was spiked into a feed stream as the spiking duration (tspike) was varied from 1 to 40 min. A static mixer was employed to mix the salt spike with the feed stream, which then passed through a single-layered nylon membrane inserted in a filter holder. The RTD curve was obtained by measuring the conductivity of the collected samples. An analytical model, the PFR-2CSTR model, was employed to predict the outlet concentration from the system. The slope and peak of the RTD curves were well-aligned with the experimental findings when τPFR = 4.3 min, τCSTR1 = 4.1 min, and τCSTR2 = 1.0 min. CFD simulations were performed to describe the flow and transport of the inert tracers through the static mixer and the membrane filter. The RTD curve spanned more than 30 min, much longer than tspike, since solutes were dispersed within processing units. The flow characteristics in each processing unit correlated with the RTD curves. Our detailed analysis of the transient inline spiking system would be helpful for implementing this protocol in continuous bioprocessing.
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Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.
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Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.
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Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.
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Currently, humanity is suffering from a highly contagious and infectious novel coron-avirus disease. Due to the unavailability of any specifically approved therapy to eradicate this pathogenic virus, day by day, it is claiming more and more lives of humans. Observing the current scenario, human civilization seems to be in dangerous situation, and the development of a potential vaccine against this invisible enemy may take some more time. It was observed that the individual immune system plays an important role in the fight against the novel coronavirus. Additionally, the innate immune system of the host acts as the first line of defense against invading pathogenic virus-es. The host innate immune cells can detect and detoxify the evading viruses. Thus, boosting the innate immune response via targeting activator or inhibitory immune check points pathways for en-hancing T-cell immune response may potentially help the patients to fight against this deadly virus. The aim of this editorial is to discuss in brief about the pathogenesis of COVID-19, the role of innate immunity and autophagy during viral clearance.Copyright © 2021 Bentham Science Publishers.