scholarly journals In-host Modelling of COVID-19 in Humans

2020 ◽  
Author(s):  
Esteban A. Hernandez-Vargas ◽  
Jorge X. Velasco-Hernandez
Keyword(s):  
Immune Responses ◽  
Target Cell ◽  
Viral Infections ◽  
Cell Model ◽  
Influenza Infection ◽  
Severe Disease ◽  
Reproductive Number ◽  
Infected Cells ◽  
Eclipse Phase ◽  
The Impact

ABSTRACTCOVID-19 pandemic has underlined the impact of emergent pathogens as a major threat for human health. The development of quantitative approaches to advance comprehension of the current outbreak is urgently needed to tackle this severe disease. In this work, several mathematical models are proposed to represent SARS-CoV-2 dynamics in infected patients. Considering different starting times of infection, parameters sets that represent infectivity of SARS-CoV-2 are computed and compared with other viral infections that can also cause pandemics.Based on the target cell model, SARS-CoV-2 infecting time between susceptible cells (mean of 30 days approximately) is much slower than those reported for Ebola (about 3 times slower) and influenza (60 times slower). The within-host reproductive number for SARS-CoV-2 is consistent to the values of influenza infection (1.7-5.35). The best model to fit the data was including immune responses, which suggest a slow cell response peaking between 5 to 10 days post onset of symptoms. The model with eclipse phase, time in a latent phase before becoming productively infected cells, was not supported. Interestingly, both, the target cell model and the model with immune responses, predict that virus may replicate very slowly in the first days after infection, and it could be below detection levels during the first 4 days post infection. A quantitative comprehension of SARS-CoV-2 dynamics and the estimation of standard parameters of viral infections is the key contribution of this pioneering work.

scholarly journals Third doses of COVID-19 vaccines reduce infection and transmission of SARS-CoV-2 and could prevent future surges in some populations

2021 ◽  
Author(s):  
Billy J Gardner ◽  
A. Marm Kilpatrick
Keyword(s):  
Vaccine Coverage ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Reproductive Number ◽  
Vaccine Protection ◽  
Contact Rates ◽  
Previous Infection ◽  
Antibody Titers ◽  
Protection Against Infection ◽  
The Impact

Background Vaccines have greatly reduced the impact of COVID-19 globally. Unfortunately, evidence indicates that immunity wanes following vaccination, especially with the Delta variant (B.1.617.2). Protection against severe disease and death remain high, but protection against milder disease and infection have dropped significantly. A third booster dose of two-dose vaccines has been approved in several countries to individuals at higher risk of severe disease to protect those individuals, but the benefit to boosting immunity in younger healthy individuals and the effects on transmission are less clear. Methods Here we use relationships between neutralizing antibody titers and vaccine protection against infection and transmission, combined with data on waning and boosting of neutralizing antibody titers to examine the impact of a third dose of the Pfizer vaccine on infection and transmission and its impact on the pathogen effective reproductive number Rt. Findings Eight months of waning reduced protection of the Pfizer vaccine against all infections from 80.0% (95% CI: 77% to 83%) to 60.4% (95% CI: 53% to 67%); a third dose (which increased neutralizing antibody titers 25.9- fold relative to levels after 8 months of waning) increased protection to 87.2% (95% CI: 83% to 91%). Increased protection against infection and transmission from third doses reduced Rt by 21% to 66% depending on vaccine coverage and previous infection and reduced Rt below 1 when vaccination coverage was high or contact rates were well below pre-pandemic levels. Interpretation A third dose of the Pfizer vaccine could reduce transmission of SARS-CoV-2, which would reduce infection in unvaccinated individuals and breakthrough infections in vaccinated individuals. While vaccination of unvaccinated individuals, especially in developing countries, would be more effective for reducing disease than providing a third dose to vaccinated individuals, the benefit of a third dose in reducing transmission is sizeable and increases with vaccine coverage and contact rates among individuals.

GLOBAL PROPERTIES OF A MODEL OF IMMUNE EFFECTOR RESPONSES TO VIRAL INFECTIONS

2007 ◽  
Vol 10 (04) ◽  
pp. 495-503 ◽  
Author(s):  
XIA WANG ◽  
XINYU SONG
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lyapunov Functions ◽  
Viral Infections ◽  
Reproductive Number ◽  
Asymptotically Stable ◽  
Globally Asymptotically Stable ◽  
Immune Effector ◽  
Global Properties ◽  
Ctl Immune Response

This article proposes a mathematical model which has been used to investigate the importance of lytic and non-lytic immune responses for the control of viral infections. By means of Lyapunov functions, the global properties of the model are obtained. The virus is cleared if the basic reproduction number R0 ≤ 1 and the virus persists in the host if R0 > 1. Furthermore, if R0 > 1 and other conditions hold, the immune-free equilibrium E0 is globally asymptotically stable. The equilibrium E1 exists and is globally asymptotically stale if the CTL immune response reproductive number R1 < 1 and the antibody immune response reproductive number R2 > 1. The equilibrium E2 exists and is globally asymptotically stable if R1 > 1 and R2 < 1. Finally, the endemic equilibrium E3 exists and is globally asymptotically stable if R1 > 1 and R2 > 1.

scholarly journals Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?

2020 ◽  
Author(s):  
Renata Silverio ◽  
Daniela Caetano Gonçalves ◽  
Márcia Fábia Andrade ◽  
Marilia Seelaender
Keyword(s):  
Body Composition ◽  
Immune System ◽  
Nutritional Status ◽  
Immune Responses ◽  
Lean Mass ◽  
Severe Disease ◽  
Cytokine Storm ◽  
Risk Of Infection ◽  
Elderly Individuals ◽  
The Impact

ABSTRACT Coronavirus disease 2019 (COVID-19) is an emerging disease that has reached pandemic status by rapidly spreading worldwide. Elderly individuals and patients with comorbidities such as obesity, diabetes, and hypertension show a higher risk of hospitalization, severe disease, and mortality by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These patients frequently show exacerbated secretion of proinflammatory cytokines associated with an overreaction of the immune system, the so-called cytokine storm. Host nutritional status plays a pivotal role in the outcome of a variety of different infectious diseases. It is known that the immune system is highly affected by malnutrition, leading to decreased immune responses with consequent augmented risk of infection and disease severity. Body composition, especially low lean mass and high adiposity, has consistently been linked to worsened prognosis in many different diseases. In this review, evidence concerning the impact of nutritional status on viral infection outcomes is discussed.

scholarly journals Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael Z. Zulu ◽  
Suhas Sureshchandra ◽  
Amanda N. Pinski ◽  
Brianna Doratt ◽  
Weining Shen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Immune Cell ◽  
Severe Disease ◽  
Low Grade ◽  
Igg Antibody ◽  
Aged Patients ◽  
Prevalence Of Obesity ◽  
Antibody Titers ◽  
The Impact

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.

scholarly journals Flavivirus infections induce a Golgi stress response in vertebrate and mosquito cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mercedes Viettri ◽  
José L. Zambrano ◽  
Romel Rosales ◽  
Gerson I. Caraballo ◽  
Ana Lorena Gutiérrez-Escolano ◽  
...  
Keyword(s):  
Stress Response ◽  
Golgi Complex ◽  
Stress Responses ◽  
Viral Infections ◽  
Vesicular Transport ◽  
Positive Control ◽  
Mosquito Cells ◽  
Infected Cells ◽  
The Impact ◽  
Replicative Cycle

AbstractThe stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. No examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3 and increased expression of pathway targeted genes. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on the Golgi complex imposed by virion and NS1 processing and secretion.

scholarly journals Broadly Reactive IgG Responses to Heterologous H5 Prime-Boost Influenza Vaccination Are Shaped by Antigenic Relatedness to Priming Strains

mBio ◽  
2021 ◽  
Author(s):  
Jiong Wang ◽  
Dongmei Li ◽  
Sheldon Perry ◽  
Shannon P. Hilchey ◽  
Alexander Wiltse ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccination ◽  
B Cell ◽  
Immune Evasion ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Antigenic Relatedness ◽  
Antigenic Shift ◽  
Exposure History ◽  
The Impact

The antigenic shift and draft of hemagglutinin (HA) in influenza viruses is accepted as one of the major reasons for immune evasion. The analysis of B cell immune responses to influenza infection and vaccination is complicated by the impact of exposure history and antibody cross-reactions between antigenically similar influenza strains.

scholarly journals Antibiotics Against COVID-19 and Mitochondria? Urgent Thinking Out of the Box

2020 ◽  
Author(s):  
Jaroslaw Tyszka ◽  
Karolina Kobos ◽  
Aleksandra Tyszka
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Local Health ◽  
Antiviral Immune Response ◽  
Health Authorities ◽  
Treatment Data ◽  
The Moment ◽  
The Impact

Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients&rsquo; immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

scholarly journals Flavivirus Infection Induce a Golgi Stress Response in Vertebrate and Mosquito Cells

2021 ◽  
Author(s):  
Mercedes Viettri ◽  
José L. Zambrano ◽  
Romel Rosales-Ramirez ◽  
Ana Lorena Gutierrez-Escolano ◽  
Juan E Ludert
Keyword(s):  
Stress Response ◽  
Golgi Complex ◽  
Stress Responses ◽  
Viral Infections ◽  
Vesicular Transport ◽  
Positive Control ◽  
Mosquito Cells ◽  
Infected Cells ◽  
Flavivirus Infection ◽  
The Impact

Abstract The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. Few examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on Golgi complex imposed by virion and NS1 processing and secretion.

scholarly journals The Circadian Clock, the Immune System, and Viral Infections: The Intricate Relationship Between Biological Time and Host-Virus Interaction

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 83 ◽  
Author(s):  
Gianluigi Mazzoccoli ◽  
Manlio Vinciguerra ◽  
Annalucia Carbone ◽  
Angela Relógio
Keyword(s):  
Viral Infections ◽  
Mutual Influence ◽  
Biological Clock ◽  
Life Forms ◽  
The Body ◽  
Viral Agent ◽  
Biological Time ◽  
Infected Cells ◽  
Time Variations ◽  
The Impact

Living beings spend their lives and carry out their daily activities interacting with environmental situations that present space-time variations and that involve contact with other life forms, which may behave as commensals or as invaders and/or parasites. The characteristics of the environment, as well as the processes that support the maintenance of life and that characterize the execution of activities of daily life generally present periodic variations, which are mostly synchronized with the light–dark cycle determined by Earth’s rotation on its axis. These rhythms with 24-h periodicity, defined as circadian, influence events linked to the interaction between hosts and hosted microorganisms and can dramatically determine the outcome of this interplay. As for the various pathological conditions resulting from host–microorganism interactions, a particularly interesting scenario concerns infections by viruses. When a viral agent enters the body, it alters the biological processes of the infected cells in order to favour its replication and to spread to various tissues. Though our knowledge concerning the mutual influence between the biological clock and viruses is still limited, recent studies start to unravel interesting aspects of the clock–virus molecular interplay. Three different aspects of this interplay are addressed in this mini-review and include the circadian regulation of both innate and adaptive immune systems, the impact of the biological clock on viral infection itself, and finally the putative perturbations that the virus may confer to the clock leading to its deregulation.

scholarly journals Assessment of Lymph Node Stromal Cells as an Underlying Factor in Age-Related Immune Impairment

2019 ◽  
Vol 74 (11) ◽  
pp. 1734-1743 ◽  
Author(s):  
April R Masters ◽  
Alexxus Hall ◽  
Jenna M Bartley ◽  
Spencer R Keilich ◽  
Erica C Lorenzo ◽  
...  
Keyword(s):  
T Cells ◽  
Steady State ◽  
Immune Responses ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Influenza Infection ◽  
Cell Subset ◽  
The Elderly ◽  
Age Related ◽  
The Impact

Abstract Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.

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