scholarly journals Daily viral kinetics and innate and adaptive immune responses assessment in COVID-19: a case series

2020 ◽  
Author(s):  
Pauline Vetter ◽  
Christiane Eberhardt ◽  
Benjamin Meyer ◽  
Paola Andrea Martinez Murillo ◽  
Giulia Torriani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Tract ◽  
Infectious Virus ◽  
Upper Respiratory Tract ◽  
Innate Response ◽  
Viral Control ◽  
Adaptive Immune Responses ◽  
Viral Loads ◽  
Viral Shedding ◽  
Adaptive Immune

AbstractBackgroundViral shedding patterns and its correlation with the immune responses of mildly symptomatic COVID-19 patients are still poorly characterized.MethodsWe enrolled the first five COVID-19 patients quarantined in our institution; none received immunomodulatory treatment. We monitored shedding of viral RNA and infectious virus by RT-PCR and cell culture from the upper respiratory tract, and characterized the kinetics of systemic innate and adaptive immune responses.ResultsDespite mild clinical disease, high viral loads and shedding of infectious virus were observed from the respiratory tract, with isolation of infectious virus and prolonged positivity by PCR up to day 7 and 19 post onset of symptoms, respectively. Robust innate responses characterized by an increase in activated CD14+CD16+ monocytes and cytokine responses were observed as early as 2 days after symptoms onset. Cellular and humoral SARS-CoV-2 specific adaptive responses were detectable in all patients.ConclusionInfectious virus shedding was limited to the first week of symptom onset in mild cases. A strong innate response, characterized by the mobilization of activated monocytes during the first days of infection, as well as SARS-CoV-2 specific antibodies were detectable, even in patients with mild disease.SummaryWe describe viral and immune profiles of the first five SARS-CoV-2 patients in our institution, showing high viral loads and infectious viral shedding in early acute disease. Mild patients mount an innate response sufficient for viral control and specific immunity.

scholarly journals Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models

2021 ◽  
pp. eabh0755
Author(s):  
Neeltje van Doremalen ◽  
Jyothi N. Purushotham ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Trenton Bushmaker ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Direct Contact ◽  
Infectious Virus ◽  
Rhesus Macaques ◽  
Upper Respiratory Tract ◽  
Preclinical Models ◽  
Viral Loads ◽  
Viral Shedding ◽  
Nasal Swabs ◽  
Upper Respiratory

ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper respiratory tract. Here, we investigated whether intranasally administered ChAdOx1 nCoV-19 reduces detection of virus in nasal swabs after challenging vaccinated macaques and hamsters with SARS-CoV-2 carrying a D614G mutation in the spike protein. Viral loads in swabs obtained from intranasally vaccinated hamsters were decreased compared to control hamsters, and no viral RNA or infectious virus was found in lung tissue after a direct challenge or after direct contact with infected hamsters. Intranasal vaccination of rhesus macaques resulted in reduced virus concentrations in nasal swabs and a reduction in viral loads in bronchoalveolar lavage and lower respiratory tract tissue. Intranasal vaccination with ChAdOx1 nCoV-19/AZD1222 reduced virus concentrations in nasal swabs in two different SARS-CoV-2 animal models, warranting further investigation as a potential vaccination route for COVID-19 vaccines.

scholarly journals Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2090
Author(s):  
Edin J. Mifsud ◽  
Miku Kuba ◽  
Ian G. Barr
Keyword(s):  
Influenza Virus ◽  
Immune System ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Innate Immune System ◽  
Innate Immune ◽  
Upper Respiratory Tract ◽  
Adaptive Immune ◽  
Upper Respiratory

The innate immune system is the host’s first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

scholarly journals Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

2012 ◽  
Vol 87 (5) ◽  
pp. 2489-2495 ◽  
Author(s):  
J. Pega ◽  
D. Bucafusco ◽  
S. Di Giacomo ◽  
J. M. Schammas ◽  
D. Malacari ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Tract ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Infected Cattle ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Disrupting Bordetella Immunosuppression Reveals a Role for Eosinophils in Coordinating the Adaptive Immune Response in the Respiratory Tract

2020 ◽  
Vol 8 (11) ◽  
pp. 1808 ◽  
Author(s):  
Monica C. Gestal ◽  
Uriel Blas-Machado ◽  
Hannah M. Johnson ◽  
Lily N. Rubin ◽  
Kalyan K. Dewan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Respiratory Pathogens ◽  
Adaptive Immune Responses ◽  
Eosinophil Recruitment ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Lymphoid Aggregates ◽  
Allergy And Asthma

Recent findings revealed pivotal roles for eosinophils in protection against parasitic and viral infections, as well as modulation of adaptive immune responses in the gastric mucosa. However, the known effects of eosinophils within the respiratory tract remain predominantly pathological, associated with allergy and asthma. Simulating natural respiratory infections in mice, we examined how efficient and well-adapted pathogens can block eosinophil functions that contribute to the immune response. Bordetella bronchiseptica, a natural pathogen of the mouse, uses the sigma factor btrS to regulate expression of mechanisms that interfere with eosinophil recruitment and function. When btrS is disrupted, immunomodulators are dysregulated, and eosinophils are recruited to the lungs, suggesting they may contribute to much more efficient generation of adaptive immunity induced by this mutant. Eosinophil-deficient mice failed to produce pro-inflammatory cytokines, to recruit lymphocytes, to organize lymphoid aggregates that resemble Bronchus Associated Lymphoid Tissue (BALT), to generate an effective antibody response, and to clear bacterial infection from the respiratory tract. Importantly, the failure of eosinophil-deficient mice to produce these lymphoid aggregates indicates that eosinophils can mediate the generation of an effective lymphoid response in the lungs. These data demonstrate that efficient respiratory pathogens can block eosinophil recruitment, to inhibit the generation of robust adaptive immune responses. They also suggest that some post-infection sequelae involving eosinophils, such as allergy and asthma, might be a consequence of bacterial mechanisms that manipulate their accumulation and/or function within the respiratory tract.

scholarly journals Innate and Adaptive Immune Responses in Chronic Hepatitis C Virus and Hepatitis B Virus Infection with High Viral Loads

2019 ◽  
Author(s):  
Yutaka Kishida
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Viral Loads ◽  
Adaptive Immune ◽  
B Virus

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

scholarly journals SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels.

2021 ◽  
Author(s):  
Heba H Mostafa ◽  
chun Huai Luo ◽  
C. Paul Morris ◽  
Maggie Li ◽  
Nicholas J Swanson ◽  
...  
Keyword(s):  
Cell Culture ◽  
Respiratory Tract ◽  
Large Scale ◽  
Infectious Virus ◽  
Time Frame ◽  
Molecular Testing ◽  
Upper Respiratory Tract ◽  
Symptomatic Infection ◽  
Viral Loads ◽  
Upper Respiratory

Abstract Introduction COVID-19 large scale immunization in the US has been associated with infrequent breakthrough positive molecular testing. Whether a positive test is associated with a high viral RNA load, specific viral variant, recovery of infectious virus, or symptomatic infection is largely not known. Methods In this study, we identified 133 SARS-CoV-2 positive patients who had received two doses of either Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines, the 2nd of which was received between January and April of 2021. The positive samples were collected between January and May of 2021 with a time that extended from 2 to 100 days after the second dose. Samples were sequenced to characterize the whole genome and Spike protein changes and cycle thresholds that reflect viral loads were determined using a single molecular assay. Local SARS-CoV-2 IgG antibodies were examined using ELISA and specimens were grown on cell culture to assess the recovery of infectious virus as compared to a control unvaccinated cohort from a matched time frame. Results Of 133 specimens, 24 failed sequencing and yielded a negative or very low viral load on the repeat PCR. Of 109 specimens that were used for further genome analysis, 68 (62.4%) were from symptomatic infections, 11 (10.1%) were admitted for COVID-19, and 2 (1.8%) required ICU admission with no associated mortality. The predominant virus variant was the alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted when genomes were compared to a large control cohort from a matched time frame. A significant reduction of the recovery of infectious virus on cell culture as well as delayed time to the first appearance of cytopathic effect was accompanied by an increase in local IgG levels in respiratory samples of vaccinated individuals but upper respiratory tract IgG levels were not different between symptomatic or asymptomatic infections. Conclusions Vaccination reduces the recovery of infectious virus in breakthrough infections accompanied by an increase in upper respiratory tract local immune responses.

scholarly journals Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Pauline Vetter ◽  
Christiane S. Eberhardt ◽  
Benjamin Meyer ◽  
Paola Andrea Martinez Murillo ◽  
Giulia Torriani ◽  
...  
Keyword(s):  
Immune Response ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Case Series ◽  
Viral Rna ◽  
Adaptive Responses ◽  
Innate Response ◽  
Viral Control ◽  
Virus Shedding ◽  
Viral Loads

ABSTRACT Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14+ CD16+ monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease. IMPORTANCE This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.

scholarly journals Strategies for Immunomonitoring after Vaccination and during Infection

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 365
Author(s):  
Lucille Adam ◽  
Pierre Rosenbaum ◽  
Olivia Bonduelle ◽  
Behazine Combadière
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Data Integration ◽  
High Throughput ◽  
Viral Control ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Holistic Approaches ◽  
Immune Efficacy

Immunomonitoring is the study of an individual’s immune responses over the course of vaccination or infection. In the infectious context, exploring the innate and adaptive immune responses will help to investigate their contribution to viral control or toxicity. After vaccination, immunomonitoring of the correlate(s) and surrogate(s) of protection is a major asset for measuring vaccine immune efficacy. Conventional immunomonitoring methods include antibody-based technologies that are easy to use. However, promising sensitive high-throughput technologies allowed the emergence of holistic approaches. This raises the question of data integration methods and tools. These approaches allow us to increase our knowledge on immune mechanisms as well as the identification of key effectors of the immune response. However, the depiction of relevant findings requires a well-rounded consideration beforehand about the hypotheses, conception, organization and objectives of the immunomonitoring. Therefore, well-standardized and comprehensive studies fuel insight to design more efficient, rationale-based vaccines and therapeutics to fight against infectious diseases. Hence, we will illustrate this review with examples of the immunomonitoring approaches used during vaccination and the COVID-19 pandemic.

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