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

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 qua...

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Published inmSphere Vol. 5; no. 6
Main Authors Vetter, Pauline, Eberhardt, Christiane S., Meyer, Benjamin, Martinez Murillo, Paola Andrea, Torriani, Giulia, Pigny, Fiona, Lemeille, Sylvain, Cordey, Samuel, Laubscher, Florian, Vu, Diem-Lan, Calame, Adrien, Schibler, Manuel, Jacquerioz, Frederique, Blanchard-Rohner, Géraldine, Siegrist, Claire-Anne, Kaiser, Laurent, Didierlaurent, Arnaud M., Eckerle, Isabella
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 11.11.2020
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Abstract 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. 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.
AbstractList 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. 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.
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.
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.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.
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. 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.
Author Laubscher, Florian
Vu, Diem-Lan
Kaiser, Laurent
Cordey, Samuel
Didierlaurent, Arnaud M.
Lemeille, Sylvain
Schibler, Manuel
Calame, Adrien
Vetter, Pauline
Eberhardt, Christiane S.
Martinez Murillo, Paola Andrea
Torriani, Giulia
Meyer, Benjamin
Jacquerioz, Frederique
Siegrist, Claire-Anne
Blanchard-Rohner, Géraldine
Eckerle, Isabella
Pigny, Fiona
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  fullname: Vetter, Pauline
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  givenname: Christiane S.
  surname: Eberhardt
  fullname: Eberhardt, Christiane S.
  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland, Division of General Pediatrics, Geneva University Hospitals, Geneva, Switzerland, Emory Vaccine Center, Emory University, Atlanta, Georgia, USA
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  givenname: Benjamin
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  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
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  givenname: Paola Andrea
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  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
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  givenname: Giulia
  surname: Torriani
  fullname: Torriani, Giulia
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 6
  givenname: Fiona
  surname: Pigny
  fullname: Pigny, Fiona
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
– sequence: 7
  givenname: Sylvain
  surname: Lemeille
  fullname: Lemeille, Sylvain
  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
– sequence: 8
  givenname: Samuel
  surname: Cordey
  fullname: Cordey, Samuel
  organization: Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 9
  givenname: Florian
  surname: Laubscher
  fullname: Laubscher, Florian
  organization: Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 10
  givenname: Diem-Lan
  surname: Vu
  fullname: Vu, Diem-Lan
  organization: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 11
  givenname: Adrien
  surname: Calame
  fullname: Calame, Adrien
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland
– sequence: 12
  givenname: Manuel
  surname: Schibler
  fullname: Schibler, Manuel
  organization: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 13
  givenname: Frederique
  surname: Jacquerioz
  fullname: Jacquerioz, Frederique
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 14
  givenname: Géraldine
  surname: Blanchard-Rohner
  fullname: Blanchard-Rohner, Géraldine
  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland, Division of General Pediatrics, Geneva University Hospitals, Geneva, Switzerland
– sequence: 15
  givenname: Claire-Anne
  surname: Siegrist
  fullname: Siegrist, Claire-Anne
  organization: Center for Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland, Division of General Pediatrics, Geneva University Hospitals, Geneva, Switzerland
– sequence: 16
  givenname: Laurent
  surname: Kaiser
  fullname: Kaiser, Laurent
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland
– sequence: 17
  givenname: Arnaud M.
  surname: Didierlaurent
  fullname: Didierlaurent, Arnaud M.
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Emory Vaccine Center, Emory University, Atlanta, Georgia, USA
– sequence: 18
  givenname: Isabella
  surname: Eckerle
  fullname: Eckerle, Isabella
  organization: Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland, Faculty of Medicine, University of Geneva, Geneva, Switzerland, Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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Issue 6
Keywords COVID-19
SARS-CoV-2
cytokines
antibody response
viral load
immunity
Language English
License Copyright © 2020 Vetter et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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content type line 23
Pauline Vetter, Christiane S. Eberhardt, Benjamin Meyer, and Paola Andrea Martinez Murillo contributed equally. Author order reflects their clinical (Pauline Vetter), cell-mediated (Christiane S. Eberhardt), serological (Benjamin Meyer), and cytokine (Paola Andrea Martinez Murillo) immunological work, but without any differences in their positions reflecting their contributions.
Arnaud M. Didierlaurent and Isabella Eckerle are co-senior authors.
Citation Vetter P, Eberhardt CS, Meyer B, Martinez Murillo PA, Torriani G, Pigny F, Lemeille S, Cordey S, Laubscher F, Vu D-L, Calame A, Schibler M, Jacquerioz F, Blanchard-Rohner G, Siegrist C-A, Kaiser L, Didierlaurent AM, Eckerle I. 2020. Daily viral kinetics and innate and adaptive immune response assessment in COVID-19: a case series. mSphere 5:e00827-20. https://doi.org/10.1128/mSphere.00827-20.
ORCID 0000-0002-9902-5069
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Snippet This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other...
Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We...
ABSTRACT Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19)....
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SubjectTerms Adaptive Immunity
Adult
Aged
Antibodies, Viral - metabolism
antibody response
Betacoronavirus - immunology
Betacoronavirus - isolation & purification
Biomarkers - metabolism
Clinical Laboratory Techniques
Clinical Science and Epidemiology
Coronavirus Infections - diagnosis
Coronavirus Infections - immunology
Coronavirus Infections - virology
COVID-19
COVID-19 Testing
cytokines
Cytokines - metabolism
Humans
immunity
Immunity, Innate
Kinetics
Middle Aged
Pandemics
Pneumonia, Viral - diagnosis
Pneumonia, Viral - immunology
Pneumonia, Viral - virology
SARS-CoV-2
Severity of Illness Index
Viral Load
Virus Shedding
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Title Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series
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