The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 – Results from a prospective cohort of outpatient COVID-19 cases

Puchinger, Kerstin; Castelletti, Noemi; Rubio-Acero, Raquel; Geldmacher, Christof; Eser, Tabea M.; Deák, Flora; Paunović, Ivana; Bakuli, Abhishek; Saathoff, Elmar; Meyer, Alexander; Markgraf, Alisa; Falk, Philine; Reich, Jakob; Riess, Friedrich; Girl, Philipp; Müller, Katharina; Noller, Jessica Michelle Guggenbuehl; Wölfel, Roman; Höelscher, Michael; Kroidl, Inge; Wieser, Andreas; Olbrich, Laura; Alamoudi, Emad; Anderson, Jared L.; Baumann, Maximilian; Behlen, Marieke; Beyerl, Jessica; Böhnlein, Rebecca; Brauer, Anna; Britz, Vera; Bruger, Jan; Caroli, Friedrich; Contento, Lorenzo; Diekmannshemke, Jana; Do, Anna; Dobler, Gerhard; Eberle, Ute; Eckstein, Judith; Frese, Jonathan; Forster, Felix; Frahnow, Turid; Fröschl, Günter; Geisenberger, Otto; Gillig, Kristina; Heiber, Arlett; Hinske, Christian; Hoefflin, Janna; Hofberger, Tim; Höfinger, Michael; Hofmann, Larissa; Horn, Sacha; Huber, Kristina; Janke, Christian; Kappl, Ursula; Kiani, Charlotte; Kroidl, Arne; Laxy, Michael; Leidl, Reiner; Lindner, Felix; Mayrhofer, Rebecca; Mekota, Anna-Maria; Hk, Müller; Metaxa, Dafni; Pattard, Leonie; Pletschette, Michel; Prückner, Stephan; Pusl, Konstantin; Raimúndez, Elba; Rothe, Camila; Schäfer, Nicole; Schandelmaier, Paul; Schneider, Lara; Schultz, Sophie; Schunk, Mirjam; Schwettmann, Lars; Seibold, Heidi; Sothmann, Peter; Stapor, Paul; Theis, Fabian J.; Thiel, Verena; Thiesbrummel, Sophie; Thur, Niklas; Waibel, Julia; Wallrauch, Claudia; Winter, Simon; Wolff, Julia; Wullinger, Pia; Yaqine, Houda; Zange, Sabine; Zeggini, Eleftheria; Zimmermann, Thomas; Zielke, Anna; Ibraheem, Mohamed; Ahmed, Mohamed; Becker, Marc; Diepers, Paulina; Schälte, Yannik; Garí, Mercè; Pütz, Peter; Pritsch, Michael; Fingerle, Volker; Gleut, Ronan Le; Gilberg, Leonard; Brand, Isabel; Diefenbach, Maximilian N.; Weinauer, Franz; Martin, Silke; Quenzel, Ernst-Markus; Durner, Jürgen; Radon, Katja; Fuchs, Christiane; Hasenauer, Jan

doi:10.1016/j.virol.2022.02.002

Cited by 10 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Weekly blood samples were collected during four visits after confirmed diagnosis. In addition, data from outpatient non-BTI cases (n = 15) matched for time after PCR diagnosis, age, and sex from a similarly designed prospective COVID-19 Cohort Munich (KoCo19) sub-study were included in the analyses; a detailed description of the study design, setting, and population was previously published ( 18 , 19 ). In brief, individuals with a documented positive SARS-CoV-2 RT-PCR result were recruited in a prospective longitudinal cohort from May to December 2020 under the umbrella of the KoCo19 studies.…”

Section: Methodsmentioning

confidence: 99%

Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

Ahmed

Diepers²,

Janke³

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

SARS-CoV-2 vaccine breakthrough infections frequently occurred even before the emergence of Omicron variants. Yet, relatively little is known about the impact of vaccination on SARS-CoV-2-specific T cell and antibody response dynamics upon breakthrough infection. We have therefore studied the dynamics of CD4 and CD8 T cells targeting the vaccine-encoded Spike and the non-encoded Nucleocapsid antigens during breakthrough infections (BTI, n=24) and in unvaccinated control infections (non-BTI, n=30). Subjects with vaccine breakthrough infection had significantly higher CD4 and CD8 T cell responses targeting the vaccine-encoded Spike during the first and third/fourth week after PCR diagnosis compared to non-vaccinated controls, respectively. In contrast, CD4 T cells targeting the non-vaccine encoded Nucleocapsid antigen were of significantly lower magnitude in BTI as compared to non-BTI. Hence, previous vaccination was linked to enhanced T cell responses targeting the vaccine-encoded Spike antigen, while responses against the non-vaccine encoded Nucleocapsid antigen were significantly attenuated.

show abstract

Section: Methodsmentioning

confidence: 99%

Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

Ahmed

Diepers²,

Janke³

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…A total of 37 patients with acute COVID-19 were recruited into this study between May and December 2020 under the umbrella of the longitudinal KoCo19 Study 49 . All participants tested positive for SARS-CoV-2 via RT-PCR.…”

Section: Study Participantsmentioning

confidence: 99%

“…Nasopharyngeal viral loads were quantified as described previously 49 . Briefly, RT-PCR was performed using a TANBead Maelstrom 9600 (Taiwan Advanced Nanotech Inc.) with an OptiPure Viral Auto Plate Kit (Taiwan Advanced Nanotech Inc.).…”

Section: Upper Airways Viral Loadsmentioning

confidence: 99%

Early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion

Eser

Baranov

Huth

et al. 2022

Preprint

View full text Add to dashboard Cite

Despite intensive research since the emergence of SARS-CoV-2, it has remained unclear precisely which components of the early immune response protect against the development of severe COVID-19. To address this issue, we performed a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We found that soluble and transcriptional markers of systemic inflammation peaked during the first week after symptom onset and correlated directly with the upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4+ and CD8+ T cells correlated inversely with various inflammatory markers and UA-VLs. In addition, we observed high frequencies of activated CD4+ and CD8+ T cells in acutely infected nasopharyngeal tissue, many of which expressed genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of functionally active T cells in the infected epithelium was further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identified an immune correlate of protection against SARS-CoV-2, which could inform the development of more effective vaccines to combat the acute and chronic illnesses attributable to COVID-19.

show abstract

“…For this longitudinal cohort, which has been described in detail by Puchinger et al. [42], PCR‐positive individuals and their respective household members were enrolled, and blood samples were collected in the Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU, Munich, Germany between May 2020 and February 2021 at defined timepoints after primary diagnosis during household visits or at a central testing facility with approval from the LMU ethics committee (no. 20–371) [42].…”

Section: Methodsmentioning

confidence: 99%

Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID‐19 and after yellow fever vaccination

Winheim¹,

Eser

Deák

et al. 2022

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

Dysregulation of the myeloid cell compartment is a feature of severe disease in hospitalized COVID‐19 patients. Here, we investigated the response of circulating dendritic cell (DC) and monocyte subpopulations in SARS‐CoV‐2 infected outpatients with mild disease and compared it to the response of healthy individuals to yellow fever vaccine virus YF17D as a model of a well‐coordinated response to viral infection. In SARS‐CoV‐2‐infected outpatients circulating DCs were persistently reduced for several weeks whereas after YF17D vaccination DC numbers were decreased temporarily and rapidly replenished by increased proliferation until 14 days after vaccination. The majority of COVID‐19 outpatients showed high expression of CD86 and PD‐L1 in monocytes and DCs early on, resembling the dynamic after YF17D vaccination. In a subgroup of patients, low CD86 and high PD‐L1 expression were detected in monocytes and DCs coinciding with symptoms, higher age, and lower lymphocyte counts. This phenotype was similar to that observed in severely ill COVID‐19 patients, but less pronounced. Thus, prolonged reduction and dysregulated activation of blood DCs and monocytes were seen in a subgroup of symptomatic non‐hospitalized COVID‐19 patients while a transient coordinated activation was characteristic for the majority of patients with mild COVID‐19 and the response to YF17D vaccination.

show abstract

The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 – Results from a prospective cohort of outpatient COVID-19 cases

Cited by 10 publications

References 27 publications

Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections

Early nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways and reduced systemic inflammation before seroconversion

Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID‐19 and after yellow fever vaccination

Contact Info

Product

Resources

About