Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

Thomopoulos, Thomas; Rosati, Margherita; Terpos, Evangelos; Stellas, Dimitris; Hu, Xintao; Karaliota, Sevasti; Bouchla, Anthi; Katagas, Ioannis; Antoniadou, Anastasia; Mentis, Αndreas; Papageorgiou, Sotirios G.; Politou, Marianna; Bear, Jenifer; Donohue, Duncan; Kotanidou, Anastasia; Kalomenidis, Ioannis; Korompoki, Eleni; Burns, Robert T.; Pagoni, Maria; Grouzi, Elisavet; Labropoulou, Stavroula; Stamoulis, Kostantinos A.; Bamias, Aristotelis; Tsiodras, Sotirios; Dimopoulos, Meletios Α.; Pavlakis, George N.; Pappa, Vasiliki; Felber, Barbara K.

doi:10.3390/v13091844

Cited by 6 publications

(8 citation statements)

References 42 publications

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“…Additional correlation analysis of clinical parameters and antibody levels revealed that anti-spike IgG levels and neutralizing antibody titers were negatively correlated with viral load at inclusion ( Supplementary Figure 1B ). The connection between viral load and both spike and nucleocapsid antibody levels has been shown previously ( 39 , 40 ). Furthermore, there was negative correlation of neutralizing antibody titers and anti-spike IgG levels to CRP at inclusion ( Supplementary Figure 1C ).…”

Section: Resultssupporting

confidence: 64%

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

et al. 2023

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IntroductionAfter more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.MethodsHere, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.ResultsWe found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.ConclusionBy exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

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Section: Resultssupporting

confidence: 64%

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

et al. 2023

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“…In our 8-month follow-up, we also reported that 76% of the patients still had detectable Neutralizing Antibodies (NAb) (1). Many studies reported short-term follow-up observations of less than 6 months (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), whereas others reported longitudinal observations, typically spanning less than 12 months post symptom onset (1,4,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Some studies reported contraction of anti-COVID humoral responses with a stronger initial decline (1,4,(23)(24)(25)27).…”

Section: Introductionmentioning

confidence: 64%

“…An important aspect of monitoring humoral responses has been having access to plasma from the same patients over 14 months. Most reports were based on cross-sectional analysis spanning less than 6 months (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) or up to 12 months (1,4,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Depending on the patient cohort, several studies reported a stronger initial contraction (1,4,(23)(24)(25)27) of anti-COVID humoral responses.…”

Section: Discussionmentioning

confidence: 99%

“…These data demonstrate re-exposure to SARS-CoV-2 with strong anamnestic responses to both Spike and Nucleocapsid. Of note, patient A's antibody endpoint titers were very high with a magnitude reached only by few patients in the very early phase (1-2 months post symptom onset; Figure 1) (1,2,14), indicating a very strong recall response. Patient A's antibodies also potently recognized the Spike-RBD of the Alpha, Beta, Delta and Mu variants (Figure 4B).…”

Section: Convalescent Patient With Sars-cov-2 Re-exposure a Case-reportmentioning

confidence: 99%

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Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

2021

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Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a sequential evaluation of anti-SARS-CoV-2 antibodies in convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset. We report persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist better than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant, the prevalent strain of the present pandemic. These data show that convalescent patients maintain functional antibody responses for more than one year after infection, suggesting a strong long-lasting response after symptomatic disease that may offer a prolonged protection against re-infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months post-infection indicating SARS-CoV-2 re-exposure. These antibodies showed stronger cross-reactivity to a panel of Spike-RBD including Beta, Delta and Mu and neutralization of a panel of Spike variants including Beta and Gamma. This patient provides an example of strong anti-Spike recall immunity able to control infection at an asymptomatic level. Together, the antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity to the current variants of concern and show strong functional properties.

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“…Additional correlation analysis of clinical parameters and antibody levels revealed that anti-spike IgG levels and neutralizing antibody titers were negatively correlated with viral load at inclusion (Supplementary Figure 1B). The connection between viral load and both spike and nucleocapsid antibody levels has been shown previously 37,38 . Furthermore, there was negative correlation of neutralizing antibody titers and anti-spike IgG levels to CRP at inclusion (Supplementary Figure 1C).…”

Section: Study Outline and Clinical Parametersmentioning

confidence: 79%

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

Hopkins

Govender

Svanberg

et al. 2022

Preprint

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After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.

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Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

Cited by 6 publications

References 42 publications

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19

Sequential Analysis of Binding and Neutralizing Antibody in COVID-19 Convalescent Patients at 14 Months After SARS-CoV-2 Infection

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

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