Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection

Orologas-Stavrou, Nikolaos; Politou, Marianna; Rousakis, Pantelis; Kostopoulos, Ioannis V.; Ntanasis‐Stathopoulos, Ioannis; Jahaj, Edison; Tsiligkeridou, Eleni; Gavriatopoulou, Maria; Kastritis, Efstathios; Kotanidou, Anastasia; Dimopoulos, Meletios Α.; Tsitsilonis, Ourania E.; Terpos, Evangelos

doi:10.3390/v13010026

Cited by 32 publications

(34 citation statements)

References 43 publications

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“…Using flow cytometric analysis, our group first determined the relative frequencies of different immune cell subsets in the peripheral blood. We and others have previously shown cell subset frequencies remain altered into the convalescent phase after SARS-CoV-2 infection ( 1 , 8 ), but few reports comprehensively address whether this persists into late convalescence or is associated with PASC. Here, cell frequencies were reported as a frequency of the overall CD45 + population per each individual as done previously ( 1 ).…”

Section: Resultsmentioning

confidence: 97%

“…We next investigated longitudinal phenotypic differences in T cells between those experiencing persistent symptoms and those with resolved disease. Our group and others have observed T cell activation that persists into the early convalescent phase following SARS-CoV-2 infection ( 1 , 8 ), but few studies have investigated phenotypic differences into the intermediate and late phases of convalescence, particularly in individuals with prolonged symptom syndromes. One recent study observed longitudinal changes in T cell activation independent of ongoing symptoms ( 9 ).…”

Section: Resultsmentioning

confidence: 99%

“…Our group and others have characterized the acute immune response to COVID-19 finding dramatic immune dysregulation in peripheral blood samples from infected individuals (1-7), especially in those with severe infection. Evidence suggests some of these immune perturbations persist into the convalescent phase of infection (1,8,9). Antigen-specific immune responses during the acute and early convalescent stages of infection have been found to play an important role in overall patient outcomes (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Files¹,

Sarkar²,

Fram.³

et al. 2021

JCI Insight

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A subset of COVID-19 patients exhibit Post-Acute Sequalae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median=74 days) compared to 30 who had symptom resolution in 20 days or less.Individuals with prolonged symptom duration maintained antigen-specific T-cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and cTfh populations during late convalescence while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 S-protein. Significant correlations between symptom duration and both SARS-CoV-2-specific T cells and antibodies were observed.Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2-specific immune responses are maintained in patients suffering from prolonged post-COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Files¹,

Sarkar²,

Fram.³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

show abstract

“…Here, in the light on the complex immune dysregulation that occurs during acute infection (11,12), we hypothesize that COVID-19 could have long-term impact on immune functions, such as the ones observed in patients that experienced bacterial sepsis (13). Indeed, immune profiling of SARS-CoV-2 recovered patients indicates persistent changes in the phenotype of innate (monocytes and granulocytes) but most importantly in adaptive (T, B, and NKT) immune cells (14)(15)(16).…”

Section: Introductionmentioning

confidence: 97%

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Brauns

Azouz

Grimaldi

et al. 2021

Preprint

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Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.

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“…T cell immunity arises, as anticipated, during infection, and the quality and quantity of the same varies according to the intensity of disease. [31,48,51,63,65,67,68,70,74,89,91,93,94,98,102,[109][110][111].…”

Section: Correlations With Immunity or Protectionmentioning

confidence: 99%

Passive Immunity Should and Will Work for COVID-19 for Some Patients

Cimolai¹

2021

CHI

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In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose-and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

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Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection

Cited by 32 publications

References 43 publications

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Passive Immunity Should and Will Work for COVID-19 for Some Patients

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