Abstract

Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16− NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence.

Highlights

  • COVID-19, the disease caused by the Severe Acute Syndrome Coronavirus (SARSCoV)-2, is a potentially fatal disease with approximately 20% of patients experiencing severe symptoms, 14% developing respiratory distress requiring supplemental oxygen, and5% requiring hospitalization in Intensive Care Units (ICUs)

  • The median time from the onset of symptoms or a positive PCR for SARS-Co-V was 61.5 days. These donors were divided in 3 groups according to PCR and IgG/IgA evaluation, and/or severity of resolved COVID-19

  • (+) individuals had detectable IgG and/or IgA anti-SARS-CoV-2 Abs but were not hospitalized and 24 individuals who were positive for both PCR and anti-SARS-CoV-2 Abs had required hospitalization during the course of COVID-19

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Summary

Introduction

COVID-19, the disease caused by the Severe Acute Syndrome Coronavirus (SARSCoV)-2, is a potentially fatal disease with approximately 20% of patients experiencing severe symptoms, 14% developing respiratory distress requiring supplemental oxygen, and5% requiring hospitalization in Intensive Care Units (ICUs). It affects multiple organs leading to multi-systemic failure and often to death [1], COVID-19 is apparently related to excessive host inflammatory responses and it looks more similar to a disease of the immune system [2]. Still, it is elusive how this new virus evades the immune system and escapes hosts’ immune surveillance, some delineated pathways of invasion may be similar to mechanisms used by other coronaviruses [3]. Pronounced lymphopenia (i.e., low numbers of CD3+ and CD4+ T cells, of the Th1-type and regulatory T cells (Tregs); very low numbers of CD8+ T, B and natural killer (NK) cells) and T and NK cell exhaustion

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