Scand J Immunol . Humoral and Cellular Immune Responses in Critically Ill Influenza A/H1N1 Infected Patients

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Scand J Immunol


. 2021 Apr 23;e13045.
doi: 10.1111/sji.13045. Online ahead of print.
Humoral and Cellular Immune Responses in Critically Ill Influenza A/H1N1 Infected Patients


Abira Paramsothy ¹ , Sarah Lartey Jalloh ¹ , Richard A Davies ¹ , Anne-Berit Guttormsen ^{2 3} , Rebecca J Cox ^{1 4} , Kristin G-I Mohn ^{1 5}



Affiliations

• PMID: 33891354
• DOI: 10.1111/sji.13045

Abstract

There is limited knowledge of influenza-specific immune responses and their kinetics in critically ill patients. We investigated humoral and cellular immune responses after critical influenza A/H1N1 infection and hypothesized that dysfunctionality or absence of immune responses could contribute to more severe illness. We followed 12 patients hospitalized with severe influenza infection; the majority admitted to intensive care unit (ICU). Blood samples were collected at days 10 and 19 and at 5 months. Antibody responses to surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) of A/H1N1pdm09 were quantified by hemagglutination inhibition, microneutralization, ELISA and ELLA assays. Influenza-specific antibody levels and avidity were measured separately for head and stalk domains of H1. Cytokine secreting CD4⁺ and CD8⁺ T cells responses to conserved influenza epitopes (M1, NP and PB1) were analyzed by Fluorospot. Overall, the patients retained a high level of functional HA- and NA-specific antibodies over the study period. During the acute phase (up to 3 weeks from symptom onset), antibodies specific to H1 stalk increased earlier and were present in higher amount compared to H1 head-specific antibodies. The NA-specific antibodies and the non-neutralizing HA-specific antibody response for H1 head and H1 full-length showed a significant decline from acute to convalescent phase. Despite high total IgG concentrations, avidity to H1 head and H1 full-length protein remained low at all time points. Similarly, CD8⁺ T-cell responses were continuously measured at low levels. In conclusion, our study found that critically ill patients were characterized by low HA specific antibody avidity and CD8⁺ T-cell response.

Keywords: Critical illness; Immune response; Influenza A/H1N1.