chuka_lis (chuka_lis) wrote,

Особенности иммунного ответа и тяжесть течения

Познавательная работа от чилийских ученых. Отслежено во времени.
Большая часть уделена клеточному иммунитету, который, в случаях среднего и тяжелого ковида, активно задействован в войне с коронавирусом, но несет потери, и, имхо, часть патологий ковида поясняется именно этой проигрываемой войной. Тк есть и истощение, и подстегивание клеточного иммунитета.Чем тяжелее, тем более "разрегулированным" видится иммунный ответ по сравнению с более легким течением.
У тех у кого был тяжелый ковид, имумнный ответ был более сильным (и на уровне клеточного, и антител) .
"patients that required invasive mechanical ventilation display an exacerbated innate and adaptive immune response typified by increased frequencies of plasmablasts, monocytes, Th1 equivalents, and S-specific IgG, which may provide relevant information regarding the progression of severe COVID-19 pathology."
Хотя, вопрос еще, что причина а что следствие. И как это согласуется с завирушенностью.
Восстановление иммунитета начинается месяца через 3. Даже утех кто болел сравнительно не тяжело. У тех кто болел тяжелее- это занимает больше времени.
Специфический иммунитет у тех кто болел дольше и тяжелее, держится на приличном уровне до года. Хотя, и постепенно снижается при этом.

Although SARS-CoV2 infection generally leads to a mild disease in a large proportion of infected individuals, 5-15% of COVID-19 patients develop a severe pathology that progresses to pneumonia and respiratory failure (35–38). In this context, the immune cell landscape of severe COVID-19 patients is reported to be dysregulated (14,19,31,32), and detailed insights on the cellular dynamicsof severe COVID-19 patients are urgently needed to identify potential disease intervention points. In this work, we analyzed immune cell dynamics of moderate, severe, and convalescent COVID-19 patients and further investigated the dynamics of severe patients in terms of oxygen dependence and long-term trajectories of ICU patients during the acute symptomatic stage and after recovery. Previous studies have shown dysregulation of innate and adaptive immune cell compartments in patients with moderate, severe, and convalescent COVID-19 (14,19,22). Our data revealed statistically significant changes in immune cell subset composition between severe and convalescent patients, including neutrophils, basophils, eosinophils, pDCs, B cells, plasmablasts, activated CD8+and CD4+T cells and Th1 equivalents, providing a complete description of the dynamics of acute COVID-19 responses. In addition, we detected alterations in the composition and function of monocytes in severe COVID-19patients with an abundance of HLA-DR low monocytes, which indicate dysfunctional monocyte function (17,32). Furthermore, even though single-cell transcriptome studies revealed an upregulation of PD-L1 expression in neutrophils from severe COVID-19 patients (32), our data on surface PD-L1 expression in neutrophils showed an opposite effect, indicating that additional studies should be conducted to clarify this issue. In this context, multiparametric flow cytometry analysis for COVID-19 patients’ immunophenotyping does not necessarily correlate with changes observed at the transcriptomic level As per adaptive immune parameters, the frequencies of plasmablasts and activated CD8+and CD4+ T cells were increased in severe COVID-19 patients. Additionally, we also found higher frequency of PD-1+CD8+and CD4+T cells, suggestive of potential T cell exhaustion. As expected, antibody data indicated that moderate and severe COVID-19 patients produce S-specific IgM, IgG, and IgA. However, in contrast to previous observations (19,20), our data show that convalescent patients no longer express detectable levels of S-specific IgM, which may reflect differences in the time of sample collection between these studies.Interestingly, we also detected differences related to immune subset composition among severe COVID-19 sub-cohorts, which were associated to the intensity of respiratory support defined as the type of oxygen, severity measured by PaO2:FiO2, and the presence of organ dysfunction defined by the WHO classification. In addition, a clinical debate persists as to why some severe COVID-19 patients get worse rapidly and require IMV while others display a more stable pathological course. In this context, we identified specific immune cell types that distinguished between severe COVID-19 patients under HFNC (displaying a more stable clinical course) versus patients who access rapidly to mechanical ventilation (Scores 6 and 7-9, respectively). These changes include increased frequencies of plasmablasts, monocytes, eosinophils, Th1 equivalents and underrepresentation of granzyme B+ producing CD8+ T cells in ventilated severe COVID-19 patients. How exactly these cell types contribute to promote or prevent the pathology remains to be fully elucidated. Furthermore, we provide a longitudinal study of a small set of ICU patients which shows that innate and adaptive immune cells that were dysregulated during the onset of the pathology, including neutrophils, plasmablasts, activated CD4+and CD8+T cells, or that were underrepresented such as basophils, begin to regain normal proportions during recovery. Severe patients also synthesized markedly elevated levels of S-specific IgG during the entire time of the study, suggesting the generation of long-term immunity against the virus after infection. It remains to be clarified which of these immune alterations persists in time and have clinical significance in patients, emphasizing the need for more data emerging from longitudinal follow-ups of different cohorts of patients. Nevertheless, these data are consistent with very recent reports showing durable immune responses in recovered COVID-19 patients with heterogeneous degrees of disease severity after 8 months of infection (34,39).Finally, our data is relevant considering that COVID-19 studies emerging from Latin America remain poorly represented in the literature. In addition, during this study, there have been drastic changes in the prevalence of SARS-CoV2 variants in Chile. The original variants present during the first half of 2020 have been replaced successively by VOCs alpha(B.1.1.7), and later by VOC gamma (P.1), and by VOI lambda (C.37) in the Chilean population (data from the national consortium of SARS-CoV-2 genome surveillance, In Chile, the gamma and lambda variants have dominated the genomic landscape of SARS-CoV-2 in the first half of 2021, are also prevalent in many Latin American countries and remain conspicuously understudied. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory.
Tags: иммунитет, коронавирус, статьи

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