Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

Abstract

Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

Meta-analysis reveals consistent immune response patterns in COVID-19 infected patients at single-cell resolution

“…For the other studies included in the current manuscript, the raw sequencing data are available in European Genome-phenome Archive (EGAS00001004481 for Chua et al 5 ), GEO (GSE149689 for Lee et al 1 , GSE150728 for Wilk et al, GSE145926 for Liao et al 9 ) and Genome Sequence Archive (PRJCA002413 for Wen et al 4 , PRJCA002564 for Zhang et al 3 , PRJCA002579 for Yu et al 7 , GSE147143 for He et al 6 ). Details are listed in Table 1 .…”

“…To understand the pathology and immune response in COVID-19 patients, a number of single-cell RNA sequencing (scRNA-seq) experiments have been performed on different cell types obtained from human patients [1][2][3][4][5][6][7] . Studies on diseases caused by influenza and other respiratory viruses have shown that the peripheral immune response plays an important role in the defence against the infections and disease progression 1 .…”

The herd immunity to SARS-CoV-2 among the population of the Nizhny Novgorod region amid the COVID-19 epidemic

“…Обследование 53 волонтеров, имевших в анамнезе диагноз COVID-19, установленный в лечебно-профилактическом учреждении, показало, что доля серопревалентных составила 47,2% (95% ДИ 30, 6). Приведенные данные вызывают вопрос о причинах столь низкой сероконверсии после болезни.…”

“…Аналогичная закономерность наблюдалась при оценке наличия антител в зависимости от результатов ПЦР: в группе с положительной ПЦР доля сероположительных составила 53,4% (95% ДИ 30, 6). В этой связи возникает вопрос: связан ли факт обнаружения РНК SARS-CoV-2 с субклинической или бессимптомной формами COVID-19, а если связан, то являются ли подобные лица носителями активного вируса и насколько они опасны для окружающих?…”

“…Недостаточность адаптивного иммунитета может не только затруднить элиминацию внедрившегося вируса, но и снизить эффективность контроля над другими патогенами, создав предпосылки для обострения других патологических состояний, как это имеет место при заболевании COVID-19 лиц с преморбидным фоном [5]. С другой стороны, избыточный гуморальный ответ может привести к антителозависимому усилению вирусной инфекции [5,6].…”