Abstract
Severe COVID-19 is associated with profound lymphopenia and an elevated neutrophil to lymphocyte ratio. We applied a novel dimer avoidance multiplexed polymerase chain reaction next-generation sequencing assay to analyze T (TCR) and B cell receptor (BCR) repertoires. Surprisingly, TCR repertoires were markedly diminished during the early onset of severe disease but recovered during the convalescent stage. Monitoring TCR repertoires could serve as an indicative biomarker to predict disease progression and recovery. Panoramic concurrent assessment of BCR repertoires demonstrated isotype switching and a transient but dramatic early IgA expansion. Dominant B cell clonal expansion with decreased diversity occurred following recovery from infection. Profound changes in T cell homeostasis raise critical questions about the early events in COVID-19 infection and demonstrate that immune repertoire analysis is a promising method for evaluating emergent host immunity to SARS-CoV-2 viral infection, with great implications for assessing vaccination and other immunological therapies.
Highlights
The current outbreak of coronavirus disease (COVID-19) was first reported in Wuhan, China [1, 2]
Dynamic Repertoire Changes Over the Disease Course of COVID-19
We amplified the immune repertoires including all T cells receptors (TCRs) chains (TCR-alpha, TRA; TCR-beta, TRB; TCR-delta, TRD; TCR-gamma, TRG) and B cell receptor (BCR) chains (IgH, including the various IgH isotypes; IgK; and IgL) in one PCR reaction in an unbiased way, based on a strategy of using the first set of primer pairs for each V-J to allow extension with tags that enabled a second set of primers to be utilized for global amplification of all seven chains
Summary
The current outbreak of coronavirus disease (COVID-19) was first reported in Wuhan, China [1, 2]. The virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a virus closely related to SARS-CoV, endemic in 2003 [3]. The virus caused low respiratory tract pneumonia, but it affects multiple organs such as the kidney, liver, brain, gastrointestinal tract, and heart. Immune Profiling of SARS-CoV-2 Patients fever, cough, shortness of breath, and chest pain. The pneumonia in those with this disease is characterized by bilateral groundglass opacities identified on chest CT scans [4, 5]. The majority of COVID-19 patients show mild or moderate symptoms and recover after proper clinical care. Some COVID-19 patients rapidly develop severe pneumonia, subsequent multiorgan failure, and death [6]. Pathologic examination reveals diffuse alveolar damage, proteinaceous plugs, and a prominent myeloid infiltrate and a paucity of lymphocytes [7,8,9,10]
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