The Relationship Between Convergent IGH Signatures and Severity of COVID-19 Patients by Next-Generation Sequencing of B-Cell Repertoire

Abstract

ObjectTo reveal convergent IGH signatures and the association with severity of coronavirus disease 2019 (COVID-19) patients.MethodA total of 25 COVID-19 inpatients were classified into three clinical conditions: mild, severe, and critical. We analyzed convergent IGH signatures by ImmuHub® B-cell receptor (BCR) profiling system.ResultsIGH singleton frequency in patients is significantly lower than that of healthy donors (HDs). The clonality index of IGH in patients is significantly higher than that in HDs. Nevertheless, no significant difference was observed among the three groups. The difference in IGH clonality (top five clones) between post- and pretreatment was significant in the improvement and deterioration groups. Three common public motifs were shared by all COVID-19 patients: ARDYGG, RWYFDY, and YYYYGMDV.ConclusionB cells could recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and produce clonal expansion. Patients who had better outcomes after treatment had higher IGH clonality. Three common public motifs—ARDYGG, RWYFDY, and YYYYGMDV—might be used for vaccine development (ChiCTR2000029626).

The characteristics of BCR‐CDR3 repertoire in COVID‐19 patients and SARS‐CoV‐2 vaccinated volunteers

“…Ma et al 43 found that the clonal expansion of BCR‐CDR3 was more pronounced in 33 symptomatic COVID‐19 patients than in 5 asymptomatic and 11 healthy controls. Multiple other laboratories have reported the same association 44–47 …”

“…Multiple other laboratories have reported the same association. [44][45][46][47] The clonality changes of BCR-CDR3 in SARS-CoV-2 vaccine recipients are similar to those in infected individuals. BCR-CDR3 clonality significantly expanded at 14 days after the Ad5-nCoV vaccination 48 ; mRNA vaccine recipients had significantly clonal expanded memory B cells.…”

“…Simultaneously, some studies have reported lower SHM levels of BCR in COVID-19 patients compared to healthy individuals, 42,47 implying individual differences and significant deviation of SHM distribution caused by SARS-CoV-2 infection. 67 detected that the overlap rate of Jaccard index ranged from 0.36% to 6.57% between different COVID-19 patients, peaking at around 2-3 weeks; Cai et al 45 [48][49][50]61,81,82 or recovery from the infection. 15,36,37,74,[76][77][78] Antibodies have been synthetically prepared according to the sequence of heavy and light chains of these response B cells, and confirmed their ability to neutralize SARS-CoV-2 in vitro.…”

“…The BCR‐CDR3 sequences shared by COVID‐19 patients or SARS‐COV‐2 vaccine recipients can provide practical techniques and schemes for understanding the molecular mechanism of SARS‐CoV‐2 B cell response, progress monitoring, potential antibody therapy, and vaccine development. Galson et al 40 identified 1254 SARS‐CoV‐2 specific BCR‐CDR3 clonotypes and found that these clonotypes were shared by at least 254 COVID‐19 patients from the United Kingdom, the United States, and China; Robbiani et al 36 discovered IGHV1‐58 / IGKV3‐20 and IGHV3‐30 / IGKV1‐39 antibodies recurring in different COVID‐19 patients; Nielsen et al 17 identified there were multiple clusters of BCR‐CDR3 in COVID‐19 patients (85% H‐CDR3 AA were the same); He et al 66 found different COVID‐19 patients shared around 0.44%–1.23% of the heavy chain antibody clonotypes; Xiang et al 67 detected that the overlap rate of Jaccard index ranged from 0.36% to 6.57% between different COVID‐19 patients, peaking at around 2–3 weeks; Cai et al 45 discovered conserved BCR‐CDR3 motifs such as “ARDYGG” in COVID‐19 patients; Bullen et al 69 screened several shared H‐CDR3 sequences (such as AAPDCSSTSCYDAFDI) from the CoV‐Ab database.…”