Incidence and immunomic features of apyretic COVID-19 in patients affected by solid tumors: a prospective cohort study

Abstract

Background and rationale: Little is known about SARS-CoV-2 seroconversion in asymptomatic patients affected by solid cancer, and whether it is associated with specific transcriptomics changes in peripheral blood mononuclear cells (PBMC).

Methods: Patients affected by solid cancer treated in a top comprehensive cancer center in Italy during the first COVID-19 pandemic wave, and negative for COVID-19-symptoms since the first detection of COVID-19 in Italy, were prospectively evaluated by SARS-CoV-2 serology in the period between April 14th and June 23rd 2020. Follow-up serologies were performed, every 21-28 days, until August 23rd 2020. All SARS-CoV-2 IgM + patients underwent confirmatory nasopharyngeal swab (NPS). PBMCs from a subset of SARS-CoV-2 IgM + patients were collected at baseline, at 2 months, and at 7 months for transcriptome sequencing.

Results: SARS-CoV-2 serology was performed on 446 of the 466 recruited patients. A total of 14 patients (3.14%) tested positive for at least one SARS-CoV-2 immunoglobulin in the period between April 14th and August 23rd 2020. Incidence of SARS-CoV-2 IgM decreased from 1.48% in the first month of the accrual to 0% in the last month. Viral RNA could not be detected in any of the NPS. PBMC serial transcriptomic analysis showed progressive downregulation of interleukin 6 upregulated signatures, chemokine-mediated signaling and chemokine-chemokine receptor KEGG pathways. B- and T-cell receptor pathways (p-values = 0.0002 and 0.017 respectively) were progressively upregulated.

Conclusions: SARS-CoV-2 seroconversion rate in asymptomatic patients affected by solid cancer is consistent with that of asymptomatic COVID-19 assessed in the general population through NPS at the peak of the first wave. Transcriptomic features over time in IgM + asymptomatic cases are suggestive of previous viral exposure.

Keywords: Asymptomatic infection; COVID-19; Cancer; Serology; Transcriptome sequencing.

Fig. 1

Study diagram. Patients were recruited in the period between April 14th and June 23rd. May 18th corresponds to the end of lockdown measures in Italy. Follow-up serologies were performed until August 23rd at a distance of at least 21 days from each other

Fig. 2

PBMCs transcriptomic profile assessed on peripheral blood samples collected from two positive patients for SARS-CoV-2 IgM at baseline (T1), 2 months (T2), and 7 months (T3) from the first serology. The top 5 depleted (A) and enriched (B) immunologic signatures with the highest variance across samples were selected for the transcriptomic analysis

Fig. 3

KEGG enrichment analysis of genes pertaining to the B-cell receptor signaling pathway in the RNA extracted from PBMCs collected from two SARS-CoV-2 IgM+ patients. Genes encoding for the star-marked elements, including LYN, SHIP, CD81, PI3K, Rac, CaN, Ras, BCL-10, MEK 1/2, IKKα, IP1, and NFkB, and implied in the B-cell receptor signaling pathway, were found to be increasingly upregulated in these patients over time (p-value = 0.0002)