Clinical and Immunological Characteristics of Prolonged SARS-CoV-2 Omicron Infection in Hematologic Disease (preprint)

Prolonged viral shedding (PVS) occurs when severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is not adequately cleared and has been associated with poor outcomes. However, it remains unclear whether the immunological and clinical characteristics of Omicron PVS in hematologic disease (HD) are identical to those of earlier variants. We retrospectively analyzed 160 patients with HD with Omicron breakthrough infections. Although the hospitalization rate was high (21.3 %), deaths attributable to COVID-19 occurred in only 2.5% of the cases. PVS developed in 36.9% of the evaluable patients. Factors such as B- and CD4+ T-cell depletion, recent use of anti-CD20 antibodies and bendamustine were found to be significant predictors of PVS. Analysis of T cell phenotypes showed an increase in exhausted CD4+ T cells in PVS, but not in CD8+ cells.  Neutralizing activities against recombinant spike proteins for three Omicron subvariants were significantly reduced. Notably, despite the high frequency of PVS, many patients previously treated with anti-CD20 antibodies and bendamustine ultimately recovered. Late-onset interstitial pneumonia is a fatal complication that can occur regardless of viral clearance. Despite the use of high-dose corticosteroids and potent antivirals, the optimal treatment for PVS remains unclear and should be individualized until a more effective strategy is established.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study (preprint)

Introduction: This study assessed the immunogenicity and safety of BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment using two immunoassays. Methods: We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients with chronic diseases; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 {+/-} 1 weeks after the second vaccination. Anti-acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics). Results: Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody titer, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p<0.001 on Architect; 4.0 vs 1.2 U/mL, p<0.001, on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p=0.005, on Architect; 213 vs 573 A/mL, p=0.002, on Elecsys). The adjusted odds ratio (OR) for seroprotection was significantly lower in the lung cancer patients. Analysis of the anticancer treatment types showed that the adjusted OR for seroprotection was significantly lower in lung cancer patients receiving cytotoxic agents. Lung cancer patients showed no increase in the number of adverse reactions. Conclusions: BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased antibody titers and showed acceptable safety. However, the immunogenicity in these patients could be inadequate compared with that in non-cancer patients.