Chapter 13 - The effect of COVID-19 on cancer immunotherapy and cancer care

: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), identified in Wuhan, China, in December 2019, rapidly spread globally to become a devastating global pandemic. The SARS-CoV-2 (coronavirus disease 2019 [COVID-19]) respiratory illness was initially reported in the United States in the state of Washington in January 2020. COVID-19 respiratory virus proved to be an extremely contagious illness with clinical features of fever, cough, dyspnea, malaise, and rapidly progressing severe interstitial pneumonia. Since the beginning of 2020, COVID-19 has been responsible for an unimagined level of deaths and socioeconomic disruption. The patient with malignancy and a suppressed immune system was, as expected, at increased risk for contracting COVID-19. Patients with cancer, when infected, had a more difficult clinical course and an increased rate of mortality. In the intervening 2+ years, much has been learned regarding the ability of the patient with cancer's immune system to not only fight the progression of their cancer but to effectively respond to newly available mRNA vaccines against COVID-19. As the pandemic continues, careful management of the vulnerable patient with cancer is essential.

Impacts of viral pathogenesis and vaccine immunization on the host humoral immune response in SARS-CoV-2 and associated variants of concern (VOCs) infection

The clinical outcomes in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection include asymptomatic disease or mild disease with influenza-like symptoms or severe disease condition following death by pneumonia and acute respiratory distress syndrome (ARDS). The current mRNA- and vector-based vaccines successfully addressed the antigenic challenges of the parental SARS-CoV-2 strain. However, recent concerns are being raised against some SARS-CoV-2 variants, which have the potential to escape natural immunity and vaccine-induced immune recognition partially, leading to a possible increase in transmissibility and disease severity. The coronavirus disease-19 (COVID-19)-induced rapid changes in human immune profiles might be instigating the evolution of SARS-CoV-2 with a higher propensity. Therefore, we require critical surveillance on the genomic sequence and structural conformation of the evolving variants and phenotypic impacts of the accumulating mutations on the host-immune response for possible updates in the booster vaccine sequence, if required. Here, we will highlight the role of accumulating mutations in SARS-CoV-2 genomic sequences leading to the host-immune escape by regulating the T cell- and B cell-mediated responses in infected, unvaccinated, and vaccinated individuals. © 2023 Elsevier Inc. All rights reserved.

Immunological Findings in a Group of Individuals Who Were Poor or Non-Responders to Standard Two-Dose SARS-CoV-2 Vaccines.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. However, data on the poor or non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of this study was to comprehensively compare the immunological characteristics of poor or non-responders to SARS-CoV-2 vaccines in the 18-59-year group with those in the ≥60-year group using internationally recognized cut-off values. The main outcome was effective seroconversion characterized by an anti-SARS-CoV-2 spike IgG level of at least a four-fold increase from baseline. Profiling of naïve immune cells was analyzed prior to vaccination to demonstrate baseline immunity. The outcomes of effective seroconversion in patients aged 18-59 years with those in patients aged ≥60 years were compared. The quantitative level of anti-spike IgG was significantly lower in individuals aged ≥60 and men aged 18-59 years. There were 7.5% of poor or non-responders among the 18-59 years and 11.7% of poor or non-responders in the ≥60 years using a four-fold increase parameter. There were 37.0-58.1% with low lymphocyte count (<1000/mm3), 33.3-45.2% with low CD4 cell counts (<500/mm3), and 74.1-96.8% with low B cell counts (<100/mm3) in the non-seroconversion group. An individual with an anti-SARS-CoV-2 spike IgG titer below 50 BAU/mL might be considered a poor or non-responder between 14 and 90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended to poor or non-responders as soon as possible to reduce disease severity and mortality.

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile.

Cellular immune defects associated with suboptimal responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4+, and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses, and enhances comparatively more T helper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants.

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.

Robust and Functional Immune Memory Up to 9 Months After SARS-CoV-2 Infection: A Southeast Asian Longitudinal Cohort.

The duration of humoral and cellular immune memory following SARS-CoV-2 infection in populations in least developed countries remains understudied but is key to overcome the current SARS-CoV-2 pandemic. Sixty-four Cambodian individuals with laboratory-confirmed infection with asymptomatic or mild/moderate clinical presentation were evaluated for Spike (S)-binding and neutralizing antibodies and antibody effector functions during acute phase of infection and at 6-9 months follow-up. Antigen-specific B cells, CD4+ and CD8+ T cells were characterized, and T cells were interrogated for functionality at late convalescence. Anti-S antibody titers decreased over time, but effector functions mediated by S-specific antibodies remained stable. S- and nucleocapsid (N)-specific B cells could be detected in late convalescence in the activated memory B cell compartment and are mostly IgG+. CD4+ and CD8+ T cell immune memory was maintained to S and membrane (M) protein. Asymptomatic infection resulted in decreased antibody-dependent cellular cytotoxicity (ADCC) and frequency of SARS-CoV-2-specific CD4+ T cells at late convalescence. Whereas anti-S antibodies correlated with S-specific B cells, there was no correlation between T cell response and humoral immune memory. Hence, all aspects of a protective immune response are maintained up to nine months after SARS-CoV-2 infection and in the absence of re-infection.