Non-hospitalised, vaccinated adults with COVID-19 caused by Omicron BA.1 and BA.2 present with changing symptom profiles compared to those with Delta despite similar viral kinetics (preprint)

Introduction The impact of COVID-19 vaccination on disease in the community has been limited, as a result of both SARS-CoV-2 Variants of Concern that partially escape vaccine-induced immunity. We sought to characterise symptoms and viral loads over the course of COVID-19 infection in otherwise-healthy vaccinated adults, representative of the general population, to assess whether current self-isolation guidance remains justified. Methods In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral kinetics between infections caused by VOCs Delta and Omicron (sub-variants BA.1 and BA.2) and investigated applicability of UK NHS isolation guidelines to these newer VOCs. Results 373 infection episodes were reported among 349 participants. Across VOCs, symptom duration was similar, however symptom profiles differed significantly among infections caused by Delta, Omicron BA.1 and BA.2. Anosmia was reported in <10% of participants with BA.1 and BA.2, compared to 42% with Delta infection, coryza fatigue and myalgia predominated. Most notably, viral load trajectories and peaks did not differ between Delta, BA.1 and BA.2, irrespective of symptom severity, VOC or vaccination status. Conclusion COVID-19 isolation guidance should not differ based on symptom severity or febrile illness and must remain under review as new SARS-CoV-2 VOCs emerge and population immunity changes. Our study emphasises the ongoing transmission risk of Omicron sub-variants in vaccinated adults with mild symptoms that may extend beyond current isolation periods.

Immune responses following third COVID-19 vaccination are reduced in patients with hematologic malignancies compared to patients with solid cancer (preprint)

Not all patients with cancer, in particular those with hematogic malignancies, develop functional immunity against SARS-CoV-2 variants of concern (VOC) following COVID-19 vaccines. Durability of vaccine-induced immunity after two doses and the impact of a third dose were evaluated in CAPTURE (NCT03226886), a longitudinal prospective cohort study of vaccine responses in patients with cancer. In evaluating 316 patients, at a median of 111 days following two doses of either BNT16b2 or ChadOX, we observed a time-dependant decline in neutralising antibody titres (NAbT) in a proportion of patients, where NAbTs became undetectable against Delta and Beta in 17% and 15% of patients, respectively. Vaccine-induced T cell responses declined in 44% of patients. Patients with breakthrough infections following two vaccines doses were characterised by absent/low NAbT to Delta prior to infection. Administration of the third vaccine dose boosted NAb responses against VOC in the majority of patients with cancer, especially those with solid cancer. In patients with hematologic malignancies who had undetectable NAbT against Delta after two vaccine doses, 54% did not develop NAb against both Beta and Delta following the third dose. Third vaccine dose boosted T cell responses were boosted in patients with both solid and hematologic malignancies. These results provide critical information on vaccine responses in patients with cancer, especially against VOCs and support widespread access to a third COVID-19 vaccination in this patient group.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study (preprint)

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wild-type (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study (preprint)

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

Cytokine release syndrome in a patient with colorectal cancer following vaccination with BNT162b2 (tozinameran) (preprint)

We present a case of cytokine release syndrome (CRS) that occurred five days after vaccination with BTN162b2 (tozinameran), an mRNA COVID-19 vaccine, in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-y/IL-2R/IL-18/IL-16/IL-10), and steroid responsiveness.