COVID-19, which is caused by SARS-CoV-2, emerged into our lives more than a year ago.¹ Since then, it has become a pandemic that has affected millions of people globally, changing social behaviors and habits, bearing global economic burden, and, foremost, leaving 2.7 million individuals worldwide with vast residual illness.²

The durability of response to the SARS-CoV-2 BNT162b2 vaccine (Pfizer-BioNTech) in adults aged 60 years and older has yet to be determined. The immune response to 2 doses of BNT162b2 is lower in individuals aged 65 to 85 years vs 18 to 55 years.¹ Among 4868 health care workers receiving 2 BNT162b2 doses, a significant waning of the humoral response (IgG, neutralizing antibodies) within 6 months of the second dose was observed, especially among adults aged 65 years and older.² After a fourth SARS-CoV-2 wave in Israel, the Israeli Ministry of Health authorized, at the end of July 2021, a third BNT162b2 vaccine dose for individuals aged 60 years and older, which was subsequently expanded to younger age groups.

We recently reported initial findings from a prospective cohort study which evaluated the antispike (anti-S) IgG antibody response to the SARS-CoV-2 BNT162b2 messenger RNA (mRNA) vaccine (BioNTech-Pfizer) in patients with solid tumors on active anticancer treatment vs healthy controls.¹ After a median of approximately 5.5 weeks from the second vaccine dose, 90% of the patients with cancer (90/102) and 100% of the healthy controls (78/78) were seropositive, and the median IgG titer in the patients was significantly lower than that in the controls:1931 (interquartile range [IQR], 509-4386) AU/mL vs 7160 (IQR, 3129-11241) AU/mL; P < .001.¹

Both humoral and cellular anamnestic responses are significant for protective immunity against SARS-CoV-2. In the current study, the responses in elderly people before and after a fourth vaccine dose of BNT162b2 were compared to those of individuals immunized with three vaccine doses. Although a boost effect was observed, the high response following the third administration questions the necessity of an early fourth boost.

Objective To evaluate the durability of response 3 months after the third BNT162b2 vaccine in adults aged 60 years and older. Design Prospective cohort study. Setting Single tertiary centre. Participants Healthcare workers/family members aged ≥60 years old who received the third BNT162b2 dose. Interventions Blood samples were drawn immediately before (T0), 10–19 days (T1) and 74–103 days (T2) after the third dose. Primary and secondary outcome measures Anti-spike IgG titres were determined using a commercial assay and seropositivity was defined as ≥50 arbitrary units (AU)/mL. Neutralising antibody titres were determined at T2. Adverse events, COVID-19 infections and Clinical Frailty Scale (CFS) levels were documented. Results The analysis included 97 participants (median age, 70 years (IQR, 66–74), 58% CFS level 2). IgG titres, which increased significantly from T0 to T1 (median, 440 AU/mL (IQR, 294–923) and median, 25 429 AU/mL (IQR, 14 203–36 114), respectively; p<0.001), decreased significantly by T2, but all remained seropositive (median, 8306 AU/mL (IQR, 4595–14 701), p<0.001 vs T1). In a multivariable analysis, only time from the second vaccine was significantly associated with lower IgG levels at T2 (p=0.017). At T2, 60 patients were evaluated for neutralising antibodies; all were seropositive (median, 1294 antibody titres; IQR, 848–2072). Neutralising antibody and anti-spike IgG levels were correlated (r=0.6, p<0.001). No major adverse events or COVID-19 infections were reported. Conclusions Anti-spike IgG and neutralising antibody levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults aged ≥60 years, although the decline in IgG is concerning. A third dose of vaccine in this population should be top priority.

Background: Computed tomography (CT)-derived body composition parameters, including skeletal muscle and fat indices, are prognosticators in oncology. Most studies focus on baseline body-composition parameters; however, changes during treatment may provide better prognostic value. Standardized methods for measuring/reporting these parameters remain limited. Methods: This retrospective study included patients who were treated with immunotherapy for non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma between 2017 and 2024 and had technically adequate baseline and follow-up CT scans. Body composition was analyzed using a novel, fully automated software (CompoCT) for L3 slice selection and segmentation. Body composition indices (e.g., skeletal muscle index [SMI]) were calculated by dividing the cross-sectional area by the patient’s height squared. Results: The cohort included 376 patients (mean [SD] age 66.4 [11.4] years, 67.3% male, 72.6% NSCLC, 14.6% RCC, and 12.8% melanoma). During a median follow-up of 21 months, 220 (58.5%) died. Baseline body composition parameters were not associated with mortality, except for a weak protective effect of higher SMI (HR = 0.98, p = 0.043). In contrast, longitudinal decreases were strongly associated with increased mortality. Relative decreases in SMI (HR, 1.17; 95% CI, 1.07–1.27) or subcutaneous fat index (SFI) (HR, 1.11; 95% CI, 1.07–1.15) significantly increased mortality risk. Multivariate models showed similar concordance (0.65) and identified older age, NSCLC tumor type, and relative decreases in SMI and SFI (per 5% units) as independent predictors of mortality. Conclusions: Longitudinal decreases in skeletal muscle and subcutaneous fat were independent predictors of mortality in immunotherapy-treated patients. Automated CT-based body composition analysis may support treatment decisions during immunotherapy.