Association of Influenza Vaccination With SARS-CoV-2 Infection and Associated Hospitalization and Mortality Among Patients Aged 66 Years or Older.

Importance: Vaccine effectiveness studies have rarely implemented strategies to reduce the healthy vaccinee bias arising from differences in health care-seeking behavior between vaccinated and unvaccinated individuals. Although previous observational studies suggest that influenza vaccination is associated with a reduced risk of SARS-CoV-2-associated outcomes, the healthy vaccinee bias may have led to overestimating the vaccination effect. Objective: To estimate the association between influenza vaccination and SARS-CoV-2-associated outcomes. Design, Setting, and Participants: This cohort study was conducted over 2 consecutive influenza vaccination campaigns (2019-2020 and 2020-2021), owing to the substantial COVID-19 burden and the greater validity of influenza vaccination data in the studied age group. The study population included community-dwelling adults aged 66 years or older in Ontario, Canada. Exposure: Influenza vaccination for a given season. Main Outcomes and Measures: The outcomes of interest included SARS-CoV-2 infection, SARS-CoV-2-associated hospitalization, SARS-CoV-2-associated death, and a composite of SARS-CoV-2-associated hospitalization or death. Cox proportional hazards models were used to measure the association between influenza vaccination and SARS-CoV-2-associated outcomes, censoring individuals who moved into long-term care, received COVID-19 vaccines, or died before the observation period end date. Primary care periodic health examinations (PHEs) were explored as a negative tracer exposure (ie, no association expected with SARS-CoV-2 outcomes) and as an effect modifier of the association between influenza vaccination and SARS-CoV-2 outcomes. Results: Of 2 922 449 individuals aged 66 years or older (54.2% female) living in Ontario, 2 279 805 were included in the study. Among these, 1 234 647 (54.2%) were female and 1 045 158 (45.8%) were male; their mean (SD) age was 75.08 (7.21) years. Those who had received influenza vaccination exhibited a lower incidence of SARS-CoV-2 infection than unvaccinated individuals for the 2019-2020 cohort (adjusted hazards ratio [aHR], 0.78; 95% CI, 0.73-0.84) and the 2020-2021 cohort (aHR, 0.76; 95% CI, 0.74-0.78). This association was also observed for SARS-CoV-2-associated hospitalization or death (2019-2020: aHR, 0.83; 95% CI, 0.74-0.92; 2020-2021: aHR, 0.66; 95% CI, 0.63-0.70). Similarly, undergoing a PHE was also associated with a lower incidence of SARS-CoV-2 infection (aHR, 0.85; 95% CI, 0.78-0.91) and SARS-CoV-2-associated hospitalization or death (aHR, 0.80; 95% CI, 0.70-0.90), and modified the association between influenza vaccination and SARS-CoV-2 infection for vaccinated individuals who underwent PHE (aHR, 0.62; 95% CI, 0.52-0.74) and for vaccinated individuals who did not undergo PHE (aHR, 0.81; 95% CI, 0.76-0.87), and also SARS-CoV-2-associated hospitalization or death in vaccinated individuals who underwent PHE (aHR, 0.66; 95% CI, 0.49-0.88) and vaccinated individuals who did not undergo PHE (aHR, 0.85, 95% CI, 0.76-0.95). Conclusions and Relevance: The findings of this cohort study suggest that undergoing a PHE may at least partially modify the association between influenza vaccination and SARS-CoV-2-associated outcomes in individuals aged 66 years or older, providing evidence of the healthy vaccinee bias that may affect vaccine effectiveness studies.

Safety and Immunogenicity After a Three-Dose SARS-CoV-2 Vaccine Schedule in Allogeneic Stem Cell Transplant Recipients.

In allogeneic stem cell transplant (Allo-SCT) recipients, the cell-mediated and humoral immunogenicity of the 3-dose SARS-CoV-2 vaccination schedule has not been investigated in prospective studies. In a prospective cohort, we recruited 122 Allo-SCT recipients since August 2021, when Ontario began offering a 3-dose vaccine schedule for Allo-SCT recipients. We determined humoral and cell-mediated immunity and adverse effects of the 3-dose SARS-COV-2 vaccination schedule in Allo-SCT recipients. In immunogenicity analysis (n = 95), the median (interquartile range [IQR]) antibody titer against the receptor-binding domain (RBD) of the spike (S) protein after the third dose (10,358.0 U/mL [IQR = 673.9-31,753.0]) was significantly higher than that after the first (10.2 U/mL [IQR = 0.6-37.0]) and the second doses (125.6 U/mL [IQR = 2.8-1251.0]) (P < .0001). The haploidentical donor status was an independent risk factor (adjusted odds ratio = 7.67, 95% confidence interval [CI], 1.86-31.60) for suboptimal antibody response (anti-RBD < 100 U/mL). S-specific CD4+ and CD8+ T-cell responses were measured in a subset of Allo-SCT recipients (n = 20) by flow cytometry. Most developed antigen-specific CD4+ (55%-80%) and CD8+ T-cells (80%) after 2 doses of vaccine. Frequencies of CD4+ polyfunctional (P = .020) and IL-2 monofunctional (P = .013) T-cells significantly increased after the third dose. Twenty-three episodes (23/301 doses [7.6%]) of new-onset or worsening pre-existing graft-versus-host disease (GVHD) occurred, including 4 episodes after the third dose. We observed 4 relapses (3.27%). Seven patients developed SARS-CoV-2 infection despite vaccination, although none required hospitalization. In conclusion, the 3-dose SARS-CoV-2 vaccine schedule provided immunity associated with a low risk of GVHD and other adverse effects. This prospective cohort showed that the third dose of SARS-CoV-2 vaccine in allogeneic stem cell transplant recipients promoted better humoral and cellar immune responses than after the initial series without increasing the risk of GVHD or severe adverse effects.

Concurrent Infection with SARS-CoV-2 and Pneumocystis jirovecii in Immunocompromised and Immunocompetent Individuals.

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11-83) years), including 66% immunosuppressed individuals (23% HIV-infected and 41% on long-term corticosteroid therapy). Patients were characteristically severely ill (mechanical ventilation: 70%), associated with 41% mortality. The median lymphocyte count was 527 cells/mm3 (range: 110-2200), and the median CD4+ T cell count was 206 cells/mm3 (range: 8-1021). We identified three patterns of concurrent COVID-19 and P. jirovecii infection. The first pattern (airway colonization with a low burden of P. jirovecii) does not seem to modify the COVID-19 course of illness. However, P. jirovecii superinfection, typically occurring weeks after COVID-19 diagnosis as a biphasic illness, and P. jirovecii coinfection characteristically results in progressive multilobar pneumonia, which is associated with poor outcomes. To support this categorization, we reported three patients with concurrent PJP and COVID-19 identified in our institution, presenting these clinical scenarios. The diagnosis of PJP requires a high index of suspicion, since clinical and radiological characteristics overlap with COVID-19. Observational studies are necessary to determine the PJP burden in patients with COVID-19 requiring hospitalization.

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

BACKGROUND: Several studies have described the clinical features of COVID-19 in solid-organ transplant recipients. However, many have been retrospective or limited to more severe cases (hospitalized) and have not routinely included serial virological sampling (especially in outpatients) and immunologic assessment. METHODS: Transplant patients diagnosed with COVID-19 based on a respiratory sample PCR were prospectively followed up to 90 d. Patients provided consent for convalescent serum samples and serial nasopharyngeal swabs for SARS-CoV-2 antibody (antinucleoprotein and anti-RBD) and viral load, respectively. RESULTS: In the 161 SOT recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%), and death (15.6%). Increasing age (OR, 1.031; 95% CI, 1.001-1.062; P = 0.046) and ≥2 comorbid conditions (OR, 3.690; 95% CI, 1.418-9.615; P = 0.007) were associated with the need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at ≥14 d postsymptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 d (IQR, 5.5-18.0) and shedding beyond 30 d was observed in 6.7% of patients. The development of antibody did not have an impact on viral shedding. CONCLUSIONS: This study demonstrates the spectrum of COVID-19 illness in transplant patients. Risk factors for severe disease are identified. The majority form antibody by 2 wk with differential stability over time. Prolonged viral shedding was observed in a minority of patients. Reduction of immunosuppression was a safe strategy.