Vaccine Effectiveness, School Reopening, and Risk of Omicron Infection Among Adolescents Aged 12-17 Years.

PURPOSE: The BNT162b2 (Pfizer-BioNTech) is approved for adolescents aged 12-17 years. We estimated BNT162b2 vaccine effectiveness (VE) and a booster dose effectiveness in adolescents aged 12-17 years and the impact of opening schools and the Omicron variant on risk of SARS-CoV-2 infection in adolescents. METHODS: We used logistic regression with a test-negative design controlling for gender and race to estimate BNT162b2 VE and the effectiveness of a booster dose in adolescents aged 12-17 years. To evaluate the effect of school opening on Omicron transmission, we used Cox proportional hazards regression to compare adolescents to a reference group of adults aged 22-33 or aged 65+ years, investigating whether risk for adolescents increased relative to the reference group after school opened. RESULTS: We found that adolescents who received two BNT162b2 doses had significant protection against Omicron infection in the first three months following their second dose (VE = 54.5%, confidence interval [CI]: [17.8%-76.9%], p = .014) but no protection afterwards. Receiving a booster dose was associated with lower risk of infection (odds ratio = 0.48, CI: [0.33-0.69], p < .0001) and restored efficacy to a similar level (VE = 56.3%, CI: [36.5%-70.6%], p < .0001). We observed a statistically significant increase (p = .04) in adolescent infection risk relative to adults in the period of Omicron predominance. DISCUSSION: The BNT162b2 vaccine is effective at preventing SARS-CoV-2 infection in adolescents but immunity against Omicron wanes rapidly and booster doses are needed to retain protection. More research is needed to determine the effect of school reopening on spread in the Omicron-dominant period.

COVID-19 vaccine effectiveness against omicron (B.1.1.529) variant infection and hospitalisation in patients taking immunosuppressive medications: a retrospective cohort study.

Background: There is a scarcity of research regarding the effectiveness of the mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in patients taking immunosuppressant medications, and no data are published to date pertaining to their effectiveness against omicron (B.1.1.529) variant SARS-CoV-2 infection and hospitalisation. We aimed to assess the relationship between immunosuppressive medications, mRNA vaccination, omicron infection, and severe COVID-19 outcomes (ie, hospitalisation, ICU admission, death). Methods: We did a retrospective cohort study and included vaccinated and unvaccinated people aged 18 years or older in the Michigan Medicine health-care system, USA, during the omicron-dominant period of the pandemic (Dec 16, 2021-March 4, 2022). We collected data from electronic health records (demographics, diagnoses, medications) combined with immunisation data from the Michigan State Registry to determine vaccination status, and we collected COVID-19-related hospitalisation data by chart review. We used a Cox proportional hazards model based on calendar time to assess the effectiveness of the mRNA-1273 and BNT162b2 vaccines in people taking immunosuppressive medications (conventional synthetic disease-modifying antirheumatic drugs [DMARDs], biologic DMARDs, or glucocorticoids within the past 3 months), while controlling for participant characteristics. Using the same model, we assessed the effect of different classes of medication such as immunosuppressive DMARDs, immunomodulatory DMARDs, and glucocorticoids on SARS-CoV-2 infection and hospitalisation due to COVID-19. All analyses were done using complete cases after removing participants with missing covariates. Findings: 209 492 people were identified in Michigan Medicine, including 165 913 who were vaccinated and 43 579 who were unvaccinated. 41 078 people were excluded because they were younger than 18 years, partially vaccinated, had received a vaccine other than the two vaccines studied, or had incomplete covariate data. 168 414 people were included in the analysis; 97 935 (58%) were women, 70 479 (42%) were men, and 129 816 (77%) were White. 5609 (3%) people were taking immunosuppressive medications. In patients receiving immunosuppressants, three doses of BNT162b2 had a vaccine effectiveness of 50% (95% CI 31-64; p<0·0001) and three doses of mRNA-1273 had a vaccine effectiveness of 60% (42-73; p<0·0001) against SARS-CoV-2 infection. Three doses of either vaccine had an effectiveness of 87% (95% CI 73-93; p<0·0001) against hospitalisation due to COVID-19. Receipt of immunosuppressive DMARDs (hazard ratio 2·32, 95% CI 1·23-4·38; p=0·0097) or glucocorticoids (2·93, 1·77-4·86; p<0·0001) and a history of organ or bone marrow transplantation (3·52, 2·01-6·16; p<0·0001) were associated with increased risk of hospitalisation due to COVID-19 compared with those who had not received immunosuppressive medications or transplant. Interpretation: People taking immunosuppressive DMARDs or glucocorticoids are at substantially higher risk of hospitalisation due to COVID-19 than the general population. However, the mRNA-1273 and BNT162b2 vaccines remain effective within this group, and it is important that patients taking these medications remain up to date with vaccinations to mitigate their risk. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Association between COVID-19 restrictions and emergency department presentations for paediatric mental health in Victoria, Australia.

Objective To determine the association between coronavirus disease 2019 (COVID-19) restrictions and paediatric mental health emergency department presentations. Methods Secondary analysis of Victorian Emergency Minimum Dataset data from 38 Victorian public hospital emergency departments. Paediatric patients (birth to <18 years) attending emergency departments with an International Classification of Disease-Australian Modification (ICD-10-AM) diagnosis of a mental health problem between 1 January 2018 and 31 October 2020 were included. We compared pre-COVID-19 (1 January 2018-27 March 2020) to the COVID-19 period (28 March-26 October 2020) to examine the number of mental health presentations by patient age, socioeconomic status, location, and emergency department triage category. A Poisson regression prediction model was built for each diagnosis group to predict the presentation number in the COVID-19 period, assuming the pandemic and associated restrictions had not happened. Results There were 15 898 presentations (589 presentations/month on average) in the pre-COVID-19 period and 4747 presentations (678 presentations/month on average) in the COVID-19 period. Compared with predicted presentations, there was an increase in observed presentations for eating disorders throughout lockdown (on average, an increase of 36 presentations/month) and for anxiety (11/month) and self-harm (18/month). There were no meaningful changes for mood disorders or developmental and behavioural problems, and presentations for substance abuse mostly fell. Conclusions Pandemic restrictions were associated with increased emergency department presentations for eating disorders and, to a lesser extent, anxiety and self-harm. Given the ongoing pandemic, clinicians and policy makers must work together to find timely, accessible solutions to better manage these conditions.

Comparative Effectiveness of Coronavirus Disease 2019 (COVID-19) Vaccines Against the Delta Variant.

BACKGROUND: There is a lack of data regarding how the Delta variant of coronavirus disease 2019 (COVID-19) has impacted the effectiveness of the BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines at preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalization. METHODS: We compared the effectiveness of the three vaccines during the pre- and post-Delta variant period (before and after 1 July 2021) in a large cohort of vaccinated and unvaccinated patients in the Michigan Medicine healthcare system. We assessed vaccine effectiveness (VE) using 2 analyses: an inverse propensity weighted (IPW) Kaplan-Meier (KM) analysis based on time from vaccination, and a Cox model based on calendar time with vaccination as a time-varying covariate. RESULTS: Compared to Ad26.COV2.S recipients, the risk of hospitalization for COVID-19 in the post-Delta variant period was lower for BNT162b2 recipients (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: [.14-.98]; P = .05) and mRNA-1273 recipients (HR = 0.21; 95% CI: [.07-.64]; P = .006). Recipients of the mRNA-1273 vaccine had a lower risk of SARS-CoV-2 infection than Ad26.COV2.S recipients (HR = 0.6; 95% CI: [.43-.83]; P = .003) and BNT162b2 recipients (HR = 0.64; 95% CI: [.54-.76]; P < .001). After 1 July, efficacy against SARS-CoV-2 infection declined for Ad26.COV2.S recipients (VE = 76% before; VE = 49% after; P = .02), BNT162b2 recipients (VE = 87% before; VE = 52% after; P < .001), and mRNA-1273 recipients (VE = 92% before; VE = 70% after; P < .001). Waning immunity and the Delta variant contributed independently and significantly to this decline. CONCLUSIONS: Although there is a substantial decline in effectiveness, the approved COVID-19 vaccines remain effective against infection and hospitalization due to the Delta variant. The mRNA-based vaccines are more effective than the Ad26.COV2.S vaccine.

Efficacy of COVID-19 vaccines in patients taking immunosuppressants.

OBJECTIVES: We intended to assess the effectiveness of all three US Food and Drug Administration approved COVID-19 vaccines at preventing SARS-CoV-2 infection and COVID-19 hospitalisation in a large cohort of individuals on immunosuppressants for a diverse range of conditions. METHODS: We studied the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Johnson & Johnson-Janssen) vaccines among individuals who take immunosuppressants (including disease-modifying antirheumatic drugs and glucocorticoids) by comparing vaccinated (n=97688) and unvaccinated (n=42094) individuals in the Michigan Medicine healthcare system from 1 January to 7 December 2021, using Cox proportional hazards modelling with time-varying covariates. RESULTS: Among vaccinated and unvaccinated individuals, taking immunosuppressants increased the risk of SARS-CoV-2 infection (adjusted HR (aHR)=2.17, 95% CI 1.69 to 2.79 for fully vaccinated and aHR=1.40, 95% CI 1.07 to 1.83 for unvaccinated). Among individuals taking immunosuppressants, we found: (1) vaccination reduced the risk of SARS-CoV-2 infection (aHR=0.55, 95% CI 0.39 to 0.78); (2) the BNT162b2 and mRNA-1273 vaccines were highly effective at reducing the risk of SARS-CoV-2 infection (n=2046, aHR=0.59, 95% CI 0.38 to 0.91 for BNT162b2; n=2064, aHR=0.52, 95% CI 0.33 to 0.82 for mRNA-1273); (3) with a smaller sample size (n=173), Ad26.COV2.S vaccine protection did not reach statistical significance (aHR=0.34, 95% CI 0.09 to 1.30, p=0.17); and (4) receiving a booster dose reduced the risk of SARS-CoV-2 infection (aHR=0.42, 95% CI 0.24 to 0.76). CONCLUSIONS: The mRNA-1273 and BNT162b2 vaccines are effective in individuals who take immunosuppressants. However, individuals who are vaccinated but on immunosuppressants are still at higher risk of SARS-CoV-2 infection and COVID-19 hospitalisation than the broader vaccinated population. Booster doses are effective and crucially important for individuals on immunosuppressants.

Actionable lessons for the US COVID vaccine program.

When attempting to provide lessons for other countries from the successful Israeli COVID-19 vaccine experience, it is important to distinguish between the modifiable and non-modifiable components identified in the article by Rosen, et al. Two specific modifiable components included in the Israeli program from which the US can learn are (a) a national (not individual state-based) strategy for vaccine distribution and administration and (b) a functioning public health infrastructure. As a federal government, the US maintains an often complex web of state and national authorities and responsibilities. The federal government assumed responsibility for the ordering, payment and procurement of COVID vaccine from manufacturers. In designing the subsequent steps in their COVID-19 vaccine distribution and administration plan, the Trump administration decided to rely on the states themselves to determine how best to implement guidance provided by the Centers for Disease Control and Prevention (CDC). This strategy resulted in 50 different plans and 50 different systems for the dissemination of vaccine doses, all at the level of each individual state. State health departments were neither financed, experienced nor uniformly possessed the expertise to develop and implement such plans. A national strategy for the distribution, and the workforce for the provision, of vaccine beyond the state level, similar to that which occurred in Israel, would have provided for greater efficiency and coordination across the country. The US public health infrastructure was ill-prepared and ill-staffed to take on the responsibility to deliver > 450 million doses of vaccine in an expeditious fashion, even if supply of vaccine was available. The failure to adequately invest in public health has been ubiquitous across the nation at all levels of government. Since the 2008 recession, state and local health departments have lost > 38,000 jobs and spending for state public health departments has dropped by 16% per capita and spending for local health departments has fallen by 18%. Hopefully, COVID-19 will be a wakeup call to the US with regard to the need for both a national strategy to address public health emergencies and the well-maintained infrastructure to make it happen.