Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization

Emerging in November 2021, the SARS-CoV-2 Omicron variant of concern exhibited marked immune evasion resulting in reduced vaccine effectiveness against SARS-CoV-2 infection and symptomatic disease. Most vaccine effectiveness data on Omicron are derived from the first Omicron subvariant, BA.1, which caused large waves of infection in many parts of the world within a short period of time. BA.1, however, was replaced by BA.2 within months, and later by BA.4 and BA.5 (BA.4/5). These later Omicron subvariants exhibited additional mutations in the spike protein of the virus, leading to speculation that they might result in even lower vaccine effectiveness. To address this question, the World Health Organization hosted a virtual meeting on December 6, 2022, to review available evidence for vaccine effectiveness against the major Omicron subvariants up to that date. Data were presented from South Africa, the United Kingdom, the United States, and Canada, as well as the results of a review and meta-regression of studies that evaluated the duration of the vaccine effectiveness for multiple Omicron subvariants. Despite heterogeneity of results and wide confidence intervals in some studies, the majority of studies showed vaccine effectiveness tended to be lower against BA.2 and especially against BA.4/5, compared to BA.1, with perhaps faster waning against severe disease caused by BA.4/5 after a booster dose. The interpretation of these results was discussed and both immunological factors (i.e., more immune escape with BA.4/5) and methodological issues (e.g., biases related to differences in the timing of subvariant circulation) were possible explanations for the findings. COVID-19 vaccines still provide some protection against infection and symptomatic disease from all Omicron subvariants for at least several months, with greater and more durable protection against severe disease.

Assessing COVID-19 vaccine effectiveness against Omicron subvariants: Report from a meeting of the World Health Organization.

Emerging in November 2021, the SARS-CoV-2 Omicron variant of concern exhibited marked immune evasion resulting in reduced vaccine effectiveness against SARS-CoV-2 infection and symptomatic disease. Most vaccine effectiveness data on Omicron are derived from the first Omicron subvariant, BA.1, which caused large waves of infection in many parts of the world within a short period of time. BA.1, however, was replaced by BA.2 within months, and later by BA.4 and BA.5 (BA.4/5). These later Omicron subvariants exhibited additional mutations in the spike protein of the virus, leading to speculation that they might result in even lower vaccine effectiveness. To address this question, the World Health Organization hosted a virtual meeting on December 6, 2022, to review available evidence for vaccine effectiveness against the major Omicron subvariants up to that date. Data were presented from South Africa, the United Kingdom, the United States, and Canada, as well as the results of a review and meta-regression of studies that evaluated the duration of the vaccine effectiveness for multiple Omicron subvariants. Despite heterogeneity of results and wide confidence intervals in some studies, the majority of studies showed vaccine effectiveness tended to be lower against BA.2 and especially against BA.4/5, compared to BA.1, with perhaps faster waning against severe disease caused by BA.4/5 after a booster dose. The interpretation of these results was discussed and both immunological factors (i.e., more immune escape with BA.4/5) and methodological issues (e.g., biases related to differences in the timing of subvariant circulation) were possible explanations for the findings. COVID-19 vaccines still provide some protection against infection and symptomatic disease from all Omicron subvariants for at least several months, with greater and more durable protection against severe disease.

Post-vaccination T cell immunity to omicron.

In late 2021, the omicron variant of SARS Coronavirus 2 (SARS-CoV-2) emerged and replaced the previously dominant delta strain. Effectiveness of COVID-19 vaccines against omicron has been challenging to estimate in clinical studies or is not available for all vaccines or populations of interest. T cell function can be predictive of vaccine longevity and effectiveness against disease, likely in a more robust way than antibody neutralization. In this mini review, we summarize the evidence on T cell immunity against omicron including effects of boosters, homologous versus heterologous regimens, hybrid immunity, memory responses and vaccine product. Overall, T cell reactivity in post-vaccine specimens is largely preserved against omicron, indicating that vaccines utilizing the parental antigen continue to be protective against disease caused by the omicron variant.

Systematic review of primary and booster COVID-19 sera neutralizing ability against SARS-CoV-2 omicron variant.

Virus neutralization data using post-vaccination sera are an important tool in informing vaccine use policy decisions, however, they often pose interpretive challenges. We systematically reviewed the pre-print and published literature for neutralization studies against Omicron using sera collected after both primary and booster vaccination. We found a high proportion of post-primary vaccination sera were not responding against Omicron but boosting increased both neutralizing activity and percent of responding sera. We recommend reporting percent of responders alongside neutralization data to portray vaccine neutralization ability more accurately.

Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.

Background: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. Methods: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. Results: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). Conclusions: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

Post-vaccination T cell immunity to omicron

In late 2021, the omicron variant of SARS Coronavirus 2 (SARS-CoV-2) emerged and replaced the previously dominant delta strain. Effectiveness of COVID-19 vaccines against omicron has been challenging to estimate in clinical studies or is not available for all vaccines or populations of interest. T cell function can be predictive of vaccine longevity and effectiveness against disease, likely in a more robust way than antibody neutralization. In this mini review, we summarize the evidence on T cell immunity against omicron including effects of boosters, homologous versus heterologous regimens, hybrid immunity, memory responses and vaccine product. Overall, T cell reactivity in post-vaccine specimens is largely preserved against omicron, indicating that vaccines utilizing the parental antigen continue to be protective against disease caused by the omicron variant.

A Systematic Review of Coronavirus Disease 2019 Vaccine Efficacy and Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Disease.

Billions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, dramatically reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and severity in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. In this study, we conduct a systematic review of COVID-19 vaccines through February 2022. We included efficacy data from Phase 3 clinical trials for 15 vaccines undergoing World Health Organization Emergency Use Listing evaluation and real-world effectiveness for 8 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include protection against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for partial or complete vaccination, and against variants of concern Alpha, Beta, Gamma, Delta, and Omicron. We additionally review the epidemiological principles behind the design and interpretation of vaccine efficacy and effectiveness studies, including important sources of heterogeneity.

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease

Billions of doses of COVID-19 vaccines have been administered globally, dramatically reducing SARS-CoV-2 incidence and severity in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines through February 2022. We included efficacy data from Phase 3 clinical trials for 15 vaccines undergoing WHO Emergency Use Listing evaluation and real-world effectiveness for 8 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include protection against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for partial or complete vaccination, and against variants of concern Alpha, Beta, Gamma, Delta, and Omicron. We additionally review the epidemiological principles behind the design and interpretation of vaccine efficacy and effectiveness studies, including important sources of heterogeneity.

Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults.

BackgroundSARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children.MethodsWe compared receptor binding domain-binding antibody (RBDAb) titers and SARS-CoV-2-neutralizing antibody titers, measured by pseudovirus-neutralizing antibody assay in serum specimens obtained from children aged 0-4 years and 5-17 years and in adults aged 18-62 years at the time of enrollment in a prospective longitudinal household study of SARS-CoV-2 infection.ResultsAmong 56 seropositive participants at enrollment, children aged 0-4 years had more than 10-fold higher RBDAb titers than adults (416 vs. 31, P < 0.0001) and the highest RBDAb titers in 11 of 12 households with seropositive children and adults. Children aged 0-4 years had only 2-fold higher neutralizing antibody than adults, resulting in higher binding-to-neutralizing antibody ratios compared with adults (2.36 vs. 0.35 for ID50, P = 0.0004).ConclusionThese findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutralizing antibody to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.FundingCDC (award 75D30120C08737).

Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression.

BACKGROUND: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. METHODS: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1-6 months after full vaccination. FINDINGS: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer-BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9-29·8) among people of all ages and 20·7 percentage points (10·2-36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4-41·6) in people of all ages and 32·0 percentage points (11·0-69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1-15·4) in people of all ages and 9·5 percentage points (5·7-14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. INTERPRETATION: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20-30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. FUNDING: Coalition for Epidemic Preparedness Innovations.

Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Study.

BACKGROUND: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn-, 449 CoV-/HDSpn+ and 3149 CoV-/HDSpn- cases with no significant difference in co-detection frequency by sex (range 51.2%-64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%-34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%-43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%-28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%-7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%-33.3% (P = 0.58) and mortality was 10.0% versus 9.2%-12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.

A global agenda for older adult immunization in the COVID-19 era: A roadmap for action.

Given our global interconnectedness, the COVID-19 pandemic highlights the urgency of building a global system that can support both routine and pandemic/epidemic adult immunization. As such, a framework to recommend vaccines and build robust platforms to deliver them to protect the rapidly expanding demographic of older adults is needed. Adult immunization as a strategy has the broad potential to preserve and improve medical, social, and economic outcomes, including maintaining functional ability that benefits older adults, their families, communities, and countries. While we will soon have multiple vaccines against COVID-19, we must recognize that we already have a variety of vaccines against other pathogens that can keep adults healthier. They can prevent simultaneous co-infection with COVID-19, and may favorably impact- the outcome of a COVID-19 illness. Further, administering a vaccine against COVID-19 requires planning now to determine delivery strategies impacting how older adults will be immunized in a timely manner. A group of international experts with various backgrounds from health and aging disciplines met to discuss the evidence case for adult immunization and crucial knowledge gaps that must be filled in order to implement effective policies and programs for older adult immunization. This group, coming together as the International Council on Adult Immunization (ICAI), outlined a high-level roadmap to catalyze action, provide policy guidance, and envision a global adult immunization platform that can be adapted by countries to fit their local contexts. Further meetings centered around the value of adult immunization, particularly in the context of COVID-19. There was agreement that programs to deliver existing influenza, pneumococcal, herpes zoster vaccines, and future COVID-19 vaccines to over a billion older adults who are at substantially higher risk of death and disability due to vaccine-preventable diseases are more urgent than ever before. Here we present a proposed framework for delivering routine and pandemic vaccines. We call upon the global community and governments to prioritize action for integrating robust adult immunization programs into the public health agenda.