Transplacental transmission of SARS-CoV-2 immunoglobulin G antibody to infants from maternal COVID-19 vaccine immunization before pregnancy

The coronavirus disease 2019 (COVID-19) vaccine generates functional antibodies in maternal circulation that are detectable in infants, while the information is restricted to the usage of COVID-19 vaccine during pregnancy. In this study, we aimed to evaluate the effect of maternal COVID-19 vaccines before pregnancy. Infants were included from mothers with no inactivated COVID-19 vaccine, 1-, 2-, and 3-dose before pregnancy, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies were tested. Comparative analysis was done between the groups. A total of 130 infants were enrolled in the study. Significantly higher levels of SARS-CoV-2 IgG antibodies in infants born to mothers with 3-dose COVID-19 vaccine before pregnancy compared with 1- and 2-dose groups (p < 0.0001). The levels of antibodies decreased significantly with age in infants born to mothers with the 3-dose COVID-19 vaccine before pregnancy (r = −0.338, p = 0.035), and it was still higher than that 2-dose COVID-19 vaccine group. The maternal SARS-CoV-2 antibodies produced from the inactivated COVID-19 vaccine before pregnancy can be transferred to newborns via the placenta. Maternal immunization with 3-dose of the COVID-19 vaccine before pregnancy could be more beneficial for both mothers and infants.     

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ‘‘BBB”) or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ‘‘BBM”) at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.     

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53–0.83), 33.59 million hospitalizations (22.41–39.31), and 0.62 million deaths (0.40–0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68–1.99%) and the infected fatality rate is 0.38‰ (0.33–0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30–3.85) and 20.33 (2.01–25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.     

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T_1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T_1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.     

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4⁺ and CD8⁺ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7–55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, −0.52; p < 0.001) but not in VAC-ex (rho −0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.     

Humoral and cellular immunity of two-dose inactivated COVID-19 vaccination in Chinese children: A prospective cohort study

Children are the high-risk group for COVID-19, and in need of vaccination. However, humoral and cellular immune responses of COVID-19 vaccine remain unclear in vaccinated children. To establish the rational immunization strategy of inactivated COVID-19 vaccine for children, the immunogenicity of either one dose or two doses of the vaccine in children was evaluated. A prospective cohort study of 322 children receiving inactivated COVID-19 vaccine was established in China. The baseline was conducted after 28 days of the first dose, and the follow-up was conducted after 28 days of the second dose. The median titers of receptor binding domain (RBD)-IgG, and neutralizing antibody (NAb) against prototype strain and Omicron variant after the second dose increased significantly compared to those after the first dose (first dose: 70.0, [interquartile range, 30.0–151.0] vs. second dose: 1261.0 [636.0–2060.0] for RBD-IgG; 2.5 [2.5–18.6] vs. 252.0 [138.6–462.1] for NAb against prototype strain; 2.5 [2.5–2.5] vs. 15.0 [7.8–26.5] for NAb against Omicron variant, all p < 0.05). The flow cytometry results showed that the first dose elicited SARS-CoV-2 specific cellular immunity, while the second dose strengthened SARS-CoV-2 specific IL-2⁺ or TNF-α⁺ monofunctional, IFN-γ⁺TNF-α⁺ bifunctional, and IFN-γ⁻IL-2⁺TNF-α⁺ multifunctional CD4⁺ T cell responses (p < 0.05). Moreover, SARS-CoV-2 specific memory T cells were generated after the first vaccination, including the central memory T cells and effector memory T cells. The present findings provide scientific evidence for the vaccination strategy of the inactive vaccines among children against COVID-19 pandemic.     

Immunogenicity after two doses of inactivated virus vaccine in healthcare workers with and without previous COVID-19 infection: Prospective observational study

Vaccines have been seen as the most important solution for ending the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the antibody levels after inactivated virus vaccination. We included 148 healthcare workers (74 with prior COVID-19 infection and 74 with not). They received two doses of inactivated virus vaccine (CoronaVac). Serum samples were prospectively collected three times (Days 0, 28, 56). We measured SARS-CoV-2 IgGsp antibodies quantitatively and neutralizing antibodies. After the first dose, antibody responses did not develop in 64.8% of the participants without prior COVID-19 infection. All participants had developed antibody responses after the second dose. We observed that IgGsp antibody titers elicited by a single vaccine dose in participants with prior COVID-19 infection were higher than after two doses of vaccine in participants without prior infection (geometric mean titer: 898 and 607 AU/ml). IgGsp antibodies, participants with prior COVID-19 infection had higher antibody levels as geometric mean titers at all time points (p < 0.001). We also found a positive correlation between IgGsp antibody titers and neutralizing capacity (r_s = 0.697, p < 0.001). Although people without prior COVID-19 infection should complete their vaccination protocol, the adequacy of a single dose of vaccine is still in question for individuals with prior COVID-19. New methods are needed to measure the duration of protection of vaccines and their effectiveness against variants as the world is vaccinated. We believe quantitative IgGsp values may reflect the neutralization capacity of some vaccines.     

Longitudinal study comparing IgG antibodies induced by heterologous prime-boost COVID-19 vaccine

Vaccines are critical cost-effective tools to control the COVID-19 pandemic. The heterologous prime-boost vaccination has been used by many countries to overcome supply issues, so the effectiveness and safety of this strategy need to be better clarified. This study aims to verify the effect of heterologous prime-boost COVID-19 vaccination on healthcare professionals from Dante Pazzanese Hospital in Brazil. It was performed serological assays of vaccinated individuals after 2-dose of CoronaVac (Sinovac; n = 89) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca; n = 166) followed by a BNT162b2 booster (Pfizer-BioNTech; n = 255). The serum antibodies anti-S (spike), anti-N (nucleocapsid), and anti-RBD (receptor binding domain) were assessed by enzyme-linked immunosorbent assay. The heterologous booster dose induced a 10-fold higher anti-Spike antibody regardless of the 2-dose of a prime vaccine. It was strikingly observed that BNT162b2 enhanced levels of anti-spike antibodies, even in those individuals who did not previously respond to the 2-dose of CoronaVac. In conclusion, the heterologous scheme of vaccination using mRNA as a booster vaccine efficiently enhanced the antibody response against SARS-CoV-2, especially benefiting those elderly who were seronegative with a virus-inactivated vaccine.     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Differences in incidence and fatality of COVID-19 by SARS-CoV-2 Omicron variant versus Delta variant in relation to vaccine coverage: A world-wide review

We aim to evaluate the evolution differences in the incidence and case fatality rate (CFR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants. The average incidence and CFRs were described between different countries. A gamma generalized linear mixed model (GLMM) was used to compare the CFRs of Delta and Omicron variants based on vaccination coverage. Totally, 50 countries were included for analyses. The incidence of coronavirus disease 2019 (COVID-19) ranged from 0.16/100,000 to 82.95/100,000 during the Delta period and 0.03/100,000 to 440.88/100,000 during the Omicron period. The median CFRs were 8.56 (interquartile range [IQR]: 4.76–18.39) during the Delta period and 3.04 (IQR: 1.87–7.48) during the Omicron period, respectively. A total of 47 out of 50 countries showed decreased CFRs of the Omicron variant with the rate ratio ranging from 0.02 (95% confidence interval [CI]: 0.01–0.03) (in Cambodia) to 0.97 (95% CI: 0.87–1.08) (in Ireland). Gamma GLMM analysis showed that the decreased CFR was largely a result of the decreased pathogenicity of Omicron besides the increased vaccination coverage. The Omicron variant shows a higher incidence but a lower CFR around the world as a whole, which is mainly a result of the decreased pathogenicity by SARS-CoV-2's mutation, while the vaccination against SARS-CoV-2 still acts as a valuable measure in preventing people from death.     

The impact of COVID-19 vaccination programme in the Republic of San Marino: Focus on effectiveness of Gam-Covid-Vac

ObjectiveThe adenovirus-based vaccine Gam-COVID-Vac (Sputnik V) showed promising effectiveness in a phase 3 clinical trial; however, data concerning its impact at a population level are scarce. The Republic of San Marino (RSM) conducted a SARS-CoV-2 vaccination programme mainly based (>80%) on Gam-COVID-Vac. Our aims were to investigate the impact of Gam-COVID-Vac vaccination programme and its effectiveness in a retrospective observational study based on the entire RSM population aged ≥12 years.MethodsWe calculated the incidence rate and the vaccine effectiveness (VE) in the entire RSM population not previously infected, against SARS-CoV-2 infection and COVID-19–related hospitalization, from 25 February to 1 October 2021, considering any vaccine and separately according to the vaccine used. Vaccine effectiveness was calculated using a multivariable negative binomial regression model as 1-Incidence Rate Ratio.ResultsDuring the study period, 21 568/28 791 (74.9%) not previously infected subjects received at least one dose of the Gam-COVID-Vac (84%) or BNT162b2, vaccines with 98% completing the vaccination schedule. Overall, 1634 SARS-CoV-2 infections and 166 COVID-19-related hospitalizations were observed with 17 COVID-19-related deaths reported. Incidence rates of SARS-CoV-2 infection and COVID-19-related hospitalization were 7.11 and 0.49/100 000 person-days in the fully vaccinated population, respectively. The adjusted overall VE was 67.6% (95% CI: 61.8–72.5) against SARS-CoV-2 infection and 87.9% (95% CI: 77.4–93.5) against COVID-19-related hospitalizations.Gam-COVID-Vac against SARS-CoV-2 infection VE peaked 91.8% (95% CI: 86.3–95.1) in the first bimester from the second dose, declining to 57.8% (95% CI: 42.2–69.2) at 6 months. Protection against hospitalization with COVID-19 was overall 91.6% (95% CI: 81.5–96.2), with no relevant waning trend over time.DiscussionOur study demonstrated the effectiveness of overall vaccination (Gam-COVID-Vac [84%] and BNT162b2 [16%]) in the prevention SARS-CoV-2 infection (pre-Omicron variant), waning over time but still with sustainable effectiveness against COVID-19-related hospitalization in the Republic of San Marino.     

Ability of SpikoGen®, an Advax-CpG adjuvanted recombinant spike protein vaccine,to induce cross-neutralising antibodies against SARS-CoV-2 variants

SpikoGen® vaccine is a subunit COVID-19 vaccine expressed in insect cells comprising recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A Phase 2 trial was conducted in 400 adult participants randomised 3:1 to receive two intramuscular doses of SpikoGen® vaccine or saline placebo 3 weeks apart. Some Phase 2 trial participants later enrolled in a separate booster study and received a third dose of SpikoGen® vaccine. This stored serum was used to assess the ability of SpikoGen® vaccine to induce cross-neutralising antibodies against SARS-CoV-2 variants of concern. Sera taken at baseline and 2 weeks after the second vaccine dose from baseline seronegative Phase 2 subjects was evaluated using a panel of spike pseudotype lentivirus neutralisation assays for the ability to cross-neutralise a wide range of SARS-CoV-2 variants, including Omicron BA.1, BA.2 and BA.4/5. Stored samples of subjects who participated in both the 2-dose Phase 2 trial and a third dose booster trial 6 months later were also analysed for changes in cross-neutralising antibodies over time and dose. Two weeks after the second dose, sera broadly cross-neutralised most variants of concern, albeit with titres against Omicron variants being ~10-fold lower. While Omicron titres fell to low levels 6 months after the second vaccine dose in most subjects, they showed a ~20-fold rise after the third dose booster, after which there was only a ~2-3-fold difference in neutralisation of Omicron and the ancestral strains. Despite being based on the ancestral Wuhan sequence, after two doses, SpikoGen® vaccine induced broadly cross-neutralising serum antibodies. Titres then reduced over time but were rapidly restored by a third dose booster. This resulted in high neutralisation including against the Omicron variants. This data supports ongoing use of SpikoGen® vaccine for protection against recent SARS-CoV-2 Omicron variants.     

Vaccine effectiveness against Delta,Omicron BA.1, and BA.2 in a highly vaccinated Asian setting: a test-negative design study

ObjectivesWe compared the vaccine effectiveness over time of the primary series and booster against infection and severe disease with the Delta, Omicron BA.1, and BA.2 variants in Singapore, an Asian setting with high vaccination coverage.MethodsWe conducted a test-negative case-control study on all adult residents in Singapore who underwent PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute hospitals. Individuals with a negative PCR from 1 September, 2021, to 30 November, 2021, and 1 December, 2021, to 25 April, 2022, served as controls for the Delta and Omicron variants respectively, and PCR-positive individuals within these two time periods served as cases. Associations between vaccination status and SARS-CoV-2 infection and severe disease with the Delta or Omicron variants were measured using Poisson regressions. Vaccine effectiveness was calculated by taking 1 minus risk ratio.ResultsThere were 68 114 individuals comprising 58 495 controls and 9619 cases for the Delta period, of whom 53 093 completed the primary series and 9161 were boosted. For the Omicron period, 104 601 individuals comprising 80 428 controls, 8643 BA.1 cases, and 15 530 BA.2 cases were included, of whom 29 183 and 71 513 were vaccinated with the primary series and boosted, respectively. The primary series provided greater protection against infection with Delta (45%, 95% CI 40–50%) than against infection with Omicron (21%, 95% CI 7–34% for BA.1; 18%, 95% CI 6–29% for BA.2) at <2 months from vaccination. Vaccine effectiveness of the booster was similar against infection with BA.1 (44%, 95% CI 38–50%) and BA.2 (40%, 95% CI 35–40%). Protection against severe disease by the booster for BA.1 (83%, 95% CI 76–88%) and BA.2 (78%, 95% CI 73–82%) was comparable to that by the primary series for Delta (80%, 95% CI 73–85%).ConclusionOur findings support the use of a booster dose to reduce the risk of severe disease and mitigate the impact on the healthcare system in an Omicron-predominant epidemic.     

An Outbreak of Breakthrough Infections by the SARS-CoV-2 Delta Variant in a Psychiatric Closed Ward

BackgroundA rapid decline in immunity and low neutralizing activity against the delta variant in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees has been observed. This study describes an outbreak of coronavirus disease 2019 (COVID-19) breakthrough infections caused by the SARS-CoV-2 delta variant in a psychiatric closed ward.MethodsData from epidemic intelligence service officers were utilized to obtain information regarding demographic, vaccination history, and clinical data along with SARS-CoV-2 PCR test results for a COVID-19 outbreak that occurred in a closed psychiatric ward.ResultsAmong the 164 residents, 144 (87.8%) received two doses of vaccines and 137 (95.1%) of them received ChAdOx1 nCoV-19 vaccine. The mean interval between the second vaccination and COVID-19 diagnosis was 132.77 ± 40.68 days. At the time of detection of the index case, SARS-CoV-2 had spread throughout the ward, infecting 162 of 164 residents. The case-fatality ratio was lower than that in the previously reported outbreak before the vaccination (1.2%, 2/162 vs. 6.9%, P = 0.030). Prolonged hospitalization occurred in 17 patients (11.1%) and was less prevalent in the vaccinated group than in the unvaccinated group (8.5% vs. 25.0%, P = 0.040).ConclusionThe findings of this study highlight that while vaccination can reduce mortality and the duration of hospitalization, it is not sufficient to prevent an outbreak of the SARS-CoV-2 delta variant in the present psychiatric hospital setting.     

Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.     

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5–11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99–15.08]), new cough (aOR: 2.38, [95% CI: 1.69–3.36]), headache (aOR: 1.90, [95% CI: 1.28–2.81), fever (aOR: 1.83, [95% CI: 1.29–2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75–6.97]), or household contact (aOR: 2.66, [95% CI: 1.96–3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.     

Effectiveness of MRNA booster vaccine among healthcare workers in New York City during the Omicron surge,December 2021 to January 2022

ObjectiveTo describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance.MethodsIn a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness.ResultsAmong the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic.DiscussionStudy demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.     

Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

The potential clinical utility of measuring severe acute respiratory syndrome coronavirus 2-specific T-cell responses

BackgroundBoth humoral and cell-mediated responses are associated with immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although our understanding of the potential role of T-cell responses in the context of coronavirus disease 2019 (COVID-19) is rapidly increasing, more information is still needed.ObjectivesTo provide an overview of the role of T-cell immunity in COVID-19, in the context of natural infection and post-vaccination, and discuss the potential utility of measuring SARS-CoV-2-specific T-cell responses, drawing on experience of the use of interferon-γ release assays (IGRAs) in tuberculosis (TB).SourcesPubMed articles up to 16 April 2021.ContentT-cell responses can be detected very early in the course of COVID-19, earlier than the detection of antibody responses, and are correlated with COVID-19 outcome. Lower CD4⁺ and CD8⁺ T-cell counts are markers of more severe disease, longer duration of viral RNA positivity and increased mortality. In line with natural infection, SARS-CoV-2 vaccination stimulates robust T-cell responses, which probably play an important role in protection; data on long-term T-cell responses are currently limited. The utility of measuring T-cell responses is already well established in both aiding the diagnosis of TB infection using IGRAs, and evaluation of T-cell responses to TB vaccine candidates. A variety of assays have already been developed to measure SARS-CoV-2-specific T-cell responses, including IGRAs, intracellular cytokine staining and activation-induced markers. IGRAs based on SARS-CoV-2 antigens can distinguish between convalescent and uninfected healthy blood donors.ImplicationsSimple assays for measuring the quantity and function of T-cell responses may have utility in the prognostication of COVID-19, and for monitoring immune responses to SARS-CoV-2 vaccination and population-based immunity to SARS-CoV-2 variants of interest.