Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha,Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study

BackgroundThe continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period.Methods and findingsA Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: −0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals.ConclusionsTwo vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Mie Agermose Gram and colleagues estimate vaccine effectiveness against infection and COVID-19 hospitalization with the Alpha, Delta or Omicron variant in Denmark.     

Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study

BackgroundEmerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants.Methods and findingsIn a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231–556] and 214 [95% CI 153–299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11–30] and 14 [95% CI 8–25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02–0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data.ConclusionsOverall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

Marit J. van Gils and colleagues investigate antibody responses against diverse emerging SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands.     

The humoral and cellular immune evasion of SARS-CoV-2 Omicron and sub-lineages

The recently discovered SARS-CoV-2 variant Omicron (B.1.1.529) has rapidly become a global public health issue. The substantial mutations in the spike protein in this new variant have raised concerns about its ability to escape from pre-existing immunity established by natural infection or vaccination. In this review, we give a summary of current knowledge concerning the antibody evasion properties of Omicron and its subvariants (BA.2, BA.2.12.1, BA.4/5, and BA.2.75) from therapeutic monoclonal antibodies and the sera of SARS-CoV-2 vaccine recipients or convalescent patients. We also summarize whether vaccine-induced cellular immunity (memory B cell and T cell response) can recognize Omicron specifically. In brief, the Omicron variants demonstrated remarkable antibody evasion, with even more striking antibody escape seen in the Omicron BA.4 and BA.5 sub-lineages. Luckily, the third booster vaccine dose significantly increased the neutralizing antibodies titers, and the vaccine-induced cellular response remains conserved and provides second-line defense against the Omicron.     

Changes in the associations of race and rurality with SARS-CoV-2 infection,mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study

BackgroundWe examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study.Methods and findingsIn a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2–related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations.ConclusionsIn this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.

George Ioannou and co-workers study the distribution of SARS-CoV-2 infections and outcomes among the United States population.     

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls

ObjectiveData for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design.MethodsStudy participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection.ResultsWe evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001).ConclusionSARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.     

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India,June–July 2021: A population-based cross-sectional study

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.     

Clinical characteristics of 310 SARS-CoV-2 Omicron variant patients and comparison with Delta and Beta variant patients in China

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread, data on the clinical characteristics of infected patients are limited. In this study, the demographic, clinical characteristics, and laboratory data of 310 SARS-CoV-2 Omicron variant patients treated at Haihe Hospital of Tianjin were collected and analyzed. Information on these patients was compared to 96 patients with the Delta variant of concern (VOC) and 326 patients with the Beta VOC during the previous coronavirus disease 2019 (COVID-19) outbreak in Harbin. Of the 310 patients infected with the Omicron variant, the median age was 35 years. Most patients were clinically classified as mild (57.74%), and the most common symptoms were cough (48.71%), fever (39.35%), and sore throat (38.26%). The results for different vaccination groups in the Omicron group showed that the median of “SARS-CoV-2 specific IgG” after 2 or 3 doses of vaccination was higher than the unvaccinated group (all Ps < 0.05). Older age was associated with a higher proportion of moderate cases and lower asymptomatic and mild cases based on clinical classifications. Compared to the Delta and Beta groups, the median age of the Omicron group was younger. The total number of asymptomatic patients and mild patients in the Omicron virus group was higher than the Delta and Beta groups (60.97% vs. 54.17% vs. 47.55%). This study presented the clinical characteristics of the first group of patients infected with the Omicron variant in Tianjin, China, and compared their clinical features with patients infected by the Delta and Beta variants, which would increase our understanding of the characteristics of SARS-CoV-2 Omicron variant.     

High-resolution melting analysis to discriminate between the SARS-CoV-2 Omicron variants BA.1 and BA.2

High-resolution melting (HRM) analysis was conducted to discriminate between SARS-CoV-2 Omicron variant BA.1 (B.1.1.529.1) and subvariant BA.2 (B.1.1.529.2). We performed two-step PCR consisting of the first PCR and the second nested PCR to prepare the amplicon for HRM analysis, which detected G339D, N440K, G446S and D796Y variations in the SARS-CoV-2 spike protein. The melting temperatures (Tms) of the amplicons from the cDNA of the Omicron variant BA.1 and subvariant BA.2 receptor binding domain (RBD) in spike protein were the same: 75.2 °C (G339D variation) and 73.4 °C (D796Y variation). These Tms were distinct from those of SARS-CoV-2 isolate Wuhan-Hu-1, and were specific to the Omicron variant. In HRM analyses that detected the N440K and G446S variations, the Tms of amplicons from the cDNA of the Omicron variant BA.1 and subvariant BA.2 RBDs were 73.0 °C (N440K and G446S variations) and 73.5 °C (G446S variation). This difference indicates that the SARS-CoV-2 Omicron variants BA.1 and BA.2 can be clearly discriminated. Our study demonstrates the usefulness of HRM analysis after two-step PCR for the discrimination of SARS-CoV-2 variants.     

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study

Background:The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection.Methods:We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex.Results:Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI −0.67 to −0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (−27.31) and outpatient (−0.87) encounters.Interpretation:We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

The public health effects of the COVID-19 pandemic are difficult to overstate.¹ More than 600 million SARS-CoV-2 infections and 6.5 million deaths have been reported worldwide as of September 2022,² which are likely gross undercounts as many infections go undetected.³Long-term morbidity can be caused by SARS-CoV-2 infection.^4–9 In the first pandedmic wave, as many as 27% of people admitted to hospital died or were readmitted within 60 days, and as many as 70% of people who were not admitted to hospital reported at least 1 symptom 4 months after infection.^10,11 By the World Health Organization (WHO) definition, about 10%–20% of those infected acquire a post-COVID-19 condition (long COVID).^12,13Analysis of 10 prospective surveys and the medical records of 1.1 million patients with COVID-19 diagnosis codes before the emergence of the Omicron variant showed similar findings: 7.8%–17% had symptoms 12 weeks after self-reported COVID-19, with 1.2%–4.8% reporting debilitating symptoms.¹⁴ Estimates of long COVID vary by methodology (e.g., definitions of initial infection and timing of symptoms, timing of data collection), but risk is thought to be influenced by infection severity, type of variant, patient characteristics, vaccination¹⁵ and, potentially, previous infection.¹⁶ Because each new SARS-CoV-2 infection carries some risk of long COVID, everyone remains at risk for developing the condition.Health care funders, policy-makers and clinicians need a clear understanding of the impact of long COVID on use of health care resources to allocate resources equitably now and plan for future needs.¹⁷ We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario.     

Ancestral SARS-CoV-2, but not Omicron,replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air–liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.

Children typically experience more mild symptoms of COVID-19 when compared to adults; why is this? This study uses nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not the Omicron variant, replicate less efficiently in pediatric nasal epithelial cells.     

SARS-CoV-2 seropositivity and COVID-19 among 5 years-old Amazonian children and their association with poverty and food insecurity

BackgroundThe epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children.Methodology/Principal findingsWe retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2–48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9–8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4–9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2–2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8–3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and–even more markedly–of having had clinically apparent COVID-19 by the age of 5 years.Conclusions/SignificanceChildhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease.     

SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: A cross-sectional study

BackgroundHealthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce.Methods and findingsWe conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26–0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62–0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction.ConclusionsEthnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.

In a cross-sectional study, Dr. Christopher A. Martin and colleagues investigate factors associated with SARS-CoV-2 vaccine uptake in a multi-ethnic healthcare workforce in UK.     

Immunogenicity,effectiveness and safety of COVID-19 vaccine in older adults living in nursing homes: A real-life study

IntroductionBNT162b2 (BioNTech and Pfizer) is a nucleoside-modified mRNA vaccine that provides protection against SARS-CoV-2 infection and is generally well tolerated. However, data about its efficacy, immunogenicity and safety in people of old age or with underlying chronic conditions are scarce.PurposeTo describe BNT162b2 (BioNTech and Pfizer) COVID-19 vaccine immunogenicity, effectiveness and reactogenicity after complete vaccination (two doses), and immunogenicity and reactogenicity after one booster, in elders residing in nursing homes (NH) and healthy NH workers in real-life conditions.MethodsObservational, ambispective, multicenter study. Older adults and health workers were recruited from three nursing homes of a private hospital corporation located in three Spanish cities. The primary vaccination was carried out between January and March 2021. The follow-up was 13 months. Humoral immunity, adverse events, SARS-CoV-2 infections, hospitalizations and deaths were evaluated. Cellular immunity was assessed in a participant subset.ResultsA total of 181 residents (mean age 84.1 years; 89.9% females, Charlson index ≥2: 45%) and 148 members of staff (mean age 45.2 years; 70.2% females) were surveyed (n:329). After primary vaccination of 327 participants, vaccine response in both groups was similar; ≈70% of participants, regardless of the group, had an antibody titer above the cut-off considered currently protective (260 BAU/ml). This proportion increased significantly to ≈ 98% after the booster (p < 0.0001 in both groups). Immunogenicity was largely determined by a prior history of COVID-19 infection. Twenty residents and 3 workers were tested for cellular immunity. There was evidence of cellular immunity after primary vaccination and after booster. During the study, one resident was hospitalized for SARS-CoV-2. No SARS-CoV-2-related deaths were reported and most adverse events were mild.ConclusionsOur results suggest that the BNT162b2 mRNA COVID-19 vaccine is immunogenic, effective and safe in elderly NH residents with underlying chronic conditions.     

Transmission and containment of the SARS-CoV-2 Delta variant of concern in Guangzhou,China: A population-based study

BackgroundThe first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak.Methodology/Principal findingsGuangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (R_t) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42–6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29–6.11) to 3.78 (95% CI: 2.74–4.81) days. The incubation period increased with age (P<0.001). A hierarchical prevention and control strategy against COVID-19 was implemented in Guangzhou, with R_t decreasing from 6.83 (95% credible interval [CrI]: 3.98–10.44) for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Individuals with partial or full vaccination schedules with BBIBP-CorV or CoronaVac accounted for 15.3% of the COVID-19 cases. Clinical symptoms were milder in partially or fully vaccinated cases than in unvaccinated cases (odds ratio [OR] = 0.26 [95% CI: 0.07–0.94]).Conclusions/SignificanceThe hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19.     

Cross-variant protection against SARS-CoV-2 infection in hamsters immunized with monovalent and bivalent inactivated vaccines

Rapid development and successful use of vaccines against SARS-CoV-2 might hold the key to curb the ongoing pandemic of COVID-19. Emergence of vaccine-evasive SARS-CoV-2 variants of concern (VOCs) has posed a new challenge to vaccine design and development. One urgent need is to determine what types of variant-specific and bivalent vaccines should be developed. Here, we compared homotypic and heterotypic protection against SARS-CoV-2 infection of hamsters with monovalent and bivalent whole-virion inactivated vaccines derived from representative VOCs. In addition to the ancestral SARS-CoV-2 Wuhan strain, Delta (B.1.617.2; δ) and Theta (P.3; θ) variants were used in vaccine preparation. Additional VOCs including Omicron (B.1.1.529) and Alpha (B.1.1.7) variants were employed in the challenge experiment. Consistent with previous findings, Omicron variant exhibited the highest degree of immune evasion, rendering all different forms of inactivated vaccines substantially less efficacious. Notably, monovalent and bivalent Delta variant-specific inactivated vaccines provided optimal protection against challenge with Delta variant. Yet, some cross-variant protection against Omicron and Alpha variants was seen with all monovalent and bivalent inactivated vaccines tested. Taken together, our findings support the notion that an optimal next-generation inactivated vaccine against SARS-CoV-2 should contain the predominant VOC in circulation. Further investigations are underway to test whether a bivalent vaccine for Delta and Omicron variants can serve this purpose.     

Hetero-bivalent nanobodies provide broad-spectrum protection against SARS-CoV-2 variants of concern including Omicron

SARS-CoV-2 variants with adaptive mutations have continued to emerge, causing fresh waves of infection even amongst vaccinated population. The development of broad-spectrum antivirals is thus urgently needed. We previously developed two hetero-bivalent nanobodies (Nbs), aRBD-2-5 and aRBD-2-7, with potent neutralization activity against the wild-type (WT) Wuhan isolated SARS-CoV-2, by fusing aRBD-2 with aRBD-5 and aRBD-7, respectively. Here, we resolved the crystal structures of these Nbs in complex with the receptor-binding domain (RBD) of the spike protein, and found that aRBD-2 contacts with highly-conserved RBD residues and retains binding to the RBD of the Alpha, Beta, Gamma, Delta, Delta plus, Kappa, Lambda, Omicron BA.1, and BA.2 variants. In contrast, aRBD-5 and aRBD-7 bind to less-conserved RBD epitopes non-overlapping with the epitope of aRBD-2, and do not show apparent binding to the RBD of some variants. However, when fused with aRBD-2, they effectively enhance the overall binding affinity. Consistently, aRBD-2-5-Fc and aRBD-2-7-Fc potently neutralized all of the tested authentic or pseudotyped viruses, including WT, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.1.1 and BA.2. Furthermore, aRBD-2-5-Fc provided prophylactic protection against the WT and mouse-adapted SARS-CoV-2 in mice, and conferred protection against the Omicron BA.1 variant in hamsters prophylactically and therapeutically, indicating that aRBD-2-5-Fc could potentially benefit the prevention and treatment of COVID-19 caused by the emerging variants of concern. Our strategy provides new solutions in the development of broad-spectrum therapeutic antibodies for COVID-19.Subject terms: X-ray crystallography, Innate immunity     

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.Subject terms: Mechanisms of disease, Molecular modelling     

Recipients of COVID-19 vaccines face challenges of SARS-CoV-2 variants

The coronavirus disease 19 (COVID-19) has been rampant since 2019, severely affecting global public health, and causing 5.75 million deaths worldwide. So far, many vaccines have been developed to prevent the infection of SARS-CoV-2 virus. However, the emergence of new variants may threat vaccine recipients as they might evade immunological surveillance that depends on the using of anti-SARS-CoV-2 antibody to neutralize the viral particles. Recent studies have found that recipients who received two doses of vaccination plus an additional booster shoot were able to quickly elevate neutralization response and immune response against wild-type SARS-CoV-2 virus and some initially appeared viral variants. In this review, we assessed the real-world effectiveness of different COVID-19 vaccines by population studies and neutralization assays and compared neutralization responses of booster vaccines in vitro. Finally, as the efficacy of COVID-19 vaccine is expected to decline over time, continued vaccination should be considered to achieve a long-term immune protection against coronavirus.