Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar.

BACKGROUND: Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear. METHODS: We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19-related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022. The association of booster status with infection was estimated with the use of Cox proportional-hazards regression models. RESULTS: In a population of 2,239,193 persons who had received at least two doses of BNT162b2 or mRNA-1273 vaccine, those who had also received a booster were matched with persons who had not received a booster. Among the BNT162b2-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 2.4% (95% confidence interval [CI], 2.3 to 2.5) in the booster cohort and 4.5% (95% CI, 4.3 to 4.6) in the nonbooster cohort after 35 days of follow-up. Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19-related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1). Among the mRNA-1273-vaccinated persons, the cumulative incidence of symptomatic omicron infection was 1.0% (95% CI, 0.9 to 1.2) in the booster cohort and 1.9% (95% CI, 1.8 to 2.1) in the nonbooster cohort after 35 days; booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273-vaccinated cohorts. CONCLUSIONS: The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19-related hospitalization and death. (Funded by Weill Cornell Medicine-Qatar and others.).

Covid-19 Vaccine Protection among Children and Adolescents in Qatar.

BACKGROUND: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses. METHODS: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies - one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models. RESULTS: Among children, the overall effectiveness of the 10-µg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-µg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-µg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose. CONCLUSIONS: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.).

Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections.

BACKGROUND: The protection conferred by natural immunity, vaccination, and both against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the BA.1 or BA.2 sublineages of the omicron (B.1.1.529) variant is unclear. METHODS: We conducted a national, matched, test-negative, case-control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19). RESULTS: The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-1.1%; 95% CI, -7.1 to 4.6), but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection and two doses of BNT162b2 was 55.1% (95% CI, 50.9 to 58.9), and the effectiveness of previous infection and three doses of BNT162b2 was 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273. CONCLUSIONS: No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine-Qatar and others.).

Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar.

BACKGROUND: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear. METHODS: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021. RESULTS: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months. CONCLUSIONS: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).

Coronavirus Disease 2019 Disease Severity in Children Infected With the Omicron Variant.

SHORT SUMMARY: Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old. BACKGROUND: There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. METHODS: We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score-matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days. RESULTS: Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score-matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI], .07-.18). Those aged 6-11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI, .33-.66 for 6-11 year olds; aOR, 0.45; 95% CI, .21-.94 for 12 to <18 year olds). CONCLUSIONS: Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old.

Severity of Illness in Persons Infected With the SARS-CoV-2 Delta Variant vs Beta Variant in Qatar.

Importance: The Delta variant is now the predominant circulating SARS-CoV-2 strain worldwide. Severity of illness in persons infected with the SARS-CoV-2 Delta variant compared with the Beta variant is not known. Objective: To directly compare clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs those infected with the Beta variant in Qatar. Design, Setting, and Participants: This retrospective cohort study used data from the national COVID-19 database in Qatar, which includes information on all individuals who were ever tested for SARS-CoV-2 using a reverse transcriptase-polymerase chain reaction test and all individuals who received any SARS-CoV-2 vaccine in Qatar. Among persons with confirmed SARS-CoV-2 infection between March 22 and July 7, 2021, those infected with the Delta variant were identified and were propensity score matched with control individuals infected with the Beta variant. The variants were ascertained by variant genotyping of the positive samples. Exposures: SARS-CoV-2 infection with the Delta or Beta variant. Main Outcomes and Measures: The main outcomes were admission to the hospital, admission to the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, or death among those infected with the Delta or Beta variant overall and stratified by vaccination status. Results: Among 1427 persons infected with the Delta variant (252 [55.9%] male; median age, 34 years [IQR, 17-43 years]) and 5353 persons infected with the Beta variant (233 [51.7%] male; median age, 34 years [IQR, 17-45 years]), 451 propensity score-matched pairs were identified. Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4-24.0]; P = .01) or to have mild-moderate or severe-critical disease outcomes (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with persons infected with the Beta variant. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (adjusted odds ratio [aOR], 2.53; 95% CI, 1.72-3.72). Compared with being unvaccinated, being vaccinated with a second dose more than 3 months before infection was associated with lower odds of any adverse outcome among persons infected with the Delta variant (aOR, 0.11; 95% CI, 0.04-0.26) and among those infected with the Beta variant (aOR, 0.22; 95% CI, 0.05-0.98). Protection was similar among those who received a second vaccine dose less than 3 months before infection, but having received only a single dose was not associated with a lower odds of any severe outcome among those infected with the Delta variant (aOR, 1.12; 95% CI, 0.41-3.06) or those infected with the Beta variant (aOR, 0.74; 95% CI, 0.20-2.72). Conclusions and Relevance: In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

COVID-19 disease severity in persons infected with the Omicron variant compared with the Delta variant in Qatar.

Background: Understanding the disease severity associated with the Omicron variant of the SARS-CoV-2 virus is important in determining appropriate management strategies at the individual and population levels. We determined the severity of SARS-CoV-2 infection in persons infected with the Omicron vs the Delta variant. Methods: We identified individuals with SARS-CoV-2 infection with Delta and propensity-score matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. We excluded temporary visitors to Qatar, those with a prior documented infection, those ≤18 years old, and those with <14 days of follow up after the index test positive date. We determined the rates of admission to the hospital, admission to intensive care unit, mechanical ventilation, or death among those infected with the Delta or Omicron variants. Results: Among 9763 cases infected with the Delta variant and 11 310 cases infected with the Omicron variant, we identified 3926 propensity-score matched pairs. Among 3926 Delta infected, 3259 (83.0%) had mild, 633 (16.1%) had moderate and 34 (0.9%) had severe/critical disease. Among 3926 Omicron infected, 3866 (98.5%) had mild, 59 (1.5%) had moderate, and only 1 had severe/critical disease (overall P < 0.001). Factors associated with less moderate or severe/critical disease included infection with Omicron variant (aOR = 0.06; confidence interval (CI) = 0.05-0.09) and vaccination including a booster (aOR = 0.30; 95% CI = 0.09-0.99). Conclusions: Omicron variant infection is associated with significantly lower severity of disease compared with the Delta variant. Vaccination continues to offer strong protection against severe/critical disease.

Duration of COVID-19 mRNA Vaccine Effectiveness against Severe Disease.

Waning immunity following administration of mRNA-based COVID-19 vaccines remains a concern for many health systems. We undertook a study to determine if recent reports of waning for severe disease could have been attributed to design-related bias by conducting a study only among those detected with a first SARS-CoV-2 infection. We used a matched case-control study design with the study base being all individuals with first infection with SARS-CoV-2 reported in the State of Qatar between 1 January 2021 and 20 February 2022. Cases were those detected with first SARS-CoV-2 infection requiring intensive care (hard outcome), while controls were those detected with first SARS-CoV-2 infection who recovered without the need for intensive care. Cases and controls were matched in a 1:30 ratio for the calendar month of infection and the comorbidity category. Duration and magnitude of conditional vaccine effectiveness against requiring intensive care and the number needed to vaccinate (NNV) to prevent one more case of COVID-19 requiring intensive care was estimated for the mRNA (BNT162b2/mRNA-1273) vaccines. Conditional vaccine effectiveness against requiring intensive care was 59% (95% confidence interval (CI), 50 to 76) between the first and second dose, and strengthened to 89% (95% CI, 85 to 92) between the second dose and 4 months post the second dose in persons who received a primary course of the vaccine. There was no waning of vaccine effectiveness in the period from 4 to 6, 6 to 9, and 9 to 12 months after the second dose. This study demonstrates that, contrary to mainstream reports using hierarchical measures of effectiveness, conditional vaccine effectiveness against requiring intensive care remains robust till at least 12 months after the second dose of mRNA-based vaccines.

SARS-CoV-2 vaccine effectiveness in preventing confirmed infection in pregnant women.

BackgroundSARS-CoV-2 infection in pregnancy is associated with a higher risk of pregnancy-related complications and neonatal respiratory distress and hospitalization. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known.MethodsAll women with confirmed pregnancy who presented to the national referral hospital in Qatar between December 20, 2020, and May 30, 2021, with at least 1 SARS-CoV-2 test and not testing prior to pregnancy were included. We determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection during pregnancy using both cohort and test-negative case-control designs. Analyses were adjusted for age group, nationality, and gestational age.ResultsAmong 4534 pregnant women, there were 407 vaccinated and 407 unvaccinated women in the matched cohort analysis. Vaccine effectiveness was 87.6% (95%CI 44.1%-97.2%) at least 14 days after the second dose. There were 386 test-positive and 834 matched women in the test-negative case control analysis. Vaccine effectiveness was 86.8% (95%CI 47.5%-98.5%) at least 14 days after the second dose. Adjustment for age, nationality, and gestational age yielded similar results for both designs. In the test-negative analysis, vaccine effectiveness at least 14 days after the first dose but before the second dose was 40.8% (95% CI 0.0%-80.4%). Of the 386 test-positive pregnant women, 74 cases were Alpha variant, 163 cases were Beta variant, and 156 cases were variants of unknown status. There were 9 severe or critical disease cases and no deaths in the test-positive pregnant women, all of whom were unvaccinated.ConclusionThe mRNA vaccines provide a high level of protection against documented SARS-CoV-2 infection, which supports the inclusion of pregnant women in vaccination campaigns.FUNDINGHamad Medical Corporation, Weill Cornell Medicine Qatar, and the Ministry of Public Health Qatar.

Outcomes Among Patients with Breakthrough SARS-CoV-2 Infection After Vaccination.

BACKGROUND: Breakthrough infections after SARS-CoV-2 vaccination have been reported. Clinical outcomes in these persons are not widely known. METHODS: We evaluated all vaccinated persons with breakthrough infection ≥14 days after the second vaccine dose and unvaccinated controls matched on age, sex, nationality, and reason for testing between December 23, 2020 and March 28, 2021 in Qatar. Our primary outcome was severe disease defined as hospitalization, mechanical ventilation, or death. RESULTS: Among 456 persons cases of breakthrough infection and 456 unvaccinated matched controls with confirmed infection, median age was 45 years, 60.7% were males, and ≥1 comorbid condition was present in 61.2% of the vaccinated and 47.8% of the unvaccinated persons (P=0.009). Severe disease was recorded in 48 (10.5%) of the vaccinated and 121 (26.5%) of the unvaccinated group (P<0.001). Factors associated with severe disease included increasing age (HR vs. <40 years old: >40-60 years, HR 2.32; >60-70 years, HR 4.34; >70 years, HR 5.43); presence of symptoms at baseline (HR 2.42, 95%CI 1.44-4.07); and being unvaccinated (HR 2.84, 95%CI 1.80-4.47). CONCLUSIONS: In persons with breakthrough SARS-CoV-2 infection, increasing age is associated with a higher risk of severe disease or death, while vaccination is associated with a lower risk. Presence of comorbidities was not associated with severe disease or death among persons with breakthrough infection.

Risk factors for breakthrough SARS-CoV-2 infection in vaccinated healthcare workers.

BACKGROUND AND OBJECTIVE: The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar. METHODS: We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection. RESULTS: Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection. CONCLUSION: Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination.