Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections.

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination.

Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study.

BACKGROUND: Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year. METHODS: This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19. FINDINGS: Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273). INTERPRETATION: Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination. FUNDING: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center.

Influenza prevalence and vaccine efficacy among diabetic patients in Qatar.

Seasonal influenza viruses may lead to severe illness and mortality in patients with comorbidities, including Diabetes Mellitus (DM). Vaccination against influenza in DM patients may reduce influenza incidence and severity. Before the emergence of the COVID-19 pandemic, influenza infections were the most prevalent respiratory infections in Qatar. Still, reports about influenza prevalence and vaccine efficacy in DM patients have not been reported. This study aimed to analyze influenza prevalence among other respiratory infections and assess influenza vaccine efficacy in DM patients in Qatar. Statistical analysis was performed on data obtained from Hamad Medical Corporation (HMC) database for patients that visited the emergency department (ED) with respiratory-like illnesses. The analysis was done for the period between January 2016 to December 2018. Among 17,525 patients who visited HMC-ED with clinical symptoms of respiratory infections, 2611(14.9%) were reported to have DM. Among DM patients, influenza was the most prevalent respiratory pathogen at 48.9%. Influenza virus A (IVA) was the most circulating type, contributing to 38.4%, followed by IVB contributing to 10.4% of total respiratory infections. Among the typed IVA-positive cases, 33.4% were H1N1, and 7.7% were H3N2. A significant decrease in influenza infections was reported in vaccinated DM patients (14.5%) when compared to non-vaccinated patients (18.9%) (p-value = 0.006). However, there was no significant relaxation in the clinical symptoms among vaccinated DM patients compared to their non-vaccinated counterparts. In conclusion, influenza was the most common etiology for respiratory viral infection among diabetic patients at the leading healthcare provider in Qatar. Although vaccination reduced the incidence rate among DM patients, it was less effective in preventing symptoms. Further studies on a larger cohort and for a more extended period are required to investigate influenza prevalence and vaccine efficacy among DM patients.

A new One Health Framework in Qatar for future emerging and re-emerging zoonotic diseases preparedness and response.

One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022-2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface.

Protection from previous natural infection compared with mRNA vaccination against SARS-CoV-2 infection and severe COVID-19 in Qatar: a retrospective cohort study.

BACKGROUND: Understanding protection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination is important for informing vaccine mandate decisions. We compared protection conferred by natural infection versus that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar. METHODS: We conducted two matched retrospective cohort studies that emulated target trials. Data were obtained from the national federated databases for COVID-19 vaccination, SARS-CoV-2 testing, and COVID-19-related hospitalisation and death between Feb 28, 2020 (pandemic onset in Qatar) and May 12, 2022. We matched individuals with a documented primary infection and no vaccination record (natural infection cohort) with individuals who had received two doses (primary series) of the same vaccine (BNT162b2-vaccinated or mRNA-1273-vaccinated cohorts) at the start of follow-up (90 days after the primary infection). Individuals were exact matched (1:1) by sex, 10-year age group, nationality, comorbidity count, and timing of primary infection or first-dose vaccination. Incidence of SARS-CoV-2 infection and COVID-19-related hospitalisation and death in the natural infection cohorts was compared with incidence in the vaccinated cohorts, using Cox proportional hazards regression models with adjustment for matching factors. FINDINGS: Between Jan 5, 2021 (date of second-dose vaccine roll-out) and May 12, 2022, 104 500 individuals vaccinated with BNT162b2 and 61 955 individuals vaccinated with mRNA-1273 were matched to unvaccinated individuals with a documented primary infection. During follow-up, 7123 SARS-CoV-2 infections were recorded in the BNT162b2-vaccinated cohort and 3583 reinfections were recorded in the matched natural infection cohort. 4282 SARS-CoV-2 infections were recorded in the mRNA-1273-vaccinated cohort and 2301 reinfections were recorded in the matched natural infection cohort. The overall adjusted hazard ratio (HR) for SARS-CoV-2 infection was 0·47 (95% CI 0·45-0·48) after previous natural infection versus BNT162b2 vaccination, and 0·51 (0·49-0·54) after previous natural infection versus mRNA-1273 vaccination. The overall adjusted HR for severe (acute care hospitalisations), critical (intensive care unit hospitalisations), or fatal COVID-19 cases was 0·24 (0·08-0·72) after previous natural infection versus BNT162b2 vaccination, and 0·24 (0·05-1·19) after previous natural infection versus mRNA-1273 vaccination. Severe, critical, or fatal COVID-19 was rare in both the natural infection and vaccinated cohorts. INTERPRETATION: Previous natural infection was associated with lower incidence of SARS-CoV-2 infection, regardless of the variant, than mRNA primary-series vaccination. Vaccination remains the safest and most optimal tool for protecting against infection and COVID-19-related hospitalisation and death, irrespective of previous infection status. FUNDING: The Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, Weill Cornell Medicine-Qatar; Qatar Ministry of Public Health; Hamad Medical Corporation; Sidra Medicine; Qatar Genome Programme; and Qatar University Biomedical Research Center.

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.).

Comparative analysis of within-host diversity among vaccinated COVID-19 patients infected with different SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly evolving RNA virus that mutates within hosts and exists as viral quasispecies. Here, we evaluated the within-host diversity among vaccinated and unvaccinated individuals (n = 379) infected with different SARS-CoV-2 Variants of Concern. The majority of samples harbored less than 14 intra-host single-nucleotide variants (iSNVs). A deep analysis revealed a significantly higher intra-host diversity in Omicron samples than in other variants (p value < 0.05). Vaccination status and type had a limited impact on intra-host diversity except for Beta-B.1.315 and Delta-B.1.617.2 vaccinees, who exhibited higher diversity than unvaccinated individuals (p values: <0.0001 and <0.0021, respectively). Three immune-escape mutations were identified: S255F in Delta and R346K and T376A in Omicron-B.1.1.529. The latter 2 mutations were fixed in BA.1 and BA.2 genomes, respectively. Overall, the relatively higher intra-host diversity among vaccinated individuals and the detection of immune-escape mutations, despite being rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals.

Duration of immune protection of SARS-CoV-2 natural infection against reinfection.

BACKGROUND: The future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection, and protection against severe reinfection, in Qatar, between February 28, 2020 and June 5, 2022. METHODS: Three national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naïve and unvaccinated. Associations were estimated using Cox proportional-hazard regression models. RESULTS: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% CI: 84.8-86.2%). Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~ 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical, or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age. CONCLUSIONS: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.

Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections

In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness in small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination.

Severity, Criticality, and Fatality of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Beta Variant.

Beta (B.1.351)-variant coronavirus disease 2019 (COVID-19) disease was investigated in Qatar. Compared with the Alpha (B.1.1.7) variant, odds (95% confidence interval) of progressing to severe disease, critical disease, and COVID-19-related death were 1.24-fold (1.11-1.39), 1.49-fold (1.13-1.97), and 1.57-fold (1.03-2.43) higher, respectively, for the Beta variant.

COVID-19 Disease Severity in Persons Infected With Omicron BA.1 and BA.2 Sublineages and Association With Vaccination Status.

This retrospective study compares the severity of SARS-CoV-2 infection among persons infected with BA.1 and BA.2 sublineages by vaccination status.

Protection of Omicron sub-lineage infection against reinfection with another Omicron sub-lineage.

There is significant genetic distance between SARS-CoV-2 Omicron (B.1.1.529) variant BA.1 and BA.2 sub-lineages. This study investigates immune protection of infection with one sub-lineage against reinfection with the other sub-lineage in Qatar during a large BA.1 and BA.2 Omicron wave, from December 19, 2021 to March 21, 2022. Two national matched, retrospective cohort studies are conducted to estimate effectiveness of BA.1 infection against reinfection with BA.2 (N = 20,994; BA.1-against-BA.2 study), and effectiveness of BA.2 infection against reinfection with BA.1 (N = 110,315; BA.2-against-BA.1 study). Associations are estimated using Cox proportional-hazards regression models after multiple imputation to assign a sub-lineage status for cases with no sub-lineage status (using probabilities based on the test date). Effectiveness of BA.1 infection against reinfection with BA.2 is estimated at 94.2% (95% CI: 89.2-96.9%). Effectiveness of BA.2 infection against reinfection with BA.1 is estimated at 80.9% (95% CI: 73.1-86.4%). Infection with the BA.1 sub-lineage appears to induce strong, but not full immune protection against reinfection with the BA.2 sub-lineage, and vice versa, for at least several weeks after the initial infection.

COVID-19 risk score as a public health tool to guide targeted testing: A demonstration study in Qatar.

We developed a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar. The Qatar national COVID-19 testing database, encompassing a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021, was analyzed. Logistic regression analyses were implemented to derive the COVID-19 risk score, as a tool to identify those at highest risk of having the infection. Score cut-off was determined using the ROC curve based on maximum sum of sensitivity and specificity. The score's performance diagnostics were assessed. Logistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The ROC curve was generated and the area under the curve was estimated at 0.63 (95% CI: 0.63-0.63). The score had a sensitivity of 59.4% (95% CI: 59.1%-59.7%), specificity of 61.1% (95% CI: 61.1%-61.2%), a positive predictive value of 10.9% (95% CI: 10.8%-10.9%), and a negative predictive value of 94.9% (94.9%-95.0%). The concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources.

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.