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.

Nanomedicine as a Potential Tool against Monkeypox.

Human monkeypox is a rare viral zoonosis that was first identified in 1970; since then, this infectious disease has been marked as endemic in central and western Africa. The disease has always been considered rare and self-limiting; however, recent worldwide reports of several cases suggest otherwise. Especially with monkeypox being recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era, its spread across the globe marks a new epidemic. Currently, there is no proven treatment for human monkeypox, and questions about the necessity of developing a vaccine persist. Notably, if we are to take lessons from the COVID-19 pandemic, developing a nanomedicine-based preventative strategy might be prudent, particularly with the rapid growth of the use of nanotechnology and nanomaterials in medical research. Unfortunately, the collected data in this area is limited, dispersed, and often incomplete. Therefore, this review aims to trace all reported nanomedicine approaches made in the monkeypox area and to suggest possible directions that could be further investigated to develop a counteractive strategy against emerging and existing viruses that could diminish this epidemic and prevent it from becoming a potential pandemic, especially with the world still recovering from the COVID-19 pandemic.

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.

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.

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.).

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.

Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar.

SARS-CoV-2 Omicron BA.1 and BA.2 subvariants are genetically divergent. We conducted a matched, test-negative, case-control study to estimate duration of protection of the second and third/booster doses of mRNA COVID-19 vaccines against BA.1 and BA.2 infections in Qatar. BNT162b2 effectiveness was highest at 46.6% (95% CI: 33.4-57.2%) against symptomatic BA.1 and at 51.7% (95% CI: 43.2-58.9%) against symptomatic BA.2 infections in the first three months after the second dose, but declined to ~10% or below thereafter. Effectiveness rebounded to 59.9% (95% CI: 51.2-67.0%) and 43.7% (95% CI: 36.5-50.0%), respectively, in the first month after the booster dose, before declining again. Effectiveness against COVID-19 hospitalization and death was 70-80% after the second dose and >90% after the booster dose. mRNA-1273 vaccine protection showed similar patterns. mRNA vaccines provide comparable, moderate, and short-lived protection against symptomatic BA.1 and BA.2 Omicron infections, but strong and durable protection against COVID-19 hospitalization and death.

Burden and disease pathogenesis of influenza and other respiratory viruses in diabetic patients.

Over the past two decades, diabetes mellitus (DM) has been receiving increasing attention among autoimmune diseases. The prevalence of type 1 and type 2 diabetes has increased rapidly and has become one of the leading causes of death worldwide. Therefore, a better understanding of the genetic and environmental risk factors that trigger the onset of DM would help develop more efficient therapeutics and preventive measures. The role and mechanism of respiratory viruses in inducing autoimmunity have been frequently reported. On the other hand, the association of DM with respiratory infections might result in severe complications or even death. Since influenza is the most common respiratory infection, DM patients experience disease severity and increased hospitalization during influenza season. Vaccinating diabetic patients against influenza would significantly reduce hospitalization due to disease severity. However, recent studies also report the role of viral vaccines in inducing autoimmunity, specifically diabetes. This review reports causes of diabetes, including genetic and viral factors, with a special focus on respiratory viruses. We further brief the burden of influenza-associated complications and the effectiveness of the influenza vaccine in DM patients.