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ObjectivesTo estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance.DesignRetrospective, test-negative, case-control study, with matched analysis.SettingProvince of Buenos Aires, Argentina, between 12/1/21-4/1/21.Participants422,144 individuals ≥50 years who had received two or three doses of COVID-19 vaccines and were tested for SARS-CoV-2.Main outcome measures: Odds ratios of confirmed SARS-CoV-2 infection, hospitalisations and death after administering different boosters, compared to a two-dose primary scheme.ResultsOf 221,933(52.5%) individuals with a positive test, 190,884(45.2%) had received a two-dose vaccination scheme and 231,260(54.8%) a three-dose scheme. The matched analysis included 127,014 cases and 180,714 controls.The three-dose scheme reduced infections (OR 0.81[0.80-0.83]) but after 60 days protection dropped (OR 1.04[1.01-1.06]). The booster dose decreased the risk of hospitalisations and deaths after 15-59 days (ORs 0.28[0.25-0.32] and 0.25[0.22-0.28] respectively), which persisted after administration for 75[66-89] days.Administration of a homologous booster after a primary scheme with vectored-vaccines provided low protection against infections (OR 0.94[0.92-0.97] and 1.05[1.01-1.09] before and after 60 days). Protection against hospitalisations and death was significant (OR 0.30[0.26-0.35] and 0.29[0.25-0.33] respectively) but decreased after 60 days (OR 0.59[0.47-0.74] and 0.51[0.41- 0.64] respectively).The inoculation of a heterologous booster after a primary course with ChAdOx1 nCoV-19, rAd26-rAd5, BBIBP-CorV, or heterologous schemes, offered some protection against infection (OR 0.70[0.68-0.71]), which decreased after 60 days (OR 1.01[0.98-1.04]). The protective effect against hospitalisations and deaths (OR 0.26[0.22-0.31] and 0.22[0.18-0.25] respectively) was clear and persisted after 60 days (OR 0.43[0.35-0.53] and 0.33[0.26-0.41]).ConclusionsThis study shows that, during Omicron predominance, heterologous boosters provide an enhanced protection and longer effect duration against COVID-19-related hospitalisations and death in individuals older than 50, compared to homologous boosters.

BackgroundAlthough paediatric clinical presentations of COVID-19 are usually less severe than in adults, serious illness and death have occurred. Many countries started the vaccination rollout of children in 2021; still, information about effectiveness in the real-world setting is scarce. The aim of our study was to evaluate vaccine effectiveness (VE) against COVID-19-associated-hospitalisations in the 3-17-year population during the Omicron outbreak.MethodsWe conducted a retrospective cohort study including individuals aged 3-17 registered in the online vaccination system of the Buenos Aires Province, Argentina. mRNA-1273 and BNT162b2 were administered to 12-17-year subjects; and BBIBP-CorV to 3-11- year subjects. Vaccinated group had received a two-dose scheme by 12/1/2021. Unvaccinated group did not receive any COVID-19 vaccine between 12/14/2021-3/9/2022, which was the entire monitoring period. Vaccine effectiveness (VE) against COVID-19-associated hospitalisations was calculated as (1-OR) x100.FindingsBy 12/1/2021, 1,536,435 individuals aged 3-17 who had received zero or two doses of SARS-CoV-2 vaccines were included in this study. Of the latter, 1,440,389 were vaccinated and 96,046 not vaccinated. VE were 78·0% [68·7-84·2], 76·4%[62·9-84·5] and 80·0%[64·3-88·0] for the entire cohort, 3-11 subgroup and 12-17 subgroup, respectively. VE for the entire population was 82·7% during the period of Delta and Omicron overlapping circulation and decreased to 67·7% when Omicron was the only variant present.InterpretationThis report provides evidence of high vaccine protection against associated-hospitalisations in the paediatric population during the Omicron outbreak but suggests a decrease of protection when Omicron became predominant. Application of a booster dose in children aged 3-11 warrants further consideration.Research in contextEvidence before this studyThere is limited evidence on the effectiveness of vaccines in the pediatric population, particularly in children aged 3-11 years after the SARS-CoV-2 B.1.1.529 (Omicron) variant’s emergence.We searched preprint and peer-reviewed published articles in PubMed, medRxiv, and SSRN for observational studies, with no language restrictions, using the term “COVID-19 OR SARS-CoV-2” AND “vaccine effectiveness” OR “vaccine impact” AND “children” OR “pediatric” AND “Omicron” published between December 1, 2021, and April 1, 2022. We found 4 studies that included subjects in the 3-17-year population who received a two-dose-scheme of any of the available vaccines-according to each country’s authorisation. Three studies were from the US; two were test-negative-case-control studies and one was a retrospective non-peer-reviewed cohort study. The reported vaccine effectiveness (VE) for 2-doses of BNT162b2-mRNA (Pfizer-BioNTech) in preventing hospitalisations during Omicron predominance was 48-78%; and it was 40-92% for 5-11 and 12-17-year subgroups, respectively. The fourth was a cohort study still in preprint form conducted in Chile and utilized an inactivated vaccine, CoronaVac (SinoVac), widely used in Latin-America. VE for two doses of CoronaVac in the 3-5-year subgroup against hospitalisations was 64% and 69% against ICU admissions.Added value of this studyUp to date, there are no published studies about the effectiveness of the BBIBP-CorV vaccine against hospitalisation in the pediatric population. Additionally, there are no real-world studies from low and middle-income countries about VE in the 12-17 aged population during the Omicron outbreak.This study shows that VE after 14 days or more from two-dose-scheme was 78·0% [68·7-84·2], 76·4% [62·9-84·5] and 80·0% [64·3-88·0] for the 3-17-year entire group, and for 3-11-year (BBIBP-CorV) and 12-17-year (mRNA vaccines) subgroups, respectively. VE for the 3-17-year entire group was 82·7% during the period of Delta and Omicron overlapping circulation and decreased to 67·7% when Omicron was the only variant present. These effects were consistent across all subgroups.Implications of all the available evidenceOur results provide evidence of high vaccine protection against COVID-19 associated-hospitalisations in the pediatric population during the Omicron outbreak, but suggest a decrease of protection when Omicron became predominant. Application of a booster dose in children aged 3-11 warrants further consideration.

Objective To estimate the effectiveness of a two dose vaccine schedule (mRNA-1273, BNT162b2, and BBIBP-CorV) against SARS-CoV-2 infection and covid-19 related death and short term waning of immunity in children (3-11 years old) and adolescents (12-17 years old) during periods of delta and omicron variant predominance in Argentina. Design Test negative, case-control study. Setting Database of the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina. Participants 844 460 c hildren and adolescents without previous SARS-CoV-2 infection eligible to receive primary vaccination schedule who were tested for SARS-CoV-2 by polymerase chain reaction or rapid antigen test from September 2021 to April 2022. After matching with their corresponding controls, 139 321 (60.3%) of 231 181 cases remained for analysis. Exposures Two dose mRNA-1273, BNT162b2, and BBIBP-CorV vaccination schedule. Main outcome measures SARS-CoV-2 infection and covid-19 related death. Conditional logistic regression was used to estimate the odds of SARS-CoV-2 infection among two dose vaccinated and unvaccinated participants. Vaccine effectiveness was estimated as (1–odds ratio)×100%. Results Estimated vaccine effectiveness against SARS-CoV-2 infection was 61.2% (95% confidence interval 56.4% to 65.5%) in children and 66.8% (63.9% to 69.5%) in adolescents during the delta dominant period and 15.9% (13.2% to 18.6%) and 26.0% (23.2% to 28.8%), respectively, when omicron was dominant. Vaccine effectiveness declined over time, especially during the omicron period, from 37.6% (34.2% to 40.8%) at 15-30 days after vaccination to 2.0% (1.8% to 5.6%) after ≥60 days in children and from 55.8% (52.4% to 59.0%) to 12.4% (8.6% to 16.1%) in adolescents. Vaccine effectiveness against death related to SARS-CoV-2 infection during omicron predominance was 66.9% (6.4% to 89.8%) in children and 97.6% (81.0% to 99.7%) in adolescents. Conclusions Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time. Trial registration National Registry of Health Research IS003720.

Background A first-dose of various vaccines provides acceptable protection against infections by SARS-CoV-2 and evolution to the most severe forms of COVID-19. The recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), was proven efficacious but information about effectiveness in the real-world setting is lacking. The aim of our study was to investigate the association between the rollout of the first component (rAd26) of Gam-COVID-Vac and PCR-positive tests, hospitalisations and deaths. Methods We conducted a retrospective cohort study which analyzed individuals aged 60-79 who self-registered in the online vaccination system of the Province of Buenos Aires, Argentina, from December 29, 2020 to March 21, 2021. Exclusion criteria were having a previous positive RT-PCR or antigen tests for SARS-CoV-2, having received other vaccines, or two doses of any vaccine. Proportions of new laboratory-confirmed SARS-CoV-2 infections, hospitalisations and deaths until 83 days of vaccination were compared between vaccinated and unvaccinated subjects. Vaccine effectiveness for the three outcomes was calculated as (1–OR) × 100. Kaplan-Meier cumulative incidence curves were constructed. Findings During the study period 415995 registered subjects received the first component of Gam-COVID-Vac; 40387 belonged to the 60-79 age group, and were compared to 38978 unvaccinated. Vaccine effectiveness for preventing laboratory-confirmed infections was 78•6% [CI95% 74·8 - 81·7]; and for reducing hospitalizations and deaths was, respectively, 87·6% [CI95% 80·3 - 92·2] and 84·8% [CI95% 75·0 - 90·7]. Effectiveness was high across all subgroups. Interpretation Similarly to other vaccines, the administration of one dose of Gam-COVID-Vac was effective for a wide range of COVID-19–related outcomes., Facultad de Ciencias Médicas

Fil: Sanchis, Pablo Antonio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Quimica Biologica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Quimica Biologica de la Facultad de Ciencias Exactas y Naturales; Argentina

Cancer is a risk factor for SARS-CoV-2 infection. Recent reports have shown that prostate cancer (PCa) patients undergoing androgen-deprivation therapies (ADT) were partially protected from COVID-19. The human myxovirus resistance gene 1 (MX1) is expressed in many tissues, including prostate, and we have previously demonstrated its antitumoral activity in PCa. This protein participates in the antiviral response and it is an IFN-stimulated gene (ISGs), especially during influenza virus infection. There are ongoing clinical trials for COVID-19 prevention and/or treatment using type I or III interferons. However, IFN administration could enhance a "cytokine-storm" causing a hyper-inflammatory response and contributing to organ failure. In this work, we performed bioinformatics analyses in a case-control study from SARS-CoV-2 positive (n=403) and negative (n=50) patients. We analyzed the response to infection assessing gene expression profiles in nasopharyngeal swabs of key host cell receptors (ACE2, TMPRSS2, BSG/CD147, CTSB, CTSL, ADAM17) and antiviral proteins (MX1, MX2, NRF2, IRF3, HIF1A, HMOX1).SARS-CoV-2 positive cases had higher ACE2, but lower TMPRSS2, BSG/CD147 and CTSB expression. Patient age negatively affected ACE2 expression. MX1 and MX2 were higher in SARS-CoV-2 positive individuals, and negative trends were observed as patients' age increased. Principal Component Analysis determined that ACE2, MX1, MX2 and BSG/CD147 expressions were able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment.Given that MX1 was differentially expressed between COVID-19 and non-COVID-19 patients, we evaluated MX1 expression in A549 and Calu3 lung cell lines. MX1 was significantly up-regulated upon infection with SARS-CoV-2.Since ADT reduces SARS-CoV-2 infection incidence, we aim to study MX1 regulation by dihydrotestosterone (DHT). We browsed publicly available ChIP-seq experiments evaluating androgen receptor (AR) binding sites in different PCa cell lines under DHT stimulation. Results indicated enriched AR binding sites on the MX1 sequence. Therefore, we treated LNCaP cells with DHT, observing a significant decrease in MX1 mRNA levels. Accordingly, we observed a significant increase of MX1 gene expression in PCa patients after ADT treatment.In summary, our study findings support differences in ACE2, MX1, MX2 and BSG/CD147 expression between COVID-19 and non-COVID-19 patients; and point out to MX1 as a critical responder in SARS-CoV-2 infection. Furthermore, we demonstrated MX1 modulation by ADT. Taking into consideration the fact that PCa patients that underwent ADT were less prone to present the infection, we propose this gene as an alternative druggable target for COVID-19 patients, especially those with PCa as a previous condition. Citation Format: Juan Antonio Bizzotto, Pablo Sanchis, Sofia Lage-Vickers, Rosario Lavignolle, Agustina Sabater, Mercedes Abbate, Ayelen Toro, Florencia Cascardo, Santiago Olszevicki, Nicolas Anselmino, Estefania Labanca, Emiliano Ortiz, Elba Vazquez, Javier Cotignola, Geraldine Gueron. Androgen-deprivation therapy boosts MX1 expression, a silent effector against COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 710.

In a published case-control study (GSE152075) from SARS-CoV-2 positive (n=403) and negative patients (n=50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher ACE2, but lower TMPRSS2, BSG/CD147 and CTSB expression compared with negative cases. COVID-19 patients’ age negatively affected ACE2 expression. MX1 and MX2 were higher in COVID-19 patients. A negative trend for MX1 and MX2 was observed as patients’ age increased. Principal Component Analysis determined that ACE2, MX1, MX2, and BSG/CD147 expression was able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that MX1 expression significantly increased for each unit of viral load increment. Altogether, these findings support differences in ACE2, MX1, MX2, and BSG/CD147 expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection., Graphical Abstract, HIGHLIGHTS ● COVID-19 patients present a distinct expression pattern for antiviral genes. ● MX1 antiviral gene expression is triggered by SARS-CoV-2. ● MX1 can be induced by hemin, a FDA-approved drug. ● MX1 raises as a potential druggable target.