Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the Omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

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.

Effectiveness of BBIBP-CorV, BNT162b2 and mRNA-1273 vaccines against hospitalisations among children and adolescents during the Omicron outbreak in Argentina

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{middle dot}0% [68{middle dot}7-84{middle dot}2], 76{middle dot}4%[62{middle dot}9-84{middle dot}5] and 80{middle dot}0%[64{middle dot}3-88{middle dot}0] for the entire cohort, 3-11 subgroup and 12-17 subgroup, respectively. VE for the entire population was 82{middle dot}7% during the period of Delta and Omicron overlapping circulation and decreased to 67{middle dot}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 contextO_ST_ABSEvidence before this studyC_ST_ABSThere 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) variants 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 countrys 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{middle dot}0% [68{middle dot}7-84{middle dot}2], 76{middle dot}4% [62{middle dot}9-84{middle dot}5] and 80{middle dot}0% [64{middle dot}3-88{middle dot}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{middle dot}7% during the period of Delta and Omicron overlapping circulation and decreased to 67{middle dot}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.

Temporal Increase in Neutralization Potency of SARS-CoV-2 Antibodies and Reduced Viral Variant Escape after Sputnik V Vaccination

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOCs: Alpha, Beta, Gamma, and Delta) and a local variant of interest (VOI: Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. A collection of 472 serum samples obtained between January and September 2021 was used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity to the first-wave linages of SARS-CoV-2 and VOC are maintained within four months of vaccination. In addition, an improved antibody cross-neutralizing ability to circulating variants of concern (Beta, Gamma and Delta) was observed over time of vaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least four month and show a reduction of VOC escape over time of vaccination.

Timing of Convalescent plasma administration and 28-day mortality for COVID-19 pneumonia.

Convalescent plasma administration (CPA) is widely used to treat Covid-19, but its effectiveness remains controversial. Here we report the results of an Expanded Access Program of CPA in the province of Buenos Aires, Argentina. We evaluated the relationship between the timing of CPA and 28-day mortality in 4719 hospitalized patients with COVID-19 pneumonia. Early ([≤]3 days from admission) CPA was associated to decreased mortality in patients in the general ward and in the Intensive Care Unit not requiring mechanical ventilation. This suggests that the favorable effect of CPA might be related both to disease acuity and to the therapeutic window.

Prevention of severe COVID-19 in the elderly by early high-titer plasma

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression. MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate [≥]30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible. Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%. A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed. ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives. Funded by The Bill & Melinda Gates Foundation and The Fundacion INFANT Pandemic Fund. Registered in the Direccion de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163). All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

Estimating COVID-19 cases and outbreaks on-stream through phone-calls

One of the main problems in controlling COVID-19 epidemic spread is the delay in confirming cases. Having information on changes in the epidemic evolution or outbreaks rise before lab-confirmation is crucial in decision making for Public Health policies. We present an algorithm to estimate on-stream the number of COVID-19 cases using the data from telephone calls to a COVID-line. By modeling the calls as background (proportional to population) plus signal (proportional to infected), we fit the calls in Province of Buenos Aires (Argentina) with coefficient of determination R2 > 0.85. This result allows us to estimate the number of cases given the number of calls from a specific district, days before the lab results are available. We validate the algorithm with real data. We show how to use the algorithm to track on-stream the epidemic, and present the Early Outbreak Alarm to detect outbreaks in advance to lab results. One key point in the developed algorithm is a detailed track of the uncertainties in the estimations, since the alarm uses the significance of the observables as a main indicator to detect an anomaly. We present the details of the explicit example in Villa Azul (Quilmes) where this tool resulted crucial to control an outbreak on time. The presented tools have been designed in urgency with the available data at the time of the development, and therefore have their limitations which we describe and discuss. We consider possible improvements on the tools, many of which are currently under development.

EFFECT OF CONVALESCENT PLASMA ON MORTALITY IN PATIENTS WITH COVID-19 PNEUMONIA

BackgroundConvalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our objective was to compare epidemiological characteristics and outcomes between patients who received convalescent plasma for COVID-19 and those who did not, admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic. MethodsThis is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program. ResultsWe analyzed 3,529 patients with pneumonia, predominantly male, aged 62{+/-}17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred. Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor. ConclusionsOur study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with decreased mortality. Key PointsO_LIPreliminary evidence showed that convalescent plasma might be beneficial in COVID-19. C_LIO_LIIn a cohort of 3,529 patients with pneumonia due to COVID-19, convalescent plasma was administered to 868 patients, without major adverse effects. C_LIO_LIConvalescent plasma was independently associated with decreased mortality. C_LI