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. (preprint)

Objectives: To estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after applying a homologous or heterologous third-dose (booster) in individuals who had previously received primary vaccination schemes with rAd26-rAd5, ChAdOx1 nCoV-19, BBIBP-CorV or a heterologous combination, during the period of Omicron BA.1 predominance. Design: Retrospective, test-negative, case-control study, with a matched analysis. Setting: Province of Buenos Aires, Argentina. Data were extracted from the National Surveillance System and VacunatePBA, a system developed in the province, between 12/1/21-4/1/21. Participants: 422,144 adults older than 50 who had received two 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 a booster, compared to a two-dose primary scheme. Results: Of 221,933 (52.5%) individuals with a positive test, 190,884 (45.2%) had received a two-dose scheme of SARS-CoV-2 vaccines and 231,260 (54.8%) a three-dose scheme. The matched analysis included 127,014 cases and 180,714 controls. The administration of a homologous booster after a primary scheme with vectored vaccines provided a large protection against hospitalisations and death (OR 0.30 [0.26-0.35] and OR 0.29 [0.25-0.33] respectively). However, this effect was lower and waned earlier compared to heterologous boosters (OR 0.59 [0.47-0.74] and OR 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, provided some protection against infection (OR 0.70 [0.68-0.71]), which quickly decreased after 60 days (OR 1.01 [0.98-1.04]). Notwithstanding this, there was a clear protective effect against hospitalisations (OR 0.26 [0.22-0.31]) and deaths (OR 0.22 [0.18-0.25]) that persisted after 60 days (OR 0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Conclusions: This 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.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia. (preprint)

IntroductionEarly identification of patients with failure to prone position allows other treatments which could decrease mortality. The objective of our study was: describe the characteristics, behavior of oxygenation and pulmonary mechanics in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position. Secondary objectives were identify independent determinants of mortality; particularly, number of prone cycles associated with mortality.MethodsIt was a prospective study. All patients with <150 mmHg PaO2/FiO2 ratio and prone position were included and classified according to the PaO2/FiO2 behavior after the first prone cycle: 1) No increase, 2) Increase < 25%, 3) 25-50% increase 4) Increase >50%. The number of prone cycles was also recorded. Baseline characteristics, severity scores, respiratory mechanics and PaO2/FiO2 ratio behavior were compared between survivors and non-survivors.Statistical analysis was performed by Mann Whitney's, Chi² Test and Wilcoxon range tests. Independent factors associated with in-hospital mortality were identified by means of Cox regression.Results273 were treated with prone position over 18 months. The baseline PaO2/FiO2 was 116 [97-135] mmHg (115 [94-136] in survivors versus 117 [98-134] in non-survivors; p=0.50). After prone position, 22 patients (8%) had the same value in PaO2/FiO2 ratio; 46 patients (16%) showed an increase equal less or equal 25%; in 55 patients (21%) there was an increase between 25 and 50% over baseline; and in 150 patients (55%) the rise was greater than 50%. Mortality was 86%, 87%, 72%, 50% respectively. (p<0.001). Having debuted with PaO2/FiO2, ratio < 100 mmHg did not imply that the patient was refractory to the prone position.Of the 273 patients, 127 (46%) required 1 prone cycle, 57 (20%) 2 cycles, 50 (17%) 3 cycles, 17 (6%) had 4 cycles and 19 (7%) 5 or more cycles. Mortality was 55%, 70%, 70%, 82%, and 70% respectively (p<0.001). Factors independently associated with mortality were the percentage of increase in PaO2/FiO2 after 24 hours in prone, age, and the number of prone cycles. ConclusionsOlder patients unable to improve PaO2/FiO2 after 24 hours in prone and who require more than 1 prone cycle, may be candidates for other treatments for refractory hypoxemia.

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

Background: Although 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. Methods: We 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. Findings: By 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. Interpretation: This 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.

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

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.

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

Abstract Background Convalescent 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. Methods This 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. Results We 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. Conclusions Our study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with decreased mortality.

Ampliación de las Recomendaciones sobre el Uso de Heparina y Corticoides COVID-19

El presente documento se encuentra elaborado en el marco del Proyecto "Capacitación Situada y Permanente"emitido por Resolución 723/20201 , Dirección Nacional de Talento Humano y Conocimiento. Las recomendaciones fueron desarrolladas por expertos de la Sociedad Argentina de Terapia Intensiva y se han generado a partir del dispositivo "Tele-Revistas de Terapia Intensiva"en base a las principales controversias y dudas presentadas por los diferentes hospitales participantes.