Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Preparedness strategies in neonatology units during the COVID-19 pandemic: A survey conducted at maternity centers in Argentina. / Estrategias de preparación en unidades de neonatología durante la pandemia de COVID-19: Encuesta en maternidades de la Argentina.

INTRODUCTION: The objective of this study was to analyze available resources, guidelines in use, and preparedness to care for newborn infants at maternity centers in Argentina during the COVID-19 pandemic. METHOD: Cross-sectional study based on a survey administered to medical and nursing staff. In May 2020, Argentine facilities with more than 500 annual births were contacted; 58 % of these were from the public sector. RESULTS: In total, 104/147 facilities answered (71 %). All had guidelines for care during the pandemic, and 93 % indicated they had been trained on how to use them. A companion was not allowed during childbirth in 26 % of private facilities and in 60 % of public ones (p < 0.01). Deferred cord clamping was recommended in 87 %; rooming-in with asymptomatic newborns was promoted in 62 %; breastfeeding using protective measures was recommended in 70 %; and breast milk using a bottle, in 23 %. In 94 %, family visiting in the Neonatology Unit was restricted. Difficulties included the unavailability of individual rooms for symptomatic newborn infants and a potential shortage of health care staff and personal protective equipment. CONCLUSIONS: All facilities are aware of the national guidelines to fight the pandemic. Most have the resources to comply with the recommended protective measures. There is uncertainty as to whether personal protective equipment, staff, and physical space available at the different facilities would be enough if cases increased significantly.

Introducción. El objetivo de este estudio fue analizar recursos disponibles, guías utilizadas y preparación para la atención de neonatos en maternidades de Argentina durante la pandemia de COVID-19. Método. Estudio transversal mediante una encuesta enviada a equipos médicos y de enfermería. En mayo de 2020, se contactaron instituciones de más de 500 nacimientos anuales en la Argentina, el 58 % del sector público. Resultados. Respondieron 104/147 instituciones (el 71 %). Todas contaban con guías para la atención durante la pandemia, y un 93 % refirió haber recibido capacitación para su uso. No autorizaban la presencia de acompañante en el parto el 26 % de instituciones privadas y el 60 % de las públicas (p < 0,01). El 87 % recomendaba ligadura oportuna del cordón, el 62 % promovía internación conjunta en neonatos asintomáticos, un 70 % recomendaba la puesta al pecho con medidas de protección, y el 23 %, leche materna mediante biberón. El 94 % restringía el ingreso de familiares a Neonatología. Las dificultades incluyeron imposibilidad de contar con habitaciones individuales para neonatos sintomáticos y potencial limitación del personal de salud y equipos de protección personal. Conclusiones. Todas las instituciones conocen las guías nacionales para enfrentar la pandemia. La mayoría cuenta con recursos para respetar las medidas de protección recomendadas. Existe incertidumbre sobre si, ante un aumento significativo en el número de casos, serán suficientes los elementos de protección personal, el personal y el espacio físico disponible en los distintos centros.

Toward the Next-Generation COVID-19 Vaccines That Circumvent Antigenic Drift while Defusing Viral Infection.

The emergence of vaccine-resistant variants suggests a complicated endemic scenario in the vaccination aftermath for COVID-19. The situation prompts us to enquire whether the antigen adopted by extant vaccines, the trimeric spike (S) protein, is the optimal in the sense of inducing an immunity that leaves the virus with no evolutionary route of evasion. The patterns of glycosylation camouflage suggest that the answer is negative while also suggesting an alternative antigen that appears to be better optimized, eliciting an additional immune attack as the virus gets primed for cell penetration. This type of vaccine is expected to induce antibodies capable of defusing the virus during the priming phase while also circumventing antigenic drift.

SARS-CoV-2 Glycosylation Suggests That Vaccines Should Have Adopted the S1 Subunit as Antigen.

Extant SARS-CoV-2 vaccines use the trimeric spike (S) protein as antigen. In the virus, the spike region is extensively glycosylated, modulating immune surveillance. Because they have been defused, many epitopes in the vaccine sidetrack the immune response. Only the receptor binding domain within the S1 subunit is well-exposed to antibody recognition. After proteolytic virus activation, the S1 subunit offers additional epitopes with antibody exposure. Thus, vaccines adopting the S1 subunit as antigen would have been more efficacious than the existing ones.

Glycosylation of SARS-CoV-2 Steers Evolutionary Outcomes in the Postvaccination Phase.

There is a need to assess evolutionary outcomes for SARS-CoV-2 in the postvaccination phase. The role of virus glycosylation in deterring the development of vaccine resistance is weighed against the epitopes of extant vaccines and the modulation of induced immune surveillance on antigens containing glycosylation sites.

COVID-19 Evolution in the Post-Vaccination Phase: Endemic or Extinct?

This piece addresses the urge to assess the evolutionary fate of SARS-CoV-2 in a post-vaccination phase. The possibilities of COVID-19 becoming endemic or extinct are weighed against verifiable properties of extant vaccines and observed genetic trends already apparent under the mild selection pressure exerted almost exclusively by social rules.

Defusing SARS-CoV-2: Emergency Brakes in a Vaccine Failure Scenario.

Deactivation of primed SARS-CoV-2 prior to cell entry constitutes an emergency brake in COVID-19 infection if vaccine-induced antibodies fail to block recognition of the human angiotensin-converting enzyme 2 (hACE2) receptor. The timing and locus for the therapeutic intervention are dictated by the cell entry mechanism and by the selective advantage of the dominant D614G mutation.

Therapeutically Targeted Destabilization of the Quaternary Structure of the Spike Protein in the Dominant G614 Strain of SARS-CoV-2.

The evolutionary change of SARS-CoV-2 is of the outmost concern. With a more stable phenotype, mutation D614G has become dominant. Its structural impact prompts the development of an antibody that destabilizes the virus quaternary structure where it is most vulnerable. Vaccine-related antigenic regions are different from the proposed epitope, hence avoiding therapeutic redundancy.

Achilles' Heel of SARS-CoV-2 Structure.

Guided by evolutionarily signaled vulnerabilities in the structure of SARS-CoV-2, we identify epitopes in free monomers of the spike protein that steer the generation of induced or administered antibodies geared at promoting destabilization of the virus quaternary structure, thereby hampering infectivity.

Structural Impact of Mutation D614G in SARS-CoV-2 Spike Protein: Enhanced Infectivity and Therapeutic Opportunity.

With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic clues on the enhanced infectivity. The D614G substitution creates a sticky packing defect in subunit S1, promoting its association with subunit S2 as a means to stabilize the structure of S1 within the S1/S2 complex. The results raise the therapeutic possibility of immunologically targeting the epitope involved in stabilizing the G614 phenotype as a means of reducing the infection efficacy of SARS-CoV-2. This therapeutic modality would not a-priori interfere directly with current efforts toward the immunological targeting of the RBD epitope; hence, it could be exploited as a complementary treatment.