Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

[Pneumococcal conjugate vaccines in pediatrics, its impact on Public Health]. / Vacunas conjugadas contra neumococo en pediatría, su impacto en la Salud Pública.

Streptococcus pneumoniae (also known as pneumococcus) is part of the natural bacterial flora of the nasal and pharyngeal mucosa, colonizes mainly the nasopharynx, and causes this carriage to precede pneumococcal disease, thus becoming the main source of propagation among people, especially in children. Since 1983, when the first 23-component anti-pneumococcal vaccine was authorized, different conjugated vaccines have been developed according to the circulating serotypes that cause invasive pneumococcal diseases (IPD), reducing the incidence and mortality of these diseases considerably. In November 2021, a group of experts held a virtual meeting to update and analyze the impact that pneumococcal vaccines have generated on the countries' public health, especially during the COVID-19 pandemic. The recommendations that emerged included the need to look for alternatives in serotype-independent vaccines after the introduction of pneumococcal conjugate vaccines (PCV) in the national immunization schedules, as well as to strengthen the surveillance of serotypes, focusing on those not included in the current vaccines. The objective of this report is to communicate the conclusions of the group of experts that in November 2021 analyzed the impact of pneumococcal vaccines on public health in the countries, in order to generate recommendations applicable in Latin America.

Analytics Saves Lives During the COVID-19 Crisis in Chile

During the COVID-19 crisis, the Chilean Ministry of Health and the Ministry of Sciences, Technology, Knowledge and Innovation partnered with the Instituto Sistemas Complejos de Ingeniería (ISCI) and the telecommunications company ENTEL, to develop innovative methodologies and tools that placed operations research (OR) and analytics at the forefront of the battle against the pandemic. These innovations have been used in key decision aspects that helped shape a comprehensive strategy against the virus, including tools that (1) provided data on the actual effects of lockdowns in different municipalities and over time;(2) helped allocate limited intensive care unit (ICU) capacity;(3) significantly increased the testing capacity and provided on-the-ground strategies for active screening of asymptomatic cases;and (4) implemented a nationwide serology surveillance program that significantly influenced Chile's decisions regarding vaccine booster doses and that also provided information of global relevance. Significant challenges during the execution of the project included the coordination of large teams of engineers, data scientists, and healthcare professionals in the field;the effective communication of information to the population;and the handling and use of sensitive data. The initiatives generated significant press coverage and, by providing scientific evidence supporting the decision making behind the Chilean strategy to address the pandemic, they helped provide transparency and objectivity to decision makers and the general population. According to highly conservative estimates, the number of lives saved by all the initiatives combined is close to 3,000, equivalent to more than 5% of the total death toll in Chile associated with the pandemic until January 2022. The saved resources associated with testing, ICU beds, and working days amount to more than 300 million USD.

COVID-19 in Latin America: A Snapshot in Time and the Road Ahead.

Since its initial detection in Brazil in February 2020, SARS-CoV-2 and the associated COVID-19 pandemic have continued to devastate Latin America. Specific comorbidities, as well as sociodemographic and lifestyle factors that may be more prevalent in underserved areas, have been identified as risk factors for COVID-19 infection or associated adverse outcomes. Dynamics of infections and deaths in Latin America have varied by country and temporally, as has SARS-CoV-2 variant prevalence; however, more recently, the Delta and subsequent Omicron variants have become ubiquitous. Successful pandemic responses have involved robust infection mitigation measures, testing, and smart deployment of healthcare resourcing. While in some Latin American countries up to 90% of the population is fully vaccinated (i.e., 2 doses) against COVID-19, other countries have failed to reach the World Health Organization's 70% target. Continued focus on comprehensive surveillance, strategies to maximize vaccine availability and uptake, and mitigation of collateral damage on other aspects of public health and social services are critical for managing the COVID-19 pandemic. This review summarizes the COVID-19 experience in Latin America, including epidemiology and vaccination. Key learnings and future considerations for the ongoing pandemic response are also discussed.

COVID-19 lateral flow IgG seropositivity and serum neutralising antibody responses after primary and booster vaccinations in Chile: a cross-sectional study.

BACKGROUND: By June 30, 2022, 92·6% of the Chilean population older than 18 years had received a full primary SARS-CoV-2 vaccine series, mostly with CoronaVac (Sinovac Biotech), and 78·4% had received a booster dose, mostly heterologous with BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (AstraZeneca). We previously reported national seroprevalence data from lateral flow testing of IgG SARS-CoV-2 antibodies up to 16 weeks after primary vaccination. Our aim here was to study IgG seropositivity dynamics up to 30 weeks after primary vaccination and, in CoronaVac recipients, up to 26 weeks after booster vaccination, and to establish the correlation between lateral flow tests and neutralising antibody titres. METHODS: In this cross-sectional study, testing stations for SARS-CoV-2 IgG detection were selected and installed from March 12, 2021, in hotspots in 24 large Chilean cities, and were maintained until March 31, 2022. Individuals voluntarily approaching the testing stations were invited to perform a rapid lateral flow test via a finger prick and complete a questionnaire. Between Aug 12, 2021, and April 1, 2022, volunteers seeking medical care in the Mutual de Seguridad de la Cámara Chilena de la Construcción provided blood samples for lateral flow testing and neutralising antibody studies; inclusion criteria were age at least 18 years, history of complete primary vaccination series with CoronaVac, BNT162b2, or ChAdOx1, or no vaccine, and no previous COVID-19 diagnosis. We tested the difference in IgG positivity across time, and between primary and booster doses, in all eligible participants with complete records, controlling for age, gender, and comorbidities. We also assessed the predictive power of neutralising antibody titres and sociodemographic characteristics on the probability of IgG positive results using multivariable logistic regression. FINDINGS: Of 107 220 individuals recruited at the testing stations, 101 070 were included in our analysis (59 862 [59·2%] women and 41 208 [40·8%] men). 65 902 (65·2%) received primary vaccination series with CoronaVac, 18 548 (18·4%) with BNT162b2, and 606 (0·6%) with ChAdOx1, and 16 014 (15·8%) received no vaccine. Among the 61 767 individuals with a complete primary vaccination series with CoronaVac, 608 (1·0%) received a CoronaVac booster, 10 095 (16·3%) received a BNT162b2 booster, and 5435 (8·8%) received a ChAdOx1 booster. After ChAdOx1 primary vaccination, seropositivity peaked at week 5 after the second dose, occurring in 13 (92·9%, 95% CI 79·4-100·0) of 14 individuals. In participants who received a complete CoronaVac primary series, the decline in seropositivity stabilised at week 18 after the second dose (86 [44·7%, 95% CI 41·8-47·7] of 1087 individuals), whereas after receiving BNT162b2, seropositivity declined slightly by week 25 after the second dose (161 [94·2%, 90·6-97·7] of 171). A lower proportion of individuals who received the CoronaVac primary series and a homologous booster were seropositive (279 [85·6%, 95% CI 81·8-89·4] of 326) by weeks 2-18 than those who received a BNT162b2 booster (7031 [98·6%, 98·4-98·9] of 7128) or a ChAdOx1 booster (2893 [98·0%, 97·5-98·5] of 2953). The correlation between IgG positivity and log of the infectious dose in 50% of neutralising antibodies was moderate, with a sensitivity of 81·4% (95% CI 76·3-86·6) and specificity of 92·5% (73·3-100·0). INTERPRETATION: Dynamic monitoring of IgG positivity to SARS-CoV-2 can characterise antibody waning over time in the absence or presence of booster doses, providing relevant data for the design of vaccination strategies. The correlation between lateral flow test IgG titres and neutralising antibody concentrations suggests that they could be a quick and effective surveillance tool to measure protection against SARS-CoV-2. FUNDING: Instituto Sistemas Complejos de Ingeniería, Subsecretaría de Redes Asistenciales, Ministry of Health, Chile, and Mutual de Seguridad de la Cámara Chilena de la Construcción.

Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos

Abstract Background: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. Aim: To determine clinical outcome of RVI, compared to BI in children with HSCT. Methods: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. Results: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88);only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). Conclusion: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study.

BACKGROUND: By July 14, 2021, 81·3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72·3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75·3% of vaccines dispensed) or Pfizer-BioNTech's mRNA BNT162b2 vaccine (20·9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy. METHODS: From March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021. FINDINGS: Of 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59·6%) had received at least one dose of the CoronaVac vaccine, 8947 (15·9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24·5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28·1% (95% CI 25·0-31·2; 220 of 783 individuals), reaching a peak of 77·4% (75·5-79·3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79·4% (75·7-83·1; 367 of 462 individuals), increasing to 96·5% (94·9-98·1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6·0% (4·4-7·6; 49 of 810 individuals) to 18·7% (12·5-24·9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p<0·0001), and for individuals aged 60 years and older compared with people aged 18-39 years for both vaccines (p<0·0001), 3-16 weeks after the second dose. INTERPRETATION: IgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients. Prolonged IgG monitoring will allow further evaluation of seropositivity overtime, providing data, in conjunction with effectiveness studies, for possible future re-assessment of vaccination strategies. FUNDING: Instituto Sistemas Complejos de Ingeniería and Ministerio de Salud Chile. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Prevalence in Blood in a Large School Community Subject to a Coronavirus Disease 2019 Outbreak: A Cross-sectional Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. METHODS: The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4-19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. RESULTS: The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2-11.8) for 1009 students and 16.6% (95% CI, 12.1-21.9) for 235 staff. Among students, positivity was associated with a younger age (P = .01), a lower grade level (P = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P = .03), and a history of contact with a confirmed case (P < .001). Among staff, positivity was higher in teachers (P = .01) and in those previously RT-PCR positive (P < .001). Excluding RT-PCR-positive individuals, antibody positivity was associated with fever in adults and children (P = .02 and P = .002, respectively), abdominal pain in children (P = .001), and chest pain in adults (P = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P = .01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.