Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera (preprint)

The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.

Offspring cardiometabolic outcomes and postnatal growth trajectories after exposure to maternal SARS-CoV-2 infection (preprint)

Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known. Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for cardiometabolic diagnoses by 18 months after birth, compared with unexposed offspring born during the COVID-19 pandemic. Design. This retrospective cohort study included the live offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020 - December 31, 2021) at 8 hospitals within 2 health systems in Massachusetts. Exposure. SARS-CoV-2 positivity on polymerase chain reaction (PCR) test during pregnancy. Main Outcome Measures. Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to cardiometabolic disorders. Offspring weight-for-age, length-for-age, and body mass index (BMI)-for-age z-scores at birth, 6 months, 12 months, and 18 months of age. Results. The full study cohort includes 29,510 live born offspring (1,599 exposed and 27,911 unexposed offspring). 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis by 18 months of age (crude OR 1.47 [95% CI: 1.10-1.94], p=0.007; adjusted OR 1.37 [1.01-1.83]; p=0.04). These diagnoses were preceded by significantly greater mean BMI-for-age z-scores in exposed versus unexposed offspring at 6 months (mean z-score difference 0.19, 95% CI: 0.10, 0.29, p<0.001), and a greater proportion of offspring at risk of, or meeting criteria for, overweight/obesity (16.5% vs. 12.2%, p=0.006). Conclusions. Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months and greater BMI-for-age at 6 months.

Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants (preprint)

SARS-CoV-2 has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of eight SARS-CoV-2 variants. Their sera were titrated against 14 SARS-CoV-2 variants and the resulting titers visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant), and a considerably more distributed positioning among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/5, the BA.5 descendants BF.7 and BQ.1.18; the BA.2.75 descendant BN.1.3.1; and the BA.2-derived recombinant XBB.2). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. The results highlight the potential of using variant-specifically infected hamster sera for the continued antigenic characterisation of SARS-CoV-2.

SARS-CoV-2 in Mexico: An Association Among Geography, Comorbidities, and Vitamin D Deficiency.

Objective: The aim of this study was to determine the association among temperature, relative humidity, latitude, vitamin D content and comorbidities in the spread of SAR-CoV-2 in Mexico in 2 different waves. Methods: The data on SARS-CoV-2 infections and comorbidities were obtained from the Mexican entities with the highest number of positive cases and deaths in the 2 waves that have most damaged the population. Results: Low temperature, high relative humidity, vitamin D deficiency and high percentage of comorbidities were factors that correlated with a high spread of SARS-CoV-2. Interestingly, 73.8% of the population had one of the most common comorbidities that favor the spread of the virus. Conclusion: The high percentage of comorbidities and the deficient concentration of vitamin D were determining factors in the high number of infections and deaths in Mexico. Furthermore, weather conditions could contribute to and alert to the spread of SARS-CoV-2.

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

The Neurosurgery Match: COVID Comparison and Bibliometric Analysis.

INTRODUCTION: Because of the effect of COVID on academic opportunities, as well as limitations on travel, away rotations and in-person interviews, COVID-related changes could impact the neurosurgical resident demographics. Our aim was to retrospectively review the demographics of the previous four years of neurosurgery residents, provide bibliometric analysis of successful applicants, and analyze for the effects of COVID on the match cycle. METHODS: All AANS residency program websites were examined for a list of demographic characteristics for current post-graduate year (PGY) 1 to 4. Gathered information included gender, undergraduate and medical institution and state, medical degree status, and prior graduate programs. RESULTS: A total of 114 institutions and 946 residents were included in the final review. 676 (71.5%) of the residents included in the analysis were male. Of the 783 who studied within the United States, 221 (28.2%) residents stayed within the same state of his or her medical school. 104 of 555 (18.7%) residents stayed within the same state of his or her undergraduate school. Demographic information as well as geographic switching relative to medical school, undergraduate school, and hometown showed no significant changes between pre-COVID and COVID-matched cohorts overall. The median number of publications per resident significantly increased for the COVID-matched cohort (median, 1; interquartile range (IQR), 0-4.75) when compared to the non-COVID-matched cohort (median, 1; IQR, 0-3, p = 0.004) as did first author publications (median, 1; IQR, 0-1 vs median, 1; IQR, 0-1; p = 0.015), respectively. The number of residents matching into the same region in the Northeast relative to undergraduate degree was significantly greater after COVID (56 (58%) vs 36 (42%), p = 0.026). The West demonstrated a significant increase in the mean number of total publications (4.0 ± 8.5 vs 2.3 ± 4.2, p = 0.02) and first author publications (1.24 ± 2.33 vs 0.68 ± 1.47, p = 0.02) after COVID, with the increase in first author publications being significant in a test of medians. CONCLUSION: Herein we characterized the most recently matched neurosurgery applicants, paying particular attention to changes over time in relation to the onset of the pandemic. Apart from publication volume, characteristics of residents and geographical preferences did not change with the influence of COVID-induced changes in the application process.

Outcomes of SARS-CoV-2 infection in 126 children and adolescents with central nervous system tumors.

BACKGROUND: The Global Registry of COVID-19 in Childhood Cancer (GRCCC) seeks to describe the natural history of SARS-CoV-2 in children with cancer across the world. Here, we report the disease course and management of coronavirus disease 2019 (COVID-19) infection in the subset of children and adolescents with central nervous system (CNS) tumors who were included in the GRCCC until February 2021, the first data freeze. PROCEDURE: The GRCCC is a deidentified web-based registry of patients less than 19 years of age with cancer or recipients of a hematopoietic stem cell transplant and laboratory-confirmed SARS-CoV-2 infection. Demographic data, cancer diagnosis, cancer-directed therapy, and clinical characteristics of SARS-CoV-2 infection were collected. Outcomes were collected at 30 and 60 days post infection. RESULTS: The GRCCC included 1500 cases from 45 countries, including 126 children with CNS tumors (8.4%). Sixty percent of the cases were from middle-income countries, while no cases were reported from low-income countries. Low-grade gliomas, high-grade gliomas, and CNS embryonal tumors were the most common CNS cancer diagnoses (67%, 84/126). Follow-up at 30 days was available for 107 (85%) patients. Based on the composite measure of severity, 53.3% (57/107) of reported SARS-CoV-2 infections were asymptomatic, 39.3% (42/107) were mild/moderate, and 6.5% (7/107) were severe or critical. One patient died from SARS-CoV-2 infection. There was a significant association between infection severity and absolute neutrophil count less than 500 (p = .04). Of 107 patients with follow-up available, 40 patients (37.4%) were not receiving cancer-directed therapy. Thirty-four patients (50.7%) had a modification to their treatment due to withholding of chemotherapy or delays in radiotherapy or surgery. CONCLUSION: In this cohort of patients with CNS tumors and COVID-19, the frequency of severe infection appears to be low, although severe disease and death do occur. We found that greater severity was seen in patients with severe neutropenia, although treatment modifications were not associated with infection severity or cytopenias. Additional analyses are needed to further describe this unique group of patients.

Acute Kidney Injury in Critical Care COVID-19 Patients on Invasive Mechanical Ventilation: The Potential Preventive Role of Dexamethasone.

Background: A high incidence of acute kidney injury (AKI) has been reported in coronavirus disease 2019 (COVID-19) patients in critical care units and those undergoing invasive mechanical ventilation (IMV). The introduction of dexamethasone (DXM) as treatment for severe COVID-19 has improved mortality, but its effects in other organs remain under study. Objective: The objective of this study was to evaluate the association between DXM and AKI in COVID-19. Methods: In this prospective observational cohort study, we evaluated the incidence of AKI in critically ill COVID-19 patients undergoing mechanical ventilation, and the association of DXM treatment with the incidence, severity, and outcomes of AKI. The association between DXM treatment and AKI was evaluated by multivariable logistic regression. The association of the combination of DXM treatment and AKI on mortality was evaluated by Cox-regression analysis. Results: We included 552 patients. AKI was diagnosed in 311 (56%), of which 196 (63%) corresponded to severe (stage 2 or 3) AKI, and 46 (14.8%) received kidney replacement therapy. Two hundred and sixty-seven (48%) patients were treated with DXM. This treatment was associated to lower incidence of AKI (Odds Radio 0.34, 95% Confidence intervals [CI] 0.22-0.52, p < 0.001) after adjusting for age, body mass index, laboratory parameters, SOFA score, and vasopressor use. DXM treatment significantly reduced mortality in patients with severe AKI (HR 0.63, 95%CI 0.41-0.96, p = 0.032). Conclusions: The incidence of AKI is high in COVID-19 patients under IMV. DXM treatment is associated with a lower incidence of AKI and a lower mortality in the group with severe AKI.

MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats.

Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to inferring their zoonotic potential. Members of the cryptic Hipposideros bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC diversity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV-229E, CoV-2B and CoV-2Bbasal) susceptibility to immunogenetic differences amongst four Hipposideros bat species. From the 2072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, Hipposideros caffer D, were most infected with CoV-229E and SARS-related CoV-2B. Using a subset of 569 bats, we determined that much of the existent allelic and functional (i.e. supertype) MHC DRB class II diversity originated from common ancestry. One MHC supertype shared amongst all species, ST12, was consistently linked to susceptibility with CoV-229E, which is closely related to the common cold agent HCoV-229E, and infected bats and those carrying ST12 had a lower body condition. The same MHC supertype was connected to resistance to CoV-2B, and bats with ST12 were less likely be co-infected with CoV-229E and CoV-2B. Our work suggests a role of immunogenetics in determining CoV susceptibility in bats. We advocate for the preservation of functional genetic and species diversity in reservoirs as a means of mitigating the risk of disease spillover.

Experimental Pharmacology For Covid-19 Treatment: A Geoanalytical Bibliometric Analysis.

OBJECTIVE: To produce a geo-referenced map of the status of R&D in COVID-related studies in the World Methodology: Spatial mapping of bibliometric data of Cortellis Drug Discovery Intelligence through an spatial bibliometric model with the aid of a GIS (Geographic Information System) called ArcGIS and the software. RESULTS: We show the countries that have most studies related to COV ID-19 and their degree of collaboration. No drug discovery-related activity was found in South America and Africa. A geo-referenced map of the most active countries in COVID research was constructed as well as conceptual maps of the 11 most representative drugs employed for COVID treatment. CONCLUSION: The georeferenced conceptual maps produced in the present report allow not only to better understand the leading institutions in R&D in COVID-19 related drugs, but also to visualize their interactions and research relationships. This could offer, in addition to a coherent, organized multinational effort, the possibility of searching for other drugs that have been employed for other diseases and that, in terms of their conceptual relations, could represent some possibilities for treating the coronavirus SARS-2.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry.

Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified. Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing. Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021. Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population. Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test.

Dance Participation during the COVID-19 Pandemic: Experiences of Older Adult Dance Studio Members

This phenomenological study explored the effects of COVID-19's stay-at-home order on dance participation. Nine dance studio members, 60+ age, shared their lived experiences through semi-structured interviews. Interviews were transcribed and thematic analysis was conducted. Four themes emerged: Occupational disruption resulted from the loss of routine with sudden adaptation;virtual dance contributed positively to physical and emotional well-being;expanded virtual community addressed feelings of isolation and loneliness;and a positive outlook and hopefulness for future in-person dance. Themes underscore the importance of dance for older adults and the need to address physical, emotional, and social factors associated with un-predicted future pandemics. [ FROM AUTHOR] Copyright of Occupational Therapy in Mental Health is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID.

BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity. METHODS: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in a post-COVID cohort, compared those with or without symptoms, and correlated findings with previously measured biomarkers. RESULTS: Sixty participants (median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted) compared to 3/19 (16%) without symptoms (p = 0.02). Adjusted peak VO2 was 5.2 ml/kg/min lower (95%CI 2.1-8.3; p = 0.001) or 16.9% lower percent predicted (95%CI 4.3-29.6; p = 0.02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias were absent. CONCLUSIONS: Cardiopulmonary symptoms >1 year following COVID-19 were associated with reduced exercise capacity, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary Long COVID.

90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection.

Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro.

Psychosocial predictors of COVID-19 infection in UK biobank (N = 104 201).

BACKGROUND: Since the outbreak of COVID-19, data on its psychosocial predictors are limited. We therefore aimed to explore psychosocial predictors of COVID-19 infection at the UK Biobank (UKB). METHODS: This was a prospective cohort study conducted among UKB participants. RESULTS: The sample size was N = 104 201, out of which 14 852 (14.3%) had a positive COVID-19 test. The whole sample analysis showed significant interactions between sex and several predictor variables. Among females, absence of college/university degree [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.45-1.66] and socioeconomic deprivation (OR 1.16 95% CI 1.11-1.21) were associated with higher odds of COVID-19 infection, while history of psychiatric consultation (OR 0.85 95% CI 0.77-0.94) with lower odds. Among males, absence of college/university degree (OR 1.56, 95% CI 1.45-1.68) and socioeconomic deprivation (OR 1.12, 95% CI 1.07-1.16) were associated with higher odds, while loneliness (OR 0.87, 95% CI 0.78-0.97), irritability (OR 0.91, 95% CI 0.83-0.99) and history of psychiatric consultation (OR 0.85, 95% CI 0.75-0.97) were associated with lower odds. CONCLUSION: Sociodemographic factors predicted the odds of COVID-19 infection equally among male and female participants, while psychological factors had differential impacts.

Prevalence of neurological manifestations in COVID-19 and their association with mortality

Introduction: Articles published in the literature report neurological manifestations or "complications" of SARS-CoV-2 infection and conclude that the different neurological manifestations are relatively similar, but with different frequencies. This study aimed to determine the frequency of neurological manifestations of COVID-19 and to identify which are associated with mortality. Method(s): We performed a retrospective study of all patients diagnosed with SARS-CoV-2 infection by RT-PCR at Hospital 1degree de Octubre, in Mexico, from the beginning of the pandemic to 22 December 2020. A total of 561 patients were identified, 370 of whom presented neurological manifestations. Result(s): The global mortality rate was 37.8% (140/370), increasing to 92.4% among intubated patients (135/146). Of the 370 patients included, approximately 20% of neurological symptoms (headache, neurological impairment, anosmia, ageusia) accounted for 80% of cases of neurological manifestations. Conclusion(s): At our hospital, 80% of the patients with neurological manifestations of COVID-19 presented headache, neurological impairment, ageusia, and/or anosmia. Neurological impairment at admission or before arriving at hospital was identified as a risk factor for mortality.Copyright © 2021 Sociedad Espanola de Neurologia

Effect of Replacing Feldspar by Philippine Black Cinder on the Development of Low-Porosity Red Stoneware

Stoneware is a ceramic material with low porosity and high mechanical properties, such as the modulus of rupture. It is essentially made of clay, feldspar and quartz and is sintered to create a mixture of glass and crystalline phases. With the projected growth rate of the global ceramics market size and the country's development plan for 2023–2028, it is imperative that alternative raw materials for the manufacture of ceramic products be sourced so that the importation of these materials, such as feldspar, be minimized, if not eliminated. Cinder in the Philippines is mainly used as a filling material in pavements and residential areas. In this study, this resource is utilized as partial and full replacement of feldspar in a typical ternary diagram for stoneware production. Bars were formed from different formulations by the slip casting method and were sintered at 1200 °C. Physical and mechanical properties of the bars, such as shrinkage, loss on ignition, water absorption, apparent porosity and modulus of rupture were determined. Thermo-physical analyses were also carried out on the raw materials and on formulated powders. Meeting the requirements of the various quality standards for ceramics, the partial replacement of feldspar with black cinder (LF, LFBQ and LFBH) is feasible for wall and roof applications while full replacement of feldspar with black cinder (LB) is suitable for wider use as wall, floor, vitrified, industrial and roof tiles.

Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany-Results from the SeBluCo Study 2020-2022.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany.

[SIR model of the COVID-19 pandemic in Colombia]. / Modelo SIR de la pandemia de COVID-19 en Colombia.

OBJECTIVE: To develop a prognostic SIR model of the COVID-19 pandemic in Colombia. MATERIALS AND METHODS: A SIR model with a deterministic approach was used to forecast the development of the COVID-19 pandemic in Colombia. The states considered were susceptible (S), infectious (i) and recovered or deceased (R). Population data were obtained from the National Administrative Department of Statistics (DANE) - Population Projections 2018-2020, released in January 2020-, and data on daily confirmed cases of COVID-19 from the National Institute of Health. Different models were proposed varying the basic reproduction number (R0). RESULTS: Based on the cases reported by the Ministry of Health, 4 simulated environments were created in an epidemiological SIR model. The time series was extended until May 30, the probable date when 99% of the population will be infected. R0=2 is the basic reproduction number and the closest approximation to the behavior of the pandemic during the first 15 days since the first case report; the worst scenario would occur in the first week of April with R0=3. CONCLUSIONS: Further mitigation and suppression measures are necessary in the containment and sustained transmission phases, such as increased diagnostic capacity through testing and disinfection of populated areas and homes in isolation.

Recombinant Bacillus Calmette-Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.