Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity.

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1-6. Here we analysed the development of anti-SARS-CoV-2 antibody and T cell responses in individuals who were previously infected (recovered) or uninfected (naive) and received mRNA vaccines to SARS-CoV-2. While individuals who were previously infected sustained higher antibody titres than individuals who were uninfected post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (for example, B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (for example, B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from individuals who were previously infected and vaccinated displayed overall better neutralization capacity than plasma from individuals who were uninfected and also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the effect of emerging variants on antibody neutralizing activity.

Diverse functional autoantibodies in patients with COVID-19.

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

Sex differences in immune responses that underlie COVID-19 disease outcomes.

There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.

Longitudinal analyses reveal immunological misfiring in severe COVID-19.

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.

Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles.

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus-conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.

Soil nematode abundance and functional group composition at a global scale.

Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 1020 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.

First X-ray spectral ptychography and resonant ptychographic computed tomography experiments at the SWING beamline from Synchrotron SOLEIL.

X-ray ptychography and ptychographic computed tomography have seen a rapid rise since the advent of fourth-generation synchrotrons with a high degree of coherent radiation. In addition to quantitative multiscale structural analysis, ptychography with spectral capabilities has been developed, allowing for spatial-localized multiscale structural and spectral information of samples. The SWING beamline of Synchrotron SOLEIL has recently developed a nanoprobe setup where the endstation's first spectral and resonant ptychographic measurements have been successfully conducted. A metallic nickel wire sample was measured using 2D spectral ptychography in XANES mode and resonant ptychographic tomography. From the 2D spectral ptychography measurements, the spectra of the components of the sample's complex-valued refractive index, δ and ß, were extracted, integrated along the sample thickness. By performing resonance ptychographic tomography at two photon energies, 3D maps of the refractive index decrement, δ, were obtained at the Ni K-edge energy and another energy above the edge. These maps allowed the detection of impurities in the Ni wire. The significance of accounting for the atomic scattering factor is demonstrated in the calculation of electron density near a resonance through the use of the δ values. These results indicate that at the SWING beamline it is possible to conduct state-of-the-art spectral and resonant ptychography experiments using the nanoprobe setup.

ProSPyX: software for post-processing images of X-ray ptychography with spectral capabilities.

X-ray ptychography is a coherent diffraction imaging technique based on acquiring multiple diffraction patterns obtained through the illumination of the sample at different partially overlapping probe positions. The diffraction patterns collected are used to retrieve the complex transmittivity function of the sample and the probe using a phase retrieval algorithm. Absorption or phase contrast images of the sample as well as the real and imaginary parts of the probe function can be obtained. Furthermore, X-ray ptychography can also provide spectral information of the sample from absorption or phase shift images by capturing multiple ptychographic projections at varying energies around the resonant energy of the element of interest. However, post-processing of the images is required to extract the spectra. To facilitate this, ProSPyX, a Python package that offers the analysis tools and a graphical user interface required to process spectral ptychography datasets, is presented. Using the PyQt5 Python open-source module for development and design, the software facilitates extraction of absorption and phase spectral information from spectral ptychographic datasets. It also saves the spectra in file formats compatible with other X-ray absorption spectroscopy data analysis software tools, streamlining integration into existing spectroscopic data analysis pipelines. To illustrate its capabilities, ProSPyX was applied to process the spectral ptychography dataset recently acquired on a nickel wire at the SWING beamline of the SOLEIL synchrotron.

Fungal-mediated lung allergic airway disease: The critical role of macrophages and dendritic cells.

Fungi are abundant in the environment, causing our lungs to be constantly exposed to a diverse range of species. While the majority of these are cleared effectively in healthy individuals, constant exposure to spores (especially Aspergillus spp.) can lead to the development of allergic inflammation that underpins and worsen diseases such as asthma. Despite this, the precise mechanisms that underpin the development of fungal allergic disease are poorly understood. Innate immune cells, such as macrophages (MΦs) and dendritic cells (DCs), have been shown to be critical for mediating allergic inflammation to a range of different allergens. This review will focus on the crucial role of MΦ and DCs in mediating antifungal immunity, evaluating how these immune cells mediate allergic inflammation within the context of the lung environment. Ultimately, we aim to highlight important future research questions that will lead to novel therapeutic strategies for fungal allergic diseases.

Hepatic expression of tumor necrosis factor-α and evaluation of MAPK-p38 and NFκB signaling pathways in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is a necroinflammatory disease that occurs when genetically susceptible individuals are exposed to an environmental trigger. It is a rare disease, and its epidemiological aspects are nearly unknown in Northeast Brazil. In the literature, the activation of components of the inflammatory cascade pathways, including interleukins such as TNF-α and signaling factors like MAPK-p38 and NFκB, in the pathogenesis of AIH is well described in animal models. This study evaluated, for the first time, the immunostaining of TNF-α, MAPK-p38, and NFκB in immunohistochemical analysis of liver biopsies from AIH patients. The activation of the MAPK-p38 pathway was also studied through immunoassay analysis in the peripheral blood of AIH patients. METHODS AND RESULTS: Data from medical records of 25 AIH patients were analyzed. Histological and immunohistochemical analysis of liver tissue obtained from biopsies was performed to detect NFκB, MAPK-p38, and TNF-α. Immunoassay analysis of the MAPK-p38 pathway was performed in peripheral blood from 18 AIH patients and 8 healthy volunteers. Medical record analysis showed an average age of 33.3 years, with a female predominance in a ratio of 7.3:1. Concomitance with other autoimmune diseases was observed in 36 % of patients, with thyroid disorders being the most prominent among them, and an 8 % indication for liver transplantation. In the evaluation of autoantibodies, ANA was detected in 52 %, followed by SMA at 20 %, and Anti-LKM-1 at 16 %. Liver biopsy findings were like the global literature, with interface hepatitis and lymphoplasmacytic infiltration observed. Immunohistochemical analysis showed immunostaining for NFκB, MAPK-p38, and TNF-α, corroborating the inflammatory and immunological characteristics of the disease. Immunoassay analysis in peripheral blood confirmed the activation of the MAPK-p38 signaling pathway, with a statistically significant difference between AIH patients and healthy controls. CONCLUSIONS: The epidemiological and histological findings of AIH in this study in Northeast Brazil were like global population data. Immunohistochemical analysis of liver tissue and immunoassay analysis in peripheral blood confirmed the activation of TNF-α and the NFκB and MAPK-p38 signaling pathways in AIH patients.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

Sensorless Speed Estimation of Induction Motors through Signal Analysis Based on Chaos Using Density of Maxima.

Three-phase induction motors are widely used in various industrial sectors and are responsible for a significant portion of the total electrical energy consumed. To ensure their efficient operation, it is necessary to apply control systems with specific algorithms able to estimate rotation speed accurately and with an adequate response time. However, the angular speed sensors used in induction motors are generally expensive and unreliable, and they may be unsuitable for use in hostile environments. This paper presents an algorithm for speed estimation in three-phase induction motors using the chaotic variable of maximum density. The technique used in this work analyzes the current signals from the motor power supply without invasive sensors on its structure. The results show that speed estimation is achieved with a response time lower than that obtained by classical techniques based on the Fourier Transform. This technique allows for the provision of motor shaft speed values when operated under variable load.

Lychnophora pinaster in endangered campos rupestres: phenolic compounds and population ecogeography.

Lychnophora pinaster, known as arnica-mineira, is endemic to campos rupestres, at risk of extinction. The present study aimed to characterize the ecogeography and phenolic constituents of 11 L. pinaster populations collected in the mesoregions North, Jequitinhonha, Metropolitan of Belo Horizonte and Campos das Vertentes in the state of Minas Gerais, Brazil. Phenolic constituents were identified and quantified by Ultra-high performance liquid chromatography- mass spectrometry. Lychnophora pinaster occurs in sites at high altitude (700 and 1498 m), annual rainfall of up to 1455 m, soils with low fertility and predominantly loamy texture. Therefore, it can be considered tolerant to acidic soils, with low availability of nutrient. The most abundant substances in all populations were vitexin (18 - 1345 ng/g) and chlorogenic acid (60 - 767 ng/g). The 11 populations formed four groups in relation to the phenolic constituents, with group 1 consisting of the populations of the North Mesoregion (GM, OD) and Jetiquinhonha (DIMa), group 2, the Metropolitan of Belo Horizonte (SRM, NLSC, SM, RPS, CTRA), group 3, the North Mesoregion (ODMa and DI), and group 4, the Campos das Vertentes (CC). Among the populations, only those from the Metropolitan of Belo Horizonte showed correlation of soil properties with phenolic constituents.

Downregulation of DROSHA: Could It Affect miRNA Biogenesis in Endometriotic Menstrual Blood Mesenchymal Stem Cells?

Menstrual blood mesenchymal stem cells (MenSCs) have gained prominence in the endometriosis scientific community, given their multifunctional roles in regenerative medicine as a noninvasive source for future clinical applications. In addition, changes in post-transcriptional regulation via miRNAs have been explored in endometriotic MenSCs with a role in modulating proliferation, angiogenesis, differentiation, stemness, self-renewal, and the mesenchymal-epithelial transition process. In this sense, homeostasis of the miRNA biosynthesis pathway is essential for several cellular processes and is related to the self-renewal and differentiation of progenitor cells. However, no studies have investigated the miRNA biogenesis pathway in endometriotic MenSCs. In this study, we profiled the expression of eight central genes for the miRNA biosynthesis pathway under experimental conditions involving a two-dimensional culture of MenSCs obtained from healthy women (n = 10) and women with endometriosis (n = 10) using RT-qPCR and reported a two-fold decrease in DROSHA expression in the disease. In addition, miR-128-3p, miR-27a-3p, miR-27b-3p, miR-181a-5p, miR-181b-5p, miR-452-3p, miR-216a-5p, miR-216b-5p, and miR-93-5p, which have been associated with endometriosis, were identified through in silico analyses as negative regulators of DROSHA. Because DROSHA is essential for miRNA maturation, our findings may justify the identification of different profiles of miRNAs with DROSHA-dependent biogenesis in endometriosis.

Altered Differential Expression of Genes and microRNAs Related to Adhesion and Apoptosis Pathways in Patients with Different Phenotypes of Endometriosis.

We aim to investigate the expression of genes (MAPK1 and CAPN2) and microRNAs (miR-30a-5p, miR-7-5p, miR-143-3p, and miR-93-5p) involved in adhesion and apoptosis pathways in superficial peritoneal endometriosis (SE), deep infiltrating endometriosis (DE), and ovarian endometrioma (OE), and to evaluate whether these lesions share the same pathophysiological mechanisms. We used samples of SE (n = 10), DE (n = 10), and OE (n = 10), and endometrial biopsies of these respective patients affected with endometriosis under treatment at a tertiary University Hospital. Endometrial biopsies collected in the tubal ligation procedure from women without endometriosis comprised the control group (n = 10). Quantitative real-time polymerase chain reaction was performed. The expression of MAPK1 (p < 0.0001), miR-93-5p (p = 0.0168), and miR-7-5p (p = 0.0006) was significantly lower in the SE group than in the DE and OE groups. The expression of miR-30a (p = 0.0018) and miR-93 (p = 0.0052) was significantly upregulated in the eutopic endometrium of women with endometriosis compared to the controls. MiR-143 (p = 0.0225) expression also showed a statistical difference between the eutopic endometrium of women with endometriosis and the control group. In summary, SE showed lower pro-survival gene expression and miRNAs involved in this pathway, indicating that this phenotype has a different pathophysiological mechanism compared to DE and OE.

An analytical tool to support public policies and isolation barriers against SARS-CoV-2 based on mobility patterns and socio-economic aspects.

It is crucial to develop spatiotemporal analysis tools to mitigate risks during a pandemic. Many dashboards encountered in the literature do not consider how the geolocation characteristics and travel patterns may influence the spread of the virus. This work brings an interactive tool that is capable of crossing information about mobility patterns, geolocation characteristics and epidemiologic variables. To do so, our system uses a mobility network, generated through anonymized mobile location data, which enables the division of a region into representative clusters. The clusters' aggregated socioeconomic, and epidemiologic indicators can be analyzed through multiple coordinated views. The proposal is to enable users to understand how different locations commute citizens, monitor risk over time, and understand what locations need more assistance, considering different layers of visualization, such as clusters and individual locations. The main novelty is the interactive way to construct the mobility network that defines the social distancing level and the way that risks are managed, since many different geolocation characteristics can be considered and visualized, such as socioeconomic indicators of a location, the economic importance of a set of locations, and the connection of important neighborhoods of a city with other cities. The proposed tool was built and verified by experts assembled to give scientific recommendations to the city administration of Recife, the capital city of Pernambuco. Our analysis shows how a policymaker could use the tool to evaluate different isolation scenarios considering the trade-off between economic activity and contamination risk, where the practical insights can also be used to tighten and relax mitigation measures in other phases of a pandemic.

Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient.

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.

Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case-control analysis.

BACKGROUND: The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. METHODS AND FINDINGS: We conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. CONCLUSIONS: In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.