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A B1a–natural IgG–neutrophil axis is impaired in viral- and steroid-associated aspergillosis
A B1a–natural IgG–neutrophil axis is impaired in viral- and steroid-associated aspergillosis
The lung naturally resists Aspergillus fumigatus (Af) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis—severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use—in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.
·science.org·
A B1a–natural IgG–neutrophil axis is impaired in viral- and steroid-associated aspergillosis
Long COVID after breakthrough SARS-CoV-2 infection - s41591-022-01840-0.pdf
Long COVID after breakthrough SARS-CoV-2 infection - s41591-022-01840-0.pdf
The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, includ- ing contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infec- tion, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.
·nature.com·
Long COVID after breakthrough SARS-CoV-2 infection - s41591-022-01840-0.pdf
One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry
One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry
Background The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. Methods This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31–365 days). Results A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56–2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99–4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02–4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93–29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35–8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25–1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). Conclusions At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. Study registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.
·journals.plos.org·
One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry
Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022 - PubMed
Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022 - PubMed
spanbQuestion:/b How did population immunity against SARS-CoV-2 infection and subsequent severe disease change between December 2021, and November 2022?bFindings:/b On November 9, 2022, the protection against a SARS-CoV-2 infection with the Omicron variant was estimated to be 63% (51%-75%) in th/span …
·pubmed.ncbi.nlm.nih.gov·
Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022 - PubMed
Global impact of the first year of COVID-19 vaccination: a mathematical modelling study
Global impact of the first year of COVID-19 vaccination: a mathematical modelling study
COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage.
·thelancet.com·
Global impact of the first year of COVID-19 vaccination: a mathematical modelling study
Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
Background SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. Methods We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. Results The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. Conclusions We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No external funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by Radboud university medical center Committee on Research Involving Human Subjects (CMO) and the Erasmus Medical Center Medical Ethics Committee (METC). All samples were collected following routine institutional COVID-19 testing guidelines, the participants were not subject to any procedures for the purpose of this study and all data were anonymized prior to analysis. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data are available upon request
·medrxiv.org·
Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
Greg Foley on Twitter
Greg Foley on Twitter
Short thread on Covid and respiratory support.There are numerous grifters, and serious academics, out there who seem to think if the fatality stats are not that bad, then Covid is no big deal.— Greg Foley (@gregfoley2002) January 12, 2023
·twitter.com·
Greg Foley on Twitter
IgG-4 Related Disease: An Introduction
IgG-4 Related Disease: An Introduction
IgG4-related disease (IgG-RD) describes a group of fibroinflammatory diseases that affect a variety of tissues resulting in tumor-like effect and/or organ dysfunction. Clinical presentation varies according to the tissue(s) involved, and diagnosis relies on tissue findings of dense infiltration of IgG4-positive plasma cells and a characteristic storiform fibrosis. Treatment is mainly with glucocorticoids, while multiple immunosuppressive medications can be used as adjuvant agents. Rituximab has showed promising results, but further studies are needed.
·ncbi.nlm.nih.gov·
IgG-4 Related Disease: An Introduction
SARS-CoV-2 Omicron subvariants evolved to promote further escape from MHC-I recognition
SARS-CoV-2 Omicron subvariants evolved to promote further escape from MHC-I recognition
SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress MHC I expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 infection in vivo . While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC I, Omicron subvariants exhibit a greater ability to suppress surface MHC-I expressions. Collectively, our data suggest that, in addition to escape from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition. Significance Numerous pathogenic viruses have developed strategies to evade host CD8+ T cell-mediated clearance. Here, we demonstrated that SARS-CoV-2 encodes multiple viral factors that can modulate MHC-I expression in the host cells. We found that MHC-I upregulation was strongly suppressed during SARS-CoV-2 infection in vivo . Notably, the Omicron subvariants showed an enhanced ability to suppress MHC-I compared to the original strain and the earlier SARS-CoV-2 variants of concern (VOCs). Our results point to the inherently strong ability of SARS-CoV-2 to hinder MHC-I expression and demonstrated that Omicron subvariants have evolved an even more optimized capacity to evade CD8 T cell recognition. ### Competing Interest Statement The authors have declared no competing interest.
·biorxiv.org·
SARS-CoV-2 Omicron subvariants evolved to promote further escape from MHC-I recognition
Paxlovid senkt Risiko für Long-Covid
Paxlovid senkt Risiko für Long-Covid
Werden an Corona erkrankte Patient:innen mit Paxlovid behandelt, kann das Risiko für einen schweren Krankheitsverlauf um 89 Prozent reduziert werden. Die konsequente Behandlung mit dem Virusstatikum könnte das Risiko für Long-Covid auch bei Patient:innen reduzieren, die einer Risikogruppe angehören.
·apotheke-adhoc.de·
Paxlovid senkt Risiko für Long-Covid
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Nature Communications - Although myeloid cell dysfunction has been observed in COVID-19, the underlying mechanisms remain incompletely understood. Here, the authors demonstrate that monocytes from...
·nature.com·
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Cancer Occurrence as the Upcoming Complications of COVID-19
Cancer Occurrence as the Upcoming Complications of COVID-19
Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID‐19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi‐organ failure are hallmarks of severe COVID‐19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low‐grade inflammation in “long COVID‐19” syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammat...
·frontiersin.org·
Cancer Occurrence as the Upcoming Complications of COVID-19
Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19
Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19
Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE). Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3–18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL). Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs. Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population.
·mdpi.com·
Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19
Large COVID autopsy study finds SARS-CoV-2 all over the human body
Large COVID autopsy study finds SARS-CoV-2 all over the human body
In the most comprehensive autopsy tissue study conducted to date, researchers have found traces of the SARS-CoV-2 virus throughout the entire body, from the brain and the heart to the eyes. The findings indicate the virus can cause persistent infections in many parts of the body, months past an initial illness, and support the argument for further research into antiviral drugs as possible treatment for long COVID.
·newatlas.com·
Large COVID autopsy study finds SARS-CoV-2 all over the human body
Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study
Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study
As the coronavirus (COVID-19) pandemic approaches the three-year mark and the number of confirmed COVID-19 cases now exceeds 100 million cases in the United States and continues to climb, there have been increasing concerns raised over the future public health and economic burden of long COVID including disability and concomitant declines in labor force participation. Only a handful of US studies have explored sociodemographic and socioeconomic characteristics that may put people at risk of long COVID or have investigated the possible mental health and socioeconomic sequelae of long COVID. In this paper, I report findings from the largest multivariable analysis to date using US nationally-representative population-based data on 152,812 adults including 19,871 adults with long COVID to explore key predictors and sequelae of long COVID. An estimated 14.0% of US adults aged 18-84 years (34.55 million adults; 95% CI = 33.63 to 35.47 million adults) and 15.4% of US working-aged adults aged 18-64 years (31.14 million adults; 95% CI = 30.26 to 32.02 million adults) had developed long COVID by November 2022. I identify several sociodemographic and socioeconomic factors as predictors of long COVID including lower household income levels, being Hispanic, female, gay/lesbian or bisexual, and divorced or separated. Even after accounting for such factors, having long COVID was linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships. Overall, an estimated 27.3 million US adults with long COVID were at risk of adverse socioeconomic and health outcomes including anxiety and depression. These preliminary estimates highlight the substantial public health and economic implications of long COVID among Americans and should prompt further inquiry and intervention. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data are publicly available at: I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the author.
·medrxiv.org·
Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study
Let Them Eat Plague!
Let Them Eat Plague!
The pandemic is not over. It’s much worse than you’ve been led to believe. And unless you’ve spent the past several years reading scientific studies on the subject, it can be hard…
·unity-struggle-unity.org·
Let Them Eat Plague!
Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
Objectives To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. Design Retrospective nationwide cohort study. Setting Electronic medical records from an Israeli nationwide healthcare organisation. Population 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. Main outcome measures Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. Results Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. Conclusions This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis. Data supporting the findings of this study came from Maccabi Healthcare Services. Restrictions apply to the availability of these data, and they are therefore not publicly available. Owing to restrictions, these data can be accessed only by request to the authors and/or Maccabi Healthcare Services.
·bmj.com·
Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study