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Background: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication., Methods: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates., Results: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98))., Conclusions: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID., (© 2024. The Author(s).)

This study evaluated the explanatory factors of humoral immune response in older adults admitted to long-term care institutions in Buenos Aires, Argentina, up to 180 days after vaccination. An open-label, prospective, multicenter cohort study was conducted with volunteers who received two doses of the Sputnik V, Sinopharm, or AZD1222 vaccines. Plasma samples were analyzed at 0 and 21 days after the first dose, 21 days after the second dose, and 120 and 180 days after the first dose. Marginal linear models and generalized additives mixed models were adjusted to determine the behavior of anti-spike IgG antibody concentration over time according to exposure group (naïve/no-naïve) and vaccine. Occurrence of an outbreak of COVID-19 in long-term care institutions and comorbidities were the covariates analyzed. A total of 773 participants were included, with a mean age of 83 years (IQR: 76-89). Results showed that antibody levels in the naïve: Sinopharm group were significantly lower to the other groups (p < 0.05). Antibody levels in the no-naïve: Sinopharm group were similar to those in the naïve group who received AZD1222 (p = 0.945) or Sputnik V (p = 1). Participants exposed to outbreaks in long-term care institutions had significantly higher antibody levels, regardless of exposure group and vaccine (p < 0.001). In conclusion, previous exposure to COVID-19, type of vaccine, and admittance into a long-term care institution with a history of outbreaks are factors to be considered in future epidemic events with transmission dynamics and immunological mechanisms similar to COVID-19, in populations similar to the one analyzed.

Introduction: Following the Omicron wave in early 2022, an estimated 60-70% of the French population was infected with the SARS-CoV-2 virus. One out of ten infected subjects could have persistent symptoms three months after infection, representing a public health challenge., Current State of Knowledge: The persistent symptoms may be secondary to diverse entities with distinct mechanisms. While organic infection sequelae occur mainly after severe COVID-19, some symptoms appear to be essentially psychological in origin; in addition, many subjects present stereotyped symptoms of fluctuating intensity with no identified anatomical or psychic substratum, often in the aftermath of a benign infection. The most frequent complaints are fatigue, pain, dyspnea and difficulty concentrating., Perspectives: The hypotheses explored to explain these symptoms include: persistent immune dysfunction, inducted autoimmunity, and microbiome disturbances. Persistent viral antigens may lie at the crossroads of these mechanisms. To date, these different etiological avenues have yet to lead to the development of diagnostic tests or specific therapeutic strategies., Conclusion: Prolonged symptoms after COVID-19 correspond to heterogeneous nosological entities with poorly understood mechanisms., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than previous variants, it still poses a high risk of causing severe COVID-19 for immunocompromised populations. A systematic review was conducted to assess the burden of COVID-19 in Spain among immunocompromised patients during the omicron predominance (1/04/2022-1/04/2023), using PubMed, Cochrane Library, and EPICOVIDEHA between May and July 2023. The search retrieved 217 articles, of which a total of 5 were included. Upon analysis, it was observed that immunocompromised patients during the omicron lineage predominance continue to exhibit higher rates of hospitalizations, ICU admissions, and mortality compared to the general population affected by COVID-19. Although the pandemic has ended, the risk persists for immunocompromised individuals., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID., Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.)., Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events., Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions., Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438., Competing Interests: Declaration of interests Danielle Mowery serves as an unpaid member of the Epic Cosmos Governing Council. Romain Pirracchio received funding from the FDA CERSI grant U01FD005978 and the PCORI grant P0562155 and received a consulting honorarium from Phillips. Martin van der Laan received funding from the NIAID grant 5R01AI074345. Johanna Loomba received contract funding from the NIH RECOVER program. Emily Pfaff received funding from the NIH and PCORI. The views expressed in this manuscript are solely those of the authors and do not necessarily represent those of the National Institutes of Health, the U.S. Department of Health and Human Services or the U.S. government. Qi Long was supported by grants from the NIH., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Long COVID, a highly heterogeneous syndrome affecting millions of people worldwide, is emerging as an urgent public health threat, but data on the predictors of specific clinical manifestations over long follow-up periods are limited. The aim of this study is to investigate the role of viral variants and other predictors in long COVID incidence and clinical manifestations., Methods: All COVID-19 patients aged > 18 years and hospitalized from March 1 2020 to April 2022 in two Italian University Hospitals were enrolled. Incidence and clinical presentation of long COVID were assessed through structured questionnaires delivered by phone calls. The association between possible risk factors collected during hospitalization and long COVID was reported using an adjusted logistic regression and reported as odds ratios (ORs) with their 95% confidence intervals (CIs)., Results: Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Overall, 54% reported long COVID symptomatology between 18 and 24 months. Multivariate analysis suggested that being vaccinated against SARS-CoV-2 was associated with reduced odds of reporting any long COVID symptomatology (OR: 0.34; 95% CI: 0.21-0.58), while infection with the Delta variant was a strong predictor (OR: 9.61, p < 0.0001) for the development of post-COVID conditions characterized by neuropsychiatric symptoms., Conclusions: In this study long COVID symptoms were still highly prevalent after 18-24 months of follow-up and, when compared to wild-type virus, infection with the Delta variant was associated with a higher risk of developing a neurological post-COVID condition., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethical Committee of the University of Palermo during the session of the 28th of April 2021 (number 04/2021). The study is in accordance with the declaration of Helsinki relevant institutional guidelines. Informed consent was obtained from each participant and/or their legal guardian(s) who received information verbally and read the information letter. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab in immunocompromised patients has reduced the risk of breakthrough infection, disease, hospitalization, and COVID-19 related mortality. However, the advent of the Kraken variant (XBB.1.5) has limited the use of this monoclonal antibody, based on poor efficacy in in vitro studies The objective of the study was to evaluate the risk of breakthrough infection, symptomatic disease, hospitalization, intensive care admission, and COVID-19 related death in kidney transplant recipients receiving pre-exposure prophylaxis with Tixagevimab/Cilgavimab for COVID-19 in the era of the Kraken variant (XBB.1.5). In a prospective, observational study, we enrolled kidney transplant patients undergoing pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab at the Division of Infectious Diseases of Federico II University of Naples from February 2023 to August 2023. Each patient subsequently underwent a six-month follow-up with symptom monitoring and surveillance nasopharyngeal swab for SARS-CoV-2 RNA detection every 30 days, regardless of symptoms. Thirty-four kidney transplant patients were enrolled, and in the follow-up period only one tested positive for the nasopharyngeal swab for SARSCoV-2 research with asymptomatic infection and virological recovery on the eighth day after diagnosis of infection. Therefore, no patient developed disease, no patient needed hospitalization, and no death occurred. No adverse drug reaction to Tixagevimab/Cilgavimab occurred. Our data, although derived from a limited and uncontrolled sample, show the potential of Tixagevimab/Cilgavimab as a valid and viable therapeutic strategy in pre-exposure prophylaxis for immunocompromised patients. These findings highlight the importance of conducting clinical studies on this topic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL-6 with severe cases led to the early evaluation of the anti-IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID-19 sequelae, and biomarkers are needed to understand and anticipate these processes. Because extracellular vesicles (EVs) play an important role in viral infection and immune response, they could potentially serve as predictive and prognostic biomarkers. We isolated EVs from 39 patients with severe COVID-19, from which 29 received tocilizumab and 10 were considered controls. Blood samples, which were collected at hospitalisation before treatment, at Day 7, and Day 15 during follow-up, were assessed by immunoblot for longitudinal expression of spike (S) and nucleocapsid (N) proteins. Dynamic expression was calculated and compared with clinicopathological and experimental variables. Expression of EV S was validated by immunogold and imaging flow-cytometry, revealing an enrichment in CD9+ EVs. As a result, decreasing expression of EV viral proteins was observed in patients treated with tocilizumab. Moreover, higher increase in EV S was observed in patients with lower antibody response, hyperfibrinogenemia, lower respiratory function, higher blood pressure and shorter outcomes. These findings lay the foundation for future studies characterizing the role of EVs in multiorgan assessment and identifying biomarkers in patients with severe COVID-19 and possible long COVID., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Description: In March 2020, the White House Coronavirus Task Force determined that clinicians in the United States needed expert treatment guidelines to optimally manage patients with COVID-19, a potentially life-threatening disease caused by a new pathogen for which no specific treatments were known to be effective., Methods: The U.S. Department of Health and Human Services requested that the National Institutes of Health (NIH) take the lead in expeditiously convening a panel of experts to create "living" guidelines that would be widely accessible and capable of frequent updating as important new information became available., Recommendations: The purpose of this article is to expand on the experiences of the NIH COVID-19 Treatment Guidelines Panel (the Panel) over the past 4 years, summarize the Panel's final recommendations for COVID-19, highlight some challenges and unanswered questions about COVID-19 management, and inform future responses to public health emergencies. The Panel was formed in March 2020, and the first iteration of the guidelines was released in April 2020. Now that the public health emergency has ended, the NIH COVID-19 Treatment Guidelines have sunsetted. This role will now fall to professional societies and organizations, such as the American College of Physicians, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the World Health Organization, all of which have been active in this area., Competing Interests: Disclosures: Disclosure forms are available with the article online.

The most destructive period the world has experienced seems to be behind us. Not a single nation was spared by this disease, and many continue to struggle today. Even after recovering from COVID, patient may continue to experience some post-COVID effects, such as heart irregularities or a decline in lung vitality. In the past three years (2019-2022), the world has witnessed the power of a small entity, a single peculiar virus. Science initially appeared to be helpless in this regard, but due to the emergence of disease, pharmaceutics (the development of anti-covid drugs), immunology (the rapid antigen test), microbiology (the isolation of viruses from infected people), biotechnology (the development of recombinant vaccines), biochemistry (the blood profile, the D-dimer test), and biochemistry (blood profile, D-dimer test), biophysics (PCR, RT-PCR, CT Scan, MRI) had worked together to fight the disease. The results of these efforts are the development of new diagnostic techniques, possible treatment and finally the availability of vaccines against COVID-19. However, it is not proven that the treatment through the traditional medical system is directly active on SARS-CoV-2 but is instead indirectly acting on SARS-CoV-2 effects by improving symptoms derived from the viral disease. In India, the traditional system of medicine and tradition knowledge together worked in the pandemic and proved effective strategies in prevention and treatment of SARS-CoV-2. The use of effective masks, PPE kits, plasma therapy, yoga, lockdowns and social seclusion, use of modern antiviral drugs, monoclonal antibodies, herbal remedies, homoeopathy, hygienic practice, as well as the willpower of people, are all contributing to the fight against COVID. Which methods or practices will be effective against COVID nobody is aware since medical professionals who wear PPE kits do not live longer, and some people in India who remained unprotected and roamed freely were not susceptible to infection. The focus of this review is on the mode of transmission, diagnosis, preventive measures, vaccines currently under development, modern medicine developed against SARS-CoV-2, ayurvedic medicine used during pandemic, homoeopathic medicine used during pandemic, and specific yoga poses that can be used to lessen COVID-related symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10-20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort., Methods: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection., Results: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes., Conclusion: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve., (© 2024. The Author(s).)

Purpose: Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC., Methods: Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC., Results: Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants' SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001)., Conclusion: This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes., (© 2024. The Author(s).)

We study the prevalence of SARS-CoV-2 antibodies in a diverse population in Milwaukee County, Wisconsin from May 2021 to June 2022. We find that 99.4% (523/526) of the participants had positive results for antibodies to the SARS CoV2 spike protein over April-June 2022, soon after the early-2022 Omicron surge. Positive tests for spike protein antibodies were very high (86%; 19/22) even among unvaccinated persons who reported no knowledge of prior infection. Thus, by mid-2022, almost all persons were no longer COVID-naïve, defined as vaccination, infection (often without symptoms), or both. Nucleocapsid antibody tests, especially the Abbott test, were far less sensitive than spike protein tests, and Abbott test sensitivity faded with time since infection. Thus, studies which rely on nucleocapsid tests will understate prior infection rates. We also report large sample evidence on the performance of the Abbott and Roche spike and nucleocapsid protein tests in capturing prior vaccination, infection, or both. The Roche spike protein test outperforms the Abbott spike test, and the Roche nucleocapsid test greatly outperforms the Abbott nucleocapsid test., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Long-COVID caused by SARS-CoV-2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells-evolutionary old "multipurpose" innate immune cells-was reported recently in studies of acute infection and post-acute-COVID-19 syndrome. Mast cell activity has been suggested in long-COVID. In this case-control study, we compared data from 24 individuals with long-COVID (according to the NICE criteria) and 24 age- and sex-matched healthy individuals with a history of SARS-CoV-2 infection without developing sequelae. Serum levels of the proteases beta-tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance. TPSB2 and CPA3 levels were median (range) 26.9 (2.0-1000) and 5.8 (1.5-14.0) ng/mL, respectively, in the long-COVID group. The corresponding values in the control group were 10.9 (2.0-1000) (p = 0.93) and 5.3 (3.5-12.9) ng/mL (p = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF-36, 3.1-3.10 were revealed. We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long-COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long-term pathogenesis of long-COVID, at least in the majority of patients., (© 2024 The Author(s). Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.)

Long covid (persistent COVID-19) is a new disease with contested aetiology and variable prognosis. We report a 2-year ethnography of UK long covid clinics. Using a preformative lens, we show that multidisciplinary teams (MDTs) built working knowledge based on shared practices, mutual trust, distributed cognition (e.g. emails, record entries), relational knowledge of what was at stake for the patient, and harnessing uncertainty to open new discursive spaces. Most long covid MDTs performed the working knowledge of 'rehabilitation', a linked set of practices oriented to ensuring that the patient understood and strove to 'correct' maladaptive physiological responses (e.g. through breathing exercises) and pursued recovery goals, supported by physiotherapists, psychologists and generalist clinicians. Some MDTs with a higher proportion of doctors (e.g. cardiologists, neurologists, immunologists) enacted the working knowledge of 'microscopic damage', seeking to elucidate and rectify long covid's underlying molecular and cellular pathology. They justified non-standard investigations and medication in selected patients by co-constructing an evidentiary narrative based on biological mechanisms. Working knowledge was ontologically concordant within MDTs but sometimes discordant between MDTs. Overt ontological conflict occurred mostly when patients attending 'rehabilitation' clinics invoked the working knowledge of microscopic damage that had been generated and circulated in online support communities., (© 2024 The Author(s). Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

Host metabolic dysregulation, especially in tryptophan metabolism, is intricately linked to coronavirus disease 2019 (COVID-19) severity and its postacute sequelae (long COVID). People living with human immunodeficiency virus (HIV; PLWH) experience similar metabolic dysregulation and face an increased risk of developing long COVID. However, whether preexisting HIV-associated metabolic dysregulations contribute in predisposing PLWH to severe COVID-19 outcomes remains underexplored. Analyzing prepandemic samples from PLWH with documented postinfection outcomes, we found specific metabolic alterations, including increased tryptophan catabolism, predicting an elevated risk of severe COVID-19 and the incidence of long COVID. These alterations warrant further investigation for their potential prognostic and mechanistic significance in determining COVID-19 complications., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Amid efforts to develop effective treatments for acute COVID-19, there is growing recognition of the need to address long COVID as a key outcome measure. We argue there are 7 compelling reasons to include long COVID measurements in clincal trials investigating acute COVID-19 treatments: (1) Long COVID is not rare. (2) Long COVID is debilitating to individuals and has a high societal cost. (3) Those at high risk of severe COVID-19 are also at higher risk of developing long COVID if they are infected with COVID-19. (4) Treatments for acute COVID-19 may reduce the risk of long COVID. (5) Measures exist to track long COVID. (6) Long COVID considerations are potentially important for acute COVID-19 treatment decision making. (7) Deaths and hospitalizations due to COVID-19 are increasingly rare. While not every trial needs to include assessments of long COVID, it is worth the research burden to include assessments where possible, as this could facilitate the uptake of acute COVID-19 treatments that lessen the societal burden of long COVID., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. The views expressed are those of the authors and do not necessarily reflect those of the National Institutes of Health or the Department of Health and Human Services., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence. We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued. Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes. Third, studies should have multiple illness comparator cohorts for IACCIs such as myalgic encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses. Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity. Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this review was to determine the diagnostic accuracy of the currently available and upcoming point-of-care rapid antigen tests (RATs) used in primary care settings relative to the viral genetic real-time reverse transcriptase polymerase chain reaction (RT-PCR) test as a reference for diagnosing COVID-19/SARS-CoV-2 in adults., Introduction: Accurate COVID-19 point-of-care diagnostic tests are required for real-time identification of SARS-CoV-2 infection in individuals. Real-time RT-PCR is the accepted gold standard for diagnostic testing, requiring technical expertise and expensive equipment that are unavailable in most primary care locations. RATs are immunoassays that detect the presence of a specific viral protein, which implies a current infection with SARS-CoV-2. RATs are qualitative or semi-quantitative diagnostics that lack thresholds that provide a result within a short time frame, typically within the hour following sample collection. In this systematic review, we synthesized the current evidence regarding the accuracy of RATs for detecting SARS-CoV-2 compared with RT-PCR., Inclusion Criteria: Studies that included nonpregnant adults (18 years or older) with suspected SARS-CoV-2 infection, regardless of symptomology or disease severity, were included. The index test was any available SARS-CoV-2 point-of-care RAT. The reference test was any commercially distributed RT-PCR-based test that detects the RNA genome of SARS-CoV-2 and has been validated by an independent third party. Custom or in-house RT-PCR tests were also considered, with appropriate validation documentation. The diagnosis of interest was COVID-19 disease and SARS-CoV-2 infection. This review considered cross-sectional and cohort studies that examined the diagnostic accuracy of COVID-19/SARS-CoV-2 infection where the participants had both index and reference tests performed., Methods: The keywords and index terms contained in relevant articles were used to develop a full search strategy for PubMed and adapted for Embase, Scopus, Qinsight, and the WHO COVID-19 databases. Studies published from November 2019 to July 12, 2022, were included, as SARS-CoV-2 emerged in late 2019 and is the cause of a continuing pandemic. Studies that met the inclusion criteria were critically appraised using QUADAS-2. Using a customized tool, data were extracted from included studies and were verified prior to analysis. The pooled sensitivity, specificity, positive predictive, and negative predictive values were calculated and presented with 95% CIs. When heterogeneity was observed, outlier analysis was conducted, and the results were generated by removing outliers., Results: Meta-analysis was performed on 91 studies of 581 full-text articles retrieved that provided true-positive, true-negative, false-positive, and false-negative values. RATs can identify individuals who have COVID-19 with high reliability (positive predictive value 97.7%; negative predictive value 95.2%) when considering overall performance. However, the lower level of sensitivity (67.1%) suggests that negative test results likely need to be retested through an additional method., Conclusions: Most reported RAT brands had only a few studies comparing their performance with RT-PCR. Overall, a positive RAT result is an excellent predictor of a positive diagnosis of COVID-19. We recommend that Roche's SARS-CoV-2 Rapid Antigen Test and Abbott's BinaxNOW tests be used in primary care settings, with the understanding that negative results need to be confirmed through RT-PCR. We recommend adherence to the STARD guidelines when reporting on diagnostic data., Review Registration: PROSPERO CRD42020224250., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on Behalf of JBI.)

Purpose: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score., Methods: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L)., Results: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001)., Conclusion: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities., Trail Registration Number: The cohort is registered at www., Clinicaltrials: gov under NCT04768998., (© 2024. The Author(s).)

Aims: The long-term effects of COVID-19 (Long COVID) include 19 symptoms ranging from mild to debilitating. We examined multidimensional correlates of Long COVID symptom burden., Methods: This study focused on participants who reported having had COVID in Spring 2023 (n = 656; 85% female, mean age = 55, 59% college). Participants were categorized into symptom-burden groups using Latent Profile Analysis of 19 Long-COVID symptoms. Measures included demographics; quality of life and well-being (QOL); and COVID-specific stressors. Bivariate and multivariate associations of symptom burden were examined., Results: A three-profile solution reflected low, medium, and high symptom burden, aligning with diagnosis confirmation and treatment by a healthcare provider. Higher symptom burden was associated with reporting more comorbidities; being unmarried, difficulty paying bills, being disabled from work, not having a college degree, younger age, higher body mass index, having had COVID multiple times, worse reported QOL, greater reported financial hardship and worry; maladaptive coping, and worse healthcare disruption, health/healthcare stress, racial-inequity stress, family-relationship problems, and social support. Multivariate modeling revealed that financial hardship, worry, risk-taking, comorbidities, health/healthcare stress, and younger age were risk factors for higher symptom burden, whereas social support and reducing substance use were protective factors., Conclusions: Long-COVID symptom burden is associated with substantial, modifiable social and behavioral factors. Most notably, financial hardship was associated with more than three times the risk of high versus low Long-COVID symptom burden. These findings suggest the need for multi-pronged support in the absence of a cure, such as symptom palliation, telehealth, social services, and psychosocial support., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Observational studies reported worse COVID-19 evolution in relation to polypharmacy and reductions in COVID-19 hospital admissions and death in patients receiving chronic antihistamine treatment. The current profile of hospitalized patients with regard to different variants was analyzed to identify specific targets for future prospective trials., Methods: COVID-19 admissions to the Hospital of Terrassa (11 March 2020-28 August 2024 (n = 1457), from the integral Consorci Sanitari de Terrassa population (n = 167,386 people) were studied. Age, gender, the number of chronic treatments (nT), and immunization status were analyzed., Results: After 5 May 2023, 291 patients (54% females) required COVID hospitalization. Of these, 39% received >8 nT (23% receiving 5-7 nT), 70.2% were >70 years, and 93.4% survived. In total, 12% of patients admitted after 5 May 2024 were not vaccinated, while 59% received ≥4 vaccines (43% within the last 12 months). In total, 49% of admitted patients presented no previous infection (while 3% presented infection during the last year). Delta or Omicron variants would have accounted for ≥80% of admissions > 60 years compared to the first pandemic wave if no vaccines existed., Conclusions: Patients > 70 years who receive ≥5 nT, without prior COVID-19 infections, should be the priority for prevention, with updated vaccination and early treatments to reduce hospitalizations.

Objective: To evaluate both humoral and cellular immune responses to the COVID-19 messenger RNA (mRNA; BNT162b2) vaccine in patients with childhood-onset SLE (cSLE) compared with healthy controls and patient controls (kidney transplant (KTx) recipients)., Methods: This single-centre, cross-sectional and case-control study included 16 patients with cSLE, 19 healthy controls and 19 KTx recipients. We assessed SARS-CoV-2-specific humoral (anti-SARS-CoV-2 IgG, neutralising antibody (nAb)) and cellular (interferon gamma release assay (IGRA)) immune responses at least 1 month after administration of two doses of the mRNA vaccine., Results: Humoral immune response rates (anti-SARS-CoV-2 IgG and nAb seropositivity) in patients with cSLE were comparable to healthy controls (100% vs 100% and 100% vs 95%, respectively) but significantly higher than in KTx recipients (74% and 42%, p<0.05 for both). Cellular immune response rate measured by IGRA was lower in patients with cSLE compared with healthy controls (56.3% vs 89.5%, p=0.050) and comparable to KTx recipients (63%). IGRA-negative patients with cSLE had significantly lower total leucocyte and lymphocyte counts at vaccination time as compared with their counterparts (p=0.008 and p=0.001, respectively). No differences were found in disease activity or immunosuppressive therapies between IGRA-negative and IGRA-positive patients with cSLE., Conclusion: Patients with cSLE showed robust humoral but compromised cellular immune responses to the COVID-19 mRNA vaccine, associated with lower lymphocyte counts. These findings highlight the need for further research to enhance vaccine efficacy in this vulnerable group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Real-time reverse transcription polymerase chain reaction (RT-PCR), a standard method recommended for the diagnosis of coronavirus disease 2019 (COVID-19) requires 2-4 h to get the result. Although antigen test kit (ATK) is used for COVID-19 screening within 15-30 min, the drawback is its limited sensitivity. Hence, a rapid one-step quadruplex real-time RT-PCR assay: termed ƩS COVID-19 targeting ORF1ab, ORF3a, and N genes of SARS-CoV-2; and Avocado sunblotch viroid (ASBVd) as an internal control was developed. Based on strategies including designing high melting temperature primers with short amplicons, applying a fast ramp rate, minimizing hold time, and reducing the range between denaturation and annealing/extension temperatures; the assay could be accomplished within 25 min. The limit of detection of ORF1ab, ORF3a, and N genes were 1.835, 1.310, and 1 copy/reaction, respectively. Validation was performed in 205 combined nasopharyngeal and oropharyngeal swabs. The sensitivity, specificity, positive predictive value, and negative predictive value were 92.8%, 100%, 100%, and 97.1%, respectively with 96.7% accuracy. Cohen's Kappa was 0.93. The newly developed rapid real-time RT-PCR assay was highly sensitive, specific, and fast, making it suitable for use as an alternative method to support laboratory diagnosis of COVID-19 in outpatient and emergency departments., (© 2024. The Author(s).)

Background: This study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers., Methods: We studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns' blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors., Results: Our study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level., Conclusions: Our study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Hu, Cheng, Shen, Chuang, Ker, Sun and Shen.)

Patients undergoing maintenance hemodialysis (MHD) are a high-risk group susceptible to SARS-CoV-2 infection and long-COVID syndrome appearance. However, there is limited and unclear evidence for long COVID in MHD patients. We collected the general information, symptoms, signs and laboratory indices of 366 MHD patients infected with COVID-19 and conducted 12 months follow-up with a series of questionnaires. As a result, 285 MHD patients had long COVID, with the most common symptoms were fatigue (84.69%) and muscle weakness (72.45%). Mobility problem (p < 0.001), anxiety/depression (p = 0.002) and breathlessness (p < 0.001) were more prevalent in long COVID patients than in non-long COVID patients. Persistent long COVID people were more likely to report all domains problems of the EQ-5D-5L. Age, female, inadequate dialysis (Kt/V < 1.2), coagulation abnormalities (d-dimer > 1 mg/L) and more comorbidities were risk factors for the development of long COVID. In addition to these factors, elevated inflammatory markers (CRP > 10 mg/L) represent an extra risk factor for the persistence of long COVID symptoms in MHD patients. And more than 80% of long COVID symptoms would resolve after 1 year in MHD patients, of which the sixth month after COVID-19 infection is a critical turning point. In conclusion, more than 68% of MHD patients have long COVID, which has a poor impact on their health status and quality of life. These risk factors for the development and persistence of long COVID deserve the attention of clinicians., (© 2024 Wiley Periodicals LLC.)

Background: Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown., Methods and Results: Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β 1 - and β 2 -AR, but not to D1-dopamine receptor. These interactions were blocked by β 1 - and β 2 -AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs., Conclusion: Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Purpose of Review: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV., Recent Findings: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential., Methods: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires., Results: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found., Conclusions: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI., (© 2024. The Author(s).)

Objectives: SARS-CoV-2 infection could cause persistent lung injury or indicate potential genetic susceptibilities. Although infection-elicited hybrid immunity could protect against severe COVID-19, it remains unknown whether recent infection could reduce pneumonia risk during reinfection due to insufficient viral and chest computed tomography (CT) screening., Methods: A total of 15,598 patients, 96% fully vaccinated and 52% boosted, from Xiangyang, China, who had symptomatic COVID-19 and chest CT scans during the first Omicron BF.7 wave in December 2022 to January 2023, were followed through the second Omicron XBB.1.5 wave between May and August 2023. A total of 17,968 second-wave patients with COVID-19 with chest CT scans but without previous symptomatic COVID-19 were enrolled as first-time infection controls., Results: A total of 19.6% (3,061 of 15,598) first-wave patients were diagnosed with pneumonia. Among second-wave reinfected patients, only 0.2% (four of 2202) developed pneumonia, which was lower than the 1.7% (311 of 17,968) pneumonia prevalence among the second-wave first-time patients, with an adjusted relative risk of 0.11 (95% confidence interval: 0.04-0.29). A total of 1.3% (40 of 3,039) first-wave pneumonia survivors showed residual abnormal patterns in follow-up CT scans within 8 months after pneumonia diagnosis., Conclusions: In a highly vaccinated population, previous symptomatic Omicron infection within 8 months reduced pneumonia risk during reinfection. Uninfected individuals might need up-to-date vaccination to reduce pneumonia risk., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: the spread of SARS-CoV-2 in the population has amplified the effects of health inequalities, particularly in the most vulnerable groups such as immigrants and refugees. An assessment of the intervention to contain the COVID-19 in these population groups was essential to define new strategies for more equitable, inclusive, and effective health policies to on health., Objectives: to provide a systematic synopsis of the impact of interventions to contain the spread of SARS-CoV-2 in immigrants., Methods: data sources included major bibliographic databases. Using a study protocol, already shared with the international scientific community, two independent researchers reviewed the citations, selected and evaluated the interventions studies. Due to the heterogeneity of the interventions, a narrative synthesis was carried out., Results: three eligible studies were identified. The first study modelled the incidence of the disease in a refugee camp in Greece, based on an intervention of sectorialization of people that accessed to services, the use of masks, the early identification and isolation of cases and their family members, and the limitation of movements within the camp. The second evaluated the impact of preventive pharmacological interventions such as the use of hydroxychloroquine, ivermectin, povidone-iodine, zinc, and vitamin C, in different dosages and combinations, to a group of immigrant workers in a city dormitory in Singapore. The third study evaluated an intervention to increase vaccination coverage within a Latino immigrant community in the United States, moving the location of vaccine supply throughout the most frequented contexts by the immigrant community to access the city services. The results of the first and second studies suggest impacts for some of the proposed interventions even if they have been partially overcome due to the use of mass vaccination. The third showed a reduction in vaccine hesitancy and an increase in vaccination uptake and a snowball effect., Conclusions: the systematic review identified few heterogeneous studies, preventing any generalization of the results. Probably, the low scientific production does not reflect the successful experiences implemented. In the case of a possible resumption of the epidemic or new emergencies, it will be necessary to rely on indirect evidence and the scientific community should consider more the responsibility to evaluate and make available the experiences gained in the field. A constant monitoring activity of the evidence that will be necessary to updating the results for suggest consolidated prevention measures to for controlling the incidence of COVID-19 in immigrants during a possible resumption of the epidemic and for application in other similarly emergency contexts.

Objective: The prevalence of long-/post-COVID-associated chemosensory symptoms is reported in the literature to be significantly higher than clinical reality reflects., Methods: 1. N= 4062 adults acutely infected with SARS-CoV-2 and their symptoms transmitted by the Jena health office to the Robert Koch Institute between March 2020 and September 2021 were evaluated. 2. Part of the same cohort (N = 909 of 4062) answered an extensive questionnaire at least 3 months after the start of the infection, including existing chemosensory post-COVID-associated complaints. 3. Fourteen post-COVID Jena patients with chemosensory symptoms who had become acutely infected during the same period were diagnosed, treated and advised in our ENT specialist outpatient clinic., Results: The prevalence of chemosensory symptoms at the onset of infection was 19% (600/3187). About every second written respondent of the formerly acutely infected (441/890) remembered chemosensory symptoms during their COVID-19 infection. Of these, around 38% (167/441) complained of persistent chemosensory post-COVID symptoms after an average of 14.5 months. Only 2.3% (14/600) of the previously acutely infected patients with chemosensory symptoms sought medical help in a special consultation. Quantitative chemosensory damage could only be objectified in half, i.e. 1.2% (7/600) of the total cohort., Conclusions: Despite a high prevalence of subjective chemosensory symptoms in acutely and formerly SARS-CoV-2 infected people, there is only a low need for specialized treatment, so that, unlike other post-COVID-associated complaints, the healthcare system as a whole appears to be less significantly burdened., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Post-COVID-19 condition, or syndrome, also known as long COVID, is an infection-associated chronic condition that can develop after a SARS-CoV-2 infection and last at least 3 months to years. Despite representing a high burden for the Unified Health System (SUS), which has affected millions of Brazilians, it has received limited attention in Brazil. Prevalence studies to date have failed to include a broad representation of the population, and there has been insufficient exploration of the impact on people's lives and the burden of and barriers to accessing health services. This article presents the research protocol for the quantitative component of a mixed methods project to produce evidence to inform SUS's provision of care for long COVID. The protocol was designed to study long COVID in SUS patients hospitalised for COVID-19 in a large city in Southeast Brazil to capture symptoms and factors associated with the syndrome, effects on quality of life and employment, health needs, use of health services and barriers to accessing necessary healthcare., Methods and Analysis: An ambidirectional cohort study to capture data retrospectively and prospectively from adults previously discharged from SUS hospitals for COVID-19. The study involves up to two telephone surveys with the patients or proxies selected from a sampling plan for population estimates. Survey questions include baseline and follow-up data on demographic, socioeconomic, comorbidities, work status, health-related quality of life, vaccination status, long COVID symptoms, healthcare needs, use and barriers to access. Descriptive and appropriate multivariable analyses will be employed., Ethics and Dissemination: The project was approved by the Research Ethics Committees of participant institutions and by the Brazilian National Research Ethics Commission. All participants provided verbal consent. We plan to publish articles in scientific journals and multimedia resources for SUS professionals and the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs., (© 2024 International Union of Biochemistry and Molecular Biology.)

Recipients of cellular therapies, including hematopoietic cell transplant (HCT) and chimeric antigen receptor T-cell (CART) therapy, are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). There are limited data describing outcomes among patients in the pre- and early post-cellular therapy period during the Omicron era when multiple antiviral therapeutics were widely available. The objective of this study is to describe COVID-19 treatment and outcomes in patients diagnosed with COVID-19 during the pre- or early post-cellular therapy period. This is a single-center retrospective cohort study of adult HCT and CART recipients diagnosed with COVID-19 in the pre- and early post-cellular therapy period who tested positive for COVID-19 at our cancer center between January 1, 2022 and March 1, 2023. Primary outcomes were 30-day COVID-19-related hospitalization and death. A secondary outcome was development of persistent COVID-19, defined by a positive SARS-CoV-2 polymerase chain reaction (PCR) 31 to 90 days after COVID-19 diagnosis. Among 65 patients included, 52 (80%) received at least one COVID-19 therapeutic. The most common treatment after initial COVID-19 diagnosis was nirmatrelvir/ritonavir (29%), followed by monoclonal antibody therapy (26%) and remdesivir (11%). Of the 64 patients with at least 30 days of follow-up, 8 (12%) had at least one COVID-19-related hospitalization and one patient died, though cause of death was not due to COVID-19. Of the 8 patients hospitalized for COVID-19, one had severe disease and 7 had mild or moderate infection. Persistent COVID-19 was observed in 13/65 (20%) patients, with 4 patients requiring additional antiviral therapy. Three pre-cellular therapy patients had delays in receiving cellular therapy due to persistent COVID-19. During the Omicron era, rates of 30-day COVID-19-related hospitalization and death were relatively low in this cohort of pre- and early post-HCT and CART recipients, the majority of whom received treatment with at least one antiviral agent. Persistent COVID-19 occurred in 1 in 5 patients in the peri-cellular therapy period and led to cellular therapy treatment delays in several patients, highlighting the need for new COVID-19 treatment strategies., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus disease 2019 (COVID-19) pandemic has raised questions about its impact on pediatric asthma. This review analyzes the latest research to offer a comprehensive understanding of the dynamics between COVID-19 and pediatric asthma., Areas Covered: This narrative review examines the effects of COVID-19 on pediatric asthma, exploring clinical outcomes, immune responses, recommended treatments, the impact of SARS-CoV-2 strains, and COVID-19 vaccination. Data were sourced from databases (PubMed, Embase, and BioRxiv/MedRxiv) from January 2020 to November 2023., Expert Opinion: In response to the COVID-19 pandemic, the international scientific community rapidly developed extensive knowledge, demonstrating unprecedented cooperation. Despite these advances, questions remain about SARS-CoV-2 infection and pediatric asthma. Most research consists of epidemiological studies with varying methods, sometimes yielding contradictory results. While asthma generally did not increase the risk of severe COVID-19 in children, uncontrolled asthma was a risk factor, highlighting the importance of maintaining asthma management. Telemedicine has proven effective for asthma control and will continue to grow, despite its limitations. Notably, allergic asthma may have a protective role against severe COVID-19. We recommend COVID-19 vaccination in the pediatric age group, including those with asthma.

The COVID-19 pandemic had a disproportionate impact on ethnically minoritised and other marginalised communities, yet little is known about the impacts of long COVID-19 (LC) on this group. Living with LC takes its toll both physically, emotionally and financially and even more so when a diagnosis is hard to come by. By using qualitative interviews centring the view of undiagnosed and marginalised communities already classed as 'underserved' in the medical literature, we show the range of barriers and impacts faced by these groups in the UK, and the strategies of resilience they use. Whether trapped on a 'diagnostic odyssey' at the level of primary care, struggling to maintain employment and businesses, or managing family commitments, we argue many minoritised communities are caught in a liminal space of misrecognition, invalidation and ambiguity. We show how these impacts are generated by tensions and challenges in the process and categorisation of diagnosis, and how this effects the daily lives of many individuals already on the receiving end of health inequity. We also offer some examples and suggestions for best practices., (© 2024 The Author(s). Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for the Sociology of Health & Illness.)

Since the onset of the COVID-19 pandemic, a variety of diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as the gold standard. However, a significant challenge in COVID-19 diagnostics is the wide range of symptoms presented by patients, necessitating early and accurate diagnosis for effective management. Although RT-qPCR is a precise molecular technique, it is not immune to false-negative results. In contrast, CRISPR-based detection methods for SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, and specific, and they do not require sophisticated instruments. These methods also show promise for scalability, enabling diagnostic tests. CRISPR technology can be customized to target any genomic region of interest, making it a versatile tool with applications beyond diagnostics, including therapeutic development. The CRISPR/Cas systems provide precise gene targeting with immense potential for creating next-generation diagnostics and therapeutics. One of the key advantages of CRISPR/Cas-based therapeutics is the ability to perform multiplexing, where different sgRNAs or crRNAs can target multiple sites within the same gene, reducing the likelihood of viral escape mutants. Among the various CRISPR systems, CRISPR/Cas13 and CARVER (Cas13-assisted restriction of viral expression and readout) are particularly promising. These systems can target a broad range of single-stranded RNA viruses, making them suitable for the diagnosis and treatment of various viral diseases, including SARS-CoV-2. However, the efficacy and safety of CRISPR-based therapeutics must be thoroughly evaluated in pre-clinical and clinical settings. While CRISPR biotechnologies have not yet been fully harnessed to control the current COVID-19 pandemic, there is an optimism that the limitations of the CRISPR/Cas system can be overcome soon. This review discusses how CRISPR-based strategies can revolutionize disease diagnosis and therapeutic development, better preparing us for future viral threats.

Objective: To describe the preparedness for, epidemiological characteristics of and public health responses to the first and second waves of coronavirus disease 2019 (COVID-19) in six remote Aboriginal and Torres Strait Islander communities in Queensland from late 2021., Design: This was a descriptive epidemiological study. Data were collated by each participating public health unit. Case and outbreak characteristics were obtained from the statewide Notifiable Conditions System., Setting, Participants: Six discrete remote First Nations communities across Queensland were selected to represent a broad geographic spread across the state: Badu Island, Cherbourg, Lockhart River, Palm Island, Woorabinda and Yarrabah. People with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result recorded between 13 December 2021 and 12 June 2022 who acquired the infection and isolated in one of the six communities., Main Outcome Measures: COVID-19 vaccination coverage among First Nations people; number of COVID-19 cases reported; and attack rates for each community., Results: All six First Nations communities led the COVID-19 preparedness and planning. COVID-19 vaccination coverage rates before the first outbreak ranged from 59% to 84% for the first dose and from 39% to 76% for the second dose across the six communities. During the study period, 2624 cases of COVID-19 in these communities were notified to Queensland Health. Attack rates for each community were: Badu Island, 23%; Cherbourg, 34%; Lockhart River, 18%; and Palm Island, Woorabinda and Yarrabah, 35% each. The 2624 cases included 52 cases (2%) involving hospital admission and two cases (< 1%) in which the person died from COVID-19., Conclusions: It is likely that the co-designed, collaborative partnerships between local councils, community-controlled health services, state health services and public health units positively impacted the management and outcomes of COVID-19 in each of the six communities., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40-1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79-1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58-1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir., (© 2024. The Author(s).)

Background: The COVID-19 disease requires accurate diagnosis to effectively manage infection rates and disease progression. The study aims to assess the relationship between vaccination status and RT-PCR cycle threshold (Ct) values by comparing clinical, RDT and RT-PCR results., Methods: A total of 453 suspected COVID-19 cases were included in this study. Nasopharyngeal swabs were collected for both RDT and RT-PCR testing, with RDTs conducted on-site and RT-PCR at the Ethiopian Public Health Institute (EPHI) genomics laboratory. Detailed clinical, RDT, and RT-PCR results were analyzed. Data analysis included descriptive statistics, cross-tabulation, and Chi-Square tests to investigate the connections between diagnostic outcomes and vaccination status, with a focusing on Ct values., Results: RDT results showed 34.0% negative and 65.8% positive, while RT-PCR results indicated 35.8% negative and 64.2% positive cases. The discrepancies between RDT and RT-PCR results emphasize the importance of thorough testing. No significant association was found between vaccination status and viral load, as indicated by Ct values. Among RT-PCR positive cases, 49.8% had been vaccinated, suggesting challenges in interpreting results among vaccinated individuals. Further analysis revealed that vaccination (first or second dose) had minimal impact on Ct values, indicating limited influence of vaccination status on viral load dynamics in infected individuals., Conclusions: The study highlights the significant differences between RDT and RT-PCR outcomes, underscoring the need for a comprehensive testing approach. Additionally, the findings suggest that vaccination status does not significantly impact RT-PCR Ct values, complicating the interpretation of diagnostic results in vaccinated individuals, especially in breakthrough infections and potential false positives., (© 2024. The Author(s).)

"Long COVID", which describes a diverse set of symptoms or conditions that persist or develop after four weeks from the onset of initial SARS-CoV-2 infection has been introduced. However, the true prevalence varies worldwide. This study aimed to determine the point prevalence and clinical characteristics of long COVID at three and six months after acute COVID-19 infection in Thailand. Methods All adult patients who were diagnosed with COVID-19 by positive nasopharyngeal RT-PCR for SARS-CoV-2 at Thammasat University Hospital between October and December 2021 were recruited and followed for long COVID symptoms by telephone interviews at 3 and 6 months after an acute infection. Among 1,400 eligible COVID-19 cases, interviews were complete for 1,129 and 932 individuals at 3 and 6 months, respectively. Of those, 431 and 314 reported at least one symptom consistent with long COVID. The point prevalence was 38.2% (95% confidence interval: 35.3-41.1%) and 33.7% (95% confidence interval: 30.7-36.7%) respectively. Female gender, disease severity, and symptomatic acute infection were identified as independent risk factors. Conclusion Based on the reported symptoms, long COVID is commonly observed either at 3 or 6 months in our study., (© 2024. The Author(s).)

Since the beginning of the coronavirus disease (COVID) 2019 pandemic, thousands of articles on the topic have been published, and although there is a growing trend of research on another associated condition, long coronavirus disease, important points still remain to be clarified in this respect. Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID. However, one of the existing gaps that requires further investigation concerns a possible relationship between gut candidiasis and long COVID. While recent studies also suggest an interplay between the occurrence of these two conditions, it is not yet fully clear how this may happen, as well as the specifics regarding the possible pathophysiological mechanisms involved. In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID, a better understanding of the clinical presentation, pathophysiology and clinical management of such a relationship should be essential and useful for both, additional advances towards more targeted research and appropriate case management. Knowing more about the signs, symptoms, and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population. In light of this and the need for better outcomes, here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis, as well as suggest propositions for future related research., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. Tovani-Palone MR discontinued his affiliation with SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, India., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Long COVID, a type of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) defined by medically unexplained symptoms following infection with SARS-CoV-2, is a newly recognized infection-associated chronic condition that causes disability in some people. Substantial progress has been made in defining its epidemiology, biology, and pathophysiology. However, there is no cure for the tens of millions of people believed to be experiencing long COVID, and industry engagement in developing therapeutics has been limited. Here, we review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. Progress toward preventing and curing long COVID and other infection-associated chronic conditions will require deep and sustained investment by funders and industry., Competing Interests: Declaration of interests M.J.P. has received consulting fees from Gilead Sciences, AstraZeneca, BioVie, Apellis Pharmaceuticals, and BioNTech and research support from Aerium Therapeutics and Shionogi outside the submitted work. S.G.D. reports consulting for Enanta Pharmaceuticals, BioVie, and Pfizer and reports research support from Aerium Therapeutics outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This article investigates the factors that contributed to the proliferation of online COVID skepticism on Twitter across Italian municipalities in 2020. We demonstrate that sociodemographic factors were likely to mitigate the emergence of skepticism, whereas populist political leanings were more likely to foster it. Furthermore, pre-COVID anti-vaccine sentiment, represented by "old truthers" on Twitter, amplified online COVID skepticism in local communities. Additionally, exploiting the spatial variation in restrictive economic policies with severe implications for suspended workers in nonessential economic sectors, we find that COVID skepticism spreads more in municipalities significantly affected by the economic lockdown. Finally, the diffusion of COVID skepticism is positively associated with COVID vaccine hesitancy., (Copyright © 2024 The Authors.)

Objectives: This study aims to identify COVID-19 breakthrough infections among people with HIV (PWH) across different phases of the pandemic and explore whether differential immune dysfunctions are associated with breakthrough infections., Design and Methods: This retrospective population-based cohort study used data from an integrated electronic health record (EHR) database in South Carolina (SC). Breakthrough infection was defined as the first COVID-19 diagnosis documented in the state agency after the date an individual was fully vaccinated (ie, 2 doses of Pfizer/BNT162b2 or Moderna/mRNA-1273, or 1 dose of Janssen/Ad26.COV2.S) through June 14, 2022. We analyzed the risk and associated factors of the outcome using Cox proportional hazards models., Results: Among 7596 fully vaccinated PWH, the overall rate of breakthrough infections was 118.95 cases per 1000 person-years. When compared with the alpha-dominant period, the breakthrough infection rate was higher during both delta-dominant (HR: 1.50; 95% CI: 1.25 to 1.81) and omicron-dominant (HR: 2.86; 95% CI: 1.73 to 4.73) periods. Individuals who received a booster dose had a lower likelihood of breakthrough infections (HR: 0.19; 95% CI: 0.15 to 0.24). There was no association of breakthrough infections with degree of HIV viral suppression, but a higher CD4 count was significantly associated with fewer breakthroughs among PWH (>500 vs <200 cells/mm3: HR: 0.68; 95% CI: 0.49 to 0.94)., Conclusions: In our PWH population, the incidence of breakthrough infections was high (during both delta-dominant and omicron-dominant periods) and mainly associated with the absence of a booster dose in patients older than 50 years, with comorbidities and low CD4 count., Competing Interests: Dr. G.A.P. is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. G.A.P. provides consultative advice to AiZtech; Emergent Biosolutions; GlaxoSmithKline; Invivyd; Janssen Global Services, LLC; Merck & Co. Inc.; Moderna; Novavax; and Syneos Health. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. G.A.P. holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. G.A.P. has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. G.A.P. is an adviser to the White House and World Health Organization on COVID-19 vaccines and monkeypox, respectively., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)