Non-immunocompromised Individuals Research Articles

Impact of Immunosuppressants and Vaccination on COVID-19 Outcomes in Autoimmune Patients and Solid Organ Transplant Recipients: A Nationwide Propensity Score-Matched Study.

This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies.

The Adequacy of Current Legionnaires' Disease Diagnostic Practices in Capturing the Epidemiology of Clinically Relevant Legionella: A Scoping Review.

Legionella is an underdiagnosed and underreported etiology of pneumonia. Legionella pneumophila serogroup 1 (LpSG1) is thought to be the most common pathogenic subgroup. This assumption is based on the frequent use of a urinary antigen test (UAT), only capable of diagnosing LpSG1. We aimed to explore the frequency of Legionella infections in individuals diagnosed with pneumonia and the performance of diagnostic methods for detecting Legionella infections. We conducted a scoping review to answer the following questions: (1) "Does nucleic acid testing (NAT) increase the detection of non-pneumophila serogroup 1 Legionella compared to non-NAT?"; and (2) "Does being immunocompromised increase the frequency of pneumonia caused by non-pneumophila serogroup 1 Legionella compared to non-immunocompromised individuals with Legionnaires' disease (LD)?". Articles reporting various diagnostic methods (both NAT and non-NAT) for pneumonia were extracted from several databases. Of the 3449 articles obtained, 31 were included in our review. The most common species were found to be L. pneumophila, L. longbeachae, and unidentified Legionella species appearing in 1.4%, 0.9%, and 0.6% of pneumonia cases. Nearly 50% of cases were caused by unspecified species or serogroups not detected by the standard UAT. NAT-based techniques were more likely to detect Legionella than non-NAT-based techniques. The identification and detection of Legionella and serogroups other than serogroup 1 is hampered by a lack of application of broader pan-Legionella or pan-serogroup diagnostics.

COVID-19 Reinfection Has Better Outcomes Than the First Infection in Solid Organ Transplant Recipients.

Solid organ transplant recipients face an increased risk of severe coronavirus disease 2019 (COVID-19) and are vulnerable to repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In nonimmunocompromised individuals, SARS-CoV-2 reinfections are milder likely because of cross-protective immunity. We sought to determine whether SARS-CoV-2 reinfection exhibits milder manifestations than primary infection in transplant recipients. Using a large, prospective cohort of adult transplant patients with COVID-19, we identified patients with SARS-CoV-2 reinfections. We performed a 1:1 nearest neighbor propensity score matching to control potential confounders, including the COVID-19 variant. We compared outcomes including oxygen requirement, hospitalization, and intensive care unit admission within 30 d after diagnosis between patients with reinfection and those with the first episode of COVID-19. Between 2020 and 2023, 103 reinfections were identified in a cohort of 1869 transplant recipients infected with SARS-CoV-2 (incidence of 2.7% per year). These included 50 kidney (48.5%), 27 lung (26.2%), 7 heart (6.8%), 6 liver (5.8%), and 13 multiorgan (12.6%) transplants. The median age was 54.5 y (interquartile range [IQR], 40.5-65.5) and the median time from transplant to first infection was 6.6 y (IQR, 2.8-11.2). The time between the primary COVID-19 and reinfection was 326 d (IQR, 226-434). Three doses or more of SARS-CoV-2 vaccine are received by 87.4% of patients. After propensity score matching, reinfections were associated with significantly lower hospitalization (5.8% versus 19.4%; risk ratio, 0.3; 95% CI, 0.12-0.71) and oxygen requirement (3.9% versus 13.6%; risk ratio, 0.29; 95% CI, 0.10-0.84). In a within-patient analysis only in the reinfection group, the second infection was milder than the first (3.9% required oxygen versus 19.4%, P < 0.0001), and severe first COVID-19 was the only predictor of severe reinfection. Transplant recipients with COVID-19 reinfection present better outcomes than those with the first infection, providing clinical evidence for the development of cross-protective immunity.

Long-Term Analyses of SARS-CoV-2 Humoral and T Cell Responses and Breakthrough SARS-CoV-2 Infections after Two Doses of BNT162b2 Followed by mRNA-1273 and Bivalent Omicron-Adapted BNT162b2 Vaccines: A Prospective Study over 2 Years in Non-Immunocompromised Individuals.

Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (p < 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting.

The Association Between Physical Distancing Behaviors to Avoid COVID-19 and Health-Related Quality of Life in Immunocompromised and Nonimmunocompromised Individuals: Patient-Informed Protocol for the Observational, Cross-Sectional EAGLE Study.

Immunocompromised individuals are known to respond inadequately to SARS-CoV-2 vaccines, placing them at high risk of severe or fatal COVID-19. Thus, immunocompromised individuals and their caregivers may still practice varying degrees of social or physical distancing to avoid COVID-19. However, the association between physical distancing to avoid COVID-19 and quality of life has not been comprehensively evaluated in any study. We aim to measure physical distancing behaviors among immunocompromised individuals and the association between those behaviors and person-centric outcomes, including health-related quality of life (HRQoL) measures, health state utilities, anxiety and depression, and work and school productivity impairment. A patient-informed protocol was developed to conduct the EAGLE Study, a large cross-sectional, observational study, and this paper describes that protocol. EAGLE is designed to measure distancing behaviors and outcomes in immunocompromised individuals, including children (aged ≥6 mo) and their caregivers, and nonimmunocompromised adults in the United States and United Kingdom who report no receipt of passive immunization against COVID-19. We previously developed a novel self- and observer-reported instrument, the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19), to measure physical distancing behavior levels cross-sectionally and retrospectively. Using an interim or a randomly selected subset of the study population, the PDS-C19 psychometric properties will be assessed, including structural validity, internal consistency, known-group validity, and convergent validity. Associations (correlations) will be assessed between the PDS-C19 and validated HRQoL-related measures and utilities. Structural equation modeling and regression will be used to assess these associations, adjusting for potential confounders. Participant recruitment and data collection took place from December 2022 to June 2023 using direct-to-patient channels, including panels, clinician referral, patient advocacy groups, and social media, with immunocompromising diagnosis confirmation collected and assessed for a randomly selected 25% of immunocompromised participants. The planned total sample size is 3718 participants and participant-caregiver pairs. Results will be reported by immunocompromised status, immunocompromising condition category, country, age group, and other subgroups. All data analyses and reporting were planned to be completed by December 2023. Results are planned to be submitted for publication in peer-reviewed journals in 2024-2025. This study will quantify immunocompromised individuals' physical distancing behaviors to avoid COVID-19 and their association with HRQoL as well as health state utilities. RR1-10.2196/52643.

Dendritic Cells: Multifunctional Roles in Host Defenses to Cryptococcus Infections.

Fungal infections are an increasingly growing public health concern, and Cryptococcus is one of the most problematic fungal organisms causing substantial mortality and morbidity worldwide. Clinically, this high incidence of cryptococcosis is most commonly seen in immunocompromised patients, especially those who lack an adaptive T cell response, such as HIV/AIDS patients. However, patients with other underlying immunodeficiencies are also at an increased risk for cryptococcosis. The adaptive immune response, in particular the Th1/Th17 T-cell-mediated responses, to pulmonary Cryptococcus infections are required for host protection. Dendritic cells (DCs), encompassing multiple subsets identified to date, are recognized as the major professional antigen-presenting cell (APC) subset essential for the initiation and execution of T-cell immunity. Apart from their prominent role in orchestration of the adaptive arm of the immune defenses, DCs are fully armed cells from the innate immune system capable of the recognition, uptake, and killing of the fungal cells. Thus, DCs serve as a critical point for the endpoint outcomes of either fungal control or unrestrained fungal infection. Multiple studies have shown that DCs are required for anti-cryptococcal defense in the lungs. In addition, the role of DCs in Cryptococcus gattii infections is just starting to be elucidated. C. gattii has recently risen to prominence with multiple outbreaks in the US and Canada, demonstrating increased virulence in non-immunocompromised individuals. C. gattii infection fails to generate an inflammatory immune response or a protective Th1/Th17 T cell response, at least in part, through a lack of proper DC function. Here we summarize the multiple roles of DCs, including subsets of DCs in both mouse and human models, the roles of DCs during cryptococcal infection, and mechanisms by cryptococcal cells to attempt to undermine these host defenses.

Predominantly defective CD8+ T cell immunity to SARS-CoV-2 mRNA vaccination in lung transplant recipients

BackgroundAlthough mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness.MethodsComparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation.ResultsIonophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (< 0.01%) when tested 2 weeks after vaccination or later, but were detectable after in vitro culture of PBMCs with mRNA-1273 vaccine to enrich memory T cell responses. This was also seen in COVID-19-recovered lung transplantation recipients. Comparison of their enriched memory responses to controls revealed relatively similar CD4+ T cell memory, but markedly reduced CD8+ T cell memory both after primary vaccination or a booster dose. These responses were not correlated to age or time after transplantation. The vaccine-induced CD4+ and CD8+ responses correlated well in the healthy control group, but poorly in the transplantation groups.ConclusionsThese results reveal a specific defect in CD8+ T cells, which have key roles both in transplanted organ rejection but also antiviral effector responses. Overcoming this defect will require strategies to enhance vaccine immunogenicity in immunocompromised persons.

SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study.

The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood. We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. We tested for SARS-CoV-2 spike protein (anti-S) IgG; nucleocapsid protein (anti-N) IgG; neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains; and SARS-CoV-2-specific T-cell receptors (TCRs). The primary outcome was a comparison of anti-S IgG titers at the post-V2 time point in participants initiating vaccinations <4 months versus 4-12 months after HCT using a propensity-adjusted analysis. We also evaluated factors associated with high-level anti-S IgG titers (≥2403 U/mL) in logistic regression models. Between April 22, 2021 and November 17, 2021, 175 allogeneic HCT recipients were enrolled in the study, of whom all but one received mRNA SARS-CoV-2 vaccines. SARS-CoV-2 anti-S IgG titers, neutralizing antibody titers, and TCR breadth and depth did not significantly differ at all tested time points following the second vaccination among those initiating vaccinations <4 months versus 4-12 months after HCT. Anti-S IgG ≥2403 U/mL correlated with neutralizing antibody levels similar to those observed in a prior study of non-immunocompromised individuals, and 57% of participants achieved anti-S IgG ≥2403 U/mL at the end-of-study time point. In models adjusted for SARS-CoV-2 infection pre-enrollment, SARS-CoV-2 vaccination pre-HCT, CD19+ B-cell count, CD4+ T-cell count, and age (as applicable to the model), vaccine initiation timing was not associated with high-level anti-S IgG titers at the post-V2, post-V3, or end-of-study time points. Notably, prior graft-versus-host-disease (GVHD) or use of immunosuppressive medications were not associated with high-level anti-S IgG titers. Grade ≥3 vaccine-associated adverse events were infrequent. These data support starting mRNA SARS-CoV-2 vaccination three months after HCT, irrespective of concurrent GVHD or use of immunosuppressive medications. This is one of the largest prospective analyses of vaccination for any pathogen within the first year after allogeneic HCT and supports current guidelines for SARS-CoV-2 vaccination starting three months post-HCT. Additionally, there are few studies of mRNA vaccine formulations for other pathogens in HCT recipients, and these data provide encouraging proof-of-concept for the utility of early vaccination targeting additional pathogens with mRNA vaccine platforms. National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.

Association between Adverse Reactions and Humoral Immune Response No Longer Detectable after BNT162b2 Booster Vaccination.

In a previous study, we described a highly significant association between reactogenicity and SARS-CoV-2 RBD IgG titers and wild-type neutralization capacity in males after basic vaccination with BNT162b2. The objective of this study was to assess whether this benefit was long lasting and also evident after BNT162b2 booster vaccination. Reactogenicity was classified into three groups: no or minor injection site symptoms, moderate (not further classified) and severe adverse reactions (defined as any symptom(s) resulting in sick leave). We initially compared 76 non-immunocompromised individuals who reported either no or minor injection site symptoms or severe adverse reactions after second vaccination. In total, 65 of them took part in another blood sampling and 47 were evaluated after booster vaccination. 26 weeks after second vaccination, men who reported severe adverse reactions after second vaccination had 1.7-fold higher SARS-CoV-2 RBD IgG titers (p = 0.025) and a 2.5-fold better neutralization capacity (p = 0.006) than men with no or only minor injection site symptoms. Again, no association was found in women. Reactogenicity of BNT162b2 booster vaccination was different from second vaccination according to our classification and was no longer associated with SARS-CoV-2 RBD IgG titers or wild-type neutralization capacity. To conclude, after BNT162b2 basic vaccination, the association between reactogenicity and humoral immune response in men persisted over time but was no longer detectable after BNT162b2 booster vaccination.

A six-year hospital-based surveillance study on burden of esophageal candidiasis in Gangtok, Sikkim.

Esophageal candidiasis once thought to be restricted amongst immunocompromised patients is being increasingly reported among non-immunocompromised individuals. It is debilitating and if not treated well may cause chronic long-lasting infections. The objective of this study was to identify the various species of Candida causing esophageal candidiasis and analyse their antifungal susceptibility pattern. This was an observational, prospective study. Total of 108 patients who attended the Gastroenterology Department of Sir Thutob Namgyal Memorial Hospital, Govt of Sikkim, Gangtok, India between July 2012 - May 2018 were included in the study. They had complaints of upper gastrointestinal disturbances and chronic dyspeptic symptoms that required an endoscopy. Esophageal biopsy and brushings were taken and were transported to Microbiology Department. They were subjected to microscopic observation, fungal culture on Sabourauds dextrose agar. Preliminary species identification was done by chlamydospore formation and growth characteristics on CHROMagar Candida. Species confirmation and antifungal susceptibility testing was done on VITEK 2 system at Microbiology Department, Kasturba Medical College and Hospital, MAHE, Manipal, Karnataka, India. A total of 108 patients were screened among which 73 samples were positive for Candida species and species identification and antifungal susceptibility was performed. Forty fiveisolates were found to be C. albicans, 8 were C. glabrata, 4 were C. tropicalis, 3 were C. lusitaniae 2 were C. krusei, 2 were C. lipolyticaand 1 was C. parapsilosis. Eight isolates could not be identified and were recorded as Candida spp. C. albicans isolates were predominantly sensitive strain with susceptibility of 95% for both amphotericin B and fluconazole and 100% for caspofungin. C. glabrata showed high resistance to fluconazole with one isolate showing intermediate resistance to caspofungin. Upper gastrointestinal symptoms even in non-immunocompromised patients need to be screened by endoscopy to rule out esophageal candidiasis. With the emergence of drug resistant non albicans Candida species diagnostic testing laboratories should include Candida species identification and antifungal susceptibility testing facility to provide effective patient care.

Yellow fever vaccine safety in immunocompromised individuals: a systematic review and meta-analysis.

Yellow fever (YF) is an arbovirus with variable severity, including severe forms with high mortality. The vaccination is the most effective measure to protect against the disease. Non-serious and serious adverse events have been described in immunocompromised individuals, but previous studies have failed to demonstrate this association. This systematic review assessed the risk of adverse events after YF vaccination in immunocompromised individuals compared with its use in non-immunocompromised individuals. A search was conducted in the MEDLINE, LILACS, EMBASE, SCOPUS, DARE, Toxiline, Web of Science and grey literature databases for publications until February 2021. Randomized and quasi-randomized clinical trials and observational studies that included immunocompromised participants (individuals with HIV infection, organ transplants, with cancer, who used immunosuppressive drugs for rheumatologic diseases and those on immunosuppressive therapy for other diseases) were selected. The methodological quality of observational or non-randomized studies was assessed by the ROBINS-I tool. Two meta-analyses were performed, proportion and risk factor analyses, to identify the summary measure of relative risk (RR) in the studies that had variables suitable for combination. Twenty-five studies were included, most with risk of bias classified as critical. Thirteen studies had enough data to carry out the proposed meta-analyses. Seven studies without a comparator group had their results aggregated in the proportion meta-analysis, identifying an 8.5% [95% confidence interval (CI) 0.07-21.8] risk of immunocompromised individuals presenting adverse events after vaccination. Six cohort studies were combined, with an RR of 1.00 (95% CI 0.78-1.29). Subgroup analysis was performed according to the aetiology of immunosuppression and was also unable to identify an increased risk of adverse events following vaccination. It is not possible to affirm that immunocompromised individuals, regardless of aetiology, have a higher risk of adverse events after receiving the YF vaccine.

Characterization of Chronic Hepatitis E Virus Infection in Immunocompetent Rabbits.

Chronic hepatitis E virus (HEV) infection is frequently reported in immunocompromised patients, but has also been increasingly reported in non-immunocompromised individuals. We characterized the course of chronic HEV infection in immunocompetent rabbits. In two independent experiments, 40 specific-pathogen-free rabbits were infected with a rabbit HEV genotype 3 strain in serial diluted titers (108 to 104 copies/mL). Serum and fecal samples were collected weekly and were tested for HEV RNA, antigen, anti-HEV and liver enzymes. Rabbits that spontaneously cleared the infection before 10 weeks post-inoculation (wpi) were kept to the end of the study as recovery control. Liver tissues were collected from HEV-infected rabbits at 5, 10 and 26 wpi for histopathological analysis. Nineteen rabbits (47.5%) developed chronic HEV infection with persistent viraemia and fecal HEV shedding for >6 months. Seroconversion to anti-HEV was observed in 84.2% (16/19) of the chronically infected rabbits. Serum levels of aminotransferase were persistently elevated in most of the rabbits. Characterizations of chronic HEV infection in immunocompetent settings could be recapitulated in rabbits, which can serve as a valuable tool for future studies on pathogenesis.

Oxidative stress and endogenous DNA damage in blood mononuclear cells may predict anti-SARS-CoV-2 antibody titers after vaccination in older adults

Immune senescence in the elderly has been associated with chronic oxidative stress and DNA damage accumulation. Herein we tested the hypothesis that increased endogenous DNA damage and oxidative stress in peripheral blood mononuclear cells of older adults associate with diminished humoral immune response to SARS-CoV-2 vaccination. Increased oxidative stress and DNA double-strand breaks (DSBs) were detected in 9 non-immunocompromised individuals aged 80–96 years compared to 11 adults aged 27–44 years, before, as well as on days 1 and 14 after the first dose, and on day 14 after the second dose of the BNT162B2-mRNA vaccine (all p < 0.05). SARS-CoV-2 vaccination induced a resolvable increase in oxidative stress and DNA damage, but individual DSB-repair efficiency was unaffected by vaccination irrespective of age, confirming vaccination safety. Individual titers of anti-Spike-Receptor Binding Domain (S-RBD)-IgG antibodies, and the neutralizing capacity of circulating anti-SARS-CoV-2 antibodies, measured on day 14 after the second dose in all participants, correlated inversely with the corresponding pre-vaccination endogenous oxidative stress and DSB levels (all p < 0.05). In particular, a strong inverse correlation of individual pre-vaccination DSB levels with both the respective anti-S-RBD-IgG antibodies titers (r = −0.867) and neutralizing capacity of circulating anti-SARS-CoV-2 antibodies (r = −0.983) among the 9 older adults was evident. These findings suggest that humoral responses to SARS-CoV-2 vaccination may be weaker when immune cells are under oxidative and/or genomic stress. Whether such measurements may serve as biomarkers of vaccine efficacy in older adults warrants further studies.

Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals

ObjectivesThis study aimed to evaluate the associations between COVID-19 severity and active viral load, and to characterize the dynamics of active SARS-CoV-2 clearance in a series of archival samples taken from patients in the first wave of COVID-19 infection in the South West of the UK. MethodsSubgenomic RNA (sgRNA) and E-gene genomic sequences were measured in a retrospective collection of PCR-confirmed SARS-CoV-2-positive samples from 176 individuals, and related to disease severity. Viral clearance dynamics were then assessed in relation to symptom onset and last positive test. ResultsWhilst E-gene sgRNAs declined before E-gene genomic sequences, some individuals retained sgRNA positivity for up to 68 days. 13% of sgRNA-positive cases still exhibited clinically relevant levels of virus after 10 days, with no clinical features previously associated with prolonged viral clearance times. ConclusionsOur results suggest that potentially active virus can sometimes persist beyond a 10-day period, and could pose a potential risk of onward transmission. Where this would pose a serious public health threat, additional mitigation strategies may be necessary to reduce the risk of secondary cases in vulnerable settings.

Comparison of COVID-19 outcomes in organ transplant recipients (OTr) and non-transplant patients: a study protocol for rapid review

BackgroundThe COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals.MethodsMEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders.DiscussionThis rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics.Systematic review registrationOpen Science Framework (OSF) registration DOI: https://doi.org/10.17605/osf.io/4n9d7.

Coronavirus disease 2019 in liver transplant patients: Clinical and therapeutic aspects.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.

A case report of brain abscess caused by Nocardia farcinica

BackgroundBrain abscess due to the Nocardia genus is rarely reported and it is usually found in immunocompromised patients. Treatment of Nocardia brain abscess is troublesome and requires consideration of the severity of the underlying systemic disease. The difficulties in identifying the bacterium and the frequent delay in initiating adequate therapy often influence the prognosis of patients.Case presentationHere, we report a rare case of brain abscess caused by Nocardia farcinica. The patient’s medical history was complicated: he was hospitalized several times, but no pathogens were found. At last, bacteria were found in the culture of brain abscess puncture fluid; the colony was identified as Nocardia farcinica by mass spectrometry. Targeted antibiotic treatment was implemented, brain abscess tended to alleviate, but the patient eventually developed fungal pneumonia and died of acute respiratory distress syndrome (ARDS).ConclusionBrain abscess caused by Nocardia farcinica can appear in non-immunocompromised individuals. Early diagnosis, reasonable surgical intervention, and targeted antibiotic treatment are critical for Nocardia brain abscess treatment. In the treatment of Nocardia brain abscess, attention should paid be to the changes in patients’ immunity and infection with other pathogens, especially fungi, avoided.

OCULAR TOXOPLASMOSIS

Toxoplasmosis in humans is a zoonotic parasitic disease caused by a ubiquitous protozoan, Toxoplasma gondii. Toxoplasmosis is an opportunistic infection that can cause serious damage in immunocompromised patients. While in the non-immunocompromised individuals it is most often latent and asymptomatic, about one-third of the world’s population is estimated to be infected. Toxoplasmosis is the most common cause of posterior uveitis in non-immunocompromised individuals and the second most common cause of chorioretinitis after cytomegalovirus infection in people with HIV / AIDS. The infection can be acquired congenitally or postnatally and ocular lesions may present during or years after the occurance of the acute infection. Molecular biology techniques to diagnose ocular toxoplasmosis have been available for many years and are now accessible as standard laboratory tests in many countries. Aqueous humor or vitreous evaluation to detect parasite DNA by polymerase chain reaction or specific antibodies may provide evidence for diagnosis. Oral pyrimethamine and sulfadiazine plus corticosteroids are an effective therapy for ocular toxoplasmosis. Recent data supports the use of other treatment options, including intravitreal antibiotics. The aim of the present review is to discuss briefly the new diagnostic and treatment approaches for ocular toxoplasmosis.

Chronic Pulmonary Histoplasmosis-A Scoping Literature Review.

Chronic pulmonary histoplasmosis (CPH) is an uncommon manifestation of Histoplasma infection with features similar to pulmonary tuberculosis (TB). In endemic areas, it may be misdiagnosed as smear-negative pulmonary TB. Historical case series mainly from patients with presumed TB described a high frequency of cavitation and poor prognosis, likely resulting from delayed presentation. More recent reports suggest that CPH can present with nodules, lymphadenopathy, or infiltrates, with cavities being a less common feature. Emphysema is the main risk factor for cavitary CPH. CPH is therefore an umbrella term, with chronic cavitary pulmonary histoplasmosis and Histoplasma nodules being the main long-term manifestations in nonimmunocompromised individuals. Diagnosis relies on a high index of suspicion, use of fungal culture of respiratory samples, antibody testing, and compatible radiological picture. Treatment with itraconazole for at least 12 months is recommended. Morbidity from CPH results from slow progression of cavities and gradual loss of lung function, especially if not recognized and treated. Studies on the epidemiology of CPH are needed in order to improve understanding of the disease.

1562 Rare Intestinal Spirochetosis Masquerading as a Colonic Polyp

INTRODUCTION: Spirochetosis in colonic mucosa is exceedingly rare in non-immunocompromised individuals. There have been less than 200 cases documented and more rare with the specific B. Pilosicoli genus. Spirochetosis is also seen in individuals who engage in high risk sexual encounters. This type of spirochetosis is found mosty in dogs, cats, pigs and chickens. Symptoms in humans include diarrhea, rectal bleeding, and abdominal cramps. Colonic spirochetosis is more common in third world countries. Even in immunocompromised state of health and with all other factors there is much unknown about colonic spirochetosis. Due to its infrequency the treatment is metronidazole and repeat colonoscopy and biopsy should symptoms persist. CASE DESCRIPTION/METHODS: Patient is a 62 year old male patient who presented as an outpatient consultation for screening colonoscopy. The patient complains of abdominal pain for several months that is localized in the right upper quadrant. The patient describes the pain as moderate to sharp and only last a few minutes after onset. Patient also reported post prandial fullness, abdominal bloating and distention. The patient denied rectal bleeding, melena, constipation, or pain on evacuation. The patient denies other symptoms. The patient has no medical history and only surgery was an elective laparoscopic cholecystectomy. The Decision was made to undergo screening colonoscopy. The patient had no history of immunocompromised state or HIV/AIDS. The patient denies anal sex. Colonoscopy revealed he had two polyps. One in the ascending colon and the other in the rectum. The specimens were sent for pathology for analysis. Ascending polyp was analyzed and it demonstrated colonic mucosa consistent with intestinal spirochetosis specifically Brachyspira pilosicoli. The rectal polyp was hyperplastic no adenomatous change. DISCUSSION: This case was chosen because only 200 known cases of colonic mucosa infected with spirochetosis have been documented. The patient is not immunocompromised, does not engage in anal sex, is not in a third world country, and does not have typical symptomatology of infection with Spirochetosis. In general colonic involvement with spirochetosis is very misunderstood due to its infrequency. The genus of B.pilosicoli. Is a spirochete genus that has limited data on how many cases have been documented. The presentation as a colonic polyp as a masquerade for actice spirochetosis infection prompts further study.