Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection (LRTI) and hospitalization in infants. However, the mechanisms of immune control in infants ...remain incompletely understood. Antibody profiling against attachment (G) and fusion (F) proteins in children less than 2 years of age, with mild (outpatients) or severe (inpatients) RSV disease, indicated substantial age-dependent differences in RSV-specific immunity. Maternal antibodies were detectable for the first 3 months of life, followed by a long window of immune vulnerability between 3 and 6 months and a rapid evolution of FcγR-recruiting immunity after 6 months of age. Acutely ill hospitalized children exhibited lower G-specific antibodies compared with healthy controls. With disease resolution, RSV-infected infants generated broad functional RSV strain-specific G-responses and evolved cross-reactive F-responses, with minimal maternal imprinting. These data suggest an age-independent RSV G-specific functional humoral correlate of protection, and the evolution of RSV F-specific functional immunity with disease resolution.
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•Observed age-dependent differences in RSV antibodies in the first 2 years of life•G-responses were decreased in severe RSV disease but enriched in mild RSV infection•Strain-specific G-specific immunity, but cross-reactive F-specific immunity, evolves over time•No evidence of maternal imprinting was observed on newly evolving RSV humoral immunity
Infants are highly vulnerable to RSV infection. However, the contribution of the evolving RSV-specific humoral immune response to RSV immunity remains incompletely understood. Nziza et al. profiled pediatric humoral immunity to RSV fusion and attachment antigens. The study identifies age-dependent RSV-specific humoral profiles, demonstrating a profound window of immune vulnerability in infants, and functional immune correlates of protection against RSV disease.
Guillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the ...blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity.
We retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups.
In this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group.
Anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.
•In 170 Guillain-Barré syndrome (GBS) patients, antinuclear antibodies (ANAs) positive rate was 27.1%, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common.•GBS patients with ANAs positive group had longer days of hospitalization, more respiratory function involvement, higher levels of CSF IgG, lower scores of MRC on admission and at nadir and higher scores of HFGS on admission and at nadir, significantly higher EGRIS compared with ANAs negative group.•The anti-SSA-60 antibodies and age had a correlation with GBS severity.•In anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher scores of HFGS on admission/at nadir and lower scores of MRC at nadir.
Background: Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse oscillometry (IOS) is a ...non-invasive method that uses sound waves to estimate lung function and airway resistance. The aim of this study was to assess the usefulness of IOS in predicting the severity of bronchiectasis.
Methods: We retrospectively reviewed the IOS parameters and clinical characteristics in 145 patients diagnosed with bronchiectasis between March 2020 and May 2021. Disease severity was evaluated using the FACED score, and patients were divided into mild and moderate/severe groups.
Results: Forty-four patients (30.3%) were in the moderate/severe group, and 101 (69.7%) were in the mild group. Patients with moderate/severe bronchiectasis had a higher airway resistance at 5 Hz (R5), a higher difference between the resistance at 5 and 20 Hz (R5-R20), a higher resonant frequency (Fres), and a higher area of reactance (AX) than patients with mild bronchiectasis. R5 ≥0.43, resistance at 20 Hz (R20) ≥0.234, R5-R20 ≥28.3, AX ≥1.02, reactance at 5 Hz (X5) ≤-0.238, and Fres ≥20.88 revealed significant univariable relationships with bronchiectasis severity (p<0.05). Among these, only X5 ≤-0.238 exhibited a significant multivariable relationship with bronchiectasis severity (p=0.039). The receiver operating characteristic curve for predicting moderate-to-severe bronchiectasis of FACED score based on IOS parameters exhibited an area under the curve of 0.809.
Conclusion: The IOS assessed by the disease severity of FACED score can effectively reflect airway resistance and elasticity in bronchiectasis patients and serve as valuable tools for predicting bronchiectasis severity.
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•Galectin-9 is known for its immunomodulatory role in innate and adaptive immunity.•Plasma levels of Galectin-9 are elevated in various pathophysiological conditions.•Galectin-9 ...levels correlate positively with parameters of disease severity.•Galectin-9 is a potentially reliable, sensitive and non-invasive biomarker.
Galectin-9 (Gal-9) is a β-galactoside binding lectin known for its immunomodulatory role in various microbial infections. Gal-9 is expressed in all organ systems and localized in the nucleus, cell surface, cytoplasm and the extracellular matrix. It mediates host-pathogen interactions and regulates cell signalling via binding to its receptors. Gal-9 is involved in many physiological functions such as cell growth, differentiation, adhesion, communication and death. However, recent studies have emphasized on the elevated levels of Gal-9 in autoimmune disorders, viral infections, parasitic invasion, cancer, acute liver failure, atopic dermatitis, chronic kidney disease, type-2 diabetes, coronary artery disease, atherosclerosis and benign infertility-related gynecological disorders. In this paper we have reviewed the potential of Gal-9 as a reliable, sensitive and non-invasive biomarker of disease severity. Tracking changes in Gal-9 levels and its implementation as a biomarker in clinical practice will be an important tool to monitor disease activity and facilitate personalized treatment decisions.
COVID-19 is a viral infection that disturbs the host's immune system and causes an overproduction of cytokines leading to a cytokine storm. The present study aimed to evaluate the serum levels of 27 ...protein biomarkers to determine their association with COVID-19 disease severity.
The serum levels of 89 patients with different degrees of COVID-19 disease severity asymptomatic (n = 14), moderate (n = 14), severe (n = 30), and critical (n = 31) and 14 healthy individuals were tested for a panel of 27 cytokines and chemokines using Luminex assay (27 Bio‑Plex Pro Human Cytokine, Bio-rad™).
IL-12, IL-2 and IL-13, as well as IL-17 and GM-CSF were clearly undetectable in asymptomatic patients. IL-8 levels were higher in asymptomatic compared with other groups. Very high levels of IL-6, IL-10 and the chemokines MIP-1α, MCP-1 and IP10 were associated with disease progression, while IL-4 tends to decrease with disease severity.
Our study provides more evidence that excessive cytokine synthesis is linked to the disease progression.
•the rapid rise and decline of admissions and decreased severity of COVID-19 disease•compares 466 patients in the Omicron wave to 3962 patients in previous waves•describes disease severity of all ...admitted patients at peak bed occupancy•a lower mortality rate from Omicron compared to previous waves
The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves.
466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council.
For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years.
Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave.
Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths
compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital.
There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.
T Cell Responses to SARS-CoV-2 Sette, Alessandro; Sidney, John; Crotty, Shane
Annual review of immunology,
04/2023, Volume:
41
Journal Article
Peer reviewed
Open access
A large body of evidence generated in the last two and a half years addresses the roles of T cells in SARS-CoV-2 infection and following vaccination. Infection or vaccination induces multi-epitope ...CD4 and CD8 T cell responses with polyfunctionality. Early T cell responses have been associated with mild COVID-19 outcomes. In concert with animal model data, these results suggest that while antibody responses are key to prevent infection, T cell responses may also play valuable roles in reducing disease severity and controlling infection. T cell memory after vaccination is sustained for at least six months. While neutralizing antibody responses are impacted by SARS-CoV-2 variants, most CD4 and CD8 T cell responses are preserved. This review highlights the extensive progress made, and the data and knowledge gaps that remain, in our understanding of T cell responses to SARS-CoV-2 and COVID-19 vaccines.
Introduction: To the best of our knowledge, a new emerging viral infection induced by SARS-CoV-2 was named COVID-19 with high morbidity and mortality on a global scale. To date, COVID-19 is implied ...as a respiratory disease with varied manifestations from asymptomatic to long-standing complications. In this regard, discerning a potential prognostic value of critical outcomes in the early stages would be more appreciable to stratify the risk of disease severity and 28-day mortality. In this clinical study, we aimed to evaluate distinct laboratory biomarkers, including neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), and lactate dehydrogenase (LDH), as reliable indicators to predict disease severity in COVID-19 patients admitted in a medical referral center. Methods: Following the COVID-19 diagnosis, all consecutive patients (n=685) with confirmed SARS-CoV-2 infection were included since September 2020 for one year. Data were collected using electronic medical records. Results: Based on obtained results, NLR and serum level of LDH showed a positive correlation with length of hospital stay. Moreover, the mortality rate and MV required in patients with either positive CRP or the high levels of LDH were remarkably greater than that of the non-severe group (P=0.01). Finally, we could not find significant differences between female and male patients regarding the evaluated parameters. Conclusion: Our findings highlighted those high values of NLR, CRP, and LDH can be considered valuable clinical prognostic aids for risk stratification, identification of disease severity, and triage of patients at the time of admission.
Introduction
Coronavirus disease 2019 (COVID‐19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its ...association with COVID‐19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID‐19 as well as describe the differences in outcomes between patients with and without pre‐existing hypothyroidism using an observational, multinational registry.
Methods
In an observational cohort study we enrolled patients 18 years or older, with laboratory‐confirmed severe acute respiratory syndrome coronavirus‐2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID‐19 hospitalization, (2) in‐hospital mortality and (3) hospital‐free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality.
Results
Among the 20,366 adult patients included in the study, pre‐existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59–80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre‐existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio OR: 1.02; 95% confidence interval CI: 0.92, 1.13; p = .69), in‐hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital‐free days (estimated difference 0.01 days; 95% CI: −0.45, 0.47; p = .97). Pre‐existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis.
Conclusions
In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID‐19. Pre‐existing hypothyroidism in hospitalized patients with COVID‐19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID‐19 on the thyroid gland and its function is needed in the future.
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