Mild Disease Research Articles

Features of the covid-19 epidemic and characteristics of patients during the spread of the delta SARS-COV-2 in Russia

Aim: To study the manifestations of the COVID-19 epidemic and the clinical and epidemiological characteristics of adult patients with a new coronavirus infection during the dominance of the Delta SARS-COV-2 in the Russian Federation.Materials and Methods: Study included patients aged ≥18 years with a laboratory-confirmed diagnosis of COVID-19, detected in the period from 09/01/2021 to 11/30/2021 (n= 2 619 298) in 85 Russian regions.Results: There were 2 periods of rise and decline in the COVID-19 incidence and mortality during the spread of the Delta SARS-CoV-2 in Russia: June-September and OctoberDecember 2021 (Wald – Wolfowitz criterion, p<0,05). The median age of patients was 49 [36–63] years, 61,1% were women. Most of patients were 30–39 years old (21,0%), the lowest proportion was among 18–29 years old (12.1%) (p<0,05). Proportion of patients with mild disease was 75,4%, moderate – 18,8%, severe – 3,3%, extremely severe – 2,5% (p<0.05). Hospitalization rate was 23,7%, proportion of patients treated in the intensive care unit was 12.9%, and rate of invasive mechanical ventilation was 9,8%. The median period from the onset of symptoms to the diagnosis was 3 [1-6] days, the duration of the disease and hospitalization was 13,0 [10–16] and 12,0 [9–17] days, respectively. The median age of the deceased patients was 73 [65–82] years, of which 59,1% were women, 61,5% were persons ≥70 years old. The presence of one or more comorbidities was found in 73,9% of deceased patients (OR=17,1; 95% CI: 16,8–17,3).Conclusion: during the period of the spread of the Delta SARS-COV-2 variant in Russia, the number of patients with severe and extremely severe disease among adult patients without taking into account the vaccine history was 5,8%. Old age and the presence of concomitant diseases were key risk factors for adverse outcomes of COVID-19.

Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease.

Accumulation of pathological tau isoforms, especially hyperphosphorylated tau at serine 396 (pS396-tau) and tau oligomers, has been demonstrated in the retinas of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Previous studies have noted a decrease in retinal ganglion cells (RGCs) in AD patients, but the presence and impact of pathological tau isoforms in RGCs and RGC integrity, particularly in early AD stages, have not been explored. To investigate this, we examined retinal superior temporal cross-sections from 25 patients with MCI (due to AD) or AD dementia and 16 cognitively normal (CN) controls, matched for age and gender. We utilized the RGC marker ribonucleic acid binding protein with multiple splicing (RBPMS) and Nissl staining to assess neuronal density in the ganglion cell layer (GCL). Our study found that hypertrophic RGCs containing pS396-tau and T22-positive tau oligomers were more frequently observed in MCI and AD patients compared to CN subjects. Quantitative analyses indicated a decline in RGC integrity, with 46-55% and 55-56% reductions of RBPMS+ RGCs (P<0.01) and Nissl+ GCL neurons (P<0.01-0.001), respectively, in MCI and AD patients. This decrease in RGC count was accompanied by increases in necroptotic-like morphology and the cleaved caspase-3 apoptotic marker in RGCs of AD patients. Furthermore, there was a 2.1 to 3.1-fold increase (P<0.05-0.0001) in pS396-tau-laden RGCs in MCI and AD patients, with a greater abundance observed in individuals with higher Braak stages (V-VI), more severe clinical dementia ratings (CDR=3), and lower mini-mental state examination (MMSE) scores. Strong correlations were noted between the decline in RGCs and the total amount of retinal pS396-tau and pS396-tau+ RGCs, with pS396-tau+ RGC counts correlating significantly with brain neurofibrillary tangle scores (r= 0.71, P= 0.0001), Braak stage (r= 0.65, P= 0.0009), and MMSE scores (r= -0.76, P= 0.0004). These findings suggest that retinal tauopathy, characterized by pS396-tau and oligomeric tau in hypertrophic RGCs, is associated with and may contribute to RGC degeneration in AD. Future research should validate these findings in larger cohorts and explore noninvasive retinal imaging techniques that target tau pathology in RGCs to improve AD detection and monitor disease progression.

Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3+CD4+CD154+ T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+ T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+ T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Gestational SARS-CoV-2 Infection in a Ugandan Birth Cohort: High Incidence, Mild Maternal Disease, and Evidence of Association with Transient Infant Stunting.

Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

Unraveling the Mechanisms of MicroRNA in Suppressing Hepatitis B Virus Progression: A Comprehensive Review for Designing Treatment Strategies

: Liver cancer and cirrhosis caused by the Hepatitis B virus (HBV) remain significant global health challenges due to the virus's high prevalence and contagious nature. Hepatitis B virus can be transmitted through various means, leading to mild or severe liver disease. Although an effective prophylactic vaccine is available, it offers limited benefits for those already chronically infected. Current treatments often fail to consistently eliminate the virus and can cause severe adverse effects. In response to these challenges, researchers have begun exploring microRNAs (miRNAs) as novel therapeutic targets. Studying miRNA-virus interactions presents a promising opportunity to identify potential therapeutic targets. By manipulating host miRNAs, researchers aim to enhance antiviral defenses, restore cellular balance, and prevent viral replication. The text concludes by highlighting the potential for personalized medicine in Hepatitis B treatment, guided by individual miRNA profiles. Numerous studies have been conducted to understand how different miRNAs inhibit HBV replication, paving the way for the development of innovative and effective therapeutic strategies.

Teatime: epigallocatechin gallate targets fibroblast-epithelial cell crosstalk to combat lung fibrosis.

Epigallocatechin gallate (EGCG) is a polyphenol plant metabolite abundant in tea that has demonstrated antifibrotic properties in the lung. In this issue of the JCI, Cohen, Brumwell, and colleagues interrogated the mechanistic action of EGCG by investigating lung biopsies of patients with mild interstitial lung disease (ILD) who had undergone EGCG treatment. EGCG targeted the WNT inhibitor SFRP2, which was enriched in fibrotic fibroblasts and acted as a TGF-β target, with paracrine effects leading to pathologic basal metaplasia of alveolar epithelial type 2 cells. This study emphasizes the epithelial-mesenchymal trophic unit as a central signaling hub in lung fibrosis. Understanding and simultaneous targeting of interlinked signaling pathways, such as TGF-β and WNT, paves the road for future treatment options for pulmonary fibrosis.

Association between dietary inflammatory index and disease activity in patients with ulcerative colitis

Considering the influence of dietary factors on inflammatory markers that may affect the disease course in patients with ulcerative colitis (UC), this study aimed to assess the association between dietary inflammatory index (DII) score and disease activity in patients with ulcerative colitis. This cross-sectional study included 158 patients with UC. The Mayo Clinic score was used to determine the disease severity. A food frequency questionnaire was applied to gather the dietary information, then the Shivappa et al. method was used for the calculation of DII. An association between disease severity (dependent factor) and DII score quartiles (independent factors) was conducted by a logistic regression adjusted to different covariates. In this study, 53.8% of participants were in remission or had mild disease activity. The mean DII score was − 0.24 ± 0.66. The mean DII score was significantly lower in patients with remission (-0.34 ± 0.71) compared with patients who were in the active phase (-0.1 ± 0.57) of UC (P = 0.02). The results of the logistic regression analysis showed that after adjusting for confounding factors, the odds of severe disease were 3.33 times higher among patients who had a more pro-inflammatory diet compared with patients who had an anti-inflammatory diet [OR: 3.33 (95%CI: 1.13, 9.76), p = 0.02]. In conclusion, there was a significant association between higher intake of a pro-inflammatory diet and UC severity. So, from a clinical point of view, there is a need to apply an anti-inflammatory diet to decrease disease severity in patients with ulcerative colitis.

Long-term benefit of ustekinumab in ulcerative colitis in clinical practice: ULISES study.

Ustekinumab is approved for ulcerative colitis (UC). To assess the durability of ustekinumab in patients with UC and its short-term effectiveness, durability and tolerability in clinical practice. Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission. We included 620 patients; 155 (25%) discontinued ustekinumab during follow-up (median 12 months). Rate of discontinuation was 20% per patient-year of follow-up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1-2.1), steroids at baseline (HR 1.5; 95% CI 1.06-2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09-2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid-free clinical remission. Moderate-severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2-0.5), male sex (OR 0.5; 95% CI 0.4-0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6-0.8) were associated with lower likelihood of steroid-free clinical remission at week 16. One hundred and seventy-six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune-mediated diseases. Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies.

The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022.

Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

Effectiveness of Serious Games in Evaluating Cognitive Status of the Elderly: A Systematic Review And Meta-Analysis.

Early diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is very important in better management of these diseases, and serious games play an effective role in helping to diagnose these diseases more accurately owing to their innovative features. With respect to the diversity of available games, the purpose of this study was to investigate the effectiveness of using serious games to assess the cognitive status of the elderly at risk of MCI/AD. A systematic review was conducted and the correlation of serious game results with cognitive test scores were extracted from eligible studies for meta-analysis. We analyzed the correlation between the results of serious games with the scores of mini-mental state examination (MMSE), Addenbrooke's Cognitive Examination-revised edition (ACE-R), and Montreal Cognitive Assessment (MoCA) tests to evaluate cognitive status of the elderly at risk of MCI/AD, as well as the cognitive aspects examined by these tests. The random-effects model was used to obtain the overall correlation coefficient to assess the relationship between the results of serious games and the above mentioned paper-and-pencil tests. The correlation of game results with the MMSE, ACE-R, and MoCA was 0.604, 0.682, with 0.682, respectively. The correlation between the results of the games with the score of each cognitive aspect was also calculated. Overall, there is a positive correlation between serious game scores in terms of accurate patients' reactions with the scores of MMSE, ACE-R, and MoCA tests. Among the cognitive aspects, the highest correlation was obtained for fluency (0.591). For abstraction, however, the correlation was the lowest (0.036). In all three tests, the correlation was >0.6 and in cognitive aspects was <0.6. Thus, more studies should be conducted to develop serious games that are more in line with cognitive tests.

Association of the Mediterranean diet with arterial stiffness, inflammation, and medication use in women with systemic lupus erythematosus: An exploratory study

Patients with systemic lupus erythematosus (SLE) face increased cardiovascular risk not fully explained by traditional cardiovascular risk factors. Arterial stiffness, inflammation and disease-related therapies may be contributors to augmented cardiovascular risk, whereas healthy dietary habits could help in their management. The aim of the present study was to analyze the association of the adherence to the Mediterranean Diet with arterial stiffness, inflammation, and disease-related medication in women with SLE. A total of 76 women with SLE were included in this cross-sectional exploratory study. The adherence to the Mediterranean Diet was assessed using the Mediterranean Diet Score. Arterial stiffness was measured through pulse wave velocity (PWV). Inflammatory profile was evaluated through high-sensitivity C-reactive protein (hsCRP). The use (yes / no) and doses (mg /day and cumulative dose over the last 3 years) of corticosteroids and immunosuppressants were also registered. No association of the overall adherence to the Mediterranean Diet with PWV, hsCRP or medication use was found (all P>.05). Lower intake of full dairy products was related to greater odds of corticosteroids use (odds=1.72; P=.004), and both higher current (β=0.29; P=.024) and cumulative (β=0.21; P=.040) doses. Lower intake of red wine was associated with lower odds of immunosuppressants use (odds=0.63; P=.008). No association of the adherence to the Mediterranean Diet with arterial stiffness, inflammation or disease-related medication was observed in women with SLE with mild disease activity. However, higher dairy products and lower red wine consumption were related to lower use of disease-related medication. Future intervention studies are needed to better understand how nutritional education promoting Mediterranean Diet food groups can complement conventional SLE treatments.

Clinical practice guideline supported administration of monoclonal antibody therapy for high-risk patients with COVID-19: Experience of a quaternary care centre

Background: Immunocompromised patients remain at risk of progression to severe COVID-19 disease. Methods: We describe clinical COVID-19-related outcomes after administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) following institutional clinical practice guidelines (CPGs) in 205 high-risk patients between November 2021 and April 2022 at a Canadian quaternary care centre. Results: Median patient age was 59 years; 102 (50%) were female. Eighty-two (40%) were transplant recipients, 47 (23%) patients had hematologic malignancies, 25 (12%) had solid organ malignancies, and 51 (25%) had another indication. Forty-eight (23%) had received fewer than two doses of anti-SARS-CoV-2 vaccines. The majority (80%) had mild disease at presentation with 14% moderate and 6% severe. Median time from symptom onset to mAb administration was 3 days (IQR 2.0-5.5 days). Of those who received mAb as outpatients, 90 (93%) had favourable clinical outcomes (no COVID-19-related hospitalizations or death within 3 months). Of those who received mAb as inpatients, 93 (86%) had favourable outcomes (discharged without COVID-19-related re-admission or death), 4% were re-admitted, and 10% died. In logistic regression analysis, only disease severity at time of mAb administration was associated with unfavourable outcomes. Fewer than two vaccine doses was not associated with unfavourable outcomes, suggesting potential benefit among the under-vaccinated. There was a significant difference in adherence to CPGs between administration of mAb in outpatients versus inpatients (adherent for 85% versus 58%, p&lt;0.001), where non-adherence occurred in cases of severe disease. Conclusion: CPG-supported mAb administration for management of COVID-19 in high-risk patients was associated with favourable clinical outcomes and may be a useful model to guide future therapies.

Altered Endoplasmic Reticulum Integrity and Organelle Interactions in Living Cells Expressing INF2 Variants.

The cytoskeleton mediates fundamental cellular processes by organizing inter-organelle interactions. Pathogenic variants of inverted formin 2 (INF2) CAAX isoform, an actin assembly factor that is predominantly expressed in the endoplasmic reticulum (ER), are linked to focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) neuropathy. To investigate how pathogenic INF2 variants alter ER integrity, we used high-resolution live imaging of HeLa cells. Cells expressing wild-type (WT) INF2 showed a predominant tubular ER with perinuclear clustering. Cells expressing INF2 FSGS variants that cause mild and intermediate disease induced more sheet-like ER, a pattern similar to that seen for cells expressing WT-INF2 that were treated with actin and microtubule (MT) inhibitors. Dual CMT-FSGS INF2 variants led to more severe ER dysmorphism, with a diffuse, fragmented ER and coarse INF2 aggregates. Proper organization of both F-actin and MT was needed to modulate the tubule vs. sheet conformation balance, while MT arrays regulated spatial expansion of tubular ER in the cell periphery. Pathogenic INF2 variants also induced mitochondria fragmentation and dysregulated mitochondria distribution. Such mitochondrial abnormalities were more prominent for cells expressing CMT-FSGS compared to those with FSGS variants, indicating that the severity of the dysfunction is linked to the degree of cytoskeletal disorganization. Our observations suggest that pathogenic INF2 variants disrupt ER continuity by altering interactions between the ER and the cytoskeleton that in turn impairs inter-organelle communication, especially at ER-mitochondria contact sites. ER continuity defects may be a common disease mechanism involved in both peripheral neuropathy and glomerulopathy.

Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus.

We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests. We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI). Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5-73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34-46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7-164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1-48.5) or HCs (38.9 pmol/L, IQR 34.0-46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4-224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8-46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632-0.801), hematological (AUC, 0.740; 95% CI, 0.648-0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669-0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc. Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.

Epidemiological Features of the COVID-19 and Characteristics of Patients during the Spread of the Omicron SARS-COV-2 in Russia

Aim. To analyze dynamic of incidence and mortality of COVID-19 and clinical and epidemiological characteristics of adult patients with a new coronavirus infection during the early period of the Omicron SARS-COV-2 distribution in Russia. Materials and Methods. We conducted a retrospective analysis of the dynamics of COVID-19 incidence and mortality in Russia until 2023. Study included patients aged ≥18 years with a laboratory-confirmed diagnosis of COVID-19, detected in the period from 01/02/2022 to 14/03/2022 (n = 3 582 688) in 85 regions of Russia. Participants were included regardless their COVID-19 vaccination history. Results. We identified 6 periods of rise and decline in the COVID-19 incidence until 2023 in Russia. The 5th (January–July 2022) and the 6th (August-November 2022) periods were associated with the spread of the Omicron SARS-CoV-2. The median age of patients in the early period of Omicron spreading was 49 (36–62) years, 62.7% were women. The largest proportion of patients were represented by the age groups 30–39 and 40–49 years (19.2% each), the lowest – 18–29 years (12.3%). Proportion of patients with mild disease was 90.0%, moderate – 8.5%, severe – 0.9%, extremely severe – 0.6%. Hospitalization rate, proportion of patients treated in the intensive care unit and rate of invasive mechanical ventilation were 7.6%, 9.5% and 6.7% respectively. The median period from the onset of symptoms to the diagnosis was 2 (1–3) days, median of duration of the disease was 8 (6-10) days and median duration of hospitalization was 10 (7–14) days. The median age of the deceased patients was 77 (69–84) years, of which 50.8% were women, 72.6% were persons ≥70 years old. One or more concomitant diseases were detected among 8.7% of patients who became ill and 75.8% of those who died. The probability of hospitalization, admission to the ICU, IMV and death in patients with one or more concomitant diseases were 24.5, 3.2, 3.5 and 35.8 times higher, respectively, compared with patients without concomitant diseases. Conclusion. In the early period of the spread of the Omicron variant in Russia, among adult patients with COVID-19, excluding their vaccine history, the frequency of severe and extremely severe forms of infection was 1.5%. The elderly age and the presence of concomitant diseases remained key risk factors for the development of adverse outcomes of the COVID-19

The spectrum of systemic sclerosis-associated pulmonary hypertension: Insights from the ASPIRE registry

There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). Data for 912 systemic sclerosis patients assessed between 2000and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society(ESC/ERS) guidelines and multimodality investigations. Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15mmHg had similar haemodynamics and left atrial volumes to those with PAWP>15mmHg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.

SARS-CoV-2 infection and vaccination in patients with pituitary diseases: the experience of a Brazilian reference center.

To evaluate the prevalence and characteristics of SARS-CoV-2 infection, and the prevalence, efficacy, and safety of anti-SARS-CoV-2 vaccination in patients with pituitary diseases. Observational, cross-sectional study of adult patients with pituitary diseases followed in a reference center. Clinical data were collected and a questionnaire about SARS-CoV-2 infection, vaccination and its possible adverse effects was applied. COVID-19 disease severity was defined as mild, moderate, and severe according to the WHO classification. 145 patients were studied (79 women; age 50 ± 15.8 years; duration of pituitary disease 16.8 ± 11.5 years), the cause of pituitary disease was tumoral in 74.5%, and 45.9% were on glucocorticoid replacement due to ACTH deficiency. SARS-CoV-2 infection was confirmed in 51 patients (35.2%; 32 women; age 53.8 ± 14.8 years, 22 before vaccination), with 28 (54.9%), 17 (33.3%) and 6 (11.8%) cases of mild, moderate, and severe disease, respectively, and hospitalization was indicated in 7 (14%) cases. One mild case presented pituitary apoplexy after SARS-CoV-2 infection. Advanced age was a risk factor for COVID-19. Patients with moderate and severe forms of COVID-19 had higher prevalence of dyslipidemia and duration of pituitary disease. All but one of the participants were vaccinated against COVID-19, and 60.4% had adverse events, the most common local pain (54.0%), fever (33.3%), and headache (18.4%), with one case of alopecia and two of persistent fatigue. The prevalence of SARS-CoV-2 infection in our cohort was 35.2%, including 14% of moderate and severe cases requiring hospitalization. The vaccination was universal and safe.

Long COVID syndrome: An unfolding enigma.

Post-acute sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19), called as long COVID syndrome, is a major global public health issue after recovery from COVID-19. The disease occurs in symptomatic patients irrespective of illness severity. The symptoms continue after four wk of recovery from acute illness and persist beyond three months. Risk factors for long COVID include older age, female gender, multiple co-morbidities including diabetes mellitus, prior chronic respiratory illnesses, hospitalized patients with severe disease, especially receiving assisted ventilation, high viral load, reactivation of Epstein Barr (EB) virus and human herpes virus 6 (HH6), circulating auto antibodies against various organs and type I interferon. The prevalence varies from 10 to 20 per cent, and most data have been reported from high-income countries. Any system can get involved in long COVID. The symptoms include fatigue, cognition impairment, cough and dyspnoea, anosmia, hair loss and diarrhoea, among others. While there are no laboratory tests for confirmation of diagnosis, reduced complement C7 complexes at six months, and a two-gene biomarker including FYN and SARS-CoV-2 antisense ribonucleic acid (RNA) are emerging as potentially useful biomarkers for long COVID. There should be no alternative disease to explain various symptoms. Vaccination against SARS-CoV-2 and early use of oral antiviral nirmatrelvir within the first five days in patients with acute mild disease having various risk factors for progression to severe disease help in preventing long COVID. Several clinical trials are underway for the treatment of long COVID and the results of these are eagerly awaited. Physical and mental rehabilitation at home, at community level or in the hospital setting as appropriate is essential in patients with long COVID.

Different DLCO Parameters as Predictors of Postoperative Pulmonary Complications in Mild Chronic Obstructive Pulmonary Disease Patients with Lung Cancer.

Numerous studies have investigated methods of predicting postoperative pulmonary complications (PPCs) in lung cancer surgery, with chronic obstructive pulmonary disease (COPD) and low forced expiratory volume in 1 second (FEV1) being recognized as risk factors. However, predicting complications in COPD patients with preserved FEV1 poses challenges. This study considered various diffusing capacity of the lung for carbon monoxide (DLCO) parameters as predictors of pulmonary complication risks in mild COPD patients undergoing lung resection. From January 2011 to December 2019, 2,798 patients undergoing segmentectomy or lobectomy for non-small cell lung cancer (NSCLC) were evaluated. Focusing on 709 mild COPD patients, excluding no COPD and moderate/severe cases, 3 models incorporating DLCO, predicted postoperative DLCO (ppoDLCO), and DLCO divided by the alveolar volume (DLCO/VA) were created for logistic regression. The Akaike information criterion and Bayes information criterion were analyzed to assess model fit, with lower values considered more consistent with actual data. Significantly higher proportions of men, current smokers, and patients who underwent an open approach were observed in the PPC group. In multivariable regression, male sex, an open approach, DLCO <80%, ppoDLCO <60%, and DLCO/VA <80% significantly influenced PPC occurrence. The model using DLCO/VA had the best fit. Different DLCO parameters can predict PPCs in mild COPD patients after lung resection for NSCLC. The assessment of these factors using a multivariable logistic regression model suggested DLCO/VA as the most valuable predictor.

Lung function at 1-year follow-up in patients with persistent dyspnea after mild COVID-19 – comparisons with moderate and critical COVID-19

Aim: To assess lung function in patients with persistent dyspnea 1 year after mild coronavirus disease 2019 (COVID-19) and compare with those hospitalized with moderate or critical COVID-19. Methods: Adults with confirmed severe acute respiratory syndrome coronavirus-2 infection with mild COVID-19 and persistent dyspnea (n = 18) or with moderate (n = 34) or critical COVID-19 (n = 19) were followed up 11–13 months after initial infection. Inclusion criteria were age &lt; 65 years, no smoking history, and no preexisting respiratory diseases. Sociodemographic and clinical data were collected, and patients underwent spirometry and measurement of diffusing capacity for carbon monoxide (DLCO). Results: The non-hospitalized patients were significantly younger and more often female compared with those in the moderate and critical groups (P = 0.002 and P &lt; 0.001, respectively). No significant differences in comorbidities or body mass index (BMI) were noted between severity groups. An obstructive spirometry pattern (ratio of forced expiratory volume during the first exhalation second to forced vital capacity under the lower limit of normal (LLN)) was found in 5.6, 5.9, and 5.3% of patients in the mild, moderate, and critical groups, respectively (P = 0.995). Abnormal DLCO (&lt; LLN) rates were seen in 5.6, 16.7, and 47.4% in the mild, moderate, and critical groups, respectively (P = 0.018). DLCO, expressed as a z-score, was significantly lower in the critical group compared with the mild group after adjustment for age, sex, and BMI. Conclusion: Only a few subjects with mild COVID-19 and persistent dyspnea had abnormal lung function 1 year after initial infection, assessed based on spirometry and DLCO measurements. An obstructive spirometry pattern at 1-year follow-up was uncommon even in patients with moderate or critical COVID-19. Impaired DLCO was more common in patients with critical COVID-19.