Correlation of Lymphocyte Subpopulations, Clinical Features and Inflammatory Markers during Severe COVID-19 Onset.

BACKGROUND: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. MATERIALS/METHODS: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). RESULTS: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. CONCLUSIONS: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.

Immune-Mediated Inner Ear Disease Associated with Type 1 Autoimmune Hepatitis: A Challenging Coexistence.

Autoimmune hepatitis (AIH) is characterized by elevated serum transaminase, increased immunoglobulin G levels, presence of autoantibodies, and hepatocellular damage. Coexistence with other autoimmune diseases has been reported in almost half of patients with AIH. Here, we report a 60-year-old man who developed rapidly progressive, bilateral, asymmetrical, and asynchronous sensorineural hearing loss that was consistent with immune-mediated inner ear disease (IMIED). This devastating presentation evolved as a late manifestation in the context of a six-month systemic illness that had previously resulted in type 1 AIH. A biochemical remission with normalization of aminotransferases achieved within two months after the initiation of corticosteroids with azathioprine. Further, an acceptable response has also been achieved at the patient regarding the right ear-hearing impairment; though, treatment could not reverse the substantial decrement in hearing capability of the left ear. To our knowledge, this is the first case report of the concurrent development of type 1 AIH and IMIED.

Trichinosis Imitating an Inflammatory Systematic Disease.

Trichinellosis (trichinosis) is a parasitic infection caused by nematodes of the genus Trichinella. Pigs are the most common source of human infection. We describe a case of a 47-year-old woman presented with a wide range of intermittent symptoms including prolonged fever, dry cough, diarrhea, rash, myalgias and arthralgias. The patient was attended by physicians with various medical specialties such as dermatologists, rheumatologists and allergiologists, but they did not establish a certain diagnosis because of the gradual onset of symptoms, raising the suspicion of a systematic disease. After extensive work up, the diagnosis of trichinosis was established with femoral muscle biopsy compatible with inflammatory myopathy of parasitic etiology with trichinosis to be the predominant diagnosis. Despite the significant delay of diagnosis for almost three months, patient was treated successfully with no further complications. Trichinellosis is a food-borne treatable infection. Preventive measures include community education especially in zones where parasite prevalence is increased, improvement of farming and cooking techniques.

Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial.

INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.

Social support, adherence to Mediterranean diet and physical activity in adults: results from a community-based cross-sectional study.

There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support (P = 0·009) and social network support (P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet.

Acute Brucellosis and Cirrhosis: The Triggering Event of Fatal Liver Decompensation.

Cirrhotic patients are known to be particularly susceptible to infectious complications that may vary according to regional endemic patterns. Brucellosis, a common zoonosis with worldwide distribution, exhibits a predilection for the reticuloendothelial system and thus resulting in hepatic involvement. We describe three cirrhotic patients in whom acute brucellosis and/or its treatment served as the triggering factor of hepatic decompensation, with deleterious effects. The patients suffered from alcoholic cirrhosis and culture-proven brucellosis. All patients came from an area endemic to brucellosis. The first patient exhibited a relapsing brucellosis course with progressive deterioration of his fragile liver function. The second patient progressed rapidly to jaundice, possibly partly attributed to antibiotic pharmacotoxicity, and died during liver transplantation. The third patient eventually succumbed to diffuse intravascular coagulation. Brucellosis can be a triggering event of fatal liver decompensation in cirrhotic patients. Enhancing health literacy of the patients, particularly in endemic areas, is of paramount importance for prevention of exposure to similar pathogens.

Prevalence and Characteristics of Self-Harm in Adolescents: Meta-Analyses of Community-Based Studies 1990-2015.

OBJECTIVE: To provide meta-analytic estimates of self-harm from all community-based studies of adolescents from 1990 through 2015, estimates of suicidal risk, and characteristics including age profile, frequency, types, seeking help, and reasons. METHOD: Databases, bibliographies, and the internet were searched for cross-sectional and cohort studies of 12- to 18-year-olds. Meta-analytic estimates of the prevalence and characteristics of self-harm, risk of suicidal behaviors, and rates comparing different methods were calculated. RESULTS: One hundred seventy-two datasets reporting self-harm in 597,548 participants from 41 countries were included. Overall lifetime prevalence was 16.9% (95% CI 15.1-18.9), with rates increasing to 2015. Girls were more likely to self-harm (risk ratio 1.72, 95% CI 1.57-1.88). The mean age of starting self-harm was 13 years, with 47% reporting only 1 or 2 episodes and cutting being the most common type (45%). The most frequent reason was relief from thoughts or feelings. Slightly more than half sought help, but for most this was from a friend. Suicidal ideation (risk ratio 4.97) and attempts (risk ratio 9.14) were significantly higher in adolescents who self-harmed, but this was higher with more frequent self-harm. Methodologic factors also were associated with higher rates of self-harm. CONCLUSION: Interventions that can lower suicidal risk should be made available to adolescents who self-harm frequently as soon as possible. Preventative interventions that help adolescents deal with negative feelings should be instituted at the onset of puberty. Because friends are frequently asked for support, interventions also should be developed for peer groups.