Differences in leucocytes and inflammation-based indices among critically ill patients owing to SARS-CoV-2 variants during several successive waves of COVID-19 pandemic.

BACKGROUND/AIM: Inflammatory indices are useful informative markers in assessing the severity of the COVID-19 disease course; however, their involvements during series waves of SARS-CoV-2 virus outbreaks in critical patients with COVID-19 remain unclear. Hence, we aimed to ascertain the changing dynamics of the combined inflammatory indices (NLR, dNLR, CLR, LMR, PLR, SII, and SIRI) and their associations with clinical outcomes in severe COVID-19 patients during serial waves of SARS-CoV-2. PATIENTS AND METHODS: We retrospectively enrolled 163 severe COVID-19 patients admitted to the ICU during six SARS-CoV-2 waves. RESULTS: We found that most of patients admitted to the ICU were from the fourth wave. Patients in the fourth wave were considerably younger and had the highest percentage of ARDS than other waves. The highest CRP was found in the first wave, while the lowest in patients admitted in the sixth wave. Although most of the COVID-19 waves were marked with leukocytosis, neutrophilia, and lymphocytopenia, the lowest of both NLR and dNLR were found in the fourth wave "Delta wave" and the lowest of both CLR and SII were observed in "Omicron wave". Interestingly, during most of the COVID-19 waves, the derived combined inflammatory ratio NLR, dNLR, CLR, SII and SIRI were sustained at high levels in fatal cases at the last day of hospitalization, while these indices declined in the alive group at the end of ICU hospitalization. No major difference was identified in lymphocyte count between admission and the last day of hospitalization in both deceased and recovered COVID-19 patients during Delta and Omicron waves. Moreover, patients admitted in the Omicron wave had less severe disease compared to those admitted in the Delta wave. The Kaplan-Meier analysis revealed no significant difference in survival rates or the probability of respiratory failure between six successive COVID-19 waves. CONCLUSION: Taken together, our results showed marked differences in the alteration of nonspecific inflammation and damage in the adaptive immune response during the six serial SARS-CoV-2 waves. Considering the inflammatory response of infectious diseases, embedding inflammatory indices informative markers into routine clinical testing offers the potential to mitigate the impact of future pandemics of COVID-19 and other infectious diseases.

Deciphering the balance of IL-6/IL-10 cytokines in severe to critical COVID-19 patients.

The severity of COVID-19 is largely determined by the inflammatory response, a "Cytokine storm," that involves both pro- and anti-inflammatory cytokines. In the current study we investigated the balance of pro- and anti-inflammatory status as represented by the levels of IL-6/IL-10 in severe to critical COVID-19 patients. 66 confirmed COVID-19 patients admitted to the ICU were categorized into groups according to the mortality and respiratory failure. Data were collected retrospectively in ICU, including a peripheral immune cells and infection-related biomarker CRP. The measurements of cytokine levels were performed by Immulite analyzer for IL-6 and ELISA sandwich for IL-10. In addition, longitudinal measurement of IL-6 was performed during 5 days post admission. Longitudinal assays showed that IL-6 was sustained at a medium level within 5 days post admission in severe cases who survived or not requiring mechanical ventilation, whereas it was sustained at high levels throughout the disease course in either deceased cases or who developed respiratory failure. The ratio of IL-6/lymphocytes was positively correlated with the risk of mortality, while IL-10/lymphocytes ratio could predict respiratory failure in ICU. IL-6/IL-10 profiling revealed that deceased patients have different magnitudes of both IL-6 and IL-10 cytokine release. Notably, excessive levels of IL-6 concomitant with high levels of IL-10 were more common in diseased COVID-19 patients. Taking into account the IL-6/IL-10 profiling may help clinicians to identify the right time of anti-inflammation treatment and select patients who will respond to anti-cytokine therapies and maintain an adequate inflammatory response for SARS-CoV-2 clearance.

ERα and ERß co-expression: An indicator of aggressive tumors and hormonal sensitivity.

The estrogen receptors (ERs) ERα and ERß are important factors in breast cancer progression. Nevertheless, the molecular interplay between ERα and ERß and its clinical significance in breast cancer is controversial. The establishment of a clear association is required; therefore, the current study analyzed the expression patterns of ERα and ERß in 32 breast tumor tissues using reverse transcription-quantitative polymerase chain reaction. Furthermore, human epidermal growth factor receptor 2 (HER2) and the Ki-67 status were detected by immunohistochemistry. The results revealed that the ERα and ERß expression rates recorded were 68 and 65%, respectively. The ERα:ERß ratio exhibited a decline along with disease progression. ERα and ERß were found to be negatively correlated with HER2 status but positively correlated with Ki-67. Co-expression of ERα and ERß was associated with breast cancer aggressiveness, including higher histological grade and positive nodal status, which commonly occur following the menopause. In addition, in cases where ERß was coexpressed with ERα, HER2 expression was frequently found to be negative, whereas the Ki-67 index was upregulated. These data suggest that ERα and ERß co-expression may be an indicator of tumor aggressiveness and the sensitivity of hormonal therapy via the downregulation of HER2.

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

BACKGROUND: Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. AIM: We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. MATERIALS AND METHODS: 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. RESULTS: In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. CONCLUSION: Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones.

PSMA/PSA ratio evaluated by immunohistochemistry may improve diagnosis of prostate cancer.

Prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) measured in serum are not fully satisfactory as biomarkers of prostate cancer (PC). Results obtained in this article indicated that PSMA/PSA ratio evaluated by immunohistochemistry in normal prostate (NP), benign prostatic hyperplasia (BPH), and PC at the individual level could be a useful tool for diagnosis and prognosis of PC. PSMA and PSA were equally expressed in NP and the PSMA/PSA ratio was 1.22 ± 0.15. Data also indicated that PSMA/PSA ratio fluctuates in BPH and PC compared to NP. In BPH, the PSMA/PSA ratio was around 0.47 ± 0.02, whereas it's significantly increased in PC, about 4.95 ± 0.83. In parallel, the highest PSMA/PSA ratio was associated with high intratumoral angiogenesis in PC patients with (PSMA+,PSA+) profile.