Increased Levels of serum Pentraxin 3 in Critical Coronavirus Disease-2019 Patients.

Pentraxin 3 (PTX3) and ficolin are the plasma phase of pattern recognition receptors (PRRs) and can activate complement through classical and lectin pathways, respectively, which may contribute to disease severity. This study aimed to investigate the association between PTX3 and ficolin with disease severity in patients with coronavirus disease-2019 (COVID-19). Seventy-three COVID-19 patients and 25 healthy controls were enrolled in this study. The participants were divided into three groups as follows: 14 patients as the intensive care unit (ICU) group, 59 patients as the non-ICU group, and 25 subjects as the healthy control group. The serum levels of PTX3 and ficolin were measured by enzyme-linked immunosorbent assay (ELISA) kits. Patients in ICU and non-ICU groups had significantly higher levels of PTX3 compared to the healthy control group (p = 0.0002 and p = 0.0072, respectively). Patients in the ICU group also had an increased amount of PTX3 (1957 ± 1769 pg/ml) compared to non-ICU patients (1220 ± 1784 pg/ml). However, this difference was not significant. On the other hand, serum levels of ficolin were not different among the three groups. PTX3, as an acute phase protein, may contribute to disease severity. Its probable inflammatory role could result from the high activation of the complement system. On the other hand, it could be suggested that ficolin has no crucial role in the disease severity of COVID-19 patients.

Linkage of Lambda Interferons in Protection Against Severe COVID-19.

The most recently discovered interferon (IFN) family, type III IFNs or lambda IFNs (IFN-λs) are caused by viral infection and act in mucosal barriers, such as the respiratory tract. In this study, we assessed the serum levels of IFN-λs in new coronavirus disease-2019 (COVID-19) patients. Sixty-four COVID-19 patients were enrolled in this study. All cases were divided into the intensive care unit (ICU) and non-ICU groups according to their symptoms. Fourteen samples of healthy controls were also included. The serum levels of IFN-λ1 and IFN-λ2 were analyzed by specific enzyme-linked immunosorbent assay (ELISA) kits. The concentrations of IFN-λ1 and IFN-λ2 induced in the serum of non-ICU patients (836.7 ± 284.6 and 798.8 ± 301.5 pg/mL, respectively) were higher than found in ICU patients (81.57 ± 34.25 and 48.32 ± 28.13 pg/mL, respectively) (P = 0.004 and P = 0.006, respectively) and healthy controls (85.57 ± 33.63 and 65.82 ± 21.26 pg/mL, respectively) (P = 0.03 and P = 0.04, respectively). Meanwhile, no significant differences were found in the concentration of both cytokines between the ICU patients and healthy controls. We conclude that higher levels of IFN-λs are associated with decreased clinical manifestations in COVID-19 patients. These cytokines could be a promising therapeutic agent to avoid the overwhelming consequences of COVID-19.

Reduced frequency of T helper 17 and T helper 1 cells and their association with critical coronavirus disease 2019.

There is very little knowledge about the immune responses, particularly cellular immunity to coronavirus disease 2019 (COVID-19). The main objective of this study was to evaluate the frequency of T helper (Th) cell subtypes, including Th1, Th17, and Treg cells, in moderate-to-severe and critical COVID-19 patients compared to healthy controls. Twenty-nine moderate-to-severe and 13 critical patients confirmed for COVID-19, and 15 healthy subjects were included in this study. Interferon-γ (IFN-γ)-producing Th1 and interleukin-17A-producing Th17 and Treg cells in peripheral blood were measured with flow cytometry. The frequency of Th1 and Th17 was significantly decreased in critical patients compared to healthy subjects (aMD: -2.76 and - 2.34) and moderate-to-severe patients (aMD: -1.89 and - 1.89), respectively (p < 0.05). Differences were not significant between moderate-to-severe patients and healthy subjects for both Th1 (p = 0.358) and Th17 (p = 0.535), respectively. In contrast, significant difference was not observed between study subjects regarding the frequency of Treg cells. Patients with critical COVID-19 had a markedly lower Th1/Treg and Th17/Treg ratios compared with the controls and moderate-to-severe cases. Our study showed a dysregulated balance of Th1 and Th17 cells and its relation to the severity of COVID-19.

Pronounce expression of Tim-3 and CD39 but not PD1 defines CD8 T cells in critical Covid-19 patients.

BACKGROUND: During viral infection, inhibitory receptors play a key role in regulating CD8 T-cell activity. The objective of this research was to investigate programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), and CD39 exhaustion markers in CD8 T cells of new coronavirus disease-2019 (COVID-19) patients. METHODS: A total of 44 patients with COVID-19 (17 subjects in a critical group and 27 patients in a non-critical group) and 14 healthy controls, who were admitted to Hospitals in Babol, were recruited to the study. In subjects' peripheral blood mononuclear cells (PBMCs), we compared the phenotype of CD8 T lymphocytes, expressing PD-1, TIM-3, or CD39, both alone and in various combinations. RESULTS: The findings showed that the percentage of CD8+ cells was significantly lower in patients. Critical and non-critical patients were more likely than healthy controls to have an escalated frequency of CD8+ TIM-3+, CD8+ CD39+, and CD8+ TIM-3+ CD39+ cells. No significant differences were observed between all groups in the CD8+ PD-1+ cell counts. There was also no difference between three groups regarding the counts of CD8+ TIM-3+ PD-1+, CD8+ PD-1+ CD39+, and CD8+ TIM-3+ PD-1+ CD39+ cells. The counts of non-exhausted cells were significantly lower in critical and non-critical individuals compared to the healthy individuals' value. CONCLUSION: Patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered exhausted CD8 T lymphocytes with CD39 and TIM-3 exhaustion markers, which may account the dysregulated immune response found in COVID-19.