Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19.

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

Some Immunological Impacts of Face Mask Usage During the COVID-19 Pandemic.

<b>Background and Objective:</b> COVID-19 is a fast-spreading worldwide pandemic caused by SARS-CoV-2. The World Health Organization recommended wearing face masks. Masks have become an urgent necessity throughout the pandemic, the study's goal was to track the impact of wearing masks on immunological responses. <b>Materials and Methods:</b> This study was conducted on 40 healthy people who were working in health care at Nineveh Governorate Hospitals from September-December, 2020. They wore face masks at work for more than 8 months for an average of 6 hrs a day. The control sample included 40 healthy individuals, who wore masks for very short periods. All samples underwent immunological and physiological tests to research the effects of wearing masks for extended periods within these parameters. <b>Results:</b> The results showed a significant decrease in total White Blood Count and the absolute number of neutrophils, lymphocytes, monocytes and phagocytic activity. However, there was a significant increase in the absolute number of eosinophils in participants compared with the control. The results also suggested there were no significant differences in IgE, haemoglobin concentration and blood O₂saturation in participants who wore masks for more than 6 hrs compared to the control group. The results showed a significant increase in pulse rate in participants who wore masks for more than 6 hrs compared to the control group. The results also showed a strong correlation coefficient between the time of wearing masks and some immunological, haematological parameters. <b>Conclusion:</b> Wearing masks for long periods alters immunological parameters that initiate the immune response, making the body weaker in its resistance to infectious agents.

Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19.

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Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies.

COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.

Adenovirus-Extracellular Protein Interactions and Their Impact on Innate Immune Responses by Human Mononuclear Phagocytes.

The aim of this review is to highlight how, in a syngeneic system, human mononuclear phagocytes respond to environments containing human adenovirus (HAdV) and soluble extracellular proteins that influence their innate immune response. Soluble extracellular proteins, including immunoglobulins, blood clotting factors, proteins of the complement system, and/or antimicrobial peptides (AMPs) can exert direct effects by binding to a virus capsid that modifies interactions with pattern recognition receptors and downstream signaling. In addition, the presence, generation, or secretion of extracellular proteins can indirectly influence the response to HAdVs via the activation and recruitment of cells at the site of infection.

Investigation of immune cells on elimination of pulmonary-Infected COVID-19 and important role of innate immunity, phagocytes.

We identified types of immune cells that contribute to clearing COVID-19 during the acute phase of the infection in mouse model and human. Our results suggest that both innate and adaptive immune responses are essential for controlling COVID-19 infection. Mild infection report of children by COVID-19 comparing adults' infection causes conclusion of higher resistance of immune system of children comparing adults. Our results show innate immune system including phagocytes contribute severely to the elimination of COVID-19 in both mouse model and human. Our results also show the elimination of COVID-19 required the activation of B cells by CD4+ T cells. CD4+ T cells play an important role in elimination of COVID-19 in primary effection. We measured IgM and IgG in all patients including adults and kids (human) and found IgM and IgG in kids patients are much higher than other adults patients. It causes production of much more natural antibodies in kids' bodies to protect them against COVID-19 that shows reason of mild effection of kids comparing adults. Our observations have important ramifications for the development of novel vaccination and medicine strategies to alleviate COVID-19. The most important result is for producing any vaccine for COVID-19, increasing and producing these factors must be included: (a) Phagocytes (IgM and IgG), (b) T Cells, and (c) White Cells.

Can the Environmental Phagocyte Acanthamoeba Be a Useful Model to Study SARS-CoV-2 Pathogenicity, Infectivity, and Evasion of Cellular Immune Defenses?

Acanthamoeba and macrophages exhibit significant parallels in biochemical, physiological, cellular, and functional aspects. Given the ability of Acanthamoeba to contribute to the evolutionary gain of pathogenicity of a variety of microbial pathogens, here we propose the use of Acanthamoeba as a paradigm to study SARS-CoV-2 pathogenicity, infectivity, and evasion of cellular immune defenses.