Plasticity of natural killer cells in pregnant patients infected with SARS-CoV-2 and their neonates during childbirth.

The COVID-19 pandemic has occurred due to infection caused by the SARS-CoV-2 coronavirus, which impacts gestation and pregnancy. In SARS-CoV-2 infection, only very rare cases of vertical transmission have been reported, suggesting that fetal immune imprinting due to a maternal infection is probably a result of changes in maternal immunity. Natural killer (NK) cells are the leading maternal immune cells that act as a natural defense system to fight infections. They also play a pivotal role in the establishment and maintenance of pregnancy. While peripheral NK cells display specific features in patients infected with SARS-CoV-2 in the general population, information remains elusive in pregnant mothers and neonates. In the present study, we analyzed the characteristics of NK cells isolated from both neonatal umbilical cord blood and maternal peripheral blood close to the time of delivery. Phenotype and functions were compared in 18 healthy pregnant women and 34 COVID-19 patients during pregnancy within an ongoing infection (PCR+; N = 15) or after recovery (IgG+PCR-; N = 19). The frequency of NK cells from infected women and their neonates was correlated with the production of inflammatory cytokines in the serum. The expression of NKG2A and NKp30, as well as degranulation of NK cells in pregnant women with ongoing infection, were both negatively correlated to estradiol level. Furthermore, NK cells from the neonates born to infected women were significantly decreased and also correlated to estradiol level. This study highlights the relationship between NK cells, inflammation, and estradiol in patients with ongoing infection, providing new insights into the impact of maternal SARS-CoV-2 infection on the neonate.

Memory CD4+ T-Cell Lymphocytic Angiopathy in Fatal Forms of COVID-19 Pulmonary Infection.

The immunopathological pulmonary mechanisms leading to Coronavirus Disease (COVID-19)-related death in adults remain poorly understood. Bronchoalveolar lavage (BAL) and peripheral blood sampling were performed in 74 steroid and non-steroid-treated intensive care unit (ICU) patients (23-75 years; 44 survivors). Peripheral effector SARS-CoV-2-specific T cells were detected in 34/58 cases, mainly directed against the S1 portion of the spike protein. The BAL lymphocytosis consisted of T cells, while the mean CD4/CD8 ratio was 1.80 in non-steroid- treated patients and 1.14 in steroid-treated patients. Moreover, strong BAL SARS-CoV-2 specific T-cell responses were detected in 4/4 surviving and 3/3 non-surviving patients. Serum IFN-γ and IL-6 levels were decreased in steroid-treated patients when compared to non-steroid treated patients. In the lung samples from 3 (1 non-ICU and 2 ICU) additional deceased cases, a lymphocytic memory CD4 T-cell angiopathy colocalizing with SARS-CoV-2 was also observed. Taken together, these data show that disease severity occurs despite strong antiviral CD4 T cell-specific responses migrating to the lung, which could suggest a pathogenic role for perivascular memory CD4 T cells upon fatal COVID-19 pneumonia.

Cell-Mediated Immune Responses to COVID-19 Infection

An unprecedented outbreak of pneumonia caused by a novel coronavirus (CoV), subsequently termed COVID-19 by the World Health Organization, emerged in Wuhan City (China) in December 2019. Despite rigorous containment and quarantine efforts, the incidence of COVID-19 continues to expand, causing explosive outbreaks in more than 160 countries with waves of morbidity and fatality, leading to significant public health problems. In the past 20 years, two additional epidemics caused by CoVs have occurred: severe acute respiratory syndrome-CoV, which has caused a large-scale epidemic in China and 24 other countries;and respiratory syndrome-CoV of the Middle East in Saudi Arabia, which continues to cause sporadic cases. All of these viruses affect the lower respiratory tract and manifest as pneumonia in humans, but the novel SARS-Cov-2 appears to be more contagious and has spread more rapidly worldwide. This mini-review focuses on the cellular immune response to COVID-19 in human subjects, compared to other clinically relevant coronaviruses to evaluate its role in the control of infection and pathogenesis and accelerate the development of a preventive vaccine or immune therapies.

Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection.

In light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site, exhibiting a high helical folding propensity in aqueous solution. Our best peptide-mimics are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC50) in the nanomolar range upon binding to the virus spike protein with high affinity. These first-in-class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19).

Cell-Mediated Immune Responses to COVID-19 Infection.

An unprecedented outbreak of pneumonia caused by a novel coronavirus (CoV), subsequently termed COVID-19 by the World Health Organization, emerged in Wuhan City (China) in December 2019. Despite rigorous containment and quarantine efforts, the incidence of COVID-19 continues to expand, causing explosive outbreaks in more than 160 countries with waves of morbidity and fatality, leading to significant public health problems. In the past 20 years, two additional epidemics caused by CoVs have occurred: severe acute respiratory syndrome-CoV, which has caused a large-scale epidemic in China and 24 other countries; and respiratory syndrome-CoV of the Middle East in Saudi Arabia, which continues to cause sporadic cases. All of these viruses affect the lower respiratory tract and manifest as pneumonia in humans, but the novel SARS-Cov-2 appears to be more contagious and has spread more rapidly worldwide. This mini-review focuses on the cellular immune response to COVID-19 in human subjects, compared to other clinically relevant coronaviruses to evaluate its role in the control of infection and pathogenesis and accelerate the development of a preventive vaccine or immune therapies.