Мелочи по ковиду

[chuka_lis]

Исследования затухают, но завершаются многие ранее начатые работы.

Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and replication

Coronaviruses, including SARS-CoV-2, can cause severe disease in humans, whereas reservoir hosts like Rhinolophus bats remain asymptomatic. To investigate how host-specific protein-protein interactions (PPIs) influence infection, we generated comparative PPI maps for SARS-CoV-2 and its bat-origin relative RaTG13 using affinity purification-mass spectrometry (AP-MS) in human and Rhinolophus ferrumequinum (RFe) bat cells. This approach identified both conserved and virus- and host-specific interactions that regulate infection dynamics. Notably, SARS-CoV-2 required a non-synonymous mutation in nucleocapsid to replicate in bat cells expressing human ACE2 and TMPRSS2. Analysis of the viral protein Orf9b revealed differential interactions with mitochondrial proteins Tom70 and MTARC2. A single residue difference in Orf9b between SARS-CoV-2 and RaTG13 functions as a molecular switch, weakening Tom70 binding and immune evasion in human cells while enhancing interaction with the bat-specific restriction factor MTARC2. These findings demonstrate how a single-residue substitution can reshape virus-host interactions and contribute to immune evasion and host adaptation.

Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection

Pediatric SARS-CoV-2 infection results in clinical presentations ranging from asymptomatic/mild infection to severe pulmonary COVID-19, to Multisystem Inflammatory Syndrome in Children (MIS-C), characterized by hyperinflammation and multi-organ involvement. While various aspects of antibody responses to pediatric SARS-CoV-2 infection manifestations have been reported, parallel studies of antibody responses to viral and self-antigens are understudied. We tested whether clinical presentations of increasing severity corresponded to different antiviral antibody and autoantibody signatures. Using custom arrays, we found that, relative to uninfected subjects, all SARS-CoV-2 infection manifestations were associated with increased autoantibody production, suggesting pediatric SARS-CoV-2 infection as a risk factor for autoimmune complications. Subtle differences were seen in autoantibody patterns among infection groups, with some autoantibodies more associated with mild manifestations and others with severe ones. When we compared MIS-C and severe COVID-19 subjects, we found differences in IgG (mostly IgG1) abundance but not in Fc-mediated effector functions. Thus, MIS-C may be associated with abnormal antibody function, suggesting that this syndrome, and perhaps other post-acute sequelae of SARS-CoV-2 infection, may be associated with antibody dysfunction. Our study shows that the antibody repertoire varies with clinical presentation of SARS-CoV-2 in children and its analysis may help understand long COVID pathogenesis.

Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants

SARS-CoV-2 continues to evolve, causing repeated waves of infections around the world. It is critical to understand the features of the virus that explain its growth advantages. Recently, the SARS-CoV-2 Omicron JN.1 subvariants KP.3.1.1 and XEC were outcompeted by later JN.1 progenies, most prominently LP.8.1 and LP.8.1.1. Other recent JN.1 subvariants, such as LF.7.2.1, which became prevalent in Asia, and MC.10.1, have also been under monitoring. Subsequently, NB.1.8.1 and XFG subvariants began increasing in prevalence, as well. We found that serum neutralizing antibody titers against LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, MC.10.1 were similar to XEC in a cohort of 20 KP.2-based monovalent mRNA vaccine (KP.2 MV) recipients and in a cohort 20 adults who did not receive KP.2 MV. NB.1.8.1 and XFG were more evasive of serum neutralization than LP.8.1.1. We then characterized subvariant susceptibility to monoclonal antibody (mAb) neutralization using a panel of 12 mAbs spanning several epitopes on the SARS-CoV-2 spike, and found that LP.8.1 and XFG, MC.10.1 and NB.1.8.1, and LF.7.2.1 evade different classes of mAbs relative to earlier JN.1 subvariants, even if the tested polyclonal serum neutralizing antibody titers were not different overall. Next, we found that the receptor-binding affinity of LP.8.1 to ACE2 was the highest among the tested viruses, while that of LF.7.2.1 was lowest. Therefore, unlike most prior SARS-CoV-2 sublineage evolutionary trajectories, receptor-binding affinity, possibly reflecting enhanced transmissibility–and not increased antibody evasion–better explained the rise of LP.8.1, while the expansion of NB.1.8.1 and XFG again appear correlated with their enhanced antibody evasion.

Iodine increases pulmonary type I interferon responses and decreases COVID-19 disease severity: results from an open-label randomized clinical trial

Objective To investigate whether oral treatment with 12.5 mg iodine additional to standard of care is effective in reducing mortality and clinical deterioration of patients hospitalized with COVID-19.
Methods We performed a single center, randomized clinical trial (EudraCT 2020-001852-16) in which patients with severe covid-19 in need of hospitalization were randomized in two groups. The first group received 12.5 mg oral iodine for 8 days, the second group did not receive iodine next to the standard of care. Primary endpoints were deterioration of disease defined as transfer from the ward to the intensive care unit (ICU) or death. Next to these parameters we collected parameters in line with the recommendations made by the WHO in the early days of the pandemic. On these additional datasets we performed an exploratory analysis and investigated possible confounders and trends. The inclusion phase of the study was between October 2020 and April 2022. Finally, in vitro validations were performed.
Results Outcomes from 141 participants were analyzed, revealing no significant differences in mortality or transfers to intensive care between the iodine-treated group (67 patients) and the control group (74 patients). In an exploratory analysis we found that patients randomized to receive oral iodine had a significantly shorter stay at the ICU (p=0.016). In vitro validations proved increased virus-induced type I interferon responses upon iodine administration in pulmonary cells.
Conclusion These findings suggest that while iodine does not reduce mortality or ICU admissions, it may enhance antiviral immunity through increased type I interferon responses, contributing to shorter ICU stays in COVID-19 patients. The role of iodine in enhancing IFN-I mediated antiviral immunity warrants future research.