Corrigendum: Case report: Chronic inflammatory demyelinating polyneuropathy superimposed on Charcot-Marie-tooth type 1A disease after SARS-CoV-2 vaccination and COVID-19 infection.

[This corrects the article DOI: 10.3389/fneur.2024.1358881.].

Case report: Chronic inflammatory demyelinating polyneuropathy superimposed on Charcot-Marie-tooth type 1A disease after SARS-CoV-2 vaccination and COVID-19 infection.

Background: There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of immune mediated neuropathies like chronic inflammatory demyelinating polyneuropathy (CIDP), but the impact of SARS-CoV-2 vaccination and COVID-19 infection on genetic disorders such as Charcot-MarieTooth (CMT) remains unclear. Case presentation: A 42-year-old male with occulted CMT neuropathy type lA (CMT1A) who developed limb numbness and weakness after the second SARS-CoV-2-vaccination was confirmed by identifying characteristic repeats in the p11.2 region of chromosome 17. Due to the progressive deterioration of muscle strength over 8 weeks, limb atrophy, moderately elevated protein counts in the cerebrospinal fluid, and significant improvement with intravenous human immunoglobulin, which were characteristic of acquired inflammatory neuropathies, he was eventually diagnosed with CIDP superimposed on CMT1A. However, after a three-month plateau, the patient contracted COVID-19, which led to repeated and worsening symptoms of limb weakness and atrophy, thus was diagnosed with a recurrence of CIDP and treated with Intravenous immunoglobulin and methylprednisolone 500 mg/d for 5 consecutive days, followed by oral prednisone and mycophenolate mofetil tablets. On 2 month follow-up, he exhibited remarkable clinical improvement and could walk independently with rocking gait. After 1 year of follow-up, the patient's condition was stable without further change. Conclusion: Our case indicates that CMT1A can deteriorate after SARS-CoV-2 vaccination. Thus, SARS-CoV-2 vaccination should be considered a potential predisposing factor for CMT1A worsening. The possible superposition of CMTIA and CIDP in the context of SARS-CoV-2 infection or immunity suggests that any clinical exacerbation in patients with CMT1A should be carefully evaluated to rule out treatable superposition inflammation. In addition, electrophysiological and imaging examination of the proximal nerves, such as the axillary nerve, is helpful for the diagnosis of CIDP.

Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and related variants, are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 main protease (Mpro) plays a central role in the replication of the virus and represents an attractive drug target. Herein, we report the discovery of novel SARS-CoV-2 Mpro covalent inhibitors, including highly effective compound NIP-22c which displays high potency against several key variants and clinically relevant nirmatrelvir Mpro E166V mutants.

Postinfectious conditions challenge disease-specificity of SNOT-22.

PURPOSE: The Sino-Nasal-Outcome-Test 22 (SNOT-22) questionnaire assesses treatment outcome and health-related quality of life (HRQOL) in patients with chronic rhinosinusitis (CRS). However, given the overlap between CRS and olfaction in terms of nasal function and the definition of CRS, a fundamental question arises: can patients with olfactory dysfunction (OD) stemming from other causes attain SNOT-22 scores similar to those seen in CRS, even in the absence of CRS? Our study aimed to explore whether OD arising from various postinfectious mechanisms challenges the disease-specificity of SNOT-22 for CRS. If so, could focus on scores within specific symptom domains of SNOT-22 prove valuable in distinguishing between different etiologies. METHODS: The study adopted an observational, retrospective cohort design based on prospectively registered patients and related variables using the REDCap platform. 460 patients experiencing OD due to either (1) simple or (2) complex post-COVID-19, (3) postinfectious non-COVID-19, and (4) CRS, were included in the analysis. RESULTS: The study revealed that the total SNOT-22 score lacks disease-specificity for CRS. This is evident, because complex postinfectious mechanisms resulting from COVID-19 can produce similar symptoms in patients. Notably, elevated total scores were primarily driven by high subdomain scores within the "sleep and cognition" domain. CONCLUSIONS: The application of SNOT-22 as a screening tool needs to be approached with caution, as the total score alone does not provide disease-specific insights. A more thorough exploration of the four symptom domains and the identification of distinctive scoring patterns within the clinical context may prove pivotal in effectively differentiating between various underlying causes.

The E3 ligase TRIM22 restricts SARS-CoV-2 replication by promoting proteasomal degradation of NSP8.

Replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is mediated by a complex of non-structural proteins (NSPs), of which NSP7 and NSP8 serve as subunits and play a key role in promoting the activity of RNA-dependent RNA polymerase (RdRp) of NSP12. However, the stability of subunits of the RdRp complex has rarely been reported. Here, we found that NSP8 was degraded by the proteasome in host cells, and identified tripartite motif containing 22 (TRIM22) as its E3 ligase. The interferon (IFN) signaling pathway was activated upon viral invasion into host cells, and TRIM22 expression increased. TRIM22 interacted with NSP8 and ubiquitinated it at Lys97 via K48-type ubiquitination. TRIM22 overexpression significantly reduced viral RNA and protein levels. Knockdown of TRIM22 enhanced viral replication. This study provides a new explanation for treating patients suffering from SARS-CoV-2 with IFNs and new possibilities for drug development targeting the interaction between NSP8 and TRIM22.IMPORTANCENon-structural proteins (NSPs) play a crucial role in the replication of severe acute respiratory syndrome coronavirus 2, facilitating virus amplification and propagation. In this study, we conducted a comprehensive investigation into the stability of all subunits comprising the RNA-dependent RNA polymerase complex. Notably, our results reveal for the first time that NSP8 is a relatively unstable protein, which is found to be readily recognized and degraded by the proteasome. This degradation process is mediated by the host E3 ligase tripartite motif containing 22 (TRIM22), which is also a member of the interferon stimulated gene (ISG) family. Our study elucidates a novel mechanism of antiviral effect of TRIM22, which utilizes its own E3 ubiquitin ligase activity to hinder viral replication by inducing ubiquitination and subsequent degradation of NSP8. These findings provide new ideas for the development of novel therapeutic strategies. In addition, the conserved property of NSP8 raises the possibility of developing broad antiviral drugs targeting the TRIM22-NSP8 interaction.

Factors associated with prolonged viral shedding of SARS-CoV-2 Omicron variant infection in Shanghai: A multicenter, retrospective, observational study.

Shanghai has faced an unprecedented COVID-19 pandemic with the BA.2.2 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infection. Comprehensive insights into its epidemiology, clinical manifestations, and viral shedding dynamics are currently limited. This study encompasses 208373 COVID-19 patients that were infected with the Omicron BA.2.2 sub-lineage in Shanghai, China. Demographic information, clinical symptoms, vaccination status, isolation status, as well as viral shedding time (VST) were recorded. Among the COVID-19 patients included in this study, 187124 were asymptomatic and 21249 exhibited mild symptoms. The median VST was 8.3 days. The common clinical symptoms included fever, persistent cough, phlegm, sore throat, and gastrointestinal symptoms. Factors such as advanced age, presence of comorbidities, mild symptomatology, and delayed isolation correlated with extended VST. Conversely, female gender and administration of two or three vaccine doses correlated with a reduction in VST. This investigation offers an in-depth characterization and analytical perspective on Shanghai's recent COVID-19 surge. Prolonged viral shedding of SARS-CoV-2 was observed in elderly, male, symptomatic patients, and those with comorbidity. Female, individuals with two or three vaccine doses, as well as those isolated early, shows an effective reduced VST.

Clinical and virological features of asymptomatic and mild symptomatic patients with SARS-CoV-2 Omicron infection at Shanghai Fangcang shelter hospital.

OBJECTIVE: The objective of this study is to evaluate and compare clinical and virological characteristics of asymptomatic and mild symptomatic patients of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.2 variant infection and identify risk factors associated with the prolonged viral negative conversion duration. METHODS: We conducted a retrospective observational study in a Shanghai (China) Fangcang shelter hospital from April 9 to May 17, 2022. The patient-related demographic or clinical data were retrospectively recorded. Comparisons of demographic and clinical characteristics between asymptomatic and mild-symptomatic patients were performed. Cox regression was performed to identify the risk factors of prolonged viral negative conversion duration. RESULTS: A total of 551 patients confirmed with SARS-CoV-2 Omicron variant infection were enrolled in the study. Of these, 297 patients (53.9%) were asymptomatic and 254 patients (46.1%) had mild symptoms. When comparing the clinical and virological characteristics between the asymptomatic and mild symptomatic groups, several clinical parameters, including age, gender, time to viral clearance from the first positive swab, chronic comorbidities, and vaccination dose did not show statistically significant differences. In mild symptomatic patients, the median viral negative conversion duration (NCD) was 7 days (interquartile range [IQR]: 5-9), which was comparable to the median of 7 days (IQR: 5-10) in asymptomatic patients (p = .943). Multivariate Cox analysis revealed that patients age ≥ 60 years had a significantly higher hazard ratio (HR) for prolonged viral NCD (HR: 1.313; 95% confidence interval: 1.014-1.701, p = .039). CONCLUSION: Asymptomatic and symptomatic patients with non-severe SARS-CoV-2 Omicron BA.2.2 variant infection have similar clinical features and virological courses. Old age was an independent risk factor for prolonged SARS-CoV-2 conversion time.

C-reactive protein to lymphocyte ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 patients.

Objective: The aim of the present study is to assess the utility of C-reactive protein to Lymphocyte Ratio (CLR) in predicting short-term clinical outcomes of patients infected by SARS-CoV-2 BA.2.2. Methods: This retrospective study was performed on 1,219 patients with laboratory-confirmed SARS-CoV-2 BA.2.2 to determine the association of CLR with short-term clinical outcomes. Independent Chi square test, Rank sum test, and binary logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with their 95% CI, respectively. Results: Over 8% of patients admitted due to SARS-CoV-2 BA.2.2. were critically ill. The best cut-off value of CLR was 21.25 in the ROC with a sensitivity of 72.3% and a specificity of 86%. After adjusting age, gender, and comorbidities, binary logistic regression analysis showed that elevated CLR was an independent risk factor for poor short-term clinical outcomes of COVID-19 patients. Conclusion: C-reactive protein to Lymphocyte Ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 inflicted patients.

Effect Analysis of Different Environmental Disinfection Methods on Reducing Contamination of Surfaces by the Omicron BA.2.2 Variant of SARS-CoV-2 and the Characteristics of Fomite Contamination in the Fever Clinic in the Out-Broken of Shanghai.

This study aimed to investigate the effect of different environmental disinfection methods on reducing contaminated surfaces (CSs) by the Omicron BA.2.2 variant of SARS-CoV-2 in the fever clinic between March 20 and May 30, 2022, and to analyze the influences and related factors of CSs. This study includes survey data from 389 positive patients (SPPs) and 204 CSs in the fever clinic, including the CS type, disinfection method, length of time spent in the clinic, cycle threshold (CT) value, name, age, weight, mask type, mask-wearing compliance, hand-mouth touch frequency and sex. Associations between study variables and specified outcomes were explored using univariate regression analyses. Mask-wearing compliance had a significant negative correlation with CSs (r = - 0.446, P = 0.037). Among the 389 SPPs, 22 SPPs (CRP, 5.66%) caused CSs in the separate isolation room. A total of 219 SPPs (56.30%) were male. The mean age of SPPs was 4.34 ± 3.92 years old, and the mean CT value was 12.44 ± 5.11. In total, 9952 samples with exposure history were taken, including 204 (2.05%) CSs. Among the CSs, the positive rate of flat surfaces was the highest in public areas (2.52%) and separate isolation rooms (4.75%). Disinfection methods of ultraviolet radiation + chemical irradiation significantly reduced the CSs in both the public area (0% vs. 4.56%) and the separate isolation room (0.76% vs. 2.64%) compared with the chemical method alone (P < 0.05). Compared with ordinary SPPs, CRPs were older (6.04 year vs. 4.23 year), and the male proportion was higher (72.73% vs. 55.31%). In particular, it was found that SPPs contaminated their surroundings and therefore imposed risks on other people. Environmental disinfection with ultraviolet radiation + chemical treatment should be emphasized. The findings may be useful to guide infection control practices for the Omicron BA.2.2 variant of SARS-CoV-2.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

3ß-Acetoxy-21α-H-hop-22(29)ene, a novel multitargeted phytocompound against SARS-CoV-2: in silico screening.

The present pandemic disease COVID-19 demands an urgent need for more efficient antiviral drugs against SARS-CoV-2. Computational drug designing and discovery enable us to explore ethnomedicinal plants as a source of various lead molecules that can be used against present and future pathogens. Adiantum latifolium Lam., a common fern, is resistant to pathogens mainly due to the presence of various phytochemicals having antimicrobial properties. In our previous study, 3ß-acetoxy-21α-H-hop-22(29)ene, a terpenoid has been characterized from the methanol extract of leaves of A. latifolium. The manuscript evaluates the antiviral potency of the compound against SARS-CoV-2 through molecular docking method. Proteins essential for SARS-CoV-2 multiplication in host cells are the target sites. The study revealed strong binding affinity of the compound for all the ten proteins selected, including seven nonstructural proteins, two structural proteins and one receptor protein, with a binding energy of -4.67 to -8.76 kcal/mol. MDS and MMPBSA analysis of the best ranked complex further confirmed the results. The multitargeted compound can be considered as a natural lead molecule in drug designing against COVID-19, but requires wet-lab experimentation and clinical trials.Communicated by Ramaswamy H. Sarma.

COVID-19 Severity, Cardiological Outcome, and Immunogenicity of mRNA Vaccine on Adult Patients With 22q11.2 DS.

BACKGROUND: The contemporaneous presence of immune defects and heart diseases in patients with 22q11.2 deletion syndrome (22q11.3DS) might represent risk factors for severe coronavirus 2019 disease (COVID-19). OBJECTIVE: To analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcome in 22q11.2DS patients and immunogenicity of different doses of mRNA SARS-CoV-2 vaccine. METHODS: Longitudinal observational study on SARS-CoV-2 outcome in 60 adults with 22q11.2DS (March 2020-June 2022). Anti-Spike, and anti-receptor binding domain (RBD) antibody responses, generation of Spike-specific memory B cells (MBCs) and Spike-specific T cells at different time points before and after the mRNA BNT162b2 vaccination were evaluated in 16 22q11.2DS patients. RESULTS: We recorded a 95% rate of vaccination, with almost all patients being immunized with the booster dose. Twenty-one patients had SARS-CoV-2 infection. Three patients were infected before vaccine availability, 6 after receiving 2 doses of vaccine, and 12 after one booster dose. The SARS-CoV-2- infection had a mild course, except in one unvaccinated patient with several comorbidities who died from acute respiratory distress syndrome (fatality rate 5%). Infected patients had more frequently moderate/severe intellectual disability, lymphopenia, and lower CD4+ count. Despite major congenital heart diseases, COVID-19 did not impact cardiological conditions. The BNT162b2 vaccine induced S1-immunoglobulin G (IgG) responses, low serum S1-IgA, and slightly impaired specific MBCs response. Specific T-cell responses observed were related to lymphocytes and CD4+ T cell counts. CONCLUSIONS: The SARS-CoV-2 infection had a mild course in most patients with 22q11.2DS, even in patients with major cardiovascular diseases. Immunization induced Spike-specific IgG responses and generated specific MBCs and memory T cells. The weaker memory responses in patients with lymphopenia suggested the need for additional doses.

Association of anosmia and neutralizing antibody production in adolescents with SARS-CoV-2.

BACKGROUND: To monitor olfactory/gustatory dysfunction and its relationship to SARS-CoV-2 IgG antibody responses in an adolescent population. METHODS: Adolescents with changes in olfactory/gustatory functions were enrolled in a 15-month study. The patients were evaluated with 1) SNOT-22, 2) pediatric smell wheel, and 3) SARS-CoV-2 antibody testing. The relationship between these scores and length of anosmia, and the amount of SARS-CoV-2 IgG antibodies were assessed. A brain MRI was performed in cases of persistent special sensory symptoms. RESULTS: Eighteen patients were identified with smell and/or taste complaints. Most of the patients were female (67%) and median age was 15 years (range 11-17). Twelve patients had prior SARS-CoV-2 PCR testing, with only five patients with a positive result. The median SNOT-22 score was 16 (range 0-52) and the median smell wheel score was 6.5 (range 1-11). Patients with taste difficulty were more likely to have a score less than eight. 78% of the patients tested positive for antibodies and there was a strong negative correlation between smell wheel score and antibody level (Spearman, ρ = -0.798, p = 0.002). Five patients underwent MRI scan, and all resulted as normal olfactory bulb structures. 66% received nasal corticosteroids. 11 patients presented in follow up. CONCLUSIONS: Adolescents presenting to a pediatric ENT clinic during the SARS-CoV-2 pandemic were likely to have prolonged (>6 weeks) symptoms of SARS-CoV-2. The majority do not report positive PCR testing result but do report systemic symptoms including anosmia. This suggests that anosmia may be both a late and prolonged symptom of SARS-CoV-2.

[Comparative study of Wuhan-like and omicron-like variants of SARS-CoV-2 in experimental animal models].

INTRODUCTION: The variability of SARS-CoV-2 appeared to be higher than expected, the emergence of new variants raises concerns. The aim of the work was to compare the pathogenicity of the Wuhan and BA.1.1/Omicron variants in BALB/c mice and Syrian hamsters. MATERIALS AND METHODS: The study used strains of SARS-CoV-2: Dubrovka phylogenetically close to Wuhan-Hu-1, and LIA phylogenetically close to Omicron, BALB/c mice, transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/HEMI Hemizygous for Tg(K18-ACE2)2Prlmn, Syrian golden hamsters. Animals were infected intranasally, pathogenicity was estimated by a complex of clinical, pathomorphological and virological methods. RESULTS: Comparative studies of SARS-CoV-2 Dubrovka and LIA strains on animal models demonstrated their heterogeneous pathogenicity. In parallel infection of BALB/c mice with Dubrovka and LIA variants, the infection proceeded without serious clinical signs and lung damage. Infection with the LIA strain resulted to a systemic disease with a high concentration of viral RNA in the lungs and brain tissues of animals. The presence of viral RNA in mice infected with the Dubrovka strain was transient and undetectable in the lungs by day 7 post-infection. Unlike the mouse model, in hamsters, the Dubrovka strain had a greater pathogenicity than the LIA strain. In hamsters infected with the Dubrovka strain lung lesions were more significant, and the virus spread through organs, in particular in brain tissue, was observed. In hamsters infected with the LIA strain virus was not detected in brain tissue. CONCLUSION: The study of various variants of SARS-CoV-2 in species initially unsusceptible to SARS-CoV-2 infection is important for monitoring zoonotic reservoirs that increase the risk of spread of new variants in humans.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Genomic characteristics and viral load dynamics of a SARS-CoV-2 Omicron BA.2.2 variant from a hospitalized patient treated with molnupiravir.

We sequenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from nasal and throat swabs of a hospitalized patient during the fifth wave of coronavirus disease 2019 (COVID-19) pandemic in Hong Kong. Genomic characteristics and viral load dynamics of an Omicron BA.2.2 variant before and after molnupiravir treatment were presented.

First Detection of the SARS-CoV-2 Omicron BA.5/22B in Monaco.

The Omicron BA.5/22B variant has been designated as a "variant of concern" by the World Health Organization. We describe, here, the first evidence in Monaco of infection with an Omicron BA.5/22B variant, probably imported from the Republic of Seychelles, harboring a rare combination of non-BA.5/22B signature amino acid changes. SARS-CoV-2 neutralizing antibodies were measured with a surrogate virus neutralization test. SARS-CoV-2 genotype screening was performed on nasopharyngeal samples with a multiplex qPCR assay. The SARS-CoV-2 genome was obtained by next-generation sequencing with the Illumina COVID-seq protocol, then assembly using bioinformatics pipelines and software was performed. The BA.5/22B spike protein structure was obtained by molecular modeling. Two spouses were SARS-CoV-2-diagnosed the day they returned from a one-week trip in the Republic of Seychelles. SARS-CoV-2 qPCR screening for variant-specific mutations identified an Omicron variant BA.1/21K, BA.4/22A, or BA.5/22B. A SARS-Co-2 BA.5/22B variant genome was recovered from one of the spouses. Aside from BA.5/22B-defining amino acid substitutions, four other amino acid changes were encoded including Q556K in ORF1a, K2557R in ORF1b, and A67V and A829T in spike; only 13 genomes in sequence databases harbored these four mutations concurrently. Structural analysis of this BA.5/22B variant predicted that A829T in spike may result in a compaction that may affect conformational plasticity. Overall, our findings warrant performing genome-based genotypic surveillance to survey accurately the emergence and circulation of SARS-CoV-2 variants worldwide and point out that their first occurrence in a country is often through international travel despite implemented countermeasures.

The role of interleukin-22 in lung health and its therapeutic potential for COVID-19.

Although numerous clinical trials have been implemented, an absolutely effective treatment against coronavirus disease 2019 (COVID-19) is still elusive. Interleukin-22 (IL-22) has attracted great interest over recent years, making it one of the best-studied cytokines of the interleukin-10 (IL-10) family. Unlike most interleukins, the major impact of IL-22 is exclusively on fibroblasts and epithelial cells due to the restricted expression of receptor. Numerous studies have suggested that IL-22 plays a crucial role in anti-viral infections through significantly ameliorating the immune cell-mediated inflammatory responses, and reducing tissue injury as well as further promoting epithelial repair and regeneration. Herein, we pay special attention to the role of IL-22 in the lungs. We summarize the latest progress in our understanding of IL-22 in lung health and disease and further discuss maneuvering this cytokine as potential immunotherapeutic strategy for the effective manage of COVID-19.

Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection.

The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1+ classical, intermediate, and non-classical monocytes and the proportions of IL-22R1+ plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1+ classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1+ non-classical monocytes and mDC2 displayed HLA-DRhigh expression and were thus activated. Multivariate analysis for all IL-22R1+ myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1+ cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1+ classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1+ intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4+ T cells produced IFN-γ and IL-22, and CD4+ and CD8+ T cells produced IL-17A. CD4+ T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4+ T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.

Up-regulated serum levels of interleukin (IL)-17A and IL-22 in Egyptian pediatric patients with COVID-19 and MIS-C: Relation to the disease outcome.

Both IL-17A and IL-22 share cellular sources and signaling pathways. They have synergistic action on epithelial cells to stimulate their production of antimicrobial peptides which are protective against infections. However, both interleukins may contribute to ARDS pathology if their production is not controlled. This study aimed to investigate serum levels of IL-17A and IL-22 in relation to the disease outcome in patients with SARS-CoV-2. Serum IL-17A and IL-22 were measured by ELISA in 40 patients with SARS-CoV-2, aged between 2 months and 16 years, (18 had COVID-19 and 22 had multisystem inflammatory syndrome in children "MIS-C") in comparison to 48 age- and sex-matched healthy control children. Patients with COVID-19 and MIS-C had significantly higher serum IL-17A and IL-22 levels than healthy control children (P < 0.001). Increased serum IL-17A and IL-22 levels were found in all patients. Elevated CRP and serum ferritin levels were found in 90% of these patients. Lymphopenia, neutrophilia, neutropenia, thrombocytopenia and elevated ALT, LDH and D-dimer were found in 45%, 42.5 %, 2.5%, 30%, 32.5%, 82.5%, and 65%, respectively of these patients. There were non-significant differences between patients who recovered and those who died or had a residual illness in serum levels of IL-17A, IL-22 and the routine inflammatory markers of COVID-19. In conclusions, serum IL-17A and IL-22 levels were up-regulated in all patients with COVID-19 and MIS-C. Levels of serum IL-17A, IL-22 and the routine inflammatory markers of COVID-19 were not correlated with the disease outcome. Our conclusions are limited by the sample size.