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Vaccination against COVID-19 is the main public health approach to fight against the pandemic. The Spike (S) glycoprotein of SARS-CoV-2 is the principal target of the neutralizing humoral response. We evaluated the analytical and clinical performances of a surrogate virus neutralization test (sVNT) compared to conventional neutralization tests (cVNTs) and anti-S eCLIA assays in recovered and/or vaccinated healthcare workers. Our results indicate that sVNTs displayed high specificity and no cross-reactivity. Both eCLIA and sVNT immunoassays were good at identifying cVNT serum dilutions ≥1:16. The optimal thresholds when identifying cVNT titers ≥1:16, were 74.5 U/mL and 49.4 IU/mL for anti-S eCLIA and sVNT, respectively. Our data show that neutralizing antibody titers (Nab) differ from one individual to another and may diminish over time. Specific assays such as sVNTs could offer a reliable complementary tool to routine anti-S serological assays.

Objective: Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine., Methods: We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools., Results: A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response., Conclusion: RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response., (© 2021 American College of Rheumatology.)

Background: To manage severe or potentially severe cases of CoronaVirus Disease 2019 (COVID-19), therapeutic monoclonal antibodies targeting Spike protein of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been designed. It has been noted in vitro that upon exposure to these treatments, mutations could be selected., Case Presentation: We here report the case of an immunosuppressed patient infected with a B.1.1.7 variant, who received a combination of monoclonal antibodies, and subsequently selected mutations K417N, E484K and Q493R on Spike protein of SARS-CoV-2., Conclusions: Our case raises the importance of monitoring SARS-CoV-2 mutations in patients receiving monoclonal antibodies and having persistent excretion of the virus, in order to offer optimal management of their infection, and strengthen prevention measures to avoid subsequent transmission of these selected variants., (© 2021. The Author(s).)

Objective: Public health interventions promoted during the SARS-CoV-2 pandemic to control viral spread have impacted the occurrence of other communicable disease. Yet no studies have focused on perinatal infections with the potential for neonatal sequelae, including cytomegalovirus (CMV) and Toxoplasma gondii (TG). Here we investigate whether incidence rates of maternal primary CMV and TG infection in pregnancy were affected by the implementation of pandemic-related public health measures., Methods: A retrospective study including all pregnant women with confirmed primary CMV or TG infection in pregnancy, managed between 2018 and 2021 at two university centers. The incidence rate was calculated as the number of CMV and TG infections per 100 consultations with a 95% confidence interval (CI). Data were compared between pre-pandemic (2018-2019) and pandemic (2020 and 2021) years. The Newcombe Wilson with Continuity Correction method was employed to compare incidence rates., Results: The study population included 215 maternal primary CMV and 192 TG infections. Rate of maternal primary CMV infection decreased in 2021 compared with 2018-2019 (4.49% vs 6.40%, attributable risk [AR] 1.92, P = 0.019). By contrast, the rate of TG infection substantially increased in 2020 (6.95% vs 4.61%, AR 2.34, P = 0.006). Close contact with cats was more common among patients with TG infection in 2020 and 2021 than among pre-pandemic TG-infected women (26.3% and 24.4% vs 13.3%, P = 0.013)., Conclusion: Pandemic-related public health interventions and associated behavioral and lifestyle changes exerted a divergent effect on the incidence of primary CMV and TG infection in pregnancy, likely due to modulation of exposure to risk factors for these infections., (© 2024 International Federation of Gynecology and Obstetrics.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. At this time of uncertainty, we are struggling to provide appropriate care to hematological cancer patients. We need to weigh the risks and benefits of giving cancer treatment against the odds of infecting them with COVID-19. As hematological cancer patients are immunocompromised and there are high chances of exposure during hospital visits, they can get infected and outcome can be fatal. So in this case report, we intend to discuss the possible impact of the current COVID-19 pandemic on patients with acute leukaemia in terms of diagnosis, chemotherapy, and prophylactic measures., Competing Interests: The authors declare no competing interests., (Copyright: Louardi Mounir et al.)

Background and Objectives: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre-COVID-19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post-COVID-19 restriction era., Materials and Methods: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing., Results: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre-pandemic period (1 January 2015-31 March 2020; B19V tested n = 2,412,701, B19V NAT-positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT-positive n = 26 [0.001%]); (2) a two-year mixed-impact period (1 April 2020-31 March 2022; B19V tested n = 968,250, B19V NAT-positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT-positive n = 2 [0.0002%]); and (3) a pandemic-impact period (1 April 2022-31 March, 2023; B19V tested n = 597,668, B19V NAT-positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT-positive n = 1 [0.0002%])., Conclusion: The percentage of B19V- and HAV-positive donations was significantly reduced from the pre-pandemic period to the pandemic-impact period., (© 2024 International Society of Blood Transfusion.)

In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We investigated antibody and coronavirus disease 2019 (COVID-19)-specific T-cell mediated responses via ultra-deep immunosequencing of the T-cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike-receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ-78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti-CD38 or anti-B-cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA-1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID-19 genome after vaccination, consistent with spike-specific T-cell responses. The median spike-specific T-cell breadth was 3.11 × 10 -5 , comparable to those in healthy populations after vaccination. Although spike-specific T-cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike-specific T-cell responses. Patients receiving mRNA-1273 had higher median spike-specific T-cell breadth than those receiving BNT162b2 (p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID-19 vaccination can still elicit humoral and T-cell responses and remain an important intervention in this patient population., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Impaired immune response in multiple myeloma renders the patients vulnerable to infections, such as COVID-19, and may cause worse response to vaccines. Researchers should analyze this issue to enable the planning for special preventive measures, such as increased booster doses. Therefore, this meta-analysis aimed to evaluate the response and efficacy of COVID-19 vaccines in patients with multiple myeloma. Methods: This meta-analysis followed PRISMA 2020 guidelines, conducting a comprehensive database search using specified keywords. Study selection involved a two-phase title/abstract and full-text screening process. Data extraction was performed by two researchers, and statistical analysis involved meta-analysis, subgroup analysis based on vaccine dosage and study time, random effects meta-regression, and heterogeneity testing using the Q test. Results: The meta-analysis revealed that patients with multiple myeloma (MM) had a lower likelihood of developing detectable antibodies after COVID-19 vaccination compared to healthy controls (Log odds ratio with 95% CI: -3.34 [-4.08, -2.60]). The analysis of antibody response after different doses showed consistent lower seropositivity in MM patients (after first dose: -2.09, [-3.49, -0.69], second: -3.80, 95%CI [-4.71, -3.01], a booster dose: -3.03, [-5.91, -0.15]). However, there was no significant difference in the mean level of anti-S antibodies between MM patients and controls (Cohen's d -0.72, [-1.86, 0.43]). Evaluation of T-cell responses indicated diminished T-cell-mediated immunity in MM patients compared to controls. Seven studies reported clinical response, with breakthrough infections observed in vaccinated MM patients. Conclusions: These findings highlight the impaired humoral and cellular immune responses in MM patients after COVID-19 vaccination, suggesting the need for further investigation and potential interventions. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has exacerbated mortality rates among immunocompromised patients, accentuating the need for novel, targeted therapies. Transplant recipients, with their inherent immune vulnerabilities, represent a subgroup at significantly heightened risk. Current conventional therapies often demonstrate limited effectiveness in these patients, calling for innovative treatment approaches. In immunocompromised transplant recipients, several viral infections have been successfully treated by adoptive transfer of virus-specific T-cells (VST). This paper details the successful application of SARS-CoV-2-specific memory T-cell therapy, produced by an interferon-γ cytokine capture system (CliniMACS® Prodigy device), in three stem cell transplant recipients diagnosed with COVID-19 (case 1: alpha variant, cases 2 and 3: delta variants). These patients exhibited persistent SARS-CoV-2 PCR positivity accompanied by bilateral pulmonary infiltrates and demonstrated only partial response to standard treatments. Remarkably, all three patients recovered and achieved viral clearance within 3 to 9 weeks post-VST treatment. Laboratory follow-up investigations identified an increase in SARS-CoV-2-specific T-cells in two of the cases. A robust anti-SARS-CoV-2 S (S1/S2) IgG serological response was also recorded, albeit with varying titers. The induction of memory T-cells within the CD4 + compartment was confirmed, and previously elevated interleukin-6 (IL-6) and IL-8 levels normalized post-VST therapy. The treatment was well tolerated with no observed adverse effects. While the need for specialized equipment and costs associated with VST therapy present potential challenges, the limited treatment options currently available for COVID-19 within the allogeneic stem cell transplant population, combined with the risk posed by emerging SARS-CoV-2 mutations, underscore the potential of VST therapy in future clinical practice. This therapeutic approach may be particularly beneficial for elderly patients with multiple comorbidities and weakened immune systems. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought to the forefront the intricate relationship between SARS-CoV-2 and its impact on neurological complications, including potential links to neurodegenerative processes, characterized by a dysfunction of the protein quality control systems and ER stress. This review article explores the role of protein quality control systems, such as the Unfolded Protein Response (UPR), the Endoplasmic Reticulum-Associated Degradation (ERAD), the Ubiquitin–Proteasome System (UPS), autophagy and the molecular chaperones, in SARS-CoV-2 infection. Our hypothesis suggests that SARS-CoV-2 produces ER stress and exploits the protein quality control systems, leading to a disruption in proteostasis that cannot be solved by the host cell. This disruption culminates in cell death and may represent a link between SARS-CoV-2 and neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: With SARS-CoV-2 antibody tests on the market, healthcare providers must be confident that they can use the results to provide actionable information to understand the characteristics and dynamics of the humoral response and antibodies (abs) in SARS-CoV-2-vaccinated patients. In this way, the study of the antibody responses of healthcare workers (HCWs), a population that is immunocompetent, adherent to vaccination, and continuously exposed to different virus variants, can help us understand immune protection and determine vaccine design goals. Methods: We retrospectively evaluated antibody responses via multiplex assays in a sample of 538 asymptomatic HCWs with a documented complete vaccination cycle of 3 doses of mRNA vaccination and no previous history of infection. Our sample was composed of 49.44% males and 50.56% females, with an age ranging from 21 to 71 years, and a mean age of 46.73 years. All of the HCWs' sera were collected from April to July 2022 at the Sant'Elia Hospital of Caltanissetta to investigate the immunologic responses against anti-RBD, anti-S1, anti-S2, and anti-N IgG abs. Results: A significant difference in age between HCWs who were positive and negative for anti-N IgG was observed. For anti-S2 IgG, a significant difference between HCWs who were negative and positive compared to anti-N IgG was observed only for positive HCWs, with values including 10 (U/mL)–100 (U/mL); meanwhile, for anti-RBD IgG and anti-S1 IgG levels, there was only a significant difference observed for positive HCWs with diluted titers. For the negative values of anti-N IgG, among the titer dilution levels of anti-RBD, anti-S1, and anti-S2 IgG, the anti-S2 IgG levels were significantly lower than the anti-RBD and anti-S1 levels; in addition, the anti-S1 IgG levels were significantly lower than the anti-RBD IgG levels. For the anti-N IgG positive levels, only the anti-S2 IgG levels were significantly lower than the anti-RBD IgG and anti-S1 IgG levels. Finally, a logistic regression analysis showed that age and anti-S2 IgG were negative and positive predictors of anti-N IgG levels, respectively. The analysis between the vaccine type and mixed mRNA combination showed higher levels of antibodies in mixed vaccinated HCWs. This finding disappeared in the anti-N positive group. Conclusions: Most anti-N positive HCWs showed antibodies against the S2 domain and were young subjects. Therefore, the authors suggest that including the anti-SARS-CoV-2-S2 in antibody profiles can serve as a complementary testing approach to qRT-PCR for the early identification of asymptomatic infections in order to reduce the impact of potential new SARS-CoV-2 variants. Our serological investigation on the type of mRNA vaccine and mixed mRNA vaccines shows that future investigations on the serological responses in vaccinated asymptomatic patients exposed to previous infection or reinfection are warranted for updated vaccine boosters. [ABSTRACT FROM AUTHOR]

The medical care of immunocompromised patients with COVID-19 infection causes major hurdles in the management of these patients in clinical practice. However, poor responses to vaccinations in patients with oncological or autoimmune diseases require rapid action and effective care in this fragile patient population. Monoclonal antibodies (mAb) offer an effective therapeutic option with a favorable toxicity profile. We have retrospectively reviewed the first 100 patients treated with mAb in our clinic and assessed the individual vaccine response, side effects of mAb, hospitalization rate and mortality. None of the outpatients treated with mAb had to be hospitalized. In particular, the third SARS-CoV-2 vaccination had a significant effect on the seroconversion (37.5% vs. 77.8% positive patients) in the entire group of patients studied. No side effects of 3°/4° were observed following mAb administration; the mortality in the entire cohort was 7%. Our data and experience show good effectiveness and a favorable tolerability profile of mAb, supporting the feasibility of this therapy in everyday clinical practice. Of note, in immunocompromised patients, both the vaccination status and success need to be recorded in a systematic manner and taken into account in terms of therapeutic intervention using mAb in case of a SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) has severely affected the elderly, who are expected to display decreased immune responses due to immunosenescence. Methods This study retrospectively assesses neutralizing antibody (NAb) production up to 12 months after infection in long-term care patients. We used Roche Diagnostics immunoassay to quantify anti-spike (S) antibodies and a competitive immunoassay from YHLO as a surrogate test for NAb. Results We included 91 patients (mean age, 86 years). There was no significant variation in anti-S titers over time. There was a significant decrease of NAb titers between month 3 and month 6 but no further significant change up to month 12. Overall, 75 of 91 (82%) and 52 of 91 (57%) patients had, at least once, anti-S titers >75 U/mL and NAb titers >50 AU/mL, respectively, corresponding to a significant neutralizing activity in vitro. All 68 patients studied at M12 had detectable anti-S antibodies and 60 (88%) had detectable NAb; 60 of 68 (88%) and 29 of 68 (42.6%) still had anti-S titers >75 U/mL and NAb titers >50 AU/mL. Higher NAb titers were correlated with severe infection, higher levels of C-reactive protein, and lower lymphocyte counts. No patient developed reinfection. Conclusions Elderly people can display robust and persistent humoral response after severe acute respiratory syndrome coronavirus 2 infection, with NAb lasting up to 12 months. [ABSTRACT FROM AUTHOR]

Background: Effective SARS-CoV-2 vaccination in patients receiving treatment with B-cell depleting agents is challenging. Information on vaccination responses in these patients are a valuable tool to develop efficient vaccination regimens.Methods: In this single-center retrospective observational study, we report the humoral and cellular response in 34 patients receiving anti-CD20 antibody treatment for renal immune disease.Results: After base immunization with SARS-CoV-2-vaccines, 92.0% developed a cellular, 32.4% a humoral response. Humoral immunity correlated with B-cell counts and the timespan between anti-CD20 antibody treatment and vaccination. All patients with > 21/µl B-cells, or > 197 days after treatment showed humoral response.Conclusions: Adequate timing of SARS-CoV-2-vaccinations after anti-CD20 antibody treatment and CD19 measurements are crucial to generate immunity. Awaiting partial B-cell recovery by postponing regularly scheduled anti-CD20 treatment should be considered in patients with stable immune disease.Trial Registration: This study has been retrospectively registered in the German Clinical Trials Register (DRKS00027049) on 29/10/2021. [ABSTRACT FROM AUTHOR]

Simple Summary: CD38 remains an interesting target for anticancer therapy. Its relatively high abundance in neoplasms and crucial impact on NAD+/cADPR metabolism and the activity of T cells allows for changing the immune response in autoimmune diseases, neoplasms, and finally the induction of cell death. Antibody-dependent cell cytotoxicity is responsible for cell death induced by targeting the tumor with anti-CD38 antibodies, such as daratumumab. A wide range of laboratory experiments and clinical trials show an especially promising role of anti-CD38 therapy against multiple myeloma, NK cell lymphomas, and CD19- B-cell malignancies. More studies are required to include more diseases in the therapeutic protocols involving the modulation of CD38 activity. CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38. [ABSTRACT FROM AUTHOR]

This case report describes a 60-year-old female patient suffering from systemic sclerosis, for which she received immunomodulatory drugs. Her first SARS-CoV-2-positive nasopharyngeal sample was obtained in the emergency department, on 31 January 2022. Whole genome sequencing confirmed infection with Omicron BA.1.1. Her hospital stay was long and punctuated by many complications, including admission to the intensive care unit. At the beginning of April 2022, she started complaining of increased coughing, for which another SARS-CoV-2 RT-qPCR test was performed. The latter nasopharyngeal swab showed a strongly positive result. To support the theory of healthcare-associated reinfection, whole genome sequencing was performed and confirmed reinfection with Omicron BA.2. Since this patient was one of ten positive cases in this particular ward, a hospital outbreak investigation was performed. Whole genome sequencing data were available for five of these ten patients and showed a cluster of four patients with ≤2 small nucleotide polymorphisms difference. [ABSTRACT FROM AUTHOR]

The viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly its cell-binding spike protein gene, has undergone rapid evolution during the coronavirus disease 2019 (COVID-19) pandemic. Variants including Omicron BA.1 and Omicron BA.2 now seriously threaten the efficacy of therapeutic monoclonal antibodies and vaccines that target the spike protein. Viral evolution over a much longer timescale has generated a wide range of genetically distinct sarbecoviruses in animal populations, including the pandemic viruses SARS-CoV-2 and SARS-CoV-1. The genetic diversity and widespread zoonotic potential of this group complicates current attempts to develop drugs in preparation for the next sarbecovirus pandemic. Receptor-based decoy inhibitors can target a wide range of viral strains with a common receptor and may have intrinsic resistance to escape mutant generation and antigenic drift. We previously generated an affinity-matured decoy inhibitor based on the receptor target of the SARS-CoV-2 spike protein, angiotensin-converting enzyme 2 (ACE2), and deployed it in a recombinant adeno-associated virus vector (rAAV) for intranasal delivery and passive prophylaxis against COVID-19. Here, we demonstrate the exceptional binding and neutralizing potency of this ACE2 decoy against SARS-CoV-2 variants including Omicron BA.1 and Omicron BA.2. Tight decoy binding tracks with human ACE2 binding of viral spike receptor-binding domains across diverse clades of coronaviruses. Furthermore, in a coronavirus that cannot bind human ACE2, a variant that acquired human ACE2 binding was bound by the decoy with nanomolar affinity. Considering these results, we discuss a strategy of decoy-based treatment and passive protection to mitigate the ongoing COVID-19 pandemic and future airway virus threats. [ABSTRACT FROM AUTHOR]

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1–10) vs. 5 (1–15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046–0.96, p = 0.044 and OR 0.189, 95% CI 0.036–0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients. [ABSTRACT FROM AUTHOR]

Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases. [ABSTRACT FROM AUTHOR]

Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded via autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications. [ABSTRACT FROM AUTHOR]

Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5′-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid β-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis. [ABSTRACT FROM AUTHOR]