Respiratory Syndrome Research Articles

Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies

Background: Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited. Aim: To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20. Methods: Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023. Results: Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID. Conclusions: In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.

The introduction of a highly virulent PRRSV strain in pig farms is associated with a change in the pattern of influenza A virus infection in nurseries

The present study aimed to determine the dynamics of influenza A virus (IAV) infection in two endemically infected farms (F1 and F2), where a longitudinal follow-up of piglets was performed from birth to 8–12 weeks of age. During the study, a highly virulent isolate of porcine reproductive and respiratory syndrome virus (PRRSV) was introduced on both farms. This allowed us to examine the impact of such introduction on the patterns of infection, disease, and the antibody response of pigs to IAV infection. The introduction of the new PRRSV strain coincided with a change in the dynamics of IAV infection on both farms. In F1, the cumulative incidence of IAV increased from 20% before the outbreak to 67.5%, together with the existence of animals that tested positive for IAV (RT‒qPCR) in nasal swabs for two or more consecutive samples. In F2, the cumulative incidence of IAV increased from 50% before the PRRSV outbreak to 70%, and the proportion of prolonged IAV shedders increased sharply. Additionally, some animals were infected with the same IAV twice during the observation period. In contrast to previous reports, our study revealed that prolonged shedding was not related to the titres of maternally derived antibodies at the time of infection but was significantly (p < 0.05) related to PRRSV infection status. Notably, both before and after the PRRSV outbreak, a high proportion of IAV-infected piglets did not seroconvert, which was significantly (p < 0.05) related to the hemagglutination inhibition titres against IAV when infected.

Neurological, psychological, psychosocial complications of long-COVID and their management

AbstractSince it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed ‘long-COVID’. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms. A concise account of the clinical relevance of the neurological and psychosocial impacts of long-COVID, the effects on long-term morbidity, and varied approaches in managing patients with significant chronic neurological symptoms and conditions was extracted from the literature, analysed and reported. A comprehensive account of plausible pathophysiological mechanisms involved in the development of long-COVID, its management, and future research needs have been discussed.

Factors associated with outcome in a national cohort of rhinovirus hospitalized patients in Brazil in 2022

The common cold is the primary cause of illness in the community, with over 200 viral strains identified, and rhinovirus infections being the most prevalent. Coronavirus Disease 19 (COVID-19) is also a significant cause of severe illness. The burden of acute respiratory infections has a significant impact on the economy, resulting in absenteeism from work and school. Rhinovirus infections can exacerbate asthma and other chronic diseases, leading to hospitalization. The objective of this study is to investigate the factors associated with death and survival in patients hospitalized for rhinovirus in Brazil in 2022. This is a retrospective cohort study using data from the national surveillance of Severe Acute Respiratory Syndrome (SARS) in 2022 in Brazil, with all the norrifications. We analysed and compared clinical and epidemiological factors and outcomes between survivors and deaths in patients hospitalised for rhinovirus. The absolute and relative frequencies were calculated according to the states. Bivariate analysis was performed using chi-squared test and Fisher’s exact test, while multivariate analysis was performed using COX regression. Out of 8,130 cases of SARS caused by rhinovirus, 291 (3.58%) resulted in death while 7839 (96.47%) patients survived. The factors associated with death were invasive ventilation (p- < 0.001 HR 4.888 CI 95% 3.816–6.262), bocavirus (p- < 0.001 HR 4.204 CI 95% 2.595–6.812), immunodepression/Immunosuppression (p- < 0.001 HR 2.417 CI 95% 1. 544–3, 786), COVID-19 (p- < 0.001 HR 2.167 CI 95% 1.495–3.142), chronic neurological diseases (p-0.007 HR 1.610 CI 95% 1.137–2.280), abdominal pain (p-0.005 HR 1.734 CI 95% 1.186–2.537), age (p- < 0.001 HR 1.038 CI 95% 1.034–1.042). The survival factors identified in this study were dyspnea (p = 0.005; HR 0.683; CI 95% 0.524–0.889), cough (p < 0.001; HR 0.603; CI 95% 0.472–0.769), and asthma (p = 0.052; HR 0.583; CI 95% 0.339–1.004). Additionally, the study found that receiving a COVID-19 booster dose was also a significant survival factor (p = 0.001; HR 0.570; CI 95% 0.415–0.784). The factors associated with death were similar to those in the literature, and the factors associated with survival were also similar, except for the booster dose of the COVID-19 vaccine, which we didn’t find in any studies. Our study is the first to associate the full course of the COVID-19 vaccine with survival in those hospitalized for rhinovirus, regardless of COVID-19 and rhinovirus co-detection.

Hospital-based cross-sectional study on the clinical characteristics of children with severe acute respiratory infections in Hungary

BackgroundSevere acute respiratory infection (SARI) is a major cause for hospital admission and associated with high mortality among children worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses and respiratory syncytial virus (RSV) are the most frequently identified pathogens in children with SARI. The duration of care can be affected by the type of infection and patient characteristics. Therefore, the objective of this study was to identify factors affecting the length of hospitalization in children infected with SARS-CoV-2, influenza A and RSV.MethodsWe collected data on 713 children with SARI from the medical databases of a university hospital in Hungary. To examine whether there is a difference in the length of hospitalization in children with the SARI Kruskal-Wallis test was performed. To determine the factors that may have an impact on the duration of care a multiple logistic regression analysis was executed.ResultsOur results showed that among RSV infected patients the proportions of children requiring intensive care (8.94%), mechanical ventilation (8.94%) and oxygen therapy (13.01%) and suffering from pneumonia (29.27%) were larger than among cases with SARS-CoV-2 and influenza A infection. Considering the age distribution and the duration of care in children with SARI, cases with RSV were significantly younger (p < 0.001) and stayed longer in the hospital (median: 5 days, IQR: 4–7 days, p < 0.001) than those with SARS-CoV-2 and influenza A virus. Multiple logistic regression analysis showed that RSV infection (adjusted odds ratio (aOR): 3.25, 95% confidence interval (CI): 1.43–7.38; p = 0.005), pneumonia (aOR: 3.65, 95% CI: 2.14–6.24; p < 0.001), mechanical ventilation or oxygen therapy (aOR: 3.23, 95% CI: 1.29–8.11; p = 0.012) and underlying illnesses (aOR: 2.39, 95% CI: 1.35–4.23; p = 0.003) significantly increased the odds of hospitalization for more than 4 days.ConclusionsOur research showed that of the viruses causing SARI, RSV had the greatest clinical relevance, contributing to hospital stays of more than 4 days in a large share of paediatric patients below 1 year of age. Our results supply new information on children with SARI, and provide evidence for health policy makers to allocate additional resources to hospitals during SARI epidemics.

Structural basis for human DPP4 receptor recognition by a pangolin MERS-like coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) and the pangolin MERS-like coronavirus MjHKU4r-CoV-1 employ dipeptidyl peptidase 4 (DPP4) as an entry receptor. MjHKU4r-CoV-1 could infect transgenic mice expressing human DPP4. To understand the mechanism of MjHKU4r-CoV-1 entry into cells, we determined the crystal structures of the receptor binding domain (RBD) of MjHKU4r-CoV-1 spike protein bound to human DPP4 (hDPP4) and Malayan pangolin DPP4 (MjDPP4), respectively. The overall hDPP4-binding mode of MjHKU4r-CoV-1 RBD is similar to that of MERS-CoV RBD. MjHKU4r-CoV-1 RBD shows higher binding affinity to hDPP4 compared to the bat MERS-like coronavirus Ty-BatCoV-HKU4. Via swapping residues between MjHKU4r-CoV-1 RBD and Ty-BatCoV-HKU4 RBD, we identified critical determinants on MjHKU4r-CoV-1 that are responsible for virus usage of hDPP4. Our study suggests that MjHKU4r-CoV-1 is more adapted to the human receptor compared to the bat HKU4 coronavirus and highlights the potential of virus emergence into the human population.

Seroprevalence of anti-SARS-CoV-2 IgM and IgG and COVID-19 vaccine uptake in healthy volunteers in Nairobi, Kenya: a cross-sectional study

IntroductionSeroprevalence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies in the postvaccination period in Kenya remains to be elucidated. This study aimed to determine the seroprevalence of anti-SARS-CoV-2 IgM and IgG and evaluate Covid-19 vaccination uptake in a university setting in Nairobi.MethodsThis cross-sectional study assayed serum anti-SARS-CoV-2 IgM and IgG levels using enzyme-linked immunosorbent assays. A structured questionnaire was used to determine vaccine uptake, vaccine hesitancy and reasons for hesitancy.ResultsA total of 189 participants were enrolled (median age, 21 years; female, 50.8%). The seroprevalence of anti-SARS-CoV-2 was 12.7% for IgM and 87.8% for IgG. Anti-SARS-CoV-2 IgG titers were higher among the vaccinated vs. non-vaccinated individuals (p &amp;lt; 0.001, U = 2817.5), females vs. males (p = 0.024, U = 3616), and those vaccinated ≤ 6 months before the study vs. those vaccinated &amp;gt;1 year earlier (p = 0.002, H = 12.359). The vaccination hesitancy rate was 43.4% and the underlying reasons included mistrust (22.4%), health concerns (19.7%), and lack of information (18.4%).DiscussionThe high seroprevalence of anti-SARS-CoV-2 IgG is an indication of high exposure to SARS-CoV-2 either through natural infection or through vaccination. The high vaccine hesitancy noted necessitates community engagement, and public education to dispel myths and misinformation prior to roll out of new vaccines and other health interventions.

Effect of reduced saturation and elevated D-dimer and interleukin 6 levels on vessel density and foveal avascular zone in patients with COVID-19 bilateral pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect multiple organs, including the eyes. This study aimed to identify associations between vascular density (VD) and the foveal avascular zone (FAZ), assessed using optical coherence tomography angiography (OCTA), and baseline levels of D-dimers and interleukin 6 (IL-6) in patients with bilateral COVID-19 pneumonia, depending on oxygen saturation (SpO2) on admission. The study included patients with COVID-19 bilateral pneumonia due to SARS-CoV-2 infection who were hospitalized between March and May 2021. Ophthalmological examination was performed 2 months after hospitalization. Optical coherence tomography angiography was used for the automatic assessment of the central retinal VD and the manual assessment of FAZ. A significant monotonic negative relationship was observed between SpO2 . 90% and VD in some areas of the superficial capillary plexus (SCP) (p = 0.048) and choriocapillaris (p = 0.021), and the mean VD in the deep capillary plexus (DCP) (p = 0.048). No significant monotonic negative relationship was noted between SpO2 . 90% and the FAZ in the SCP (p = 0.075). However, there was a significant monotonic positive relationship between VD in the nasal choriocapillaris and D-dimer levels in patients with SpO2 . 90% (p = 0.003, respectively). Finally, a monotonic negative relationship was identified between foveal VD in the DCP and IL-6 levels in patients with SpO2 . 90% (p = 0.027). An OCTA study conducted 2 months after hospitalization for COVID-19 bilateral pneumonia showed reduced VD in those with SpO2 . 90% and elevated levels of D-dimers and IL-6 during hospitalization. Optical coherence tomography angiography testing can provide monitoring of ocular status in patients following SARS-CoV-2 infection, especially those who report visual disturbances.

A Novel Cell- and Virus-Free SARS-CoV-2 Neutralizing Antibody ELISA Based on Site-Specific Labeling Technology.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the global spread of coronavirus disease 2019 (COVID-19), creating an urgent need for updated methods to evaluate immune responses to vaccines and therapeutic strategies. In this study, we introduce a novel cell-free, virus-free SARS-CoV-2 neutralizing antibody ELISA (NAb-ELISA), which is based on competitive inhibition of the receptor binding domain (RBD) of spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. In this method, site-specific biotinylated hACE2-Fc-Avi recombinant protein is immobilized onto a 96-well plate for capture, and the RBD-Fc-vHRP recombinant proteins serve as detection probes. Evaluation of sera from wild type (WT) or Delta RBD-immunized mice using the NAb-ELISA and pseudovirus neutralization tests (pVNTs) demonstrated strong correlations between assays (R2 = 0.91 and 0.90 for the WT and Delta groups, respectively). Additionally, the NAb-ELISA successfully detected cross-neutralizing activity in sera, though with slightly lower correlation to pVNT (R2 = 0.70-0.83). By employing NAb-ELISA instead of an indirect ELISA for hybridoma screening, five monoclonal antibodies (mAbs) with neutralizing activities against WT, Delta, and BA.2 pseudoviruses were obtained. This assay offers a straightforward, rapid, and safe approach to characterizing vaccine-induced antibody responses and mAb neutralization activity. Notably, the NAb-ELISA platform can be quickly adapted to assess neutralizing antibody responses against emerging mutant strains, addressing the rapid mutation of the virus.

Neighborhood Socioeconomic Disadvantage Increases Risk of Severe Acute Respiratory Syndrome Coronavirus 2-Mediated Otologic Dysfunction.

We aim to use the Area Deprivation Index (ADI) to investigate the correlations between neighborhood socioeconomic disadvantage (NSD), SARS-CoV-2 vaccination rates, infection severity, and subsequent audiovestibular symptoms. In this retrospective cohort study, surveys were administered to participants ≥18 years of age who received a SARS-CoV-2 vaccination and/or tested positive for SARS-CoV-2 infection between January 2020 and September 2022. ADI scores were calculated for each patient to quantify NSD. Statistical analyses were performed to compare demographic and clinical characteristics between ADI quintiles. Of 2415 participants, the majority were female (62.8%) and White (87%), with a mean age of 60.8 years. Individuals in ADI Quintile 5 were less likely to receive second booster doses than those in Quintile 1 (58% vs. 71%, p < 0.0001). Among those infected with SARS-CoV-2, those in ADI Quintile 5 were 2.5 times more likely to be hospitalized (relative risk = 2.46, 95% confidence interval [1.03, 5.88]) than those in Quintile 1. Symptoms more likely to be experienced by participants in ADI Quintile 5 than those in Quintile 1 immediately following SARS-CoV-2 infection included headaches (28% vs. 21%, p = 0.02), aural fullness (14% vs. 6%, p < 0.0001), change of hearing (8% vs. 4%, p = 0.01), dizziness (15% vs. 8%, p < 0.01), and otalgia (8% vs. 4%, p < 0.01). Individuals experiencing greater NSD were found to have lower SARS-CoV-2 vaccine booster rates, higher rates of postinfection hospitalization, and increased rates of certain otologic and neurotologic symptoms following infection. III Laryngoscope, 2024.

Recombinant characterization and pathogenicity of a novel L1C RFLP-1-4-4 variant of porcine reproductive and respiratory syndrome virus in China

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting the pig industry worldwide and is caused by the PRRS virus (PRRSV), which has complex genetic variation due to frequent mutations, indels, and recombination. The emergence of PRRSV L1C.5 in 2020 in the United States has raised worldwide concerns about PRRSV with the RFLP 1-4-4 pattern and lineage 1C. However, studies on the pathogenic characteristics, epidemiological distribution, and effectiveness of vaccines against PRRSV with L1C and RFLP1-4-4 pattern in China are still insufficient. In this study, a novel recombinant variant of PRRSV with RFLP 1-4-4 and lineage 1C features, different from L1C.5 in the United States, was isolated in China in 2021. In pathogenicity experiments in specific pathogen-free piglets or farm piglets, 60–100% of artificially infected experimental piglets died with high fever and respiratory symptoms. Inflammatory cytokine and chemokine levels were upregulated in infected piglets. A commercially modified live vaccine against highly pathogenic PRRSV did not provide effective protection when the vaccinated piglets were challenged with the novel L1C-1-4-4 variant. Therefore, this strain merits special attention when devising control and vaccine strategies. These findings suggest that extensive joint surveillance is urgently needed and that vaccine strategies should be updated to prevent the disease from spreading further.

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Enhanced predictability and interpretability of COVID-19 severity based on SARS-CoV-2 genomic diversity: a comprehensive study encompassing four years of data.

Despite the end of the global Coronavirus Disease 2019 (COVID-19) pandemic, the risk factors for COVID-19 severity continue to be a pivotal area of research. Specifically, studying the impact of the genomic diversity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on COVID-19 severity is crucial for predicting severe outcomes. Therefore, this study aimed to investigate the impact of the SARS-CoV-2 genome sequence, genotype, patient age, gender, and vaccination status on the severity of COVID-19, and to develop accurate and robust prediction models. The training set (n = 12,038), primary testing set (n = 4,006), and secondary testing set (n = 2,845) consist of SARS-CoV-2 genome sequences with patient information, which were obtained from Global Initiative on Sharing all Individual Data (GISAID) spanning over four years. Four machine learning methods were employed to construct prediction models. By extracting SARS-CoV-2 genomic features, optimizing model parameters, and integrating models, this study improved the prediction accuracy. Furthermore, Shapley Additive exPlanes (SHAP) was applied to analyze the interpretability of the model and to identify risk factors, providing insights for the management of severe cases. The proposed ensemble model achieved an F-score of 88.842% and an Area Under the Curve (AUC) of 0.956 on the global testing dataset. In addition to factors such as patient age, gender, and vaccination status, over 40 amino acid site mutation characteristics were identified to have a significant impact on the severity of COVID-19. This work has the potential to facilitate the early identification of COVID-19 patients with high risks of severe illness, thus effectively reducing the rates of severe cases and mortality.

A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2.

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies.

Disposal of SARS-CoV-2 corpses: experiences of environmental health officers

BackgroundThough the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is no more of a public health emergency, the experiences from burying SARS-CoV-2 infectious dead bodies may remain with the workers. For Environmental Health Officers (EHOs), dealing with decedents during the SARS-CoV-2 outbreak may arouse strong feelings of pity, horror, repulsion, disgust, and anger at the tragedy. Therefore, this study aims to explore the experiences of EHOs in disposing off of confirmed or suspected SARS-CoV-2 fatalities in Ghana.MethodsUsing an 18-item interview guide, we gathered data from 27 EHOs from three regions of Ghana. We followed the steps in Descriptive Phenomenology in conducting the data analysis.Resultsi. EHOs were confronted with several occupational health and safety (OHS) hazards like physical and chemical injuries, threat of harm, and psychological harm, ii. The officers also faced severe shortage of personal protective equipment (PPE). Unfortunately, they were not provided with any form of psychological support during the period.ConclusionThe SARS-CoV-2 outbreak in Ghana exposed major fault lines in the health and safety/disaster and emergency preparedness of EHOs towards the burial of infectious disease dead bodies. Clearly, the disposal exercise failed to uphold the Sustainable Development Goals (SDGs) 4.4, 8.3, and 8.5, which advocate for the promotion of decent jobs for all.RecommendationGhana’s Ministries of Health, Local Government, and Sanitation and Water Resources need to attach Clinical Psychologists and security personnel to the disposal teams in future exercises to provide psychological support and security to the team. Though studies on the disposal of infectious bodies in Africa exist, very little is known about the experiences of EHOs in the disposal of SARS-CoV-2 dead bodies during the outbreak.

Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.

Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.

Prospective, multi-site evaluation of the Cepheid Xpert Xpress CoV-2 plus test on nasal and nasopharyngeal swabs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause millions of infections and tens of thousands of deaths per year in the United States. While the FDA authorized hundreds of SARS-CoV-2 tests during the public health emergency, significantly fewer have made the transition to being cleared or approved. There continues to be a need for FDA-authorized point-of-care SARS-CoV-2 testing that can be performed by untrained users. We conducted a large prospective study of the Cepheid Xpert Xpress CoV-2 plus test for detection of SARS-CoV-2 in both nasal and nasopharyngeal swabs by trained and untrained users. The assay demonstrated excellent clinical performance characteristics and, as a result of this study, was cleared by the FDA.

Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection.

Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein-directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti-spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2-infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection.

Characteristics of Multisystem Inflammatory Syndrome in Children Across COVID-19 Variants in Vojvodina

Background/Objectives: To investigate if the severity and presentation of multisystem inflammatory syndrome in children (MIS-C) vary between different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Methods: This retrospective study included 59 patients aged 0–18 years, diagnosed with COVID-19 and MIS-C, treated and monitored over a one-year period after discharge from hospital. The patients were grouped according to the predominant SARS-CoV-2 variant. The predominant variant of SARS-CoV-2 was assumed by the date of hospitalization. The following patient data were collected: demographic data (age, sex), information on comorbidities, body mass index, clinical data (fever and duration of febrile periods, symptoms of Kawasaki-like phenotypes, and presence of respiratory, cardiovascular, gastrointestinal, neurological and other symptoms), and laboratory and imaging findings. Results: In total, 24 (41%), 19 (32%), and 15 (25%) patients were diagnosed with MIS-C during the Alpha, Delta, and Omicron periods, respectively (63.8% were males; 36.2% were females). Comorbidities were present in 49% of patients. Respiratory symptoms were the most common during the Delta period (73%, p = 0.028). There was no statistically significant difference in the occurrence of other symptoms, laboratory findings, treatment, complications, and long-term outcomes between groups. Conclusions: No significant correlation was found between hospitalization date (used to estimate COVID-19 variant) and presentation/severity of MIS-C.

Clinical characteristics and antibody response to Omicron variants among solid carcinoma patients in China on the 2022.12–2023.4 wave of the COVID-19 pandemic

BackgroundChina experienced a surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants after adjusting its zero-coronavirus disease 2019 (COVID-19) policy. Although infections with Omicron variants are generally less severe than infections with previous SARS-CoV-2 variants, the clinical characteristics, persistent symptoms, and antibody responses in solid carcinoma patients (SCPs) with COVID-19 during the Omicron wave are unclear.MethodsWe conducted a cross-sectional study in April 2023, recruiting healthy controls (HCs) from the community and SCPs from Zhejiang Provincial People’s Hospital. Serum samples were collected, and a questionnaire was used to assess SARS-CoV-2 infection status, including demographic characteristics, clinical manifestations, and “long COVID” symptoms. Humoral immune responses were analyzed by enzyme-linked immunosorbent assays (ELISAs) targeting immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD; Omicron BA.4/5) protein and cell culture-based neutralization assays against Omicron variants (BA.4/5, BF.7, XBB.1.5, and EG.5).ResultsIn total, 298 SCPs and 258 HCs were enrolled. Self-reported COVID-19 case rates were significantly lower in SCPs than in HCs (78.5% vs. 93.8%, P&amp;lt;0.001). Common COVID-19 symptoms were similar between the two groups, primarily comprising general (92.6% vs. 84.9%) and respiratory symptoms (51.9% vs. 48.2%) after acute infection. There was no significant difference in persistent symptoms at 1–3 months post-infection (P=0.353); fatigue was the most common symptom (45.0% vs. 44.8%). SCPs exhibited lower anti-RBD-IgG titers compared with HCs (1.061 vs. 1.978, P=0.001). The 50% pseudovirus neutralization titer (pVNT50) values for prevalent Omicron strains (BA.4/5 and BF.7) were lower in SCPs than in HCs (621.0 [288.8, 1333.0] vs. 894.1 [458.5, 1637.0] and 529.6 [215.3, 1264.5] vs. 463.1 [185.2, 914.0], respectively). Levels of antibodies against subsequent variants (XBB.1.5 and EG.5) also were reduced. There were no significant differences among carcinoma types in the levels of antibodies against Omicron variants. However, SCPs who received the SARS-CoV-2 vaccine or had COVID-19 during the Omicron wave displayed higher antibody levels.ConclusionsThis study elucidated the clinical and immunological characteristics of SCPs during the Omicron wave in China after the shift away from a zero-COVID-19 policy. Our findings provide insights regarding factors that influence COVID-19 symptoms and antibody levels in this population.