COVID-19-Associated Disease Course Is Shortened in Moderate-to-Severe Atopic Dermatitis Patients Receiving Dupilumab Treatment: A Retrospective Cross-Sectional Study.

Previous studies suggest that allergic diseases may be a protective factor in SARS-CoV-2 infection. However, data regarding the impact of dupilumab, a widely used immunomodulatory medication, on COVID-19 in an allergic population are very limited. To investigate the incidence and severity of COVID-19 among moderate-to-severe atopic dermatitis (AD) patients treated with dupilumab, a retrospective cross-sectional survey was conducted among patients with moderate-to-severe AD who presented at the Department of Allergy of Tongji Hospital from 15 January 2023 to 31 January 2023. Healthy individuals matched for gender and age were also enrolled as a control. All subjects were asked about their demographic characteristics, past medical history, COVID-19 vaccination history, and medications, as well as the presence and duration of individual COVID-19-related symptoms. A total of 159 moderate-to-severe AD patients and 198 healthy individuals were enrolled in the study. Among the AD patients, 97 patients were treated with dupilumab, and 62 patients did not receive any biologicals or systemic treatments (topical treatment group). The proportions of people who were not infected with COVID in the dupilumab treatment group, topical treatment group and healthy control group were 10.31%, 9.68% and 19.19%, respectively (p = 0.057). There was no significant difference in COVID-19-related symptom scores among all groups (p = 0.059). The hospitalization rates were 3.58% in the topical treatment group and 1.25% in the healthy control group, and no patient was hospitalized in the dupilumab treatment group (p = 0.163). Compared with healthy control group and topical treatment group, the dupilumab treatment group had the shortest COVID-19-associated disease duration (dupilumab treatment group, 4.15 ± 2.85 d vs. topical treatment group, 5.43 ± 3.15 d vs. healthy control group, 6.09 ± 4.29 d; p = 0.001). Among the AD patients treated with dupilumab for different times, there was no appreciable difference (<0.5 year group, 5 ± 3.62 d vs. 0.5-1 year group, 4.84 ± 2.58 d vs. >1 year group, 2.8 ± 1.32 d; p = 0.183). Dupilumab treatment shortened the duration of COVID-19 in patients with moderate-to-severe AD. AD patients can continue their dupilumab treatment during the COVID-19 pandemic.

Discovery and characterization of SARS-CoV-2 reactive and neutralizing antibodies from humanized CAMouseHG mice through rapid hybridoma screening and high-throughput single-cell V(D)J sequencing.

The coronavirus disease 2019 pandemic has caused more than 532 million infections and 6.3 million deaths to date. The reactive and neutralizing fully human antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective detection tools and therapeutic measures. During SARS-CoV-2 infection, a large number of SARS-CoV-2 reactive and neutralizing antibodies will be produced. Most SARS-CoV-2 reactive and neutralizing fully human antibodies are isolated from human and frequently encoded by convergent heavy-chain variable genes. However, SARS-CoV-2 viruses can mutate rapidly during replication and the resistant variants of neutralizing antibodies easily survive and evade the immune response, especially in the face of such focused antibody responses in humans. Therefore, additional tools are needed to develop different kinds of fully human antibodies to compensate for current deficiency. In this study, we utilized antibody humanized CAMouseHG mice to develop a rapid antibody discovery method and examine the antibody repertoire of SARS-CoV-2 RBD-reactive hybridoma cells derived from CAMouseHG mice by using high-throughput single-cell V(D)J sequencing analysis. CAMouseHG mice were immunized by 28-day rapid immunization method. After electrofusion and semi-solid medium screening on day 12 post-electrofusion, 171 hybridoma clones were generated based on the results of SARS-CoV-2 RBD binding activity assay. A rather obvious preferential usage of IGHV6-1 family was found in these hybridoma clones derived from CAMouseHG mice, which was significantly different from the antibodies found in patients with COVID-19. After further virus neutralization screening and antibody competition assays, we generated a noncompeting two-antibody cocktail, which showed a potent prophylactic protective efficacy against SARS-CoV-2 in cynomolgus macaques. These results indicate that humanized CAMouseHG mice not only provide a valuable platform to obtain fully human reactive and neutralizing antibodies but also have a different antibody repertoire from humans. Thus, humanized CAMouseHG mice can be used as a good complementary tool in discovery of fully human therapeutic and diagnostic antibodies.

Evolution of the PB1 gene of human influenza A (H3N2) viruses circulating between 1968 and 2019.

One avian H3N2 influenza virus, providing its PB1 and HA segments, reassorted with one human H2N2 virus and caused a pandemic outbreak in 1968, killing over 1 million people. After its introduction to humanity, the pandemic H3N2 virus continued adapting to humans and has resulted in epidemic outbreaks every influenza season. To understand the functional roles of the originally avian PB1 gene in the circulating strains of human H3N2 influenza viruses, we analyzed the evolution of the PB1 gene in all human H3N2 isolates from 1968 to 2019. We found several specific residues dramatically changed around 2002-2009 and remained stable through to 2019. Then, we verified the functions of these PB1 mutations in the genetic background of the early pandemic virus, A/Hong Kong/1/1968(HK/68), as well as a recent seasonal strain, A/Jiangsu/34/2016 (JS/16). The PB1 V709I or PB1 V113A/K586R/D619N/V709I induced higher polymerase activity of HK/68 in human cells. And the four mutations acted cooperatively that had an increased replication capacity in vitro and in vivo at an early stage of infection. In contrast, the backward mutant, A113V/R586K/N619D/I709V, reduced polymerase activity in human cells. The PB1 I709V decreased viral replication in vitro, but this mutant only showed less effect on mice infection experiment, which suggested influenza A virus evolved in human host was not always consisted with highly replication efficiency and pathogenicity in other mammalian host. Overall, our results demonstrated that the identified PB1 mutations contributed to the viral evolution of human influenza A (H3N2) viruses.

High-quality trials and pharmacological studies needed as translational evidence for the application of traditional Chinese medicine Lianhua Qingwen against COVID-19.

Traditional Chinese medicine (TCM) has been employed as complementary medication against COVID-19 in China since 2020. Two years since then, TCM, with Lianhua Qingwen (LHQW) as an example, has been included in every version of official clinical protocol guidelines. Recently, LHQW is even distributed to general public at risk but not yet infected. Such common application and widely claimed positive outcome among mild to moderate patients were accompanied by a number of published studies on antiviral, antiinflammatory, and immune modulatory potential using either in vitro or animal models. However, aside from retrospective understanding and open-labeled clinical trials with relatively small subject size, major gap in conclusive proof for efficacy and safety remains due to the lack of double-blind placebo-controlled studies and comprehensive pharmacodynamic and kinetic investigations. This is also supported by a recent WHO expert meeting on this subject, which acknowledged the potential benefits of TCM in mild-moderate cases, while recommended more rigorous studies to further understand effect size, application implications, and outcome determinants. Therefore, there is an urgent need to address the exact role TCM like LHQW could play in COVID-19 management from translational evidence-based perspective. High-quality clinical trials, pharmacological studies, and real-world data from recent outbreak are recommended.

Anxiety and depression in allergic rhinitis patients during COVID-19 pandemic in Wuhan, China.

BACKGROUND: During COVID-19 pandemic, many allergic rhinitis (AR) patients stopped their treatment including pharmacotherapy and allergen immunotherapy. OBJECTIVE: This study aimed to investigate the anxiety and depression and general effect of COVID-19 pandemic on AR patients' psychological status in Wuhan, China. METHODS: In October 2019, 222 outpatients suffering from AR in our department and 133 healthy controls were enrolled. All participants were asked to finish the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) questionnaire. The demographic characteristics and the severity of AR symptoms were recorded. In April 2020, the AR patients and healthy controls were re-contacted to finish the questionnaires by telephone or online. The SAS and SDS scores in AR patients and healthy controls and the correlation with other variables were analyzed. RESULTS: For AR patients, the SAS and SDS scores were significantly higher than healthy controls. Meanwhile, the rates of anxiety and depression were 24.8% and 19.4% respectively. The education level and symptoms severity were correlated with SAS and SDS scores. Ninety-eight AR patients and 56 healthy controls finished the questionnaires after COVID-19 pandemic. The AR patients' SAS and SDS scores were lower than before COVID-19 pandemic and were correlated with AR symptom scores. The scores of healthy controls were not different with before COVID-19 pandemic. CONCLUSIONS: The occurrence of anxiety and depression is common in AR patients. Severity of symptoms and low education level are the risk factors causing anxiety and depression. COVID-19 pandemic has no significant negative impact on the AR patients' psychological status.

Exploration of CT manifestations of different clinical types of novel coronavirus pneumonia.

BACKGROUND: To explore computed tomography (CT) characteristics of the 2019 novel coronavirus (COVID-19) pneumonia and explore variations among the different clinical types. METHODS: Clinical and CT imaging data of 43 patients diagnosed with COVID-19 in our hospital and the cooperative hospital between January 15-30, 2020 were collected (27 male and 16 female). Patients were classified as common type (26 cases, 60%), severe type (14 cases, 33%) or critical type (three cases, 7%) according to the new coronavirus pneumonia treatment scheme (sixth edition). Patient clinical data and CT images were analyzed and evaluated. RESULTS: Fever was the main symptom in common type COVID-19 cases (23/26, 88.46%). Both severe and critical type COVID-19 patients had fever and cough symptoms, and dyspnea was observed in all three critical COVID-19 patients. CT manifestations in the common type COVID-19 cohort were bilateral involvement (20/26, 71%), multiple lesions (14/26, 54%), ground-glass density shadow (17/26, 65%), and some cases were accompanied by local consolidation (9/26, 35%), which is consistent with early stage COVID-19 CT performance. CT manifestations in the severe and critical types involved both lungs. Severe COVID-19 cases predominantly consisted of multiple mixed-density lesions (10/14, 71%), and a few patients showed diffuse lung glass density shadows in both lungs (4/14, 29%), which is consistent with the progression stage COVID-19 CT performance. Critical COVID-19 cases exhibited mixed-density lesions, and two cases displayed "white lung", which is the CT manifestation at the severe COVID-19 stage. Only one critical COVID-19 patient had pleural effusion. CONCLUSIONS: The CT manifestations of COVID-19 are specific and there are variations between different clinical types. Thus, CT is an important clinical tool for early diagnosis and assessment of the severity of COVID-19.

Utility of chest CT in diagnosis of COVID-19 pneumonia.

PURPOSE: We aimed to explore the imaging findings of computed tomography (CT) in diagnosing coronavirus disease 2019 (COVID-19) and its clinical value for further evaluation of suspected cases. METHODS: Files of 155 patients visiting the fever clinics at our hospital and affiliated hospitals from January 20th to February 9th, 2020 were searched. Among them, 140 cases (including 82 males and 58 females) were included as suspected COVID-19 cases based on clinical and epidemiological history; the CT image features of 70 cases with suggestive findings on CT, confirmed by positive nucleic acid test were analyzed and evaluated. The sensitivity and specificity of CT in diagnosing COVID-19 were evaluated in patients with epidemiological history. RESULTS: Of the 70 patients, 84.3% showed bilateral lung involvement on CT; 27 cases (38.6%) showed ground-glass opacity (GGO), which was mostly distributed in the subpleural area (55.7%), and this sign was mainly observed in early COVID-19 patients. In addition, 41 cases (58.6%) manifested GGO combined with focal consolidation opacity, 2 (2.8%) had flake-like consolidation opacity, with involvements of the periphery of lung field and the central zone (44.3%), and this sign was mostly observed in severe or critical patients. Concomitant signs such as pleural effusion and mediastinal lymph node enlargement were rare. Among patients with epidemiological history, the sensitivity of CT in diagnosing COVID-19 was 89.7% (70/78), and the specificity was 88.7% (55/62). CONCLUSION: CT shows high sensitivity and specificity in diagnosing COVID-19. CT is an important examination method in evaluation of suspected cases and assessment of disease severity.