Impact of chemotherapy and immunotherapy on the composition and function of immune cells in COVID-19 convalescent with gynecological tumors.

Ongoing pandemic and potential resurgence of Coronavirus disease 2019 (COVID-19) has prompted urgent efforts to investigate the immunological memory of convalescent patients, especially in patients with active cancers. Here we performed single-cell RNA sequencing in peripheral blood samples of 3 healthy donors (HDs), 4 COVID-19 patients (Covs) and 4 COVID-19 patients with active gynecological tumor (TCs) pre- and post- anti-tumor treatment. All Covs patients had recovered from their acute infection. Interestingly, the molecular features of PBMCs in TCs are similar to that in Covs, suggesting that convalescent COVID-19 with gynecologic tumors do not have major immunological changes and may be protected against reinfection similar to COVID-19 patients without tumors. Moreover, the chemotherapy given to these patients mainly caused neutropenia, while having little effect on the proportion and functional phenotype of T and B cells, and T cell clonal expansion. Notably, anti-PD-L1 treatment massively increased cytotoxic scores of NK cells, and T cells, and facilitated clonal expansion of T cells in these patients. It is likely that T cells could protect patients from SARS-CoV-2 virus reinfection and anti-PD-L1 treatment can enhance the anti-viral activity of the T cells.

Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children (preprint)

SARS-CoV-2 infection triggers adaptive immune responses from both T and B cells. However, most studies focus on peripheral blood, which may not fully reflect immune responses in lymphoid tissues at the site of infection. To evaluate both local and systemic adaptive immune responses to SARS-CoV-2, we collected peripheral blood, tonsils, and adenoids from 110 children undergoing tonsillectomy/adenoidectomy during the COVID-19 pandemic and found 24 with evidence of prior SARS-CoV-2 infection, including detectable neutralizing antibodies against multiple viral variants. We identified SARS-CoV-2-specific germinal center (GC) and memory B cells; single cell BCR sequencing showed that these virus-specific B cells were class-switched and somatically hypermutated, with overlapping clones in the adenoids and tonsils. Oropharyngeal tissues from COVID-19-convalescent children showed persistent expansion of GC and anti-viral lymphocyte populations associated with an IFN-γ-type response, with particularly prominent changes in the adenoids, as well as evidence of persistent viral RNA in both tonsil and adenoid tissues of many participants. Our results show robust, tissue-specific adaptive immune responses to SARS-CoV-2 in the upper respiratory tract of children weeks to months after acute infection, providing evidence of persistent localized immunity to this respiratory virus.

Clinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection.

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs. Single-cell RNA sequencing shows that natural killer (NK) cells and CD14+ monocytes are reduced, while regulatory T cells are increased in LDs; moreover, T and NK cells in LDs are less activated than in SDs. Importantly, most cells in LDs show reduced expression of ribosomal protein (RP) genes and related pathways, with this inversed correlation between RP levels and infection duration further validated in 103 independent patients. Our results thus indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients.

Monitoring global trends in Covid-19 vaccination intention and confidence: a social media-based deep learning study (preprint)

Abstract Background This study developed deep learning models to monitor global intention and confidence of Covid-19 vaccination in real time. Methods We collected 6.73 million English tweets regarding Covid-19 vaccination globally from January 2020 to February 2021. Fine-tuned Transformer-based deep learning models were used to classify tweets in real time as they relate to Covid-19 vaccination intention and confidence. Temporal and spatial trends were performed to map the global prevalence of Covid-19 vaccination intention and confidence, and public engagement on social media was analyzed. Findings Globally, the proportion of tweets indicating intent to accept Covid-19 vaccination declined from 64.49% on March to 39.54% on September 2020, and then began to recover, reaching 52.56% in early 2021. This recovery in vaccine acceptance was largely driven by the US and European region, whereas other regions experienced the declining trends in 2020. Intent to accept and confidence of Covid-19 vaccination were relatively high in South-East Asia, Eastern Mediterranean, and Western Pacific regions, but low in American, European, and African regions. 12.71% tweets expressed misinformation or rumors in South Korea, 14.04% expressed distrust in government in the US, and 16.16% expressed Covid-19 vaccine being unsafe in Greece, ranking first globally. Negative tweets, especially misinformation or rumors, were more engaged by twitters with fewer followers than positive tweets. Interpretation This global real-time surveillance study highlights the importance of deep learning based social media monitoring to detect emerging trends of Covid-19 vaccination intention and confidence to inform timely interventions. Funding National Natural Science Foundation of China.

Prevalence of anxiety and depression among pregnant women during the COVID-19 pandemic: a systematic review and meta-analysis (preprint)

Background COVID-19 has become a global pandemic. Its occurrence has substantially affected the psychological condition of pregnant women. The purpose of this study is to learn about the incidence of anxiety and depression among pregnant women during the pandemic, and to conduct a meta-analysis of the existing research.Methods PubMed, Web of Science and EMBASE were searched without a lower time limit and up to August 13, 2020. The incidences of anxiety and depression among pregnant women were synthesized and discussed.Results The prevalence of anxiety in 8 studies with a total sample size of 7493 individuals was 43% (95% confidence interval: 0.28-0.58), and the prevalence of depression in 7 studies with a sample size of 6116 people was 32% (95% confidence interval: 0.26-0.37). Significant heterogeneity was detected across studies of these incidence estimates. Subgroup analysis included the economic status to explore the sources of heterogeneity, and Egger’s test was conducted to examine the publication bias.Conclusions Since significant heterogeneity has been detected in studies of anxiety and depression, we must interpret the results with caution. As the COVID-19 pandemic will not end in a short time, corresponding psychological interventions must be implemented to address the mental health of pregnant women.