Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report (preprint)

Background The common infections agents causing meningitis in patients with human immunodeficiency virus (HIV) include Cryptococcus neoformans and Treponema pallidum. Furthermore, there is an elevated risk of meningitis in patients with HIV concomitantly infected with SARS-CoV-2.Case presentation: A 38-year-old male presented with headache and dizziness. After hospitalization, polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, and lumbar puncture revealed neurosyphilis with concomitant cryptococcal meningitis. He underwent Paxlovid, penicillin, antifungal and antiretroviral treatment. The patient had no other neurological symptoms and was stable during the 6-month follow-up period.Conclusions During the COVID-19 pandemic, patients with HIV, particularly those not underwent antiretroviral therapy, are at higher risk for severe infections, including central nervous system complications, due to their compromised immune systems.

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia (preprint)

Age is a major risk factor for coronavirus disease (COVID-19)-associated severe pneumonia and mortality; however, the underlying mechanism remains unclear. Herein, we investigated whether age-related deregulation of RNAi components and RNA splicing factors affects COVID-19 severity. Decreased expression of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3) correlated with increased severity of COVID-19 and SARS-CoV-2 nucleocapsid (N) protein-induced pneumonia. N protein induced autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, repressing miRNA biogenesis and RNA splicing and inducing DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 were downregulated with age in mouse lung tissues. Older mice experienced more severe N protein-induced pneumonia than younger mice. However, treatment with a poly(ADP-ribose) polymerase inhibitor (PJ34) or aromatase inhibitor (anastrozole) relieved N protein-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Option Valuation with Business Conditions and Skewness (preprint)

This paper exploits business conditions and skewness to improve option pricing. We construct a user-friendly affine framework that incorporates the observable model-free macroeconomic variables and latent skewed innovations, and this new configuration nests and outperforms a wide range of empirically well-tested models. To facilitate practical implementations, we obtain closed-form formulas for pricing SPX options under a variance-dependent kernel. Several sets of empirical studies over the 2008 Great Recession and the ongoing COVID-19 recession demonstrate significant and robust improvements in option pricing brought about by macroeconomic variables, and we find that these improvements are enhanced by the introduction of innovation skewness.

Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens (preprint)

The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.

Epileptic seizure and electroencephalographic characteristics of adult COVID-19 inpatients during the Omicron outbreak in China: a single center retrospective study (preprint)

Background This retrospective analysis assessed the characteristics of epileptic seizure and continuous electroencephalogram (CEEG) data in hospitalized patients diagnosed with COVID-19 during the Omicron outbreak.Methods CEEG was performed in 28 patients, with 17 showing unexplained altered mental status and 11 suspected of having seizures. Demographic and clinical variables, imaging results, outcomes, and comorbidities were collected.Results In total, 1,405 patients with COVID-19 infection were admitted during the study period. The proportion of patients who required intensive care unit (ICU) care and the in-hospital mortality was 16.3% and 7.8%, respectively. Among patients who underwent CEEG monitoring, 11 were in ICU, and 17 were in regular wards. Of these, 8 patients (28.5%) had severe COVID-19, whereas 6 had acute neuroimaging findings. EEG findings were not specific, with 7 patients (25%) having normal EEG results. Furthermore, 11 (39.3%) had benign EEG alterations, 6 (21.4%) had malignant, and 4 (14.3%) had highly malignant. Six patients exhibited epileptiform abnormalities, including 1 with a prior epilepsy history. Moreover, 4 patients experienced electrographic seizures, with 2 manifesting as epilepsia partialis continua and 2 as nonconvulsive status epilepticus. Periodic and rhythmic patterns were observed in 2 patients, spike-and-wave in 1 patient and generalized rhythmic delta activity in another patient. EEG attenuation without reactivity was seen in 4 patients.Conclusions Seizures can manifest as early symptoms in individuals infected with the Omicron variant of COVID-19. Despite the increased contagiousness associated with Omicron, we observed a higher prevalence of normal EEG results. This suggested that the Omicron variant may be associated with a lower likelihood of causing encephalitis or encephalopathy compared to other variants.

The STOIC2021 COVID-19 AI challenge: applying reusable training methodologies to private data (preprint)

Challenges drive the state-of-the-art of automated medical image analysis. The quantity of public training data that they provide can limit the performance of their solutions. Public access to the training methodology for these solutions remains absent. This study implements the Type Three (T3) challenge format, which allows for training solutions on private data and guarantees reusable training methodologies. With T3, challenge organizers train a codebase provided by the participants on sequestered training data. T3 was implemented in the STOIC2021 challenge, with the goal of predicting from a computed tomography (CT) scan whether subjects had a severe COVID-19 infection, defined as intubation or death within one month. STOIC2021 consisted of a Qualification phase, where participants developed challenge solutions using 2000 publicly available CT scans, and a Final phase, where participants submitted their training methodologies with which solutions were trained on CT scans of 9724 subjects. The organizers successfully trained six of the eight Final phase submissions. The submitted codebases for training and running inference were released publicly. The winning solution obtained an area under the receiver operating characteristic curve for discerning between severe and non-severe COVID-19 of 0.815. The Final phase solutions of all finalists improved upon their Qualification phase solutions.HSUXJM-TNZF9CHSUXJM-TNZF9C

Face Mask Reduces Gaze-Cueing Effect (preprint)

Recent studies have found that face masks affect social cognition and behaviour in the context of the novel coronavirus (COVID-19) pandemic. The eyes, the only part of the face not covered by face masks, are an important spatial attention cue that can trigger social attention orienting. Here, we adopted a spatial gaze-cueing task to investigate whether face masks affect social attention orienting triggered by eye gaze cues. In Experiment 1, participants were asked to determine the orientation of a target line under two types of cues—masked and non-masked faces—and two stimulus onset asynchrony (SOA) conditions (300 ms and 1000 ms). The results showed that masked faces induced a smaller gaze-cueing effect (GCE) compared to non-masked faces at 300 ms SOA, while two face types induced similar GCEs at 1000 ms SOA. Experiment 2 used mouth-obscured faces and non-masked faces as cues and found that no significant difference in GCE between the two types at either 1000 ms or 300 ms SOA, indicating that the reduction of GCE caused by the masked face was due to the social meaning expressed by the mask rather than a physical effect of masking. The present study extends previous findings to support the idea that high-level social information affects the processing of eye gaze direction and provides evidence that face masks affect social cognition and behaviour in the context of COVID-19.

Dynamic changes in the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its association with disease severity (preprint)

Background The antibiotic resistome is the collection of all the antibiotic resistance genes (ARGs) present in an individual. Whether an individual’s susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is influenced by their respiratory tract antibiotic resistome is unknown. Additional, whether a relationship exists between the respiratory tract and gut antibiotic resistance genes composition has not been fully explored. Method We recruited 66 patients with COVID-19 at three disease stages (admission, progression and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Results Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrugand Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin and Fosmidomycinwere increased in ICU patients. Upon further investigation a significantly positive correlation was found between the relative abundance in ARGs (i.e., subtypes of the Aminoglycoside and Tetracyclinetypes) in the respiratory tract and gut. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in respiratory tract and gut. We found that immune related pathways in PBMC were enhanced, and they were significantly correlated with the relative abundance of Multidrug, Vancomycin and Tetracycline ARGs. Based on the relative abundance of ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. The level of Aminoglycoside and Vancomycinin the gut was regarded as the most prominent biomarker. Conclusions Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

Feasible intervention combinations for achieving a safe exit of the Zero-COVID policy in China and its determinants: an individual- based model study (preprint)

Background Although several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how do the thresholds change with the assumed key epidemiological parameters and population characteristics.Methods We developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons).Results We identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds of them required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations.Conclusions The analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China’s cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration.

IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19). Staphylococcus aureus is one of the most common pathogenic bacteria in humans, rheumatoid arthritis (RA) is among the most prevalent autoimmune conditions. RA is a significant risk factor for SARS-CoV-2 and S. aureus infections, although the mechanism of RA and SARS-CoV-2 infection in conjunction with S. aureus infection has not been elucidated. The purpose of this study is to investigate the biomarkers and disease targets between RA and SARS-CoV-2 and S. aureus infections using bioinformatics analysis, to search for the molecular mechanisms of SARS-CoV-2 and S. aureus immune escape and potential drug targets in the RA population, and to provide new directions for further analysis and targeted development of clinical treatments. Methods The RA dataset (GSE93272) and the S. aureus bacteremia (SAB) dataset (GSE33341) were used to obtain differentially expressed gene sets, respectively, and the common differentially expressed genes (DEGs) were determined through the intersection. Functional enrichment analysis utilizing GO, KEGG, and ClueGO methods. The PPI network was created utilizing the STRING database, and the top 10 hub genes were identified and further examined for functional enrichment using Metascape and GeneMANIA. The top 10 hub genes were intersected with the SARS-CoV-2 gene pool to identify five hub genes shared by RA, COVID-19, and SAB, and functional enrichment analysis was conducted using Metascape and GeneMANIA. Using the NetworkAnalyst platform, TF-hub gene and miRNA-hub gene networks were built for these five hub genes. The hub gene was verified utilizing GSE17755, GSE55235, and GSE13670, and its effectiveness was assessed utilizing ROC curves. CIBERSORT was applied to examine immune cell infiltration and the link between the hub gene and immune cells. Results A total of 199 DEGs were extracted from the GSE93272 and GSE33341 datasets. KEGG analysis of enrichment pathways were NLR signaling pathway, cell membrane DNA sensing pathway, oxidative phosphorylation, and viral infection. Positive/negative regulation of the immune system, regulation of the interferon-I (IFN-I;IFN-α/β) pathway, and associated pathways of the immunological response to viruses were enriched in GO and ClueGO analyses. PPI network and Cytoscape platform identified the top 10 hub genes: RSAD2, IFIT3, GBP1, RTP4, IFI44, OAS1, IFI44L, ISG15, HERC5, and IFIT5. The pathways are mainly enriched in response to viral and bacterial infection, IFN signaling, and 1,25-dihydroxy vitamin D3. IFI44, OAS1, IFI44L, ISG15, and HERC5 are the five hub genes shared by RA, COVID-19, and SAB. The pathways are primarily enriched for response to viral and bacterial infections. The TF-hub gene network and miRNA-hub gene network identified YY1 as a key TF and hsa-mir-1-3p and hsa-mir-146a-5p as two important miRNAs related to IFI44. IFI44 was identified as a hub gene by validating GSE17755, GSE55235, and GSE13670. Immune cell infiltration analysis showed a strong positive correlation between activated dendritic cells and IFI44 expression. Conclusions IFI144 was discovered as a shared biomarker and disease target for RA, COVID-19, and SAB by this study. IFI44 negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation and is an important molecular target for SARS-CoV-2 and S. aureus immune escape in RA. Dendritic cells play an important role in this process. 1,25-Dihydroxy vitamin D3 may be an important therapeutic agent in treating RA with SARS-CoV-2 and S. aureus infections.

Multiple introduced lineages and the single native lineage co-driving the four waves of the COVID-19 pandemic in West Africa

Coronavirus disease 2019 (COVID-19) has become a vast burden on public health and socioeconomics in West Africa, but the epidemic situation is unclear. Therefore, we conducted a retrospective analysis of the positive rate, death rate, and diversity of SARS-CoV-2. As of March 31, 2022, a total of 894,813 cases of COVID-19 have been recorded, with 12,028 deaths, both of which were distributed in all 16 countries. There were four waves of COVID-19 during this period. Most cases were recorded in the second wave, accounting for 34.50% of total cases. These data suggest that although West Africa seems to have experienced a low and relatively slow spread of COVID-19, the epidemic was ongoing, evolving with each COVID-19 global pandemic wave. Most cases and most deaths were both recorded in Nigeria. In contrast, the fewest cases and fewest deaths were reported, respectively, in Liberia and Sierra Leone. However, high death rates were found in countries with low incidence rates. These data suggest that the pandemic in West Africa has so far been heterogeneous, which is closely related to the infrastructure of public health and socioeconomic development (e.g., extreme poverty, GDP per capita, and human development index). At least eight SARS-CoV-2 variants were found, namely, Delta, Omicron, Eta, Alpha, Beta, Kappa, Iota, and Gamma, which showed high diversity, implicating that multiple-lineages from different origins were introduced. Moreover, the Eta variant was initially identified in Nigeria and distributed widely. These data reveal that the COVID-19 pandemic in the continent was co-driven by both multiple introduced lineages and a single native lineage. We suggest enhancing the quarantine measures upon entry at the borders and implementing a genome surveillance strategy to better understand the transmission dynamics of the COVID-19 pandemic in West Africa.

Factors associated with peritraumatic stress symptoms among the frontline healthcare workers during the outbreak of COVID-19 in China

ObjectivesThis study aimed to examine the prevalence of peritraumatic stress symptoms (PTSSs), perceived threat, social support and factors contributing to clinically significant PTSS among frontline COVID-19 healthcare workers (HCWs) in China.Design and settingAn online survey through self-administered questionnaires was conducted from 18 February to 4 March 2020, during the outbreak of COVID-19.Outcomes measuresPTSS was assessed using the post-traumatic stress disorder (PTSD) self-rating scale. Demographic and socioeconomic characteristics, self-reported health, physical/psychological symptoms, perceived threat from frontline work and perceived social support were investigated. Multivariable line regression analysis distinguished factors associated with HCWs’ PTSS scores.ResultsA total of 676 (58.1%) HCWs have shown clinically significant high levels of PTSS. Only 441 (37.9%) self-reported good health. Most had physical symptom(s) (915 (78.7%)), psychological symptom(s) (906 (77.9%)), inability to vent emotions (284 (24.4%)), emotional exhaustion (666 (57.3%)) and 1037 (89.2%) needed professional respect. Moreover, social support received was less than expected, and the receipt of psychological services/help scored the lowest (3.11±1.73). Combined psychological and physical symptoms, difficulty in releasing tension and venting emotions timely, fear of infection, emotional exhaustion and depersonalisation are significantly associated with PTSS scores among frontline HCWs. Working ≥8 hours, having the senior professional title, self-reported health, enjoying perfect protection and control measures, economic subsidy and control policy on reducing discriminatory practices are negatively correlated with PTSS scores.ConclusionsDuring the outbreak of COVID-19, frontline HCWs experienced clinically significant high levels of PTSS and heavy workload, and the emergency resulted in their inadequate psychosocial support. If this is left unchecked, HCWs have a higher risk of developing PTSD. Early detection, identification and person-directed, targeted multidisciplinary interventions should be undertaken to address various influencing factors. Comprehensive measures, including setting up emotional release channels, as well as providing psychological and social support intervention for HCWs globally, are highly recommended.

Facemasks and the COVID-19 pandemic: The harm caused by improper use of facemasks is a matter of concern (preprint)

Abstract: The use of facemasks has played an important role in the prevention of COVID-19. However, inappropriate use of facemasks also brings people certain problems. Therefore, the reasonable use of facemasks is a necessary measure to protect oneself and others in the current epidemic prevention and control.

Static and dynamic behaviors of granular soil reinforced by disposable face-mask chips

The stock of disposable face masks has climbed steadily due to COVID-19, which results in an urgent worldwide environmental problem. This investigation aims to assess the potential of using waste mask chips (MC) as reinforcement in granular soil. To evaluate the mechanical properties of the mask chips - granular soil mixture (MSM), a series of monotonic and cyclic triaxial tests with different confining pressures and MC contents are conducted. Then, the shear behavior of MSM is quantified from both static (strength, stiffness, dilatancy) and dynamic (energy absorption capacity, resilient modulus, deformation) perspectives. Furthermore, based on the static and dynamic indexes, the effects of adding MC into granular soil are comprehensively analyzed. All experimental results indicate that the MSMs exbibit an increase of shear strength and a reduction of shear-induced volumetric dilation, but a decrease in stiffness. The addition of MC also leads to an increase in energy absorption but will not affect the cumulative strain of MSMs. Thus, MC has great potential to be used in the embankment construction of road and railway, backfill or reclamation construction, and so on. In addition, the influence of mask chip content on mechanical behaviors of MSM can be considered in current constitutive models for further engineering calculation and design relating to of MSMs. This experimental study provides a new perspective and thought on the recycling of waste face masks in civil engineering.

Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex (preprint)

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backwards on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here, we use cryo-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results suggest a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.

The Spring Festival Effect: The change in NO2 column concentration in China caused by the migration of human activities

The Spring Festival is the most important holiday in China, and human activity and population mobility may contribute greatly to air quality. According to the satellite-based tropospheric nitrogen dioxide (NO2) column and ground-based observational concentration of NO2 in megacities from 2013 to 2018 around the Spring Festival, we found that NO2 concentration obviously decreases, presenting a “tide phenomenon”, particularly in the megacities, with the tropospheric NO2 column density decreasing by 31.8%–44.5%. The tropospheric NO2 column density in Beijing decreased by 41.6% and rebounded by 22.3% after the festival. Vehicle sources were among the important causes of NOx emissions in the megacities, and traffic intensity decreased significantly during the festival. As the coronavirus disease 2019 (COVID-19) pandemic progresses, the traffic intensity in urban areas is decreasing significantly, with the tropospheric NO2 column density decreasing by 56.2% and rebounding by only 6.8% in 2020, without the “tide phenomenon”.

Analysis of response measures and effects of anti-cancer clinical trialon COVID-19 major public health emergency

At the beginning of 2020, with the outbreak of the nationspread coronavirus pneumonia (COVID-19), the national economy and people's lives have been deeply affected, as well as the clinical trial industry, which has brought unprecedented challenges to the management of research institutions and the implementation of clinical trial projects. This study analyzes the measures of chinese major research institutions in response to the requirements of the prevention and control of new coronavirus pneumonia. We select 76-day of 2020.01.23-2020.04.08 as time frame, to sum up the ongoing projects, treatment methods, followup medications, and loss of follow-ups of our research center, and aim to explore the feasibility of reducing the impact of clinical trials during the epidemic, as well as to accumulate experience for the remote execution of clinical trials in the future, and provide a reference for establishing relevant strategy for clinical trials under a special.

Analysis and countermeasures of the influence of COVID-19 on the commodity category of port export in China: taking Shanghai Port as an example. (Special Issue: Today's modern coastal society: technical and sociological aspects of coastal research.)

Since the end of 2019, the novel coronavirus has spread rapidly, which has affected the economy, social interaction, and foreign trade, both in China and around the world. Import and export trade has become an organic part of China's national economy. Import and export trade accounts for nearly 35% of the national economy, which is a major part of China's economic growth. This article takes Shanghai Port as an example, collecting and analyzing the exporters of Shanghai Port in China from January to May 2020. Compared with the relevant data of the same period in 2019, this article discusses the major commodity categories that are affected by the epidemic situation in the export trade volume of Shanghai Port, giving countermeasures according to the influence situation in order to stabilize the quantity of this category in the future and reduce the risk of lower port trade volume of the export commodity categories affected by public health emergencies in China's port trade. At the same time, some suggestions and countermeasures are given to the ecological environment problems affecting the sustainable development of ports.

Serum Level of Testosterone Predicts Disease Severity of Male COVID-19 Patients and is Related to T-Cell Immune Modulation by Transcriptome Analysis (preprint)

Background: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to higher level of testosterone. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet.Methods: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients.Results: Testosterone levels at admission in male COVID-19 patients (4.7 nmol/L, IQR: 2.7~7.7 nmol/L) were significantly lower than those in healthy controls (19.5 nmol/L, IQR: 14.9~22.5). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone.Conclusions: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.Funding Information: This work was supported by the the National Natural Science Foundation of China (grant numbers 82072377 and 81971919). Declaration of Interests: All authors: No reported conflicts.Ethics Approval Statement: This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board of the First Affiliated Hospital of Zhejiang University School of Medicine (IIT20210227A).