Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity.

The antibiotic resistome is the collection of all 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) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. 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. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. 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 the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the 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. 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.

Vaccination options for pregnant women during the Omicron period.

Omicron exhibits reduced pathogenicity in general population than the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the severity of disease and pregnancy outcomes of Omicron infection among pregnant women have not yet been definitively established. Meanwhile, substantial proportions of this population have doubts about the necessity of vaccination given the reports of declining efficacy of coronavirus disease 2019 (COVID-19) vaccines. Herein, we comprehensively discuss the clinical outcomes of infected pregnant women during the Omicron period and summarize the available data on the safety and efficacy profile of COVID-19 vaccination. The results found that the incidence of moderate and severe disease, maternal mortality, pregnancy loss, preterm delivery, stillbirth, preeclampsia/eclampsia, and gestational hypertension during the Omicron period are similar to those during the Pre-Delta period. In view of the effects of mass vaccination and previous natural infection on disease severity, the virulence of Omicron in pregnant women may be comparable to or even higher than that of the Pre-Delta variant. Moreover, the currently approved COVID-19 vaccines are safe and effective for pregnant women. Particularly, those who received a second or third dose had significantly less severe disease with little progression to critical illness or death compared with those who were unvaccinated or received only one dose. Therefore, in the case of the rapid spread of Omicron, pregnant women should still strictly follow preventive measures to avoid infection and receive the COVID-19 vaccine in a timely manner.

The importance of booster vaccination in the context of Omicron wave.

Omicron (B.1.1.529) was first detected in a sample collected in Botswana on November 11, 2021, and has rapidly replaced Delta as the dominant global variant given the robust transmissibility. Moreover, it displays a lower virulence than other variants. However, the pathogenicity of Omicron appears to be underestimated in view of the increasing levels of herd immunity through natural infection or vaccination. Additionally, the volume of hospitalizations and deaths increase in proportion to the number of cases due to the high transmissibility of Omicron. Therefore, vaccination remains an important public health priority. Notably, a series of important mutations in the Omicron spike protein, especially in the receptor-binding domain and N-terminal domain, appears to be associated with immune escape capacity, reducing the willingness of people to receive vaccines. Herein, we provide an in-depth discussion to assess the effectiveness of the second and third vaccination against Omicron variant. On the one hand, the two-dose vaccination program adopted by many countries is insufficient to prevent Omicron infection given the mutations correlated with immune escape and the decline in vaccine efficacy over time. On the other hand, booster dose significantly increases the protective efficacy against Omicron infection. Most importantly, heterologous third dose vaccination induces a more robust immune response than homologous booster dose. Therefore, under the special background of this pandemic, there is an urgent need to accelerate the third dose of vaccination, especially providing better booster vaccination strategies, to combat emerging Omicron variant.

Semen parameters and sex hormones as affected by SARS-CoV-2 infection: A systematic review Paramètres du sperme et hormones sexuelles affectés par l’infection par le SRAS-CoV-2: une revue systématique

Background Impaired semen quality and reproductive hormone levels were observed in patients during and after recovery from coronavirus disease 2019 (COVID-19), which raised concerns about negative effects on male fertility. Therefore, this study systematically reviews available data on semen parameters and sex hormones in patients with COVID-19. Methods Systematic search was performed on PubMed and Google Scholar until July 18, 2022. We identified relevant articles that discussed the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility. Results A total number of 1684 articles were identified by using a suitable keyword search strategy. After screening, 26 articles were considered eligible for inclusion in this study. These articles included a total of 1960 controls and 2106 patients. When all studies were considered, the results showed that the semen parameters and sex hormone levels of patients infected with SARS-CoV-2 exhibited some significant differences compared with controls. Fortunately, these differences gradually disappear as patients recover from COVID-19. Conclusion While present data show the negative effects of SARS-CoV-2 infection on male fertility, this does not appear to be long-term. Semen quality and hormone levels will gradually increase to normal as patients recover.

Dynamic Alterations in the Respiratory Tract Microbiota of Patients with COVID-19 and its Association with Microbiota in the Gut.

The role of respiratory tract microbes and the relationship between respiratory tract and gut microbiomes in coronavirus disease 2019 (COVID-19) remain uncertain. Here, the metagenomes of sputum and fecal samples from 66 patients with COVID-19 at three stages of disease progression are sequenced. Respiratory tract, gut microbiome, and peripheral blood mononuclear cell (PBMC) samples are analyzed to compare the gut and respiratory tract microbiota of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between respiratory tract microbiome and immune response. In the respiratory tract, significantly fewer Streptococcus, Actinomyces, Atopobium, and Bacteroides are found in ICU than in nICU patients, while Enterococcus and Candida increase. In the gut, significantly fewer Bacteroides are found in ICU patients, while Enterococcus increases. Significant positive correlations exist between relative microbiota abundances in the respiratory tract and gut. Defensin-related pathways in PBMCs are enhanced, and respiratory tract Streptococcus is reduced in patients with COVID-19. A respiratory tract-gut microbiota model identifies respiratory tract Streptococcus and Atopobium as the most prominent biomarkers distinguishing between ICU and nICU patients. The findings provide insight into the respiratory tract and gut microbial dynamics during COVID-19 progression, considering disease severity, potentially contributing to diagnosis, and treatment strategies.

Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis.

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. 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 non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). 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.

Assessment of the Diagnostic Ability of Four Detection Methods Using Three Sample Types of COVID-19 Patients.

Background: Viral nucleic acid detection is considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. However, unsuitable sample types and laboratory detection kits/methods lead to misdiagnosis, which delays the prevention and control of the pandemic. Methods: We compared four nucleic acid detection methods [two kinds of reverse transcription polymerase chain reactions (RT-PCR A: ORF1ab and N testing; RT-PCRB: only ORF1ab testing), reverse transcription recombinase aided amplification (RT-RAA) and droplet digital RT-PCR (dd-RT-PCR)] using 404 samples of 72 hospitalized COVID-19 patients, including oropharyngeal swab (OPS), nasopharyngeal swabs (NPS) and saliva after deep cough, to evaluate the best sample type and method for SARS-CoV-2 detection. Results: Among the four methods, dd-RT-PCR exhibited the highest positivity rate (93.0%), followed by RT-PCR B (91.2%) and RT-RAA (91.2%), while the positivity rate of RT-PCR A was only 71.9%. The viral load in OPS [24.90 copies/test (IQR 15.58-129.85)] was significantly lower than that in saliva [292.30 copies/test (IQR 20.20-8628.55)] and NPS [274.40 copies/test (IQR 33.10-2836.45)]. In addition, if OPS samples were tested alone by RT-PCR A, only 21.4% of the COVID-19 patients would be considered positive. The accuracy of all methods reached nearly 100% when saliva and NPS samples from the same patient were tested simultaneously. Conclusions: SARS-CoV-2 nucleic acid detection methods should be fully evaluated before use. High-positivity rate methods such as RT-RAA and dd-RT-PCR should be considered when possible. Furthermore, saliva after deep cough and NPS can greatly improve the accuracy of the diagnosis, and testing OPS alone is not recommended.