Severe Acute Respiratory Syndrome Coronavirus Research Articles

Impact of SARS-CoV-2 on the male reproductive tract: insights from semen analysis and cryopreservation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, affects multiple organs, including the male reproductive system. While viral infections can harm male fertility through cytokine storms, the effects of SARS-CoV-2 on fertility are still unclear. Thus, this study aimed to examine the persistence of viral RNA and inflammatory responses in semen following SARS-CoV-2 infection and the safety of conventional freezing and vitrification techniques. Semen samples from 20 patients were collected 3months post-SARS-CoV-2 infection. Samples underwent freezing and vitrification. Molecular and cellular analysis separated seminal plasma and pellets. Flow cytometry characterized immune cells. Viral RNA was extracted from plasma and sperm, followed by RT-qPCR. Cytometric Bead Array measured cytokine levels. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors were detected in both plasma and sperm fractions. Five patients exhibited viral RNA-dependent RNA polymerase, indicating potential persistence. Elevated inflammatory cytokines in plasma implied persistent inflammation affecting sperm vitality. Immune cells associated with viral clearance were identified in semen, correlating with receptor expression and cytokines. Both conventional freezing and vitrification were found safe procedures for preserving male fertility. Our study highlights the impact of SARS-CoV-2 on male reproductive health, emphasizing the persistence of viral entry receptors, potential viral RNA presence, the inflammatory environment, and the involvement of immune populations in the male reproductive tract post-infection. Importantly, we confirm the safety of conventional freezing and vitrification techniques for preserving male fertility in assisted reproductive technology programs amidst the COVID-19 pandemic.

SARS-CoV-2 S protein disrupts the formation of ISGF3 complex through conserved S2 subunit to antagonize type I interferon response.

This study unveils a new mechanism by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein attenuates the host's antiviral immune response. The interferon-inhibitory mechanism of the S protein was universal among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1, through conserved S2 domains. Our study expands the understanding of SARS-CoV-2 and other human coronaviruses in evading antiviral immune strategies, which is very important for the design and optimization of vaccine antigens, thus providing a theoretical basis for human anti-coronavirus immunity and understanding the interaction between the host and coronavirus.

Aptamer-Based Activatable Tyramide Signal Amplification for Low-Background Detection of SARS-CoV-2 Nucleocapsid Protein.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection posed a significant threat to public health and the global economy, in vitro diagnosis of the SARS-CoV-2 nucleocapsid protein proved to be an effective way for SARS-CoV-2 infection control in the past years. Tyramide signal amplification (TSA) has been extensively utilized in tissue imaging and pathological diagnosis owing to the powerful signal enhancement. However, the elevated "ALWAYS ON" fluorescence background limited the accuracy and sensitivity of the conventional TSA assay. To achieve an activated "TURN ON" signal, herein, a small molecule, termed dichlorodihydrofluorescein tyramide (T-DCFH), was synthesized for activatable TSA. Under the catalysis of horseradish peroxidase (HRP) with hydrogen peroxide (H2O2), this T-DCFH facilitates the "TURN ON" fluorescence signal. Additionally, as a recognition tool, DNA aptamer has been used for developing in vitro diagnostic approaches. Hence, based on HRP-labeled aptamers binding with SARS-CoV-2 nucleocapsid protein, we achieved aptamers-based activatable TSA detection with a higher signal-to-noise ratio than that of fluorescent dye (FITC)-labeled aptamers, while showing lower background than traditional fluorescein tyramide with "ALWAYS ON". The results demonstrated that the activated T-DCFH significantly enhances the fluorescence signal while diminishing the background noise. By employing multiple aptamers targeting, we offered a timely and accurate in vitro diagnostic approach for future emergent infectious diseases.

High-throughput screening of dual-target inhibitors for SARS-CoV-2 main protease and papain-like protease from Chebulae Fructus: in silico prediction and experimental verification

BackgroundThe unavoidable propagation of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has underscored the urgent requirement for efficacious therapeutic agents. The dried fruit of Terminalia chebula Retz., namely Chebulae Fructus, is widely used for treating bacterial and viral infectious diseases, which was witnessed to perform anti-SARS-CoV-2 activity in recommended Chinese patent medicine.AimSARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) present essential effects on SARS-CoV-2 replication and transcription, considering as the attractive targets for therapeutic intervention. In this study, we focused on the dual-target to obtain broad-spectrum antiviral candidates from Chebulae Fructus.MethodsThe identified compounds from Chebulae Fructus were used to build a library in a previous study, which were evaluated by molecular docking to screen potential antiviral agents. The SARS-CoV-2 Mpro and PLpro were expressed in E. coli cells and purified. Fluorescence resonance energy transfer (FRET) and surface plasmon resonance (SPR) were utilized to verify the affinity with dual targets. SARS-CoV-2 wild-type, Omicron BA.5 and Omicron EG.5 variants were employed to validate their antiviral activities in vitro. Molecular dynamics simulation was conducted via Gromacs 2022 software in 500 ns to unveil the conformation stability.ResultsTargeting on Mpro and PLpro, eight compounds were screened as the potential dual-target inhibitors in molecular docking. In FRET and SPR assays, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) and 1,2,3,6-tetra-O-galloyl-β-D-glucose (TGG) showed good inhibitory activities with IC50 values ranging from 1.33 to 27.37 μM, and affinity with KD values ranging from 0.442 to 0.776 μM. Satisfactorily, both PGG and TGG display antiviral activity in vitro with EC50 values ranging from 3.20 to 37.29 μM, suggesting as the promising candidates against SARS-CoV-2. In molecular dynamics simulation study, the complexes of Mpro-PGG, Mpro-TGG, PLpro-PGG, and PLpro-TGG exhibited stability over 500 ns period, unveiling the potential interactions.ConclusionPGG and TGG are the promising dual-target inhibitors of SARS-CoV-2, which may avoid drug resistance and have a good development prospect. The outcomes of this study provide an effective strategy to systematically explore the antiviral bioactive compounds from Chebulae Fructus.

Development and Evaluation of a Newcastle Disease Virus-like Particle Vaccine Expressing SARS-CoV-2 Spike Protein with Protease-Resistant and Stability-Enhanced Modifications

The ongoing global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the continuous development of innovative vaccine strategies, especially in light of emerging viral variants that could undermine the effectiveness of existing vaccines. In this study, we developed a recombinant virus-like particle (VLP) vaccine based on the Newcastle Disease Virus (NDV) platform, displaying a stabilized prefusion form of the SARS-CoV-2 spike (S) protein. This engineered S protein includes two proline substitutions (K986P, V987P) and a mutation at the cleavage site (RRAR to QQAQ), aimed at enhancing both its stability and immunogenicity. Using a prime-boost regimen, we administered NDV-VLP-S-3Q2P intramuscularly at different doses (2, 10, and 20 µg) to BALB/c mice. Robust humoral responses were observed, with high titers of S-protein-specific IgG and neutralizing antibodies against SARS-CoV-2 pseudovirus, reaching titers of 1:2200–1:2560 post-boost. The vaccine also induced balanced Th1/Th2 immune responses, evidenced by significant upregulation of cytokines (IFN-γ, IL-2, and IL-4) and S-protein-specific IgG1 and IgG2a. Furthermore, strong activation of CD4+ and CD8+ T cells in the spleen and lungs confirmed the vaccine’s ability to promote cellular immunity. These findings demonstrate that NDV-S3Q2P-VLP is a potent immunogen capable of eliciting robust humoral and cellular immune responses, highlighting its potential as a promising candidate for further clinical development in combating COVID-19.

Relationship Between Acute Severe Acute Respiratory Syndrome Coronavirus 2 Viral Clearance and Long Coronavirus 2019 (Long COVID) Symptoms: A Cohort Study.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics during acute infection and the development of long coronavirus disease 2019 (COVID-19), or "long COVID," is largely unknown. Between October 2021 and February 2022, 7361 people not known to have COVID-19 self-collected nasal swab samples for SARS-CoV-2 reverse-transcription polymerase chain reaction testing every 24-48 hours for 10-14 days. Participants whose first known SARS-CoV-2 infection was detected were surveyed for long COVID in August 2023. Their slopes of viral clearance were modeled using linear mixed effects models with random slopes and intercepts, and the relative risk (RR) of long COVID based on viral slopes was calculated using a log binomial model, adjusted for age, symptoms, and variant. Sex-based interaction terms were also evaluated for significance. A total of 172 participants were eligible for analyses, and 59 (34.3%) reported long COVID. The risk of long COVID with 3-4 symptoms (adjusted RR, 2.44 [95% confidence interval, .88-6.82]) and ≥5 symptoms (4.97 [1.90-13.0]) increased with each unit increase in slope of viral clearance. While the probability of long COVID increased with slowed viral clearance among women, the same relationship was not observed among men (interaction term: P = .02). Acute SARS-CoV-2 symptoms of abdominal pain (adjusted RR, 5.41 [95% confidence interval, 2.44-12.0]), nausea (3.01 [1.31-6.89]), and body aches (2.58 [1.26-5.30]) were most strongly associated with long COVID. We observed that slower viral clearance rates during acute COVID-19 were associated with increased risk and more symptoms of long COVID . Early viral-host dynamics appear to be mechanistically linked to the development of long COVID.

Simultaneous bilateral avascular necrosis of the humerus and femur in long COVID-19: a case report

Background. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted the widespread use of corticosteroids as a treatment strategy, particularly in cases of severe pneumonia and cytokine storm. While this therapy has saved countless lives, its side effects have also been well-documented, including the development of avascular necrosis. Case presentation. This case report presents a rare instance of simultaneous bilateral avascular necrosis (AVN) affecting both the humeral and femoral heads in a 49-year-old male patient recovering from severe COVID-19. The patient was treated with high-dose corticosteroids, receiving 1250 mg of prednisolone over five days during hospitalization for COVID-19 pneumonia. Six months after discharge, he developed persistent hip pain, which was later diagnosed as AVN in both femoral heads. During hyperbaric oxygen therapy, the patient reported new shoulder pain, and MRI confirmed stage III AVN in both humeral heads. The patient’s pain was managed with bilateral suprascapular nerve radiofrequency ablation and bilateral Pericapsular Nerve Group (PENG) blocks, which provided significant relief. Conclusions. This case emphasizes the potential for corticosteroid-induced AVN, even months after treatment, and underscores the need for long-term monitoring of patients receiving corticosteroids for COVID-19. The involvement of four major joints highlights the severe musculoskeletal complications that can arise, supporting the importance of early diagnosis and timely intervention for pain relief.

Influence of government policies on handwashing and vaccine uptake in Kenya, Uganda, and Tanzania to prevent and control COVID-19: a systematic review

IntroductionThe government's role in influencing policies related to Coronavirus disease 2019 (COVID-19) vaccine distribution and handwashing practices is essential in controlling the spread of severe acute respiratory syndrome coronavirus 2.MethodsThis study aimed to systematically review published studies to explore the influence of government policies on handwashing and vaccine uptake in Kenya, Uganda and Tanzania to prevent and control COVID-19. A comprehensive search strategy was applied across three databases, and eligibility was determined using strict inclusion and exclusion criteria. We reviewed 9 of 136 research papers following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.ResultsThe findings revealed that the government has a role in influencing policies related to COVID-19 vaccine distribution and handwashing uptake. Employment of public health campaigns and communication strategies by the government in Uganda increased vaccine acceptance and hand hygiene uptake. Similarly, government efforts to make hand hygiene accessible increased the uptake of handwashing in Tanzania. In Kenya, government efforts to increase access to soap and clean water in informal settlements and markets resulted in increased adherence to handwashing practices. Further, government incentives such as cash increased vaccination rates while vaccination reminders combined with cash incentives increased childhood immunization coverage.DiscussionOverall, this review indicates that monitoring and enforcing compliance increases vaccine and handwashing uptake across the three countries. The effectiveness of government policies on handwashing and vaccine uptake is influenced by factors such as safety, efficacy and access to information, among others. Therefore, there is a need to address these factors for the successful implementation of these policies.Systematic review RegistrationPROSPERO ID CRD42023396319, https://www.crd.york.ac.uk/prospero/.

Validation of a Nepali version of the questionnaire to assess preventive practices against the COVID-19 pandemic in the general population

BackgroundThe new coronavirus disease 2019 (COVID-19), caused by a virus in the coronavirus family called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to lack of effective treatment, the major way to breakdown the disease transmission is by application of preventive measures. For this, a preventive practice questionnaire was used to assess the preventive practice during COVID-19. A definite advantage of this questionnaire is its ability to identify individual level preventive practices. The objective of the study was to validate the Nepali version of Questionnaire to assess preventive practices against the COVID-19 pandemic in the General population.MethodsA web-based descriptive cross-sectional study was conducted from November 2022 to April 2023 using preventive practices against the COVID-19 pandemic questionnaire and was conducted among 351 respondents. The sensitivity and specificity of the questionnaire were calculated for validation. The best cutoff point for the Nepalese version of the questionnaire was identified and the area under the receiver operating characteristic curve (AUC) was calculated.ResultsThe overall prevalence of good preventive practices was 90.6%. The best cutoff points for the Nepali version of the questionnaire were 93% sensitivity and 67% specificity, respectively at a cutoff level of 47/48. The area under the curve was 0.859. Thus, the Nepalese version of the questionnaire concerning preventive practices during the COVID-19 pandemic in the general population had an accuracy of 85.9% (95% CI 0.757–0.961, p = 0.001).ConclusionThe Nepalese version of the questionnaire on preventive practices during the COVID-19 pandemic in the general population can be successfully used as a survey tool. These findings might help to detect appropriate adherence to preventive practices can be achieved in busy outpatient departments. Detecting adherence to preventive practices may help local health authorities and policymakers in identifying specific populations for future awareness campaigns during infectious disease outbreaks.

Clinical Characteristics and Prognosis in Allergic Health Workers Patients with COVID-19 Infection

Background: After a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China, at the end of 2019, the cause of coronavirus disease 2019 (COVID-19) was soon recognized as a global public health emergency. Objectives: This study aimed to investigate the clinical characteristics of allergic healthcare workers (HCWs) confirmed to have COVID-19. Methods: This study included 30 HCWs with confirmed COVID-19 at Kosar Hospital in Semnan, Iran, from February to June 2020 (15 allergic and 15 non-allergic individuals). Demographic data, clinical manifestations, and laboratory findings of the subjects were recorded. Results: Total IgE, allergen-specific IgE, and anti-SARS-CoV IgG were measured in the patients' serum. The average age of the allergic and non-allergic HCWs with COVID-19 was 33 years, and 80% were female. Malaise (76.6%), fever (60%), weakness (60%), and dry cough (56.7%) were the most common symptoms. The clinical findings showed a significantly lower percentage (33.3%) of dry cough in subjects with allergic diseases. Apart from the observed difference in the mean value of total IgE between the two groups, no significant differences were found with respect to age, duration of disease, O2 saturation, and anti-SARS-CoV-2 IgG. Conclusions: Coronavirus disease 2019 symptoms did not become severe in patients with atopic diseases. Moreover, dry cough and weakness were reported by a lower percentage of allergic HCWs.

Strategies Used by SARS-CoV-2 to Evade the Innate Immune System in an Evolutionary Perspective

By the end of 2019, the COVID-19 pandemic, resulting from the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), had diffused widely across the globe, with 770 million infected individuals and over 7 million deaths reported. In addition to its high infectivity and pathogenicity and its rapid mutation rate, the unique capacity of SARS-CoV-2 to circumvent the immune system has also contributed to the widespread nature of this pandemic. SARS-CoV-2 elicits the onset of innate immune system activation and initiates antiviral responses once it has infected the host. While battling the host’s immune responses, SARS-CoV-2 has established many countermeasures to evade attack and clearance. As the exploration of SARS-CoV-2 continues, substantial evidence has revealed that the 29 proteins synthesized by the SARS-CoV-2 genome are integral to the viral infection process. They not only facilitate viral replication and transmission, but also assist SARS-CoV-2 in escaping the host’s immune defenses, positioning them as promising therapeutic targets that have attracted considerable attention in recent studies. This review summarizes the manner in which SARS-CoV-2 interfaces with the innate immune system, with a particular focus on the continuous evolution of SARS-CoV-2 and the implications of mutations.

Effects of SARS-CoV-2 on DNA Damage Response Proteins Chk1 and P53: An in vitro Study

Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has had a global impact on millions of people's lives. Deteriorations in cellular activities induced by this lethal virus are not yet completely understood, and so its long-term consequences are unknown. There is increasing evidence that SARS-CoV-2 and its vaccinations may have a deleterious influence on DNA damage response (DDR)-associated proteins. Objective: To investigate the status of DNA integrity in COVID-19-recovered patients and post-recovered vaccinated individuals. Methods: Blood samples were taken from 88 participants who completed questionnaires and conducted face-to-face interviews. The samples were classified into four categories based on the subjects' PCR and vaccination status: PCR negative/not vaccinated, PCR positive/not vaccinated, PCR negative/vaccinated, and PCR positive/vaccinated. ELISA kits were used to determine the expression levels of TP53BP1, Chk1, and SARS-CoV-2 IgG proteins. Results: SARS-CoV-2 did not significantly reduce Chk1 expression, but it did have a significant negative influence on TP53BP1 expression when compared to the first group. Infection with SARS-CoV-2 and its vaccination resulted in increased Chk1 and IgG levels, as well as a significant increase in TP53BP1 expression compared to the second group. Conclusions: Both SARS-CoV-2 infection and the anti-SARS-CoV-2 vaccine may have a deleterious influence on DDR-associated proteins in vitro. Post-infection immunization may boost viral protection. While some studies imply that DDR effects are reversible, more research is needed to corroborate these assertions.

A comprehensive immune repertoire signature distinguishes pulmonary infiltration in SARS-CoV-2 Omicron variant infection

IntroductionThe coronavirus disease 2019 (COVID-19) global pandemic has been the most severe public health emergency since 2019. Currently, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dominant. The most prominent symptom of SARS-CoV-2 infection is respiratory. Meanwhile, the fatality of COVID-19 was mainly from pneumonia. However ,in patients with SARS-CoV-2 infection who have pneumonia and those who do not, the differences in the immune repertoire still require further investigation.MethodsWe conducted seven-chain adaptome immune repertoire analyses on patients with SARS-CoV-2 Omicron infection, both with and without pulmonary infiltration.ResultsPatients with pulmonary infiltration exhibit lymphopenia, a decreased proportion of the overall TCR repertoire alongside an increased BCR repertoire, reduced IGHD and IGHM isotype expression, a shorter mean CDR3 length for TRG, and a longer mean length for TRD, as well as diminished clonality and diversity in the TCR/BCR repertoire. Meanwhile, patients with pulmonary infiltration have distinct V-J gene usage and unique CDR3 signature, as well as BCR class switch recombination pattern. Finally, prior vaccination triggered less BCR IGHM/IGHD somatic hypermutation response, preserved the diversity of the entire adaptive immune repertoire, and provided clinical protection against severe or critical conditions following Omicron infection.DiscussionWe report a unique, comprehensive adaptive immune system signature in patients with pulmonary infiltration, which may serve as potential immunological biomarkers and therapeutic targets.

DEEP LEARNING FOR MULTI-LEVEL SEVERITY CLASSIFICATION OF COVID-19 USING CT IMAGES

Coronavirus disease 2019 (COVID-19) was witnessed in the year 2019 and is termed a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Health Organization (WHO). The preceding investigations recommended that computer tomography (CT) images comprise numerous potential indicators of infection. However, the infection may be distinct to COVID-19 which represents various difficulties for radiologists in particularly recognizing COVID-19 infections employing CT images. To bridge this gap, a multi-level severity classification for COVID-19 with fractional hunger game search optimization (FHGSO)-enabled deep max out network (DMN) employing CT images is developed. The input CT scan is allowed to the pre-processing phase conducted employing an Adaptive median filter. After that, Lung lobe segmentation is performed by deep joint segmentation. Thereafter, the image augmentation is conducted based on translation, rotation, flipping and scaling. Additionally, the augmented image is subjected to feature extraction. COVID-19’s first level classification is categorized into normal and abnormal employing deep Q-network (DQN) that is tuned by proposed exponential snake war strategy optimization (ESWSO) is obtained by the incorporation of war strategy optimization (WSO) and snake optimization (SO). If it is abnormal, the second level classification is accomplished where the disease is classified into mild, moderate and severe, which is done by DMN, trained by proposed fractional hunger game search (FHGSO) optimization, where FHGSO is obtained by the combination of hunger game search (HGS) and fractional concept. The analysis metrics employed for FHGSO_DMN are accuracy, sensitivity, and specificity achieving the maximum of 94.70%, 95.70%, and 82.70%.

A stochastic analysis and bibliometric analysis of COVID-19

COVID-19 a novel Corona Virus Disease which was caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) continues to pose a critical and urgent threat to global health. When an infected person comes in contact with a normal individual or when the infected person sneezes or coughs, the virus that triggers COVID-19 spreads.The spread of novel SARS-CoV-2 was increasing, and the threats caused by it were becoming more severe in 2021. To counter the disease and save countless lives in danger, it is necessary to predict the trend of the number of cases and deaths and then implement the policies accordingly. In this paper, the trends of the growth rate of worldwide cases and deaths were studied, and the future growth for 100 days was predicted using the Neural network model and Polynomial Regression model. For efficient planning, the countries were grouped using Principal Component Analysis and the predictions were made. The cases and deaths in different countries and states were related through the Pearson coefficient, and the heat maps were studied. Additionally, in this paper, a case study to predict the trend of cases, number of deaths and recoveries in India was also performed. The Indian states were grouped into four groups based on the Principal Component Analysis (PCA) results, and relevant remarks and trends were suggested. The growth of cases and deaths was studied, and the peaks were predicted for the next 200 days. In recent months, COVID-19 has generated a significant deal of anxiety as a global pandemic, and an increasing number of studies have been published in this area. Consequently, a bibliometric examination of these papers may offer insight into current research hot subjects and trends. We are the first to join stochastic analysis of COVID-19 effects with bibliometric analysis of COVID-19. This prediction, if taken into consideration strategically during the planning of preventive measures of COVID-19 can help to reduce the cases to a great extent.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnant Women Treated with Nirmatrelvir/Ritonavir (Paxlovid) Using Salivary Polymerase Chain Reaction: A Prospective Cohort Study

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnant Women Treated with Nirmatrelvir/Ritonavir (Paxlovid) Using Salivary Polymerase Chain Reaction: A Prospective Cohort Study

Dysbiosis of gut microbiota in COVID-19 is associated with intestinal DNA phage dynamics of lysogenic and lytic infection.

This study compared intestinal DNA phage dynamics and gut microbiota changes observed at the onset of coronavirus disease 2019 (COVID-19). The study participants included 19 healthy individuals and 19 patients with severe acute respiratory syndrome coronavirus 2 infection. Significant differences were observed in the diversity of the intestinal DNA virome after the onset of COVID-19 compared with that in healthy individuals. Classification by their tail morphology resulted in the order Caudovirales, a double-stranded DNA phage, accounting for >95% of all participants. In classifying phages based on host bacteria, a decreased number of phages infecting mainly the Clostridia class was observed immediately after the onset of COVID-19 and recovered over time. After the onset of COVID-19, two distinct movement patterns of intestinal phages and their host bacteria were observed: phage- and bacteria-predominant. The abundance of obligate anaerobes, such as Clostridium_sense_strict_1, Fusicatenibacter, and Romboutsia, and the phages hosting these bacteria decreased immediately after the onset of COVID-19, and faster phage recovery was observed compared with bacterial recovery. In contrast, the genus Staphylococcus, a facultative anaerobic bacterium, increased immediately after the onset of COVID-19, whereas the phages infecting Staphylococcus decreased. Furthermore, immediately after the onset of COVID-19, the percentage of lytic phages increased, whereas that of temperate phages decreased. These observations suggest that the gut microbiota dysbiosis observed immediately after the onset of COVID-19 may be linked to phage dynamics that control gut microbiota and may also affect the recovery from dysbiosis.IMPORTANCEBacteriophages infect and replicate with bacteria and archaea and are closely associated with intestinal bacteria. The symbiotic relationship between gut microbiota and bacteriophages is of interest, but it is challenging to study their dynamics in the human body over time. SARS-CoV-2 infection has been reported to alter the gut microbiota, which is involved in gut immune regulation and pathophysiology, although changes in the intestinal phages of patients with SARS-CoV-2 and their dynamic relationship with the gut microbiota remain unclear. SARS-CoV-2 infection, which follows a transient pathological course from disease onset to cure, may provide a reliable model to investigate these interactions in the gut environment. Therefore, this study aimed to elucidate the correlation between gut microbiota and intestinal DNA virome dynamics in COVID-19 pathogenesis. This study found that the dysbiosis observed in SARS-CoV-2 infection involves a growth strategy that depends on the phage or bacterial dominance.

The effect of sleep and shift work on the primary immune response to messenger RNA-based COVID-19 vaccination.

Shift work can cause circadian misalignment, which often results in sleeping problems and has been associated with immune dysfunction. To better understand the impact of shift work on a primary immune response to vaccination, we compared severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific humoral and cellular immune responses after one injection of the messenger RNA (mRNA)-1273 vaccine between day workers (n = 24) and night shift workers (n = 21). In addition, duration and quality of sleep were assessed for a period of 7 days around the time of vaccination using actigraphy and daily sleep diaries, and their relationship with immunogenicity of mRNA-1273 vaccination was studied. We found that median total sleep time on the 2 days immediately after vaccination, which coincided with the days that night shift workers worked night shifts, was significantly lower in night shift workers (342 and 318 min) than day workers (431 and 415 min) (both p < 0.001). There was no difference in sleep quality between day workers and night shift workers. Furthermore, no difference in the antibody response between the two groups was observed, yet night shift workers had a significantly higher virus-specific T-cell response than day workers 28 days after immunisation (p = 0.013). Multivariate regression analysis showed no association between sleep duration, sleep quality and SARS-CoV-2-specific humoral or cellular immune responses. Collectively, these findings indicate that shift work-induced sleep loss and night shift work have little to no effect on the primary immune response to mRNA-based COVID-19 vaccination.

Generation of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation

IntroductionTo analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.MethodsWe conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.ResultsIn this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication. An early circulating strain of SARS-CoV-2 caused the most severe weight loss when compared to SARS-CoV-2 variants such as Alpha, Beta and Gamma, although histopathological findings, viral replication, and cytokine expression characteristics were comparableDiscussionWe found that a distinct proteome of an early circulating strain infected lung characterized by elevated complement activation and blood coagulation, which were mild in other variants, can contribute to disease severity. Unraveling the specificity of early circulating SARS-CoV-2 strains is important in elucidating the origin of the pandemic.

A Large-Scale Serological Survey in Pets From October 2020 Through June 2021 in France Shows Significantly Higher Exposure to SARS-CoV-2 in Cats Compared to Dogs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to infect various animals, including domestic pets like dogs and cats. Many studies have documented infection in companion animals by molecular and serological methods. However, only a few have compared seroprevalence in cats and dogs from the general population, and these studies were limited by small sample sizes and collections over short periods. Our aim was to obtain a more accurate evaluation of seroprevalence in companion animals in France and to determine whether cats and dogs differ in their exposure to SARS-CoV-2. We conducted an extensive serological survey of SARS-CoV-2, collecting blood samples from 2036 cats and 3577 dogs during routine veterinary medical examinations across different regions of metropolitan France from October 2020 to June 2021. This period encompassed the peaks and onset of two waves, as well as the emergence of the first variants. A microsphere immunoassay targeting the receptor-binding domain and trimeric spike protein was used to detect anti-SARS-CoV-2 antibodies. A subset of 308 seropositive samples was tested for the presence of neutralising antibodies. We determined an overall seroprevalence of anti-SARS-CoV-2 antibodies of 7.1% (95% confidence interval [CI]: 6.4%-7.8%) among the sampled pets. Cats exhibited a significantly higher seroprevalence (9.3%; 95% CI: 8.1%-10.1%) compared to dogs (5.9%; 95% CI: 5.2%-6.8%). Among the subset of seropositive samples, 81 (26.3%; 95% CI: 21.5%-31.6%) displayed neutralizing antibodies. Furthermore, seroprevalence in both species was lower in older animals and was not associated with sex. Finally, unlike cats, seroprevalence in dogs was found to be correlated with the date of sampling. The large sample size enhances the reliability and statistical robustness of our estimates regarding pet exposure to SARS-CoV-2. This study on SARS-CoV-2 reaffirms the crucial importance of adopting a One Health approach incorporating domestic animals when managing an epidemic caused by a zoonotic virus.