Association between SARS-CoV-2 infections during pregnancy and preterm live birth

We examined associations between mild or asymptomatic prenatal SARS-CoV-2 infection and preterm live birth in a prospective cohort study. During August 2020–October 2021, pregnant persons were followed with systematic surveillance for RT-PCR or serologically confirmed SARS-CoV-2 infection until pregnancy end. The association between prenatal SARS-CoV-2 infection and preterm birth was assessed using Cox proportional-hazards regression. Among 954 pregnant persons with a live birth, 185 (19%) had prenatal SARS-CoV-2 infection and 123 (13%) had preterm birth. The adjusted hazard ratio for the association between SARS-CoV-2 infection and preterm birth was 1.28 (95% confidence interval 0.82–1.99, p = 0.28), although results did not reach statistical significance.     

SARS-CoV-2: Evolution and Emergence of New Viral Variants

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the coronavirus disease 2019 (COVID-19). The high rate of mutation of this virus is associated with a quick emergence of new viral variants that have been rapidly spreading worldwide. Several mutations have been documented in the receptor-binding domain (RBD) of the viral spike protein that increases the interaction between SARS-CoV-2 and its cellular receptor, the angiotensin-converting enzyme 2 (ACE2). Mutations in the spike can increase the viral spread rate, disease severity, and the ability of the virus to evade either the immune protective responses, monoclonal antibody treatments, or the efficacy of current licensed vaccines. This review aimed to highlight the functional virus classification used by the World Health Organization (WHO), Phylogenetic Assignment of Named Global Outbreak (PANGO), Global Initiative on Sharing All Influenza Data (GISAID), and Nextstrain, an open-source project to harness the scientific and public health potential of pathogen genome data, the chronological emergence of viral variants of concern (VOCs) and variants of interest (VOIs), the major findings related to the rate of spread, and the mutations in the spike protein that are involved in the evasion of the host immune responses elicited by prior SARS-CoV-2 infections and by the protection induced by vaccination.     

SARS-CoV-2 Infection and Pregnancy: Maternal and Neonatal Outcomes and Placental Pathology Correlations

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases (n = 2), whereas 92% of cases were negative (n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted (n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal–neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.     

Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, is one of the biggest threats to public health. However, the dynamic of SARS-CoV-2 infection remains poorly understood. Replication-competent recombinant viruses expressing reporter genes provide valuable tools to investigate viral infection. Low levels of reporter gene expressed from previous reporter-expressing recombinant (r)SARS-CoV-2 in the locus of the open reading frame (ORF)7a protein have jeopardized their use to monitor the dynamic of SARS-CoV-2 infection in vitro or in vivo. Here, we report an alternative strategy where reporter genes were placed upstream of the highly expressed viral nucleocapsid (N) gene followed by a porcine tescherovirus (PTV-1) 2A proteolytic cleavage site. The higher levels of reporter expression using this strategy resulted in efficient visualization of rSARS-CoV-2 in infected cultured cells and excised lungs or whole organism of infected K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice. Importantly, real-time viral infection was readily tracked using a noninvasive in vivo imaging system and allowed us to rapidly identify antibodies which are able to neutralize SARS-CoV-2 infection in vivo. Notably, these reporter-expressing rSARS-CoV-2, in which a viral gene was not deleted, not only retained wild-type (WT) virus-like pathogenicity in vivo but also exhibited high stability in vitro and in vivo, supporting their use to investigate viral infection, dissemination, pathogenesis, and therapeutic interventions for the treatment of SARS-CoV-2 in vivo.

Coronaviruses (CoVs) are enveloped, single-stranded, positive-sense RNA viruses that belong to the Coronaviridae family that can cause mild to severe respiratory infections in humans (1). Two CoVs have been associated with severe respiratory syndrome in the past two decades: severe acute respiratory syndrome CoV (SARS-CoV) in 2002–2003 and Middle East respiratory syndrome CoV (MERS-CoV) in 2012 to the present (2). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the Chinese city of Wuhan in December 2019 and is the causative agent of the COVID-19 pandemic (3, 4). As of June 2021, SARS-CoV-2 has been reported to be responsible for over 150 million human infection cases and more than 3 million deaths around the World (https://covid19.who.int/).Like SARS-CoV and MERS-CoV, SARS-CoV-2 mainly replicates in the upper (nasal turbinate) and lower (lungs) respiratory tract, resulting, in some cases, in fatal respiratory illness (5, 6). However, the intrahost dissemination and pathogenesis of SARS-CoV-2 are not well understood. Several animal models of SARS-CoV-2 infection have been established and have already provided very valuable information to understand the mechanism of tissue and cell tropism, replication, and pathogenesis (7–11). However, assessing the presence of SARS-CoV-2 in infected animals, organs, or tissues has required collection and processing of samples upon euthanasia, which complicates studies examining the longitudinal dynamic of a viral infection within an infected host. Recombinant (r)SARS-CoV-2 expressing reporter genes could overcome this problem and allow tracking of viral infection in vivo and in real time by monitoring the expression of the reporter gene. We and others have documented the feasibility of generating reporter-expressing rSARS-CoV-2 using a reverse genetic system (12, 13). These rSARS-CoV-2 have been genetically engineered to express the reporter gene by substituting the viral open reading frame (ORF) 7a protein with the reporter gene of interest, an experimental approach first employed to generate reporter-expressing rSARS-CoV (14). Despite these reporter-expressing rSARS-CoV-2 showing plaque phenotype, replication, and growth kinetics comparable to those of wild-type virus (rSARS-CoV-2/WT) in vitro (12, 13, 15), it is unclear whether the reporter-expressing rSARS-CoV-2 lacking ORF7a recapitulate viral pathogenicity in vivo and whether reporter gene expression levels could be efficiently tracked ex vivo using tissues or organs from infected animals, or in a whole organism in vivo.In this study, we cloned fluorescent (Venus) and luciferase (Nano luciferase, Nluc) reporter genes upstream of the SARS-CoV-2 nucleocapsid (N) gene separated by the porcine tescherovirus (PTV-1) 2A proteolytic cleavage site to generate new reporter-expressing rSARS-CoV-2 without the deletion of the ORF7a protein. In vitro, rSARS-CoV-2 expressing reporter genes from the viral N locus replicated and made viral plaques similar to those of rSARS-CoV-2/WT. Reporter-expressing rSARS-CoV-2 generated using this 2A strategy expressed higher levels of reporter gene expression compared to those rSARS-CoV-2 generated by substituting the viral ORF7a protein with the reporter gene of interest. Importantly, rSARS-CoV-2/Venus-2A and rSARS-CoV-2/Nluc-2A showed rSARS-CoV-2/WT−like pathogenicity in vivo. The higher level of Venus expression from rSARS-CoV-2/Venus-2A allowed us to detect viral infection in the lungs of infected K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice using an in vivo imaging system (IVIS). Moreover, Venus expression from rSARS-CoV-2/Venus-2A was stable up to seven passages in vitro in cultured Vero E6 cells and in vivo up to day 6 postinfection. Importantly, levels of Venus expression correlated well with viral titers detected in the lungs, demonstrating the feasibility of using Venus expression as a valid surrogate marker to evaluate SARS-CoV-2 infection. Using rSARS-CoV-2/Nluc-2A, we were able to track the dynamic of viral infection in real time and longitudinally assess SARS-CoV-2 infection in vivo. Finally, we testified to the feasibility of using the rSARS-CoV-2/Nluc-2A to rapidly and accurately identify antibodies that neutralize viral infection in vivo.Our data demonstrate that these next-generation rSARS-CoV-2 expressing reporter genes we have generated can be used to easily monitor viral infection in cultured cells and in validated animal models of infection. Importantly, our new rSARS-CoV-2/Venus-2A or rSARS-CoV-2/Nluc-2A retain similar virulence to that of rSARS-CoV-2/WT in K18 hACE2 transgenic mice and can be used to investigate viral replication, tropism, and viral dissemination and pathogenesis in vivo and to rapidly identify therapeutics for the treatment of SARS-CoV-2 infection and associated COVID-19 disease.     

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients’ information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms).     

SARS-CoV-2 and Arthropods: A Review

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that led to the unprecedented COVID-19 pandemic exemplifies how a lack of understanding and preparedness for emerging viruses can result in consequences on a global scale. Statements that SARS-CoV-2 could not be transmitted by arthropod vectors were made without experimental support. Here we review laboratory-based research, field studies, and environmental studies to evaluate the potential for the virus to be transmitted either biologically or mechanically by arthropods. Based on these data, we conclude that transmission by arthropods is highly unlikely to play a significant epidemiological role in the transmission of SARS-CoV-2.     

Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.     

Evaluation of Two Broadly Used Commercial Methods for Detection of Respiratory Viruses with a Recently Added New Target for Detection of SARS-CoV-2

The clinical symptoms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nonspecific and can be associated with most other respiratory viruses that cause acute respiratory tract infections (ARI). Because the clinical differentiation of COVID-19 patients from those with other respiratory viruses is difficult, the evaluation of automated methods to detect important respiratory viruses together with SARS-CoV-2 seems necessary. Therefore, this study compares two molecular assays for the detection of respiratory viruses, including SARS-CoV-2: the Respiratory Viruses 16-Well Assay (AusDiagnostics, Pty Ltd., Mascot, Australia) and the Allplex™ RV Essential Assay coupled with the Allplex™-nCoV Assay (Seegene Inc., Seoul, Korea). The two methods (AusDiagnostics and Alplex^TM-nCoV Assay SARS-CoV-2) had 98.6% agreement with the reference method, cobas 6800, for the detection of SARS-CoV-2. Agreement between the AusDiagnostics assay and the Alplex^TM RV Essential Assay for the detection of seven respiratory viruses was 99%. In our experience, the Respiratory Viruses 16-Well Assay proved to be the most valuable and useful medium-throughput method for simultaneous detection of important respiratory viruses and SARS-CoV-2. The main advantages of the method are high specificity for all targets included and their simultaneous detection and medium throughput with the option of having multiple instruments provide a constant run.     

SARS-CoV-2 Infection and C-Section: A Prospective Observational Study

Pregnant women are particularly vulnerable to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In addition to unfavorable perinatal outcomes, there has been an increase in obstetric interventions. With this study, we aimed to clarify the reasons, using Robson’s classification model, and risk factors for cesarean section (C-section) in SARS-CoV-2-infected mothers and their perinatal results. This was a prospective observational study that was carried out in 79 hospitals (Spanish Obstetric Emergency Group) with a cohort of 1704 SARS-CoV-2 PCR-positive pregnant women that were registered consecutively between 26 February and 5 November 2020. The data from 1248 pregnant women who delivered vaginally (vaginal + operative vaginal) was compared with those from 456 (26.8%) who underwent a C-section. C-section patients were older with higher rates of comorbidities, in vitro fertilization and multiple pregnancies (p < 0.05) compared with women who delivered vaginally. Moreover, C-section risk was associated with the presence of pneumonia (p < 0.001) and 41.1% of C-sections in patients with pneumonia were preterm (Robson’s 10th category). However, delivery care was similar between asymptomatic and mild–moderate symptomatic patients (p = 0.228) and their predisposing factors to C-section were the presence of uterine scarring (due to a previous C-section) and the induction of labor or programmed C-section for unspecified obstetric reasons. On the other hand, higher rates of hemorrhagic events, hypertensive disorders and thrombotic events were observed in the C-section group (p < 0.001 for all three outcomes), as well as for ICU admission. These findings suggest that this type of delivery was associated with the mother’s clinical conditions that required a rapid and early termination of pregnancy.     

SARS-CoV-2 leading to acute pancreatitis: an unusual presentation

During SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) pandemic, the etiologic agent of COVID-19, several studies described the involvement of other tissues besides the respiratory tract, such as the gastrointestinal tract. Angiotensin-converting enzyme-2, the functional virus host cell receptor expressed by organs and tissues, seems to have an important role in the pathophysiology and presentation of this disease. In pancreas, this receptor is expressed in both exocrine glands and islets, being a potential target for the virus and subsequent pancreatic injury. There are few articles reporting pancreatic injury in COVID-19 patients but most of them do not report acute pancreatitis. Diagnosing acute pancreatitis secondary to SARS-CoV-2 infection is challenging due to the need to rule out other etiologies as well the notable heterogeneous presentations. Herein we report the case of a patient with COVID-19 who developed severe acute pancreatitis.     

Paediatric gastrointestinal disorders in SARS-CoV-2 infection: Epidemiological and clinical implications

The coronavirus disease 2019 (COVID-19) pandemic is a threat worldwide for individuals of all ages, including children. Gastrointestinal manifestations could be the initial presenting manifestation in many patients, especially in children. These symptoms are more common in patients with severe disease than in patients with non-severe disease. Approximately 48.1% of patients had a stool sample that was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA. Children typically form 1%-8% of all laboratory-confirmed cases of SARS-CoV-2. Gastrointestinal manifestations of COVID-19 in children are not rare, with a prevalence between 0 and 88%, and a wide variety of presentations, including diarrhoea, vomiting, and abdominal pain, can develop before, with or after the development of respiratory symptoms. Atypical manifestations such as appendicitis or liver injury could also appear, especially in the presence of multisystem inflammatory disease. In this review, we discussed the epidemiology of COVID-19 gastrointestinal diseases in children as well as their implications on the diagnosis, misdiagnosis, prognosis, and faecal-oral transmission route of COVID-19 and the impact of gastrointestinal diseases on the gut microbiome, child nutrition, and disease management.     

Autoimmune liver diseases and SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.     

Insights into SARS-CoV-2 in Angola during the COVID-19 peak: Molecular epidemiology and genome surveillance

Background

In Angola, COVID-19 cases have been reported in all provinces, resulting in >105,000 cases and >1900 deaths. However, no detailed genomic surveillance into the introduction and spread of the SARS-CoV-2 virus has been conducted in Angola. We aimed to investigate the emergence and epidemic progression during the peak of the COVID-19 pandemic in Angola.

Methods

We generated 1210 whole-genome SARS-CoV-2 sequences, contributing West African data to the global context, that were phylogenetically compared against global strains. Virus movement events were inferred using ancestral state reconstruction.

Results

The epidemic in Angola was marked by four distinct waves of infection, dominated by 12 virus lineages, including VOCs, VOIs, and the VUM C.16, which was unique to South-Western Africa and circulated for an extended period within the region. Virus exchanges occurred between Angola and its neighboring countries, and strong links with Brazil and Portugal reflected the historical and cultural ties shared between these countries. The first case likely originated from southern Africa.

Conclusion

A lack of a robust genome surveillance network and strong dependence on out-of-country sequencing limit real-time data generation to achieve timely disease outbreak responses, which remains of the utmost importance to mitigate future disease outbreaks in Angola.     

Co-infection of SARS-CoV-2 and dengue virus: a clinical challenge

Many regions of the world where dengue epidemics are seasonal are also facing the COVID-19 pandemic. This is a medical concern because both diseases are difficult to distinguish since they have similar clinical symptoms and laboratory findings, and because they have different clinical management. So far, co-infection of SARS-CoV-2 and dengue virus (DENV) has not been studied. Herein we report the first case of a patient with co-infection of COVID-19 and dengue. Both infections were simultaneously laboratory confirmed by positive RT-qPCR for SARS-CoV-2 and RT-qPCR for DENV, NS1, IgM and IgG antibody tests for dengue. The patient had a favorable clinical improvement, without severe symptoms. This case emphasize that, in pandemic era, having a diagnostic of one infection does not rule out the possibility of having another infection concomitantly. In addition, underscores the importance of an accurate and timely diagnosis to prevent the spread of COVID-19.     

SARS-CoV-2 Transmission in Belgian French-Speaking Primary Schools: An Epidemiological Pilot Study

Schools have been a point of attention during the pandemic, and their closure one of the mitigating measures taken. A better understanding of the dynamics of the transmission of SARS-CoV-2 in elementary education is essential to advise decisionmakers. We conducted an uncontrolled non-interventional prospective study in Belgian French-speaking schools to describe the role of attending asymptomatic children and school staff in the spread of COVID-19 and to estimate the transmission to others. Each participant from selected schools was tested for SARS-CoV-2 using a polymerase chain reaction (PCR) analysis on saliva sample, on a weekly basis, during six consecutive visits. In accordance with recommendations in force at the time, symptomatic individuals were excluded from school, but per the study protocol, being that participants were blinded to PCR results, asymptomatic participants were maintained at school. Among 11 selected schools, 932 pupils and 242 school staff were included between January and May 2021. Overall, 6449 saliva samples were collected, of which 44 came back positive. Most positive samples came from isolated cases. We observed that asymptomatic positive children remaining at school did not lead to increasing numbers of cases or clusters. However, we conducted our study during a period of low prevalence in Belgium. It would be interesting to conduct the same analysis during a high prevalence period.     

无锡SARS-CoV-2病例的流行病学和临床复阳评价

目的 通过分析无锡新型冠状病毒肺炎(SARS-CoV-2)的传播关系、临床分级和复阳病例的临床表现评价本地病毒的传播及致病性特征.方法 以2020年1月23日至11月20日无锡市第五人民医院收治的SARS-CoV-2阳性病例为研究对象,通过分析传播的流行病学及复阳病例的临床特征,初步评价病毒的传播及致病性特征.结果 C...     

新型冠状病毒(SARS-CoV-2)变异的研究进展

2019年12月底,湖北省武汉市暴发了由新型冠状病毒(SARS-CoV-2)引起的肺炎疫情.迄今为止,该病毒引起的疫情仍在全球流行,累计感染人数超1.8亿.随着SARS-CoV-2在人群间的不断传播,其基因组不断发生变异,从SARS-CoV-2首次出现S蛋白D614G突变到被世界卫生组织列为关切的Alpha、Beta、...