ABSTRACT
Background: There is an urgent need to review the status of COVID-19 vaccine immunization in pregnant women globally so that the adverse outcomes may be prevented. Objective: To evaluate the probable outcome of COVID-19 vaccination in pregnant women. Search strategy: An electronic search was conducted over the period of 3 months (June 15-August 15, 2021). Selection criteria: The original studies evaluating safety concerns in pregnant women for COVID-19 vaccination were included. Data collection and analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for the collection of the data and reporting of the findings. The inclusion and exclusion criteria for the studies were determined based on ‘PICO principle’ (Population, Intervention, Comparator, and Outcome, Study design. Risk of bias assessment was done using National Institute of Health (NIH) tool for systematic reviews. Main results: COVID-19 vaccination in pregnant women was not associated with increased adverse effects or complications to the mother as well as developing fetus or newborn compared to non-vaccinated pregnant women. Vaccinated pregnant women showed a robust immune response against COVID-19 infection. Conclusions: COVID-19 vaccination during pregnancy causes no significant health risks for the mother or developing fetus or newborn.
Subject(s)
COVID-19ABSTRACT
Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.
Subject(s)
COVID-19 , DeathABSTRACT
Objectives There is an urgent need to review the status of COVID-19 vaccine immunization in pregnant women globally so that the adverse outcomes may be prevented. In this study we performed a systematic review of the available literature to evaluate the probable outcomes of COVID-19 vaccination in pregnant women.Methods An electronic search was conducted over the period of 3 months (June 15-August 15, 2021). The original studies evaluating safety concerns in pregnant women for COVID-19 vaccination were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for the collection of the data and reporting of the findings. The inclusion and exclusion criteria for the studies were determined based on ‘PICO principle’ (Population, Intervention, Comparator, and Outcome, Study design. Risk of bias assessment was done using National Institute of Health (NIH) tool for systematic reviews.Results COVID-19 vaccination in pregnant women was not associated with increased adverse effects or complications to the mother as well as developing fetus or newborn compared to non-vaccinated pregnant women. Vaccinated pregnant women showed a robust immune response against COVID-19 infection.Conclusions COVID-19 vaccination during pregnancy causes no significant health risks for the mother or developing fetus or newborn.
Subject(s)
COVID-19ABSTRACT
ImportanceHigher risks of contracting infection, developing severe illness and mortality are known facts in aged and male sex if exposed to the wild type SARS-CoV-2 strains (Wuhan and B.1 strains). Now, accumulating evidence suggests greater involvement of lower age and narrowing the age and sex based differences for the severity of symptoms in infections with emerging SARS-CoV-2 variants. Delta variant (B.1.617.2) is now a globally dominant SARS-CoV-2 strain, however, current evidence on demographic characteristics for this variant are limited. Recently, delta variant caused a devastating second wave of COVID-19 in India. We performed a demographic characterization of COVID-19 cases in Indian population diagnosed with SARS-CoV-2 genomic sequencing for delta variant. ObjectiveTo determine demographic characteristics of delta variant in terms of age and sex, severity of the illness and mortality rate, and post-vaccination infections. DesignA cross sectional study SettingDemographic characteristics, including vaccination status (for two complete doses) and severity of the illness and mortality rate, of COVID-19 cases caused by wild type strain (B.1) and delta variant (B.1.617.2) of SARS-CoV-2 in Indian population were studied. ParticipantsCOVID-19 cases for which SARS-CoV-2 genomic sequencing was performed and complete demographic details (age, sex, and location) were available, were included. ExposuresSARS-CoV-2 infection with Delta (B.1.617.2) variant and wild type (B.1) strain. Main Outcomes and MeasuresThe patient metadata containing details for demographic and vaccination status (two complete doses) of the COVID-19 patients with confirmed delta variant and WT (B.1) infections were analyzed [total number of cases (N) =9500, Ndelta=6238, NWT=3262]. Further, severity of the illness and mortality were assessed in subsets of patients. Final data were tabulated and statistically analyzed to determine age and sex based differences in chances of getting infection and the severity of illness, and post-vaccination infections were compared between wild type and delta variant strains. Graphs were plotted to visualize the trends. ResultsWith delta variant, in comparison to wild type (B.1) strain, higher proportion of lower age groups, particularly <20 year (0-9 year: 4.47% vs. 2.3%, 10-19 year: 9% vs. 7%) were affected. The proportion of women contracting infection were increased (41% vs. 36%). The higher proportion of total young (0-19 year, 10% vs. 4%) (p=.017) population and young (14% vs. 3%) as well as adult (20-59 year, 75% vs. 55%) women developed symptoms/hospitalized with delta variant in comparison to B.1 infection (p< .00001). The mean age of contracting infection [Delta, men=37.9 ({+/-}17.2) year, women=36.6 ({+/-}17.6) year; B.1, men=39.6 ({+/-}16.9) year and women= 40.1 ({+/-}17.4) year (p< .001)] as well as developing symptoms/hospitalization [Delta, men=39.6({+/-} 17.4) year, women=35.6 ({+/-}16.9) year; B.1, men=47({+/-}18) year and women= 49.5({+/-}20.9) year (p< .001)] was considerably lower. The total mortality was about 1.8 times higher (13% vs. 7%). Risk of death increased irrespective of the sex (Odds ratio: 3.034, 95% Confidence Interval: 1.7-5.2, p<0.001), however, increased proportion of women (32% vs. 25%) were died. Further, multiple incidences of delta infections were noted following complete vaccination. Conclusions and RelevanceThe increased involvement of young (0-19 year) and women, lower mean age for contracting infection and symptomatic illness/hospitalization, higher mortality, and frequent incidences of post-vaccination infections with delta variant compared to wild type strain raises significant epidemiological concerns. Key PointsO_ST_ABSQuestionC_ST_ABSDid SARS-CoV-2 B.1.617.2 (Delta) variant infections show varied demographic characteristics in comparison to wild type strains? FindingsIn this cross sectional study viral genomic sequences of 9500 COVID-19 patients were analyzed. As the key findings, increased involvement of young (0-19 year) and women, lower mean age for contracting infection and symptomatic illness/hospitalization, higher mortality, and frequent incidences of post-vaccination infections with delta variant in comparison to wild type (WT) strain (B.1) were observed. MeaningThe findings of this study suggest that delta variant has varied demographic characteristics reflecting increased involvement of the young and women, and increased lethality in comparison to wild type strains.
Subject(s)
COVID-19 , Hepatitis D , InfectionsABSTRACT
Younger age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent COVID waves, which are believed to be driven by new SARS-CoV-2 variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhanced key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the ACE2 receptor in the host cells, increased glycosylation of spike protein at antigenic sites, and proteolytic cleavage of the spike protein, leading to improved host cell entry and replication of the virus. The putative changes in the virus-host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host expressions of ACE2 and other proteases. The new variants can act more efficiently, and even on the lower concentrations of the viral entry receptor and associated proteases, thus can have more efficient host cell entry and greater replication resulting in higher viral load and prolonged viral shedding, and widespread tissue injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence that multiple new variants show reduced neutralization by natural and vaccine acquired antibodies, indicating repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.
Subject(s)
COVID-19 , Wounds and InjuriesABSTRACT
The pandemic of the coronavirus disease, 2019 (COVID-19) has caused millions to suffer from the disease and to die globally. Global epidemiological statistics reflect, significantly more numbers of men, aged, those suffering from co-morbidities, and people facing socio-economic inequalities, such as, racial/ethnic minorities, have been affected by COVID-19. Why the disease affects more to these specific population groups is intriguing the researchers globally. Emerging literature in COVID-19 indicates crucial role of factors intrinsic to the host behind such poor outcomes in selected individuals. Our comprehensive review of existing literature unravels a range of host factors which could have decisive role in patient outcomes in COVID-19, in terms of contracting infections, disease severity, and mortality, such as: age, sex, co-morbidities, genetic and phenotypic factors (e.g. polymorphisms or mutations, blood group etc.), clinical and laboratory parameters (at the time of hospital admission), cross protection from previous respiratory virus infections and childhood vaccinations, gut-microbiome, life style, habits and behavior (smoking and substance abuse), and socio-economic and systemic inequalities. In this article, we discuss in brief the most definitive and updated evidence for each of these host factors.
Subject(s)
COVID-19 , Anisocoria , Coronavirus InfectionsABSTRACT
Recent epidemiological studies analysing sex disaggregated patient data in COVID-19 across the world revealed a distinct sex bias in the disease morbidity as well as the mortality— both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of the molecular mechanisms leading the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce, however, existing evidence, for other viral infections, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we performed a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online literature sources including PubMed, Medline (EBSCO & Ovid), Google Scholar, Science Direct, Scopus, Bio Medical and Web of Science (WoS) were searched for the relevant data. Additionally, published literatures were also explored extensively. The time period taken to review the COVID-19 specific data was from December 1, 2019 to November 20, 2020. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as sex-linkage of viral host cell entry receptor and immune genes, sex hormone and gut microbiome mediated immune-modulation, as the possible reasons for the sex-based differences in patient outcomes in COVID-19.
Subject(s)
COVID-19 , Theileriasis , Severe Acute Respiratory SyndromeABSTRACT
Paucity of knowledge about SARS-CoV-2 specific virulence factors has greatly hampered therapeutic management of patients with COVID-19. Recently, a cluster of studies (including some preliminary reports) appeared, which presented empirical evidence for SARS-CoV-2 specific virulence factors that can explain key elements of COVID-19 pathology. In this article, we are presenting a summarized account of these newly reported studies.
Subject(s)
COVID-19ABSTRACT
Lack of standardised therapeutic approaches is arguably the significant contributor to the high burden of mortality observed in the ongoing pandemic of the Coronavirus disease, 2019 (COVID-19). Evidence is accumulating on SARS-CoV-2 specific immune cell dysregulation and consequent tissue injury in COVID-19. Currently, no definite drugs or vaccines are available against the disease; however initial results of the ongoing clinical trials have raised some hope. In this article, taking insights from the emerging empirical evidence about host-virus interactions, we deliberate upon plausible pathogenic mechanisms and suitable therapeutic approaches for COVID-19.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
IntroductionCOVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. Materials and MethodsThe data were downloaded from the Human Protein Atlas available at (https://www.proteinatlas.org/humanproteome/sars-cov-2) and the tissue specific expressions (both mRNA and protein) of ACE2 and TMPRSS2 as yielded from the studies with RNA sequencing and immunohistochemistry (IHC) were analyzed as a function of the various components of the digestive tract. A digestive system specific functional enrichment map of ACE2 gene was created using g:profiler (https://biit.cs.ut.ee/gprofiler/gost) utility and the data were visualized using Cytoscape software, version 3.7.2 (https://cytoscape.org/). ResultsThe correlated expression (transcriptomic and proteomic) of ACE2 (to which SARS-CoV-2 binds through the S-spike) was found to be enriched in the lower gastrointestinal tract (GIT) (highest in small intestine, followed by colon and rectum), and was undetectable in the upper GIT components: mouth cavity (tongue, oral mucosa, and salivary glands), esophagus, and stomach. High expression of ACE2 was noted in the glandular cells as well as in the enterocytes in the lining epithelium (including brush border epithelium). Among other digestive system organs, Gall bladder (GB) showed high expression of ACE2 in glandular cells, while any protein expression was undetectable in liver and pancreas. TMPRSS2 was found enhanced in GIT and exocrine glands of pancreas, and co-localized with ACE2 in enterocytes. ConclusionsBased on the findings of this study and supportive evidence from the literature we propose that a SARS-CoV-2 binding with ACE2 mediates dysregulation of the sodium dependent nutrient transporters and hence may be a plausible basis for the digestive symptoms in COVID-19 patients. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY
Subject(s)
Diabetes Mellitus , COVID-19 , Nystagmus, PathologicABSTRACT
The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.