Intravenous High-dose Anakinra Drops Venous Thrombosis and Myocardial Infarction in Severe and Critical COVID-19 Patients: A Propensity Score Matched Study (preprint)

Introduction: In our study, we aimed to evaluate the effect of high-dose intravenous anakinra treatment on the development of thrombotic events in severe and critical COVID-19 patients. Material and methods: This retrospective observational study was conducted at a tertiary referral center in Aksaray, Turkey. The study population consisted of two groups as follows; the patients receiving high-dose intravenous anakinra (anakinra group) added to background therapy and the patients treated with standard of care (SoC) as a historical control group. Age, gender, mcHIS scores, and comorbidities such as DM, HT, and CHD of the patients were determined as the variables to be matched. Results: We included 114 patients in SoC and 139 patients in the Anakinra group in the study. Development of any thromboembolic event (5% vs 12.3%, p = 0.038; OR:4.3) and PTE (2.9% vs 9.6%, p = 0.023; OR:5.1) were lower in the Anakinra group than SoC. No patient experienced CVA and/or clinically evident DVT both in two arms. After 1:1 PS matching, 88 patients in SoC and 88 patients in the Anakinra group were matched and included in the analysis. In survival analysis, the development of any thromboembolic event, PTE, and MI were higher in SoC compared to Anakinra. Survival rate was also lower in patients with SoC arm than Anakinra in patients who had any thromboembolic event as well as MI. Conclusion: In our study, the development of thrombosis was associated with hyperinflammation in patients with severe and critical COVID-19. Intravenous high-dose anakinra treatment decreases both venous and arterial events in patients with COVID-19.

Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery (preprint)

Objective: Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. Methods: In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. Results: In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-{gamma} response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Conclusions: Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.

Myotonic dystrophy type 1 in the COVID-19 era.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adults. People with DM1 might represent a high-risk population for respiratory infections, including COVID-19. Our aim was to evaluate the characteristics of COVID-19 infection and vaccination rate in DM1 patients. METHODS: This cross-sectional cohort study included 89 patients from the Serbian registry for myotonic dystrophies. Mean age at testing was 48.4 ± 10.4 years with 41 (46.1%) male patients. Mean duration of the disease was 24.0 ± 10.3 years. RESULTS: COVID-19 infection was reported by 36 (40.4%) DM1 patients. Around 14% of patients had a more severe form of COVID-19 requiring hospitalization. The severity of COVID-19 was in accordance with the duration of DM1. A severe form of COVID-19 was reported in 20.8% of patients who were not vaccinated against SARS-CoV-2 and in none of the vaccinated ones. The majority of 89 tested patients (66.3%) were vaccinated against SARS-CoV-2. About half of them (54.2%) received three doses and 35.6% two doses of vaccine. Mild adverse events after vaccination were recorded in 20.3% of patients. CONCLUSIONS: The percentage of DM1 patients who suffered from COVID-19 was like in general population, but with more severe forms in DM1, especially in patients with longer DM1 duration. The study indicated an overall favorable safety profile of COVID-19 vaccines among individuals with DM1 and its ability to protect them from severe COVID-19.

De-Contextual Communication: Unified System Information Theory to Investigate Usage Intention of Metaverse Technology in Digital Library Services (preprint)

During the COVID-19 pandemic, many higher education institutions chose to implement online distance learning, and some deployed metaverse technology as a virtual reality learning approach.   However, unclear factors hampered usage intentions and adoption, and no study has been conducted to date to establish the course. Thus, this study we investigate factors influencing usage intentions of metaverse technology in digital library service in higher learning institution using unified system information theory.  An online survey was administered to university staff and students, and responses were recorded using the link-scale. We compute various factors influencing metaverse technology usage intention in library services using transformation models (UTAUT, DM, ISS, and TTF). The model parameters were then empirically tested using PLS-SEM to determine the factors that influence usage intention of metaverse technology. The findings show that, depending on the user's intended task, perceptions of system use, perceived interaction, perceived usefulness, and perceived ease of use influence users' intentions to use metaverse technology in digital library systems.

COVID-19 and myotonic dystrophy: Case reports and systematic review.

INTRODUCTION: Steinert's disease is a rare genetic disorder characterized by progressive myotonia and multi-organ damage. It is associated with respiratory and cardiological complications often leading patients to exitus. These conditions are also traditional risk factors for severe COVID-19. SARS-CoV-2 has affected people with chronic diseases, but the impact on people with Steinert's disease is poorly defined, with only a few reported and described. More data are needed to understand whether this genetic disease is a risk factor for more serious evolution or death in patients with COVID-19. METHODOLOGY: The study describes two cases of patients with SD and COVID-19 and summarizes available evidence of the clinical outcome of COVID-19 in patients with Steinert's disease, by performing a systematic review of the literature (following PRISMA statements and performing PROSPERO registration). RESULTS: Overall, 5 cases were retrieved from the literature review, with a median age of 47 years, of whom 4 had advanced SD and unfortunately died. By contrast, the 2 patients from our clinical practice and 1 from literature had a good clinical outcomes. Mortality ranged from 57% (all cases) to 80% (only literature review). CONCLUSIONS: There is a high mortality rate in patients with both Steinert's disease and COVID-19. It highlights the importance of strengthening prevention strategies, especially vaccination. All SD with SARS-CoV-2 infection/COVID-19 patients should be identified early and treated to avoid complications. It is still unknown which treatment regimen is best to use in those patients. Studies on a greater number of patients are necessary to provide clinicians with further evidence.

Network Meta-Analysis on the Mechanisms underlying Type 2 Diabetes Augmentation of COVID-19 Pathologies (preprint)

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. SARS-CoV-2 virus is internalized by surface receptors, e.g., angiotensin-converting enzyme-2 (ACE2). Clinical reports suggest that non-insulin dependent diabetes mellitus (DM-II) may enhance COVID-19. This study investigated how DM-II augments COVID-19 complications through molecular interactions with cytokines/chemokines, using QIAGEN Ingenuity Pathway Analysis (IPA) and CLC Genomics Workbench 22 (CLCG-22). RNA-sequencing of islet β-cell genomes through CLCG-22 (SRA SRP287500) were analyzed to identify differential expression of islet β-cell genes (Iβ-CG). IPA’s QIAGEN Knowledge Base (QKB) was also used to retrieve 88 total molecules shared between DM-II and SARS-CoV-2 infection to characterize and identify Iβ-CG, due to close association with DM-II. Molecules directly associated with ACE2 and cytokines/chemokines were also identified for their association with SARS-CoV-2 infection. Using IPA, 3 Iβ-CG in common with both diseases, SCL2A2, PPARγ, and CPLX8, were downregulated by DM-II. Their downregulation occurred due to increased activity of cytokines/chemokines and ACE2. Collectively, this network meta-analysis demonstrated that interaction of SARS-CoV-2 with ACE2 could primarily induce endothelial cell dysfunction. Identification of common molecules and signaling pathways between DM-II and SARS-CoV-2 infection in this study may lead to further discovery of therapeutic measures to simultaneously combat both diseases.

COVID-19 Autopsies, Oklahoma, USA.

OBJECTIVES: To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. METHODS: Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. RESULTS: A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. CONCLUSIONS: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

Safety and immunogenicity of mRNA COVID-19 vaccine in inpatients with muscular dystrophy.

INTRODUCTION/AIMS: Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease-2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD. METHODS: We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28 to 30 days after the second dose, and antibody titers were measured. RESULTS: Overall, 104 (60.8%) and 115 (67.6%) patients had side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.12 to 0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI, 159.3 to 358.7). Older age (relative risk [RR] = 0.97; 95% CI, 0.95 to 0.99) and bedridden state (RR = 0.27; 95% CI, 0.14 to 0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR = 0.42; 95% CI, 0.21 to 0.85). DISCUSSION: COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs.

Dual Multi-scale Mean Teacher Network for Semi-supervised Infection Segmentation in Chest CT Volume for COVID-19 (preprint)

Automated detecting lung infections from computed tomography (CT) data plays an important role for combating COVID-19. However, there are still some challenges for developing AI system. 1) Most current COVID-19 infection segmentation methods mainly relied on 2D CT images, which lack 3D sequential constraint. 2) Existing 3D CT segmentation methods focus on single-scale representations, which do not achieve the multiple level receptive field sizes on 3D volume. 3) The emergent breaking out of COVID-19 makes it hard to annotate sufficient CT volumes for training deep model. To address these issues, we first build a multiple dimensional-attention convolutional neural network (MDA-CNN) to aggregate multi-scale information along different dimension of input feature maps and impose supervision on multiple predictions from different CNN layers. Second, we assign this MDA-CNN as a basic network into a novel dual multi-scale mean teacher network (DM${^2}$T-Net) for semi-supervised COVID-19 lung infection segmentation on CT volumes by leveraging unlabeled data and exploring the multi-scale information. Our DM${^2}$T-Net encourages multiple predictions at different CNN layers from the student and teacher networks to be consistent for computing a multi-scale consistency loss on unlabeled data, which is then added to the supervised loss on the labeled data from multiple predictions of MDA-CNN. Third, we collect two COVID-19 segmentation datasets to evaluate our method. The experimental results show that our network consistently outperforms the compared state-of-the-art methods.

Understanding the Perseverance of the Muscular Dystrophy Community One-Year into the COVID-19 Pandemic.

INTRODUCTION: In this study, we examined the long-term social and health impacts of the coronavirus disease 2019 (COVID-19) pandemic on people with muscular dystrophy. METHODS: We modified our prior COVID-19 Impact Survey to assess impacts from the continuing pandemic using feedback from muscular dystrophy experts, patients, and advocacy group/registry representatives. The survey assessed COVID-19 medical history, and the effects of the pandemic on social aspects, muscle disease, and medical care. We also used the validated 10-item Perceived Stress Scale. The de-identified, electronic survey was distributed to adults with muscular dystrophy via international patient registries and advocacy group websites from February 8, 2021 to March 22, 2021. RESULTS: Respondents (n = 1243 : 49% Facioscapulohumeral Muscular Dystrophy (FSHD); 43% Myotonic Dystrophy (DM), and 8% Limb-Girdle Muscular Dystrophy (LGMD)) were mostly women and middle-aged (range 18-90 years). Rates of COVID-19 infections were low at 8% with zero deaths. Reported recovery times were also short with only 9% reporting a recovery period greater than eight weeks, and 7% requiring hospitalization with one individual requiring a ventilator. Major challenges reported during the pandemic included stress management, particularly for those with LGMD (27%), and wearing a mask (24%). The majority reported a slight worsening of their disease state. Respondents reported moderate stress levels (stress score = 16.4; range = 0-39), with higher stress levels reported by women and those under age 30 years. Seventy-percent of participants who had telemedicine visits were satisfied with the encounters; however, most reported a preference for in-person visits. CONCLUSIONS: People with muscular dystrophy found ways to manage their stress and overcome obstacles during the COVID-19 pandemic. COVID-19 infection rates and medical complications were similar to a general population. Telemedicine visits may have a more permanent role in care.

Baseline Peripheral Blood Counts and Outcomes in Patients Presenting with COVID-19 (preprint)

Background: SARS COV-2 pandemic has significant impact on hematopoietic system. Objective: To report the incidence and pattern of baseline hematological parameters in patients with COVID-19 and their association with severity of disease and outcome. Methods: Retrospective observational study. Results: A total of 440 patients were included in the study. The mean age of the study cohort was 47.5 years. Fifty percent of patients had at least 1 comorbidity. ICU stay was required in 125 (39.6%) patients. Overall mortality in the study cohort was 3.52%. The average age of patients who died was significantly higher than that of patients who were alive (65.1 years vs 46.5 years; p= 0.000). DM, HTN, CAD and CKD were all associated with higher incidence of ICU stay and mortality. Lymphopenia < 1x109 was observed in 24.3% and eosinopenia was noted in 44.3% patients. Leukocytosis>11x109 was seen in 8.2 % of patients. The median neutrophil lymphocyte ratio (NLR) of whole cohort was 2.63. NLR, Lymphopenia, eosinopenia, leucocytosis, D dimer, lactate dehydrogenase (LDH), ferritin and IL6 levels all were associated with need for ICU transfer and mortality. Hemoglobin, red cell distribution width (RDW), PT and aPTT correlated with need for ICU transfer but not with mortality. Ferritin cutoff >751 ng/ml and IL6 levels >64pg/ml was able to identify all deaths. Ferritin (0.989) and IL-6 (0.985) had very high negative predictive value. Conclusions: Peripheral blood counts at time of hospitalization is a simple tool to predict outcomes in patients admitted with Covid-19.

COVID-19 Is A Contributing Risk Factor For Development Of DKA In Typei DM. (preprint)

Background: Viral infections trigger type 1 diabetes (T1D) in susceptible children, and may increase incidence of T1D and/or diabetic ketoacidosis (DKA) during the COVID-19 pandemic.We aimed to describe the frequency of diabetic ketoacidosis in children and to determine if COVID contribute to the risk of diabetic ketoacidosis. Objective: To study the incidence of DKA due to new-onset T1D during the COVID-19 pandemic, and whether SARS-CoV-2 infection is a triggering factor for the development of DKA in type I DM in Minia university hospital,Egypt . Methods: This retrospective cohort study of children admitted to PICU and inpatient wards due to new-onset T1D or due to DKA and diagnosed as have positive covid -19 in Mina University Hospital from 1 April to 31 October 2021. We compared the incidence, number and characteristics of children with newly diagnosed T1D and DKA during the pandemic periods. Results: An increase in the number of children with newly diagnosed type 1 diabetes (T1D) has been reported during the COVID-19 pandemic and more children with new-onset T1D now present with severe diabetic ketoacidosis (DKA). Conclusion: COVID contribute to the risk of diabetic ketoacidosis and new onset T1D among childern

Impact of IFN- β1a in treatment of a COVID-19 Patient with Beta Thalassemia and Diabetes Mellitus: A Case Report (preprint)

The present study aimed to report a case with COVID-19 with a history of chronic diseases, beta thalassemia intermedia, and DM. A 25-year-old man visited with covid 19 and treatment with IFN-β1a. According to the present report, the use of IFN-β1a was effective as a treatment option for COVID-19.

[Steinert's disease and refusal to treatment]. / Enfermedad de Steinert y rechazo de la actuación médica.

TITLE: Enfermedad de Steinert y rechazo de la actuación médica.

Death review caused by Covid 19 in Bangladesh (preprint)

Introduction: COVID- 19 pandemic had taken away lots of human life prematurely worldwide and death laid its icy hands also on Bangladesh. So, objectives of this study were to explore the monthly distributions, age, sex, co-morbidities, localities and duration of hospital stay among the COVID death cases. Methods: In this observational study six months hospital death files were collected and explored for monthly distributions, age, sex, co-morbidities, localities and hospital stay. RT-PCR positive confirmed 113 COVID deaths were enrolled and suspected COVID deaths were excluded. Ethical clearance from the hospital authority was taken before hand. Data was compiled and analyzed by SPSS-20. Results: There was a low frequency of death in May-2021 and October-2021(7.1% and 2.7% respectively) but more during June -2021 to September 2021 (12.4%, 16.8%, 42.5% and 18.6% respectively). Female deaths were little more than male deaths(53.1% vs 46.9%). Age more than 51 years were the most vulnerable where 26(23%) deaths were at age group 51- 60 years, 39(34.5%) deaths were at 61-70 years and 22(19.4%) deaths were more than 71 years. Mean age of death was found 60.66 years and mean duration of hospital stay was found 9.45 days. Maximum duration of hospital stay was 45 days for one patient. Co-morbidities of death cases revealed 52(46.00%) patients had DM and HTN both, 17(15.0%) patients had HTN, 16(14.1%) had DM, 3(2.6%) had BA and COPD, 4(3.5%) had CKD, 2(1.7%) had cancer, 3(2.6%) had CVD, 19(16.8%) had IHD and 16(14.1%) patients had no co-morbidities. Locality of the death cases revealed 44(38.9%) came from rural areas and 69(61.1%) came from urban areas. Conclusion: Higher age group and multiple co-morbidities specially DM, HTN and IHD were related with COVID deaths mostly found in our study.

Association of Underlying Comorbidities and progression of COVID-19 Infection Among 2586 Patients Hospitalized in the National Capital Region of India: A Retrospective Cohort Study (preprint)

Objectives: This study is conducted to observe the association of diabetes (DM), hypertension (HTN), and chronic kidney disease on the prognosis and mortality of COVID-19 infection in hospital admitted patients. Methods: This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. the burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis. Results: A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in comorbidity, the risk of ICU admission and mortality increases. Conclusion: Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Predominance of Distinct Autoantibodies in Response to SARS-CoV-2 Infection (preprint)

BackgroundImproved knowledge regarding the prevalence and clinical significance of the broad spectrum of autoantibodies triggered by SARS-CoV2 infection can clarify the underlying pathobiology, enhance approaches to evaluating heterogeneity of COVID-19 clinical manifestations, and potentially guide options for targeting immunosuppressive therapy as the need for more effective interventions continues to evolve. In this study, we sought to determine the prevalence of autoimmune antibodies in diverse cohort of SARS-CoV-2 positive healthcare workers and measure the extent to which factors associated with triggered autoimmunity are activated even following mild and asymptomatic infection. MethodsAntigen microarrays were used to profile reactivity of IgG autoantibodies against 91 proteins and cytokines based on autoantibody profiling studies in autoimmune diseases. ResultsIn this discovery screening study, we found that 90% of the IgG positive individuals demonstrated reactivity to at least one autoantibody. When compared to results of the same assays conducted on samples from pre-COVID-19 controls, our primary cohort of individuals with SARS-CoV-2 IgG antibody positivity had significantly elevated IgG against twelve additional proteins including CHD3, CTLA4, HARS, IFNA4, INS, MIF, MX1, RNF41, S100A9, SRP19, TROVE2, and VEGFA. These findings confirmed that all severity levels of SARS-CoV-2 infection, even asymptomatic infections, trigger a robust and diverse autoimmune response; our results also highlight the utility of multiparametric autoantibody detection in this setting. InterpretationTaken together, our findings underscore the serological diversity underlying the clinical heterogeneity of COVID-19 infection and its sequelae, including the long-Covid phenotypes. FundingThis work was supported in part by Cedars-Sinai Medical Center (JEE; SC), the Erika J Glazer Family Foundation (JEE; JEVE; SC), CSMC Precision Health Grant (JFB), the F. Widjaja Family Foundation (JGB, GYM, DM), the Helmsley Charitable Trust (JGB, GYM, DM), and NIH grants K23-HL153888 (JEE) and DK062413 (DPBM). RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSCurrently, several studies have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID-19). In contrast to cytokine storms, which tend to cause systemic, short-duration problems, autoantibodies (AABs) are thought to result in targeted, longer-term damage and development of autoimmune diseases. Added value of this studyAccording to our knowledge, we evaluated the largest number of protein antigens to characterize the prevalence and heterogeneity of the AABs signature in SARS-CoV-2 convalescent individuals. We examined autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease to acknowledge the existence of AABs even among those who had mild-to-moderate or no symptoms during their illness, as a hallmark of ongoing long-COVID syndrome. Through our analysis we suggest that VEGFA, MIF, IFNA4, SPP1 and APOH could be used as hallmark for SARS-CoV-2 infection and activation of the autoimmune system. Implications of all the available evidenceOur study comprehensively characterized the heterogeneity of the AABs signature in SARS-CoV-2 convalescent individuals. The results established a list of diagnostic signatures and potential therapeutic targets for long-Covid-19 patients although follow-up long-term studies are required. We believe that our findings will serve as a valuable resource, to drive further exploration of long-COVID syndrome pathogenesis.

COVID-19 OUTCOMES IN PREGNANCY: A REVIEW OF 275 SCREENED STUDIES (preprint)

In December 2019, a novel strain of severe acute respiratory syndrome (SARS-CoV-2), was declared as a cause of respiratory illness, called coronavirus 2019 (COVID-19), characterized by fever and cough. In diagnostic imaging, the afflicted population showed pathognomonic findings of pneumonia. What started out as an epidemic in China, rapidly spread across geographical locations with a significant daily increase in the number of affected cases. According to the World Health Organization (WHO) reports, the range of worldwide mortality is 3 to 4%. Maternal adaptations and immunological changes predispose pregnant women to a prolonged and severe form of pneumonia, which results in higher rates of maternal, fetal, and neonatal morbidity and mortality. There is limited data about the consequences of COVID-19 in pregnancy, thereby limiting the prevention, counseling, and management of these patients. The objective of this literature review is to explore pregnancy and perinatal outcomes of COVID-19, complications, morbidity, and mortality in this sub-population. We conducted a literature review pertaining to COVID-19 and pregnancy in databases such as: PubMed, Google Scholar, and Science Direct. The studies we chose to focus on were systematic reviews, meta-analysis, case series, and case reports. Twenty four articles were reviewed regarding COVID-19 and pregnancy, complications and their outcomes. Due to immunological changes during pregnancy as evidenced by the flaring of auto-immune diseases; pregnant women may be at an increased risk for infection. Women (19.7%) who had underlying comorbidities such as gestational DM, HTN, hypothyroidism, and autoimmune disease, COPD, or HBV infection were considered high risk. The most common maternal outcomes were premature rupture of membranes (PROM) and pre-eclampsia. Asthma was the most common comorbidity associated with maternal mortality. The most common neonatal complications were fetal distress leading to NICU admissions and preterm birth <37 weeks. The most common laboratory changes were elevated CRP and lymphocytopenia. Most patients underwent C-section due to their underlying comorbidities. Pregnant and lactating women did not shed viral particles through their vaginal mucus and milk, as evidenced by negative nucleic-acid tests of these secretions. Neonatal infections as demonstrated by positive RT-PCR were rare, but direct evidence supporting intrauterine transmission was not confirmed. Direct evidence indicating vertical transmission of COVID-19 is not available, but risk for transmission cannot be ruled out. Pregnant women should be closely monitored due to increased risk of adverse outcomes.

Older Age and Frailty Are Associated With Higher Mortality but Lower Intensive Care Unit Admission Among Adults Admitted to Canadian Hospitals With COVID-19: A Report From the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance Network (preprint)

Background: We report characteristics and outcomes of adults admitted to Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network hospitals with COVID-19 in 2020. Methods: Adult patients with laboratory-confirmed COVID-19 admitted to eleven sites in Ontario, Quebec, Alberta and Nova Scotia up to December 31, 2020 were enrolled in this prospective observational cohort study. Age, sex, demographics, housing, exposure characteristics, Clinical Frailty Scale, comorbidities, and outcomes including length of stay, intensive care unit (ICU) admission, mechanical ventilation, and survival were conducted. Descriptive analyses and multivariable logistic regressions were conducted. Findings: Among 2011 patients, mean age was 71·0 (range 19-105) years. 45·7% were women and 74·0% were white. 21·5% were admitted from Assisted Living facilities, 8·2% from long term care, and 2·1% from homeless shelters. The full spectrum of frailty was represented in both younger and older age groups. The majority (61·7% of adults <65 and 91·2% of those >=65) had at least one underlying comorbidity and 27·2% had obesity. Mortality was 14·3% among those not admitted to ICU, and 24·6% for those admitted to ICU. Older age and higher frailty were associated with reduced ICU admission but increased mortality. Obesity was independently associated with ICU admission but not with death. Associations between underlying comorbidities and adverse outcomes were attenuated but persisted when adjusting for frailty.Interpretation: Frailty and age were independent predictors of lower ICU use and higher mortality; when accounting for frailty, obesity was not an independent predictor of mortality, and associations of comorbidities with mortality were weakened.Funding Statement: Funding was provided by the Public Health Agency of Canada and the Canadian Institutes of Health Research.Declaration of Interests: MKA reports grant funding from the Public Health Association of Canada, CIHR, Canadian Frailty Network, Sanofi Pasteur and GSK group of companies, and payments from Pfizer, Sanofi Pasteur and Seqirus outside the submitted work. AM reports payments from GSK, Seqirus and Sanofi Pasteur, outside the submitted work. JEM reports payments from RestorBio, Sanofi, GSK, Merck and Medicago outside of the submitted work. TFH reports grants from Pfizer and GSK. ML reports payments from Sanofi, Medicago, Sequirus, and Pfizer outside the submitted work. SAM reports grants and payments from Pfizer, GSK, Merck, Novartis and Sanofi, outside the submitted work. JG, JJL, GB, LV, ME, DM-C, AA, KW, ST, SS, AMc and KK report no conflicts of interest.Ethics Approval Statement: The protocol for active COVID-19 surveillance has been approved by each local site’s Research Ethics Board.