Clinical Features and Management of COVID-19

Much has been learnt about severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) since the beginning of theCoronavirus disease 2019 (COVID-19) pandemic, including its clinical manifestations, diagnosis, and management. Unlike its zoonotic predecessor SARS-CoV which was largely a symptomatic disease where fever was a hallmark, a significant proportion of SARS-CoV-2 infections can be asymptomatic (40%), while severe disease (requiring oxygen supplementation or ventilatory support) occurs in approximately 20%, and mortality in about 2% of infected patients. Extra-pulmonary COVID-19 manifestations are also more protean, compared to SARS. Supportive care is the mainstay of treatment for most patients, but for those who progress to severe COVID-19, antivirals such as remdesivir and immunomodulatory treatment (such as corticosteroids or theJAK-inhibitor, baricitinib) may improve outcomes. While further advances in the management of COVID-19 are anticipated (including novel therapies), prevention of infection through public health measures (including vaccination), will remain as vital facets in confronting this pandemic. © 2023 by World Scientific Publishing Co. Pte. Ltd.

Copeptin as a marker of COVID-19 severity: A systematic review and meta-analysis

Introduction: Infection with SARS-CoV-2 is particularly hazardous in patients with cardiovascular pathology, diabetes or chronic lung disease. Arginine vasopressin (AVP), an antidiuretic hormone secreted in response to hemodynamic and osmotic disturbances plays a crucial role in maintenance of cardiovascular homeostasis. Copeptin has shown promising results regarding its utility in prediction of morbidity and mortality of COVID-19. Therefore, we conducted a meta-analysis to evaluate the role of copeptin in risk stratification in COVID-19. Methods: This study was designed as a systematic review and meta-analysis. We systematically searched the following databases: Scopus, Web of Science, PubMed, EMBASE, Cochrane Library through September 10th, 2022. Methodological quality was assessed using the Cochrane risk-of-bias tool. Results: Pooled analysis of four trials showed that mean copeptin plasma concentrations were higher in patients with severe course of COVID-19 than in patients with non-severe course of the disease (26.64 ± 13.59 vs. 16.75 ± 6.13, respectively;MD=9.39;95%CI: 1.38 to 17.40;I2=99%;p=0.02). Furthermore, higher copeptin concentrations in COVID-19 patients who died than in those who survived (13.25 ± 3.23 vs. 44.65 ± 26.92, respectively;MD=-31.40;95%CI:-42.93 to-19.87;p<0.001). Discussion: Results from the present meta-analysis revealed that increased copeptin plasma concentrations found in COVID-19 patients are associated with the severity of the disease. Copeptin may assist in early identification of COVID-19 progression and possibly in prediction of adverse outcomes, thus its use in risk stratification could be beneficial. Take-home message: Copeptin may assist in early identification of COVID-19 progression and possibly in prediction of adverse outcomes, thus its use in risk stratification could be beneficial. © 2022 by the authors.

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis.

BACKGROUND: The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells. AIM: To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality. METHODS: A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine's MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: "COVID-19", "proton pump inhibitors", "PPIs", "SARS-CoV-2", "outcomes", "severity" and "mortality". The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available. RESULTS: A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) (P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) (P = 0.286). CONCLUSION: Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein.

There is increasing evidence that ACE2 gene polymorphism can modulate the interaction between ACE2 and the SARS-CoV-2 spike protein affecting the viral entry into the host cell, and/or contribute to lung and systemic damage in COVID-19. Here we used in silico molecular docking to predict the effects of ACE2 missense variants on the interaction with the spike protein of SARS-CoV-2. HDOCK and FireDock simulations identified 6 ACE2 missense variants (I21T, A25T, K26R, E37K, T55A, E75G) with higher affinity for SARS-CoV-2 Spike protein receptor binding domain (RBD) with respect to wild type ACE2, and 11 variants (I21V, E23K, K26E, T27A, E35K, S43R, Y50F, N51D, N58H, K68E, M82I) with lower affinity. This result supports the hypothesis that ACE2 genetic background may represent the first "genetic gateway" during the disease progression.

SARS-CoV-2 (COVID-19) infection in pregnant women: characterization of symptoms and syndromes predictive of disease and severity through real-time, remote participatory epidemiology.

OBJECTIVE: To test whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity. To extend previous investigations on hospitalized pregnant women to those who did not require hospitalization. DESIGN: Observational study prospectively collecting longitudinal (smartphone application interface) and cross-sectional (web-based survey) data. SETTING: Community-based self-participatory citizen surveillance in the United Kingdom, Sweden and the United States of America. POPULATION: Two female community-based cohorts aged 18-44 years. The discovery cohort was drawn from 1,170,315 UK, Sweden and USA women (79 pregnant tested positive) who self-reported status and symptoms longitudinally via smartphone. The replication cohort included 1,344,966 USA women (134 pregnant tested positive) who provided cross-sectional self-reports. METHODS: Pregnant and non-pregnant were compared for frequencies of symptoms and events, including SARS-CoV-2 testing and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. RESULTS: Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity. Pregnant were more likely to have received testing than non-pregnant, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with the syndromic severity in pregnant hospitalized women. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among all non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant women who were hospitalized. CONCLUSIONS: Symptom characteristics and severity were comparable among pregnant and non-pregnant women, except for gastrointestinal symptoms. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.