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SARS-CoV-2 infection: molecular mechanisms of severe outcomes to suggest therapeutics.

ABSTRACT: Introduction:The year 2020 was defined by the 29,903 base pairs of RNA that codes for the SARS-CoV-2 genome. SARS-CoV-2 infects humans to cause COVID-19, spreading from patient-to-patient yet impacts patients very divergently.Areas covered: Within this review, we address the known molecular mechanisms and supporting data for COVID-19 clinical course and pathology, clinical risk factors and molecular signatures, therapeutics of severe COVID-19, and reinfection/vaccination. Literature and published datasets were reviewed using PubMed, Google Scholar, and NCBI SRA tools. The combination of exaggerated cytokine signaling, pneumonia, NETosis, pyroptosis, thrombocytopathy, endotheliopathy, multiple organ dysfunction syndrome (MODS), and acute respiratory distress syndrome (ARDS) create a positive feedback loop of severe damage in patients with COVID-19 that impacts the entire body and may persist for months following infection. Understanding the molecular pathways of severe COVID-19 opens the door for novel therapeutic design. We summarize the current insights into pathology, risk factors, secondary infections, genetics, omics, and drugs being tested to treat severe COVID-19.Expert opinion: A growing level of support suggests the need for stronger integration of biomarkers and precision medicine to guide treatment strategies of severe COVID-19, where each patient has unique outcomes and thus require guided treatment.

SUBMITTER: Hartog N

PROVIDER: S-EPMC8022340 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and Objectives: The severe forms of SARS-CoV-2 pneumonia are associated with acute hypoxic respiratory failure and high mortality rates, raising significant challenges for the medical community. The objective of this paper is to present the importance of early quantitative evaluation of radiological changes in SARS-CoV-2 pneumonia, including an alternative way to evaluate lung involvement using normal density clusters. Based on these elements we have developed a more accurate new predictive score which includes quantitative radiological parameters. The current evolution models used in the evaluation of severe cases of COVID-19 only include qualitative or semi-quantitative evaluations of pulmonary lesions which lead to a less accurate prognosis and assessment of pulmonary involvement. Materials and Methods: We performed a retrospective observational cohort study that included 100 adult patients admitted with confirmed severe COVID-19. The patients were divided into two groups: group A (76 survivors) and group B (24 non-survivors). All patients were evaluated by CT scan upon admission in to the hospital. Results: We found a low percentage of normal lung densities, PaO2/FiO2 ratio, lymphocytes, platelets, hemoglobin and serum albumin associated with higher mortality; a high percentage of interstitial lesions, oxygen flow, FiO2, Neutrophils/lymphocytes ratio, lactate dehydrogenase, creatine kinase MB, myoglobin, and serum creatinine were also associated with higher mortality. The most accurate regression model included the predictors of age, lymphocytes, PaO2/FiO2 ratio, percent of lung involvement, lactate dehydrogenase, serum albumin, D-dimers, oxygen flow, and myoglobin. Based on these parameters we developed a new score (COV-Score). Conclusions: Quantitative assessment of lung lesions improves the prediction algorithms compared to the semi-quantitative parameters. The cluster evaluation algorithm increases the non-survivor and overall prediction accuracy.COV-Score represents a viable alternative to current prediction scores, demonstrating improved sensitivity and specificity in predicting mortality at the time of admission.

Project description:ObjectiveTo estimate the proportion of SARS-CoV-2 infected children experiencing hospitalization, intensive care unit (ICU) admission, severe outcomes, and death.Data sourcesPubMed, Embase, and MedRxiv were searched for studies published between December 1, 2019 and May 28, 2021. References of relevant systematic reviews were also screened.Study selectionWe included cohort or cross-sectional studies reporting on at least one outcome measure (i.e., hospitalization, ICU admission, severe outcomes, death) for ≥100 children ≤21 years old within 28 days of SARS-CoV-2 positivity; no language restrictions were applied.Data extraction and synthesisTwo independent reviewers performed data extraction and risk of bias assessment. Estimates were pooled using random effects models. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.Main outcomes and measuresPercentage of SARS-CoV-2 positive children experiencing hospitalization, ICU admission, severe outcome, and death.Results118 studies representing 3,324,851 SARS-CoV-2 infected children from 68 countries were included. Community-based studies (N = 48) reported that 3.3% (95%CI: 2.7-4.0%) of children were hospitalized, 0.3% (95%CI: 0.2-0.6%) were admitted to the ICU, 0.1% (95%CI: 0.0-2.2%) experienced a "severe" outcome and 0.02% (95%CI: 0.001-0.05%) died. Hospital-based screening studies (N = 39) reported that 23.9% (95%CI: 19.0-29.2%) of children were hospitalized, 2.9% (95%CI: 2.1-3.8%) were admitted to the ICU, 1.3% (95%CI: 0.5-2.3%) experienced a severe outcome, and 0.2% (95%CI: 0.02-0.5%) died. Studies of hospitalized children (N = 31) reported that 10.1% (95%CI: 6.1-14.9%) of children required ICU admission, 4.2% (95%CI: 0.0-13.8%) had a severe outcome and 1.1% (95%CI: 0.2-2.3%) died. Low risk of bias studies, those from high-income countries, and those reporting outcomes later in the pandemic presented lower estimates. However, studies reporting outcomes after May 31, 2020, compared to earlier publications, had higher proportions of hospitalized patients requiring ICU admission and experiencing severe outcomes.Conclusion and relevanceAmong children tested positive for SARS-CoV-2, 3.3% were hospitalized, with rates being higher early in the pandemic. Severe outcomes, ICU admission and death were uncommon, however estimates vary by study population, pandemic timing, study risk of bias, and economic status of the country.Systematic review registrationPROSPERO, identifier [CRD42021260164].

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SARS-CoV-2 infection: molecular mechanisms of severe outcomes to suggest therapeutics.

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