Prior Statin vs In-Hospital Statin Usage in Severe COVID-19: Review and Meta-Analysis.

Studies have shown that statins can decrease COVID-19 mortality in hospitalized patients. This paper evaluates these studies and reviews the possible mechanism of how statins modulate COVID-19 severity. Meta-analysis of 31 retrospective studies demonstrated a reduction in mortality rate among statin users (OR 0.69, 95% CI 0.56-0.86, P = 0.0008) (HR 0.83, 95% CI 0.72-0.95, P = 0.0078). Meta-analysis of 8 randomized control studies demonstrated a nonsignificant reduction in mortality (OR 0.90, 95% CI 0.69-1.18, P = 0.461), including 4 studies with medications other than statins, and 4 studies with only statins (OR 0.88, 95% CI 95% CI 0.64-1.21, P = 0.423). Prolonged statin usage decreases the extracellular localization of ACE2, along with statins' immunomodulating effects and reduction of oxidative stress, decreases COVID-19 mortality. Hospitalized patients with COVID-19 should continue statin treatment if previously prescribed, and patients should not be started on statins, as they do not seem to provide any mortality benefit.

HIGHER HDL CHOLESTEROL LEVELS DECREASE SUSCEPTIBILITY TO COVID-19 INFECTION

Therapeutic Area ASCVD/CVD Risk Factors Background Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum lipids, such as high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Recent meta-analyses have shown an association between low serum lipid levels at hospital admission and COVID-19 severity. However, the effect of antecedent serum lipid levels on the risk of COVID-19 infection has not been explored previously. Methods Our retrospective cohort from the Arkansas Clinical Data Repository included all adults with lipid levels available within the 2 years antecedent to COVID-19 testing. We assessed the association of trajectories of lipid levels antecedent to COVID-19 testing, identified using group-based-trajectory-modeling with the risk of COVID-19 infection using multivariable log-binomial regression. We used mixed-effects linear regression to assess the trends in serum lipid levels followed up to the time of, and 2-months after COVID-19 testing. Results Among the 11001 individuals, 1340 (12.2%) tested positive for COVID-19. The median age was 59 years (IQR 46-70) and 40.8% were males. Log-binomial regression showed that the highest trajectory for antecedent serum HDL-C level was associated with a lower risk for COVID-19 infection (RR 0.63, 95% CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) levels showed no independent association with COVID-19 infection risk. But the COVID-19 infection risk was the highest in the subgroup with lower HDL-C (Trajectory 1) and higher LDL-C or higher TG (Trajectory 3). In COVID-19 patients, at the time of testing, serum HDL-C (-7.7, 95% CI -9.8 to -5.5 mg/dL), LDL-C (-6.29, 95% CI -12.2 to -0.37 mg/dL) and TC (-11.71, 95%CI -18.9 to -4.5 mg/dL), but not TG levels, were lower. These returned to pre-infection values by 2-months following COVID-19 testing. Conclusion Higher antecedent serum HDL-C, but not LDL-C, TC, and TG levels, were associated with a lower COVID-19 infection risk. Serum HDL-C, LDL-C, and TC levels declined transiently at the time of diagnosis, returning to pre-infection levels during follow-up. The results of our study could provide the impetus for clinical trials aimed at increasing HDL-C, such as CETP inhibitors, in the prevention and amelioration of COVID-19 infection or infections in general.

Mesenchymal stem cell treatment for hyperactive immune response in patients with COVID-19.

The human immune system protects the body against invasive organisms and kicks into a hyperactive mode in COVID-19 patients, particularly in those who are critically sick. Therapeutic regimens directed at the hyperactive immune system have been found to be effective in the treatment of patients with COVID-19. An evolving potential treatment option is therapy with mesenchymal stem cells (MSCs) due to their regenerative and reparative ability in epithelial cells. Clinical trials have reported the safe usage of MSC therapy. Systemic effects of MSC treatment have included a reduction in pro-inflammatory cytokines and a decrease in the levels of CRP, IL-6, and lactase dehydrogenase, which function as independent biomarkers for COVID-19 mortality and respiratory failure.

Treatment of COVID-19 is becoming increasingly difficult because of new variants, such as Delta, and more recently Omicron. Each virus variant becomes smarter at being able to evade the body's immune system, vaccines and drug treatments. The biggest challenge in treating COVID-19 is when the body's immune system starts to become hyperactive. In such a scenario, the immune system releases the compounds that are supposed to be released in small doses all at once. Thus, overwhelming the body and causing many complications. One possible solution to this is the mesenchymal stem cell. Multiple clinical trials have shown that mesenchymal stem cells can heal all different cell types in the body and stop the hyperactive immune system.

HDL cholesterol levels and susceptibility to COVID-19.

BACKGROUND: Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Low serum lipid levels during hospital admission are associated with COVID-19 severity. However, the effect of antecedent serum lipid levels on SARS-CoV-2 infection risk has not been explored. METHODS: From our retrospective cohort from the Arkansas Clinical Data-Repository, we used log-binomial regression to assess the risk of SARS-CoV-2 infection among the trajectories of lipid levels during the 2 years antecedent to COVID-19 testing, identified using group-based-trajectory modelling. We used mixed-effects linear regression to assess the serum lipid level trends followed up to the time of, and 2-months following COVID-19 testing. FINDINGS: Among the 11001 individuals with a median age of 59 years (IQR 46-70), 1340 (12.2%) tested positive for COVID-19. The highest trajectory for antecedent serum HDL-C was associated with the lowest SARS-CoV-2 infection risk (RR 0.63, 95%CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) were not independently associated with SARS-CoV-2 infection risk. In COVID-19 patients, serum HDL-C (-7.7, 95%CI -9.8 to -5.5 mg/dL), and LDL-C (-6.29, 95%CI -12.2 to -0.37 mg/dL), but not TG levels, decreased transiently at the time of testing. INTERPRETATION: Higher antecedent serum HDL-C, but not LDL-C, TC, or TG, levels were associated with a lower SARS-CoV-2 infection risk. Serum HDL-C, and LDL-C levels declined transiently at the time of infection. Further studies are needed to determine the potential role of lipid-modulating therapies in the prevention and management of COVID-19. FUNDING: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR003107.

Syndemic: A Synergistic Anthropological Approach to the COVID-19 Pandemic

This review describes the relationship between the coronavirus-related pandemic and health inequities. The latter are linked to pre-existing social and economic discriminations in terms of access to healthcare for people affected by chronic diseases. We believe that we are living in a 'syndemic pandemic';. The term 'syndemic';was originally developed by the medical anthropologist Merrill Singer in the 1990s in order to recognize the correlation between HIV/AIDS, illicit drug use, and violence in the United States. This complex interplay exacerbated the burden of the disease and the prognosis of the patient. Similarly, in COVID-19 infection, socio-economic, ethnic, and racial inequities result in higher morbidity and mortality in certain sections of society. Unfortunately, such differences are becoming too common during the COVID-19 pandemic, in terms of the incidence and prevalence of the disease, as well as inequal access to new medical advances and life-saving therapeutics for those with COVID-19, such as vaccines and monoclonal antibody treatment. Lockdown measures, imposed internationally as a response to the COVID-19 pandemic, are causing economic inequities, which complicate the issue even further. An appropriate syndemic anthropological approach is necessary to ensure that this pandemic does not increase health inequities in access to appropriate treatments.

Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant interaction with the lipid rafts in the host cell membranes and can modify the interaction of virus with host cells and the resultant disease severity. Recent studies on serum lipid levels and COVID-19 disease severity lack consistency. Objectives: Our systematic review and meta-analysis compared the serum levels of total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) between (1) COVID-19 patients vs. healthy controls; (2) severe vs. non-severe COVID-19 disease; (3) deceased vs. surviving COVID-19 patients. Methods: PRISMA guidelines were followed. We included peer-reviewed articles on observational (case-control and cohort) studies from PubMed and Embase published from the database inception until September 1, 2021. We used random-effects meta-analysis for pooled mean-differences (pMD) in lipid levels (mg/dL) for the above groups. Results: Among 441 articles identified, 29 articles (26 retrospective and 3 prospective cohorts), with an aggregate of 256,721 participants, were included. COVID-19 patients had lower TC (pMD-14.9, 95%CI-21.6 to -8.3) and HDL-C (pMD-6.9, 95%CI -10.2 to -3.7) levels (mg/dL). Severe COVID-19 patients had lower TC (pMD-10.4, 95%CI -18.7 to -2.2), LDL-C (pMD-4.4, 95%CI -8.4 to -0.42), and HDL-C (pMD-4.4, 95%CI -6.9 to -1.8) at admission compared to patients with non-severe disease. Deceased patients had lower TC (pMD-14.9, 95%CI -21.6 to -8.3), LDL-C (pMD-10.6, 95%CI -16.5 to -4.6) and HDL-C (pMD-2.5, 95%CI -3.9 to -1.0) at admission. TG levels did not differ based on COVID-19 severity or mortality. No publication bias was noted. Conclusion: We demonstrated lower lipid levels in patients with COVID-19 infection and an association with disease severity and mortality. Their potential role in COVID-19 pathogenesis and their utility as prognostic factors require further investigation.

COVID-19 Vaccine-Induced Pro-thrombotic Immune Thrombocytopenia (VIPIT): State of the Art.

In 2020, as the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic spread rapidly throughout the world, scientists worked relentlessly to develop and test the safety and effectiveness of potential vaccines. Usually, the vaccine development process involves years of investigation and testing prior to gaining approval for use in practice. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, may be manifested following the administration of viral vector vaccines. It leads to severe clot formation at unusual sites approximately in 1 out of 110.000 vaccinated persons. This side effect, although rare, represents a newly devastating clotting phenomenon manifested in otherwise healthy young adults, who are often female. An in-depth description of the specific biological mechanisms implicated in the syndrome is here summarized.

Cerebral Venous Sinus Thrombosis following COVID-19 Vaccination: Analysis of 552 Worldwide Cases.

To date, billions of vaccine doses have been administered to restrain the current COVID-19 pandemic worldwide. Rare side effects, including intravascular blood clots, were reported in the general population after vaccination. Among these, cerebral venous sinus thrombosis (CVST) has been considered the most serious one. To shed further light on such an event, we conducted a literature search for case descriptions of CVST in vaccinated people. Findings were analyzed with emphasis on demographic characteristics, type of vaccine, site of thrombosis, clinical and histopathological findings. From 258 potential articles published till September 2021, 41 studies were retrieved for a total of 552 patients. Of these, 492 patients (89.1%) had received AZD1222/Vaxzevria, 45 (8.2%) BNT162b2/CX-024414 Spikevax, 15 (2.7%) JNJ-78436735, and 2 (0.3%) Covishield vaccine. CVST occurred in 382 women and 170 men (mean aged 44 years), and the median timing from the shot was 9 days (range 2-45). Thrombi were predominantly seen in transverse (84%), sigmoid (66%), and/or superior sagittal (56%) sinuses. Brain injury (chiefly intracranial bleeding) occurred in 32% of cases. Of 426 patients with detailed clinical course, 63% were discharged in good clinical conditions, at times with variable neurological sequelae, whereas 37% deceased, largely due to brain injury. This narrative review confirmed CVST as a rare event after (adenoviral vector) COVID-19 vaccination, with a women/men rate ratio of 2.25. Though the pathogenesis of thrombosis is still under discussion, currently available histopathological findings likely indicate an underlying immune vasculitis.

Loneliness and Social Isolation: Determinants of Cardiovascular Outcomes.

One in three Americans report experiencing loneliness in everyday life, a number that has grown exponentially over the last few decades. As we respond to the SARS-COV2 pandemic with quarantine and social distancing, social isolation and feelings of loneliness are increasing among people of all ages. This presents as an opportune time to recognize the public health impact of these important psychosocial determinants. Loneliness and social isolation are associated with a higher incidence of CVD, higher healthcare utilization and worse outcomes even after controlling for conventional risk factors of CVD. In this review, we discuss loneliness and social isolation as determinants of cardiovascular outcomes, the pathophysiology of this association, and its implications in clinical practice. We discuss some of the shortcomings in the assessment of loneliness and social isolation while identifying the most commonly used rating scales for the same. Finally, we suggest modifications to interventions for loneliness and social isolation during the COVID-19 pandemic.

Adverse Cardiovascular Effects of Anti-COVID-19 Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.

Concerning the unexpected prothrombotic state following some coronavirus disease 2019 vaccines.

Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5--14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford-AstraZeneca vaccine (and probably by Janssen/Johnson & Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccine-induced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome.

The Deadly Quartet (Covid-19, Old Age, Lung Disease, and Heart Failure) Explains Why Coronavirus-Related Mortality in Northern Italy Was So High.

Since its outbreak in China at the end of 2019, the new coronavirus disease (COVID-19) was characterized by both easy spreading and high mortality. The latter proved to be way more elevated in the North of Italy -with a peak of 18.4% in region Lombardia and even 31% in the city of Bergamo and surrounding county- than in the rest of the world. In an attempt to conceptualize the reasons for such a dramatic situation, four key elements have been identified: COVID-19 itself, old age, lung disease, and heart failure. Their harmful combination has been named "The deadly quartet". The underlying risk factors, among which a lot of them are distinctive features of the population in northern Italy, have been summarized as "unmodifiable", "partially modifiable", and "modifiable", for the sake of clarity. Up-to-date scientific evidence in this field has been described in the form of a narrative and easy-to-read review.