Statin Intake and All-Cause Mortality among Older Nursing Home Residents.

BACKGROUND: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents. OBJECTIVE: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality. METHOD: This is a cross-sectional study of 1,094 older people residing in 6 nursing homes in Flanders (Belgium) between March 1, 2020 and May 30, 2020. We considered all residents who were taking statins for at least 5 days as statin users. All-cause mortality during the 3 months of data collection was the primary outcome. Propensity score overlap-weighted logistic regression models were applied with age, sex, functional status, diabetes, and cardiac failure/ischemia as potential confounders. RESULTS: 185 out of 1,094 residents were on statin therapy (17%). The statin intake was associated with decreased all-cause mortality: 4% absolute risk reduction; adjusted odds ratio 0.50; CI 0.31-0.81, p = 0.005. CONCLUSIONS: The statin intake was associated with decreased all-cause mortality in older people residing in nursing homes. More in-depth studies investigating the potential geroprotector effect of statins in this population are needed.

How will physicians respond to the next influenza pandemic?

The emergence of the H7N9 virus in China is another reminder of the threat of a global influenza pandemic. Many believe we could confront a pandemic by expanding our capacity to provide timely supplies of affordable pandemic vaccines and antiviral agents. Experience in 2009 demonstrated that this cannot and will not be done. Consequently, physicians may have little more to offer their patients than they had in the 1918 pandemic. Fortunately, several modern drugs (eg, statins, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors) can modify the host response to inflammatory illness, and laboratory and clinical studies suggest they might be used to treat pandemic patients. Unfortunately, little attention has been given to the research needed to support their use in patient care. There is no guarantee these drugs will work, but physicians will never know unless those responsible for pandemic preparedness recognize and act on the extraordinary possibility that they might save lives.

The dysfunctional host response to influenza A H7N9: a potential treatment option?

The newly emerging human pathogen influenza A H7N9 represents a potentially major threat to human health. The virus was first shown to be pathogenic in humans in 2013, and outbreaks continue to occur in China to the present time. The current incident mortality rate is disturbingly high despite the frequent use of antiviral therapy and intensive care management. If the virus gains the capacity for efficient person-to-person transmission, a global influenza pandemic could ensue with devastating consequences. In the absence of an effective vaccine, targeted regulation of the host immune response by immune modulators might be considered. Readily available, approved drugs with immune-modulating activities might prove to be a treatment option in combination with existing antiviral agents and supportive care.

Treating COVID-19: Targeting the Host Response, Not the Virus.

In low- and middle-income countries (LMICs), inexpensive generic drugs like statins, ACE inhibitors, and ARBs, especially if used in combination, might be the only practical way to save the lives of patients with severe COVID-19. These drugs will already be available in all countries on the first pandemic day. Because they target the host response to infection instead of the virus, they could be used to save lives during any pandemic. Observational studies show that inpatient statin treatment reduces 28-30-day mortality but randomized controlled trials have failed to show this benefit. Combination treatment has been tested for antivirals and dexamethasone but, with the exception of one observational study in Belgium, not for inexpensive generic drugs. Future pandemic research must include testing combination generic drug treatments that could be used in LMICs.

Statin withdrawal and treating COVID-19 patients.

Most but not all observational studies of statin treatment of COVID-19 patients suggest that treatment improves outcomes. However, almost all of these studies fail to consider that withdrawing statins after hospital admission may have detrimental effects, a finding which cardiovascular investigators have known for 15-20 years. Continuing or starting statin treatment after hospital admission consistently improves cardiovascular outcomes. Similarly, inpatient statin treatment of COVID-19 improves survival. For this reason, observational studies of the effectiveness of outpatient-documented statin treatment of COVID-19 patients must consider the negative consequences of statin withdrawal after hospital admission.

COVID-19, host response treatment, and the need for political leadership.

Health officials and scientists have warned that we face the threat of a potentially devastating influenza pandemic. Instead, we are now in the midst of a global coronavirus (COVID-19) pandemic. National and international pandemic preparedness plans have focused on developing vaccines and antiviral treatments. Another way to confront the COVID-19 pandemic (and future pandemics) might be to treat patients with inexpensive and widely available generic drugs that target the host response to infection, not the virus itself. The feasibility of this idea was tested during the Ebola outbreak in West Africa in 2014. This experience should inform our approach to treating COVID-19 patients. It could also save lives during outbreaks of other emerging infectious diseases and episodes of everyday acute critical illness. If this "bottom up" syndromic approach to treating acute critical illness were shown to be effective, it could have a dramatic impact on health, equity and security throughout the world. HIGHLIGHTS: Uncertainty about the outcome of COVID-19 is driving the social, economic and political distress associated with the pandemic. Treating the host response to COVID-19 with inexpensive and widely available generic drugs might save lives and mitigate this distress. Undertaking research on this idea will require political leadership.

Adjunctive Use of Statins for COVID-19.

The interaction between obesity, cardiometabolic disorders and COVID-19 represents a syndemic that requires both social intervention and a multipharmacological approach [...].

Hospital mortality in COVID-19 patients in Belgium treated with statins, ACE inhibitors and/or ARBs.

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17-0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.

Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection.

Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes. DESIGN: We undertook a retrospective multicenter cohort study to analyze the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were (1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and (2) asymptomatic (ie, no disease symptoms in the whole study period while still being diagnosed by polymerase chain reaction). SETTING AND PARTICIPANTS: A total of 154 COVID-19-positive subjects were identified, residing in 1 of 2 Belgian nursing homes that experienced similar COVID-19 outbreaks. MEASURES: Logistic regression models were applied with age, sex, functional status, diabetes, and hypertension as covariates. RESULTS: We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (odds ratio [OR] 2.91; confidence interval [CI] 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97). CONCLUSIONS AND IMPLICATIONS: Our data indicate that statin intake in older, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs needs to be further explored in larger observational studies as well as randomized clinical trials.

Meeting the challenge of influenza pandemic preparedness in developing countries.

Developing countries face unique difficulties preparing for an influenza pandemic. Our current top-down approach will not provide these countries with adequate supplies of vaccines and antiviral agents. Consequently, they will have to use a bottom-up approach based on inexpensive generic agents that either modify the host response to influenza virus or act as antiviral agents. Several of these agents have shown promise, and many are currently produced in developing countries. Investigators must primarily identify agents for managing infection in populations and not simply seek explanations for how they work. They must determine in which countries these agents are produced and define patterns of distribution and costs. Because prepandemic research cannot establish whether these agents will be effective in a pandemic, randomized controlled trials must begin immediately after a new pandemic virus has emerged. Without this research, industrialized and developing countries could face an unprecedented health crisis.

Pathogen Lists Do Not Tell Us What We Need to Do.

Brett-Major and others remind us that pathogen lists for emerging infectious diseases aid in the development of tools that target specific pathogens (e.g., vaccines) and help attract financial support. These lists tell us what we need to have, not what we need to do. The authors call for more research on ways to prevent these diseases (e.g., platform technologies for vaccines) and mitigate disease impact. Vaccines and new treatments that target individual pathogens have many limitations. However, we might save lives by treating patients with inexpensive generic drugs that target common features of the host response to infection. Undertaking research on this approach to treatment is what we need to do.

Confronting an influenza pandemic with inexpensive generic agents: can it be done?

Avian influenza A H5N1 presents a serious and possibly imminent pandemic threat. In such an event, adequate supplies of affordable vaccines and antiviral agents will be unavailable to most people in the world. In view of the overwhelming need for effective alternatives, generic agents that target the host immune response or the pandemic virus should be considered. Many scientists doubt the effectiveness of these agents. Nonetheless, several studies suggest that statins improve outcomes in patients with bacteraemia and pneumonia and might be similarly effective against influenza. An experimental study has shown that the fibrate gemfibrozil, a peroxisome proliferator-activated receptor (PPAR) alpha agonist, reduces mortality in H2N2 influenza virus-infected mice. There is substantial molecular cross-talk between statins and PPAR agonists, and their clinical effects are additive in patients with cardiovascular diseases. Chloroquine increases endosomal pH, impairing influenza virus release into the cytosol. Statins, fibrates, and chloroquine are produced as generic medications in developing countries. They are inexpensive, could be stockpiled, and would be available on the first pandemic day. With a lack of realistic alternatives for confronting the next pandemic, research is urgently needed to determine whether these and other generic agents could mitigate the effects of what might otherwise become an unprecedented global public-health crisis.

NEW technologies for meeting the global demand for pandemic influenza vaccines.

A new influenza pandemic is expected and if caused by the H5N1 virus it could be severe. Antiviral agents will be unavailable to most people and vaccines are regarded as the mainstay of protection. Development of inactivated H5N1 vaccines has been slow because of reluctance by US regulatory authorities to consider adjuvanted formulations and the unwillingness of Western European governments to fund vaccine trials. With effective political leadership, large amounts of live-attenuated and recombinant hemagglutinin pandemic vaccines could be produced quickly in existing facilities using egg-based technologies. New types of influenza vaccines, new technologies for their production and new adjuvants to make them more immunogenic are receiving the attention of scientists and vaccine developers. These technologies could help meet the global demand for pandemic vaccines, but only if they are coupled with improvements in the human infrastructure necessary for pandemic vaccination.