COVID-19 and critical care admissions in the UK: using routine data during a pandemic.

by:
Alice M Jackson

The Intensive Care National Audit and Research Centre (ICNARC) collates, reports and audits data for all National Health Service adult critical care admissions in the UK (England, Wales and Northern Ireland). Since the beginning of March 2020, 245 critical care units across the UK have submitted data on 6720 patients admitted with confirmed COVID-19, with data on outcomes in 4078 (61%) (1). In the report, patient demographics, markers of disease severity, length of stay, requirement for organ support and death or discharge from critical care are presented. Approximately a third of patients are from critical care units in London.

The mean age of patients was 59.4 (±12.5) years, 72% were men, half were in the two highest deprivation quintiles (where a higher number equates to more deprivation) and race was reported as Black, Asian or was unspecified (but non-White) in 34% of patients. In the 2011 England and Wales census, 14% of the whole population and 40% of people living in London identified as non-White (2). The burden of comorbidity is not well-described in the report, which only provides data about ‘very severe comorbidities’; in the case of cardiovascular disease, this is defined as cardiovascular disease with symptoms at rest in the six months prior to admission to critical care, and was present in 0.4% of patients.

Amongst 4078 patients with data on outcomes, advanced cardiovascular support (defined as the use of pharmacological inotropic or chronotropic support, or continuous cardiac output monitoring, or insertion of an intra-aortic balloon pump, or temporary cardiac pacing) was required in 27%, for a median duration of 3 (IQR 1-5) days –  5% more than required the same support when admitted to critical care with viral pneumonia from 2017-2019. As expected, nearly all of these patients (98.6%) required some form other additional organ support. Of those who required advanced cardiovascular and advanced respiratory support (n=613, 15%), the case-fatality rate during the critical care admission was 73%, increasing to 87% when renal replacement therapy was also required (n=440, 11%).

In the UK, routinely collected data like these are a rich source of information and can provide a comprehensive description of the emerging epidemiology of a new disease early in its course, such as with COVID-19. In England and Wales, population-level mortality datasets are collated and reported by the Office for National Statistics, and in Scotland by National Records for Scotland. Linkage of mortality datasets with other routine datasets, such as hospital admissions, is also possible. In Scotland, this is done through a combination of deterministic matching, which involves matching a unique patient identifier assigned to each individual in Scotland at birth, and probabilistic matching, which involves the use of other variables (such as name, date of birth or postcode) to determine whether the records belong to the same individual (3). In recent weeks, this existing infrastructure has allowed the UK to produce regular reports on health outcomes relating to COVID-19 in a timely and cost-effective fashion. Going forward, routine data such as these will not only facilitate research on the direct health effects of COVID-19, but also on the wider consequences of the pandemic.

References
1) https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports. ICNARC report on COVID-19 in critical care 24 April 2020. (Accessed 28 April 2020)

2) http://www.nomisweb.co.uk/census/2011/dc2101ew. Ethnic group by sex and age. (Accessed 28 April 2020)

3) Fleming M, Kirby B, Penny K. Record linkage in Scotland and its applications to health research. J Clin Nurs. 2012;21(19-20):2711-2721.

Multimorbidity and COVID 19: A catastrophic combination

by:
Jeemon Panniyammakal

Multimorbidity is the existence of multiple long-term mental, physical, and cognitive disorders in one patient. These could include diabetes, hypertension, lung diseases, heart attacks, stroke, kidney failure, mental health conditions, and liver problems or other chronic conditions. Multimorbid conditions often share common disease causes and consequences. The disease pattern, progression and trajectories in multimorbidity are path-dependent in nature and often determined by age, sex and socio-demographic characteristics. However, addition of COVID 19 dramatically changes the disease progression pathways and cut-short the trajectories to immediate clinical end-points in individual with multimorbidity.

Richardson et al, presented the characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area. (doi:10.1001/jama.2020.6775). Hypertension (57%), obesity (42%) and diabetes (34%) were the most common comorbid conditions in this group of patients with median age of 63 years. Nearly, 9 of 10 COVID 19 patients had more than one comorbidities. The median number of comorbid conditions were 4. Similarly, the median score on the Charlson Comorbidity Index was 4 points (Inter Quartile Range, 2-6). In short, the comorbidity burden was substantial in the affected COVID 19 cases in the New York City area. For example, the cumulative comorbidity burden corresponds to a 53% estimated 10-year survival.

Richardson and colleagues reported mortality rates only for patients with definite outcomes (discharge or death). Of the total 2634 patients with one of the definite outcomes, 553 died (21%). Nearly three of four deaths were reported in individuals with >65 years of age. There were no deaths in the age group of <18 years. Nearly, 70% of patients died in the hospital had hypertension as a comorbidity. However, only 47% of discharged patients had hypertension as a comorbidity. Diabetes was present in 40% of patients died in the hospital, while it was 26% in those who were discharged from the hospital. It is reasonably clear that individuals with comorbid conditions have poor prognosis when affected by COVID 19. Although the data are not presented separately by multmorbidity pattern, it is probably appropriate to assume that multimorbidity is associated with poor survival outcomes in COVID 19 patients.

In comparison to people with single health problems and no other comorbid conditions, people with multimorbidity are more likely to have worse general health and an increased risk of premature death. Available data indicate that COVID 19 further increases the risk of mortality in individuals with multimorbidity. We may have to devise effective public health strategies to protect individuals with multimorbidity from COVID 19. Further, such individuals may require prioritised testing and management for COVID 19. They also need to get access to their regular medications and health services essential to manage their comorbid conditions. Ignoring their immediate medical needs may lead to catastrophic consequences even if they escape from COVID 19. 

Association of renin-angiotensin system inhibitors with severity and outcomes of COVID-19 infection in hospitalized patients with hypertension

by
Lucrecia M. Burgos

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are not associated with severity and outcomes of coronavirus disease 2019 (COVID-19) infection in hospitalized patients with hypertension  in Wuhan, China according to a recent study in JAMA Cardiology1.

In this retrospective single-centre analysis, the authors analysed hospitalized patients with COVID-19 at the Central Hospital of Wuhan China from January 15, 2020, to March 15, 2020. There were 1178 patients hospitalized with COVID-19 (mean age 55.5 years; 46.3% men). Among them, 30,7% had hypertension. Patients with hypertension were older and had greater prevalence of chronic diseases; they also had more severe manifestations of COVID-19, including higher rates of acute respiratory distress syndrome and greater in-hospital mortality (21.3% vs 6.5%; P < .001). Around one-third were taking an ACEI or ARB.

Patients with and without ACEI/ARB treatment had similar comorbidities, with the exception of higher prevalence of coronary artery disease in those taking ACEIs/ARBs (23.5% vs 14.2%).  They also presented similar laboratory profile results including blood cell counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers.  The frequency of severity of illness and acute respiratory distress syndrome did not differ with respect to ACEI/ARB therapy.  ACEIs/ARBs use was similar for those who died and those who survived (27.3% vs 33.0%; P = 0.34).

In this study, the authors report data demonstrating that there was no difference in the disease progression and risk of death during hospitalization for COVID-19 with respect to various antihypertensive drugs and in the use of ACEIs/ARBs. They also confirm that patients with hypertension had more severe illness and higher mortality rates than those without hypertension, however, these previous reports did not indicate how many patients were taking ACEIs or ARBs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) use the ACE2 receptor to enter the host cells, and ACE2 negatively regulates the renin-angiotensin system by inactivating angiotensin II and likely plays a protective role against the development and progression of acute lung failure 2,3.  Animal studies have shown that expression of ACE2 is substantially increased in patients treated with ACEIs/ARBs4.  In contrast to available animal models, there are few studies in humans regarding the effects of RAAS inhibition on ACE2 expression. In a study circulating ACE2 levels were increased in patients with diabetes treated with ACEIs5. Based on these observations, some experts have speculated that use of ACEIs/ARBs leading to increased expression of ACE2 could potentially facilitate infection with COVID-19. A recent study showed that serum angiotensin II levels in patients with COVID-19 pneumonia was significantly higher compared with healthy individuals and were linearly associated with viral load and lung injury6.  Based on this, it can be postulated that SARS-CoV-2 binding to ACE2 may attenuate residual ACE2 activity, skewing the ACE/ACE2 balance to a state of heightened angiotensin II activity leading to pulmonary vasoconstriction and inflammatory and oxidative organ damage, which increases the risk for acute lung injury7.

The clinical role of this pathway in COVID-19 complications and any effect from possible modulation of this receptor is not yet fully known and going to be tested in upcoming clinical trials. A multicenter, double-blind, placebo-controlled phase 2 randomized clinical trial of starting losartan in patients with COVID-19 in outpatient settings (ClinicalTrials.gov identifier: NCT04311177) and in in-patient settings (ClinicalTrials.gov identifier: NCT04312009) is currently being planned7.

Presently, there are no data regarding a favorable effect of RAS blockade on pulmonary outcome in SARS-CoV-2-infected patients. Whether or not infectivity to viral infection is increased in patients treated with RAS blockers remains unknown8. There are no peer-reviewed experimental or clinical data demonstrating a specific benefit or risk from using ACE inhibitors, ARBs, or renin-angiotensin-aldosterone system antagonists in COVID-19 9. However, recent news media coverage of this issue have provoked concern and unfortunately even motivated some patients to discontinue RAS blockers all together.

Several professional societies have put forward their guidance regarding the use of ACEIs/ARBs in patients with COVID-19. A joint statement by the Heart Failure Society of America, American College of Cardiology, and American Heart Association recommends that these medications can be continued in patients with COVID-19 without interruption in compliance with available clinical guidelines10.

Study authors mention as a limitation that the current findings may not be generalizable to all patients with hypertension, and it is possible that ACEIs/ARBs could affect the chance of hospitalization. In addition, it is not certain whether the ACEI/ARB treatment at baseline was maintained throughout the hospitalization for all patients. Furthermore, the authors did not mention whether the inclusion of patients was consecutive. In China most patients are on ARB as opposed to an ACE inhibitor, because  the prevalence of cough requiring discontinuation of ACE inhibitor therapy was found to be significantly higher among subjects with Chinese ethnicity11,12.

To conclude, renin–angiotensin system blockade treatment should be continued.  Present evidence is insufficient to recommend use of RAS blockade prophylactically in subjects at risk or therapeutically in those infected with SARS-CoV-2. In this preliminary assessment ACEI/ARB was not associated with severity and worse outcomes of COVID-19 infection in hospitalized patients with hypertension.

Further epidemiological studies and prospective trials are urgently needed to investigate if use of ACEIs/ARBs can reduce the incidence, severity and or mortality associated with COVID-19.

References

1. Li J, Wang X, Chen J, et al. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020 Apr 23. doi: 10.1001/jamacardio.2020.1624.

2. Li  F.  Structure, function, and evolution of coronavirus spike proteins.  Annu Rev Virol. 2016;3:237-261. doi:10.1146/annurev-virology-110615-042301

3. Imai  Y, Kuba  K, Rao  S,  et al.  Angiotensin-converting enzyme 2 protects from severe acute lung failure.  Nature. 2005;436:112-116. doi:10.1038/nature03712

4. Klimas  J , Olvedy  M , Ochodnicka-Mackovicova  K ,  et al.  Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.   J Cell Mol Med. 2015;19:1965-1974. doi:10.1111/jcmm.12573

5. Soro-Paavonen  A , Gordin  D , Forsblom  C ,  et al; FinnDiane Study Group.  Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications.   J Hypertens. 2012;30:375-383. doi:10.1097/HJH.0b013e32834f04b6

6. Liu  Y , Yang  Y , Zhang  C ,  et al.  Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury.   Sci China Life Sci. 2020;63:364-374. doi:10.1007/s11427-020-1643-8

7. Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 Apr 3. doi: 10.1001/jamacardio.2020.1282. 

8. Messerli FH, Siontis GCM2, Rexhaj E. COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations. Circulation. 2020 Apr 13. doi: 10.1161/CIRCULATIONAHA.120.047022.

9. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1286

10. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. Accessed March 19, 2020.

https://professional.heart.org/professional/ScienceNews/UCM_505836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-antagonists-in-COVID-19.jsp

11. Woo KS, Nicholls MG. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese. Br J Clin Pharmacol. 1995;40:141–4.

12. Tseng DS, Kwong J, Rezvani F, Coates AO. Angiotensin-converting enzyme-related cough among Chinese-Americans. Am J Med. 2010;123:183, e11–5


Impact of the COVID-19 pandemic on interventional cardiology activity

by:
Lucrecia Maria Burgos

An important reduction in the activity in interventional cardiology has been observed during the COVID-19 epidemic according to a recent study in REC Interventional Cardiology1.

The authors carried out a survey in 81 centres involved in ST-elevation myocardial infarction (STEMI) networks in the 17 autonomous communities of Spain. Information was collected on diagnostic activity, percutaneous coronary intervention (PCI), structural interventions, and PCI in STEMI on changes in the organization of STEMI networks, and on the prevalence of COVID-19 among interventional cardiologists. Data was compared for the week of February 24 through March 1 (before the outbreak) and for the week of March 16 through March 22 (during the outbreak).  A significant decrease in the number of diagnostic procedures (─57%), PCI (─48%), structural interventions (─81%) and PCI in STEMI (─40%) has been observed. A slight increase in the use of pharmacological thrombolysis has been reported, although primary angioplasty remains the leading reperfusion strategy. Of 339 medical professionals who perform primary angioplasty procedures, 17 presented COVID-19 infection (5%).

In this study, the time to reperfusion, the clinical characteristics, as well as in-hospital complications, were not analysed. And the report of the use of lithic, was made with a non-quantitative method, asking each centre if more thrombolytic therapy has been performed.

The COVID-19 pandemic caused by infection with the SARS-CoV-2 virus has put the Spanish health system in a situation of serious overload. On March 14, 2020, the state of alarm was declared in Spain with a house confinement of the population with the aim of slowing down the progression of the epidemic. As a consequence, attention to other pathologies could have been affected, and among them the treatment of cardiovascular diseases. This is especially important in emergencies such as STEMI. In a recently reviewed study in the Heart Blog, Tam, et al 2. described the timeliness of primary percutaneous coronary intervention for STEMI in a single centre in Hong Kong, China. They reported an approximately 3-fold increase in the time from symptom onset to medical contact.

Scientific societies and health authorities have to promote that patients presenting STEMI compatible symptoms should proceed with no delay to access the health system to receive reperfusion treatment.

More studies are needed to assess whether this phenomenon occurs in other parts of the world, and to explore the factors that could explain the decrease of coronary interventions, especially in STEMI. From the World Heart Federation, we encourage to start studies that evaluate the impact of the pandemic on the health care of other cardiovascular diseases. To identify the barriers to cardiovascular disease care, and find possible solutions such as telephone advice lines or telemedicine.

References

1. Rodríguez-Leor O, Cid Alvarez B, Ojeda S et al. Impacto de la pandemia de COVID-19 sobre la actividad asistencial en cardiología intervencionista en España. REC Interv Cardiol. 2020. https://doi.org/10.24875/RECIC.M20000120

2. Tam CF, Cheung KS, Lam S, et al. Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong, China. Circ Cardiovasc Qual Outcomes. 2020:CIRCOUTCOMES120006631.


The Implications of Viral Particles in the Myocardium

by.
Darryl Leong

Systolic left ventricular dysfunction in the absence of obstructive coronary artery disease has been described in several anecdotes and case reports in patients with COVID-19. The mechanisms underlying the cardiomyopathy is unclear. In a case report, Tavazzi, et al. describe the first instance of coronavirus-like particles seen by electron microscopy in the myocardium of a patient with COVID-19 who exhibited marked impairment in systolic left ventricular function1. These particles were seen within interstitial cytopathic macrophages and not within myocytes under electron microscopy of a single endomyocardial biopsy. In addition, only low-grade myocardial inflammation was observed, with no evidence of myocyte necrosis.

While this report is valuable in that it is the first to demonstrate likely SARS-CoV-2 localization within the heart, the authors prudently avoid ascribing a causal relationship between the viral particles and the left ventricular dysfunction. Previous research has shown that viral (e.g. parvovirus B19) genomes can be found in cardiac tissue in patients with no evidence of myocarditis2. Therefore, it remains unknown whether the localization of SARS-CoV-2 in cardiac tissue is simply the result of viremia or translocation of infected macrophages, or whether it has a direct pathogenic effect on the myocardium. Further evidence of a causal relationship, such as the demonstration of active myocarditis or histologic myonecrosis is needed to build the case that SARS-CoV-2 can directly cause myocardial damage. Numerous randomized, clinical trials of antiviral therapies in patients with COVID-19 are underway or being planned. If a reduction in adverse cardiac outcomes were shown in these trials, it would strengthen the evidence of a direct causal role of COVID-19 in left ventricular dysfunction.

1.           Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, Sepe PA, Resasco T, Camporotondo R, Bruno R, Baldanti F, Paolucci S, Pelenghi S, Iotti GA, Mojoli F and Arbustini E. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020.

2.           Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R and Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation. 2005;111:887-93.

Cardiac Biomarkers and COVID19

by:
Darryl Leong

In a single-centre retrospective study of 273 patients from Wuhan, China, Han et al. reported that 10% had elevated troponin I and 12% had elevated NT-proBNP concentrations(1). Elevated cardiac biomarker levels were more common among severely ill patients as compared to milder cases. Among mild cases, 5% and 7% had elevated troponin I and NT-proBNP levels respectively. In total, 24 deaths were documented (case-fatality rate 9%). The case-fatality rate was higher among those with abnormal cardiac biomarkers (23%) as compared with those with normal cardiac biomarkers (5%).

The frequency with which cardiac biomarkers are elevated in COVID-19 is uncertain. The present study only included hospitalized patients. The threshold for hospitalization is likely to vary in different settings; if hospitalization were reserved for only the most unwell patients, then one might expect higher biomarker levels and vice versa. Also, this report does not provide data on cardiac biomarkers among non-hospitalized individuals with COVID-19. Given that only the minority of individuals with COVID-19 are hospitalized, the true prevalence of myocardial injury is uncertain.

The finding that elevated troponin and NT-proBNP are prognostically important is novel inasmuch as COVID-19 is a new infection to humans but is unsurprising based on similar observations in a variety of other clinical contexts. Little is known about the mechanisms underlying such putative cardiac injury. There have been anecdotal reports of presumed and in some cases histologically proven myocarditis. The contribution of pre-existing cardiac disease and demand ischemia or metabolic insult is unclear.

Systematic research into the cardiac complications of COVID-19 is limited as resources are stretched with the demands of treating large numbers of affected patients effectively while ensuring the safety of healthcare workers and research personnel. However, unless we can develop acceptable, safe and efficient ways of conducting epidemiologic biomarker research, as well as effective management strategies based on biomarker levels, the role of and best response to the finding of elevated cardiac biomarkers are unknown.

References:
1. Han H, Xie L, Liu R et al. Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan, China. J Med Virol 2020.

Cardiovascular implications of fatal outcomes of patients with Coronavirus disease 2019 (COVID-19)

by:
Lucrecia M. Burgos

Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying (CVD) but without myocardial injury is relatively favourable according to a recent study in JAMA Cardiology1.

In this retrospective single-centre case series, the authors analysed consecutive hospitalized patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Cardiac injury was defined as serum levels of troponin T (TnT) above the 99th percentile upper reference limit.

Among 187 patients with confirmed COVID-19, the mean age of the patients was 58.5 (±14.6), and about half were male. Overall, 35.3% had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 27.8% exhibited myocardial injury.  Compared with patients with normal TnT levels, patients with myocardial injury were older, with higher proportion of men and had significantly higher rates of comorbidities.

In-hospital mortality was different according to the presence of CVD and myocardial injury.  The mortality rate was 7.62% for patients without underlying CVD and normal TnT levels, 13.33% for those with underlying CVD and normal TnT levels. And 37.50% for those without underlying CVD but elevated TnT levels, and 69.44%  for those with underlying CVD and elevated TnTs.

The authors also found that TnT levels are significantly associated with levels of C-reactive protein (β = 0.530, P < .001) and N-terminal pro-B-type natriuretic peptide (β = 0.613, P < .001), thus linking myocardial injury to severity of inflammation and ventricular dysfunction. Also dynamic changes in TnT and NT-proBNP were observed, with significantly increased levels during hospitalization in those who ultimately died, but no such dynamic changes were evident in survivors.

Evidence is growing regarding the presence of myocardial injury in coronavirus disease. Huang et al2 reported that 12% of patients with COVID-19 were diagnosed as having acute myocardial injury, manifested mainly by elevated levels of high-sensitive troponin I. From other recent data, among 138 hospitalized patients with COVID-19, 7.2% had acute myocardial injury3. In a recently summarized study in Heart Blog, Shi S et al4 found that approximately 20% of patients had cardiac injury, and as previously reported these patients were older and had more comorbid conditions. However specific information characterizing whether patients with COVID-19 with underlying CVD who develop myocardial injury during hospitalization face greater risk and have worse in-hospital outcomes was lacking. The authors of this study conclude that in this preliminary assessment myocardial injury appears to have a significant association with the fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favourable. Therefore, it seems reasonable to classify patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury.

This study is single-centre case series with consecutive patients, it is important to mention that the authors excluded 69 patients because of incomplete data. The results were evaluated in the short term. An association between troponin levels and mortality was observed. The adjusted prognostic effect estimates were not analyzed. This is extremely important considering the differences in the baseline characteristics of patients who had myocardial injury from those who did not. Furthermore, it does not mention whether the events adjudication was blinded to troponin levels.

More studies are needed to evaluate if these patients need different treatment with aggressive strategies. And data from larger populations of multiple centres with long-term observation are warranted to further confirm the prognosis of cardiac injury in COVID-19.

References:
1. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020. Doi: 10.1001/jamacardio.2020.1017.

2. Huang C, Wang  Y, Li  X,  et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.  Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5

3. Wang D, Hu  B, Hu  C,  et al.  Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.  JAMA. Published February 7, 2020. doi:10.1001/jama.2020.1585

4. Shi S, Qin  M, Shen  B, Cai Y, Liu T, Yang F,  et al.  Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.  JAMA Cardiol. 2020. Doi:10.1001/jamacardio.2020.0950

The link between smoking and COVID 19; should we wait for more evidence to quit smoking?

by:
Jeemon Panniyammakal

Various international agencies such as the World Health Organisation, and Centre for Disease Control and Prevention consider tobacco use as a risk condition associated with susceptibility to COVID 19 and progression to adverse outcomes. Vardavas and Nikitara conducted a systematic review of evidence to evaluate the association between smoking and COVID 19 outcomes. They have included a range of outcomes including disease severity, need for mechanical ventilation and intensive care hospitalisation and death. The authors’ identified five studies covering a total population of 1349 COVID 19 patients in their systematic review. Although some of the included studies suggested that smoking may be associated with adverse outcomes in COVID 19 patients, no conclusive evidence was found.

Systematic reviews are exposed to several potential biases. Firstly, the COVID 19 data are just started emerging from various parts of the world. Absence of evidence should not be construed as evidence of absence. Secondly, in emergency situations, history taking is often ignored and habits such as tobacco use never gets reported or documented in case records. Thirdly, a lot of COVID 19 related literature may be available in languages other than English and therefore restricting the publication language to English may not be ideal. Finally, the systematic reviews should be comprehensive and ideally it should cover multiple databases.

Both smoking and COVID 19 are individually known to harm cardiovascular and respiratory systems. Given the involvement of both the cardiovascular and respiratory systems in the disease progression of COVID 19, even quitting smoking for a few days may have beneficial effects. Further, smoking is often a group activity in public settings and it could further increase susceptibility for transmission of COVID 19. Therefore, quitting smoking may have additional benefits in the COVID 19 season.

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China

by:
Lucrecia M. Burgos

Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the 2019 novel corona virus (2019-nCoV) disease (COVID-19). On the other hand, COVID-19 can, in turn, aggravate the damage to the heart, according to a meta-analysis in the Clinical Research in Cardiology Journal1.

The analysis included six studies with 1527 patients, all of the selected studies were published in 2020 with different sample patient sizes that ranged from 11 to 1099 patients.

In all of the studies, men were more likely to be infected than women and the most prevalent cardiovascular metabolic comorbidities were hypertension (17.1%, 95% CI 9.9–24.4%), cardiovascular diseases (CVD) (16.4%, 95% CI 6.6–26.1%), and diabetes (9.7%, 95% CI 6.9–12.5%).  The researchers compared the difference of the prevalence of these three diseases between severe patients and non-severe patients (or ICU vs non-ICU patients according to the data in the studies). The proportion of hypertension (RR = 2.03, 95% CI 1.54, 2.68) and CVD (RR = 3.30, 95% CI 2.03, 5.36) were both statistically significant higher in ICU/severe patients compared to non-ICU/severe patients. Diabetes accounted for 11.7% of ICU/severe cases, but 4.0% of non-ICU/severe cases, but without statistical significance P = 0.09.

Finally, they focused on the impact of the COVID-19 on the cardiac injury, only two studies that gave clear data were statistically analysed, and the data showed that 8.0% (95% CI 4.1–12.0%) patients might have suffered from an acute cardiac injury.

The authors note that due to the sample size and limited time so far, data collection is still incomplete, and most of the studies have not analysed comorbidities in death cases. So the relationship between cardiovascular metabolic diseases and COVID-19-induced death cannot be determined. In addition, the results should be interpreted with caution, since it presents considerable heterogeneity across the identified studies, and they did not conduct sensitivity and subgroup analysis.

The lack of widespread testing, national surveillance and standardized data collection, as well as the potential sampling bias in sicker, hospitalized patients with more comorbidities, has complicated efforts to accurately estimate the prevalence of cardiovascular and metabolic diseases in patients with COVID-192. Moreover, the prevalence of various cardiovascular comorbidities and their impact on clinical outcomes seem to vary considerably across different geographic locations3.

The mechanism of these associations remains unclear at this time. Potential explanations include CVD being more prevalent in those with advancing age, a functionally impaired immune system, proinflammatory state, elevated levels of ACE2, or a predisposition to COVID-19 for those with CVD4. 

The patients with pre-existing cardiovascular risk factors and CVD appear to have heightened vulnerability to develop COVID-19 and tend to have more severe disease with worse clinical outcomes. Continued monitoring of cardiovascular metabolic diseases as possible risk factors for poor prognosis should be considered.  Additional study is needed to understand the causal pathways that may increase vulnerability in this population and the potential mechanistic relationships between CVD and COVID-19 outcomes.

References:

  1. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020. DOI: https://doi.org/10.1007/s00392-020-01626-9.
  2. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-Zoccai G, et al. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic. J Am Coll Cardiol. 2020: S0735-1097(20)34637-4. DOI: https://doi.org/10.1016/j.jacc.2020.03.031.
  3. Bansal M. Cardiovascular disease and COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020. DOI: https://doi.org/10.1016/j.dsx.2020.03.013.
  4. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease. Circulation. 2020. DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.046941.

Should cardiovascular disease comorbidity scare you during the COVID-19 season?

by:
Dr. Jeemon Panniyammakal, PhD, MPH, FESC

The SARS-CoV-2 infection (corona virus infection) spread has reached pandemic proportions. Globally, as on 31 March, 2020 nearly 0.8 million corona virus disease (COVID-19) cases and 38,000 related deaths are reported. Countries around the world are particularly “shielding” or “protecting” individuals with cardiovascular disease (CVD) from external exposure (https://www.cdc.gov/coronavirus/2019-ncov/hcp/underlying-conditions.html) due to the observed spectrum of comorbidities in the initial and subsequent reports of deaths from COVID-19. 

In this context, the analyses by Zhou et al presented in the Lancet journal and published on 11th March 2020, is thought provoking and interesting (https://doi.org/10.1016/S0140-6736(20)30566-3). In their laboratory confirmed cohort of 191 COVID-19 patients (62% males) from two major centres in China, 54 patients died in the hospital. The authors’ identified several factors associated with mortality by comparing the patient characteristics across survivors and non-survivors. Let us focus on the cardiovascular disease (CVD) related conditions. Hypertension was reported in 48% (26/54) and 23% of non-survivors and survivors, respectively. Diabetes was reported in 31% (17/54) of non-survivors, while it was 14% in survivors. Similarly, coronary heart disease was reported in 24% (13/54) and 1% (2/137) of non-survivors and survivors, respectively. During the hospitalisation period, acute cardiac injury was reported in 59% (32/54) of non-survivors, while it was just 1% in survivors. Similarly, 52% (28/54) and 12% of non-survivors and survivors reported heart failure during the hospitalisation period, respectively. The multi-variate model presented in the Zhou et al paper was however not robust enough to detect meaningful differences in cardiovascular conditions across the two groups due to inadequate sample size. 

The findings from Zhou et al paper suggest that co-morbid cardiovascular conditions probably increase the risk of mortality in COVID-19 patients. Consistent findings are also reported in other papers. For example, the case fatality was reported as 3-5 times higher in COVID-19 patients with hypertension, diabetes and cardiovascular diseases in an analyses of over 72,314 cases from China (https://doi:10.1001/jama.2020.2648). However, the relatively higher background mortality rate in patients with CVD in comparison to the general population should be accounted while comparing the case fatality rate. 

The findings from Zhou et al paper also suggest that in COVID-19 patients, the infection itself can probably increase CVD complications and death. However, it is not clear whether the CVD complications are more pronounced in individuals with background cardiovascular comorbid conditions. Acute myopericarditis (pericarditis is the inflammation of the thin tissue sac that surrounds the heart) in an apparently healthy male COVID-19 patient, several days after the symptom onset and even without the symptoms and signs of interstitial pneumonia, in a recent case report indicates a possible direct association with SARS-CoV-2 infection (https://doi:10.1001/jamacardio.2020.1096). Similarly, higher incidence of myocardial injury has been reported in patients with SARS-CoV-2 infection (doi:10.1001/jamacardio.2020.0950 and doi:10.1001/jamacardio.2020.1017).   Myocardial injury, cardiac arrhythmia, cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, venous thromboembolisms are some of the known cardiovascular sequel seen in patients with COVID-19. 

The higher incidence of cardiovascular outcomes in COVID-19  may be associated directly with the infection or the physiological response to the infection and the background comorbidity status. The mechanisms could be manifold, and multifactorial. However, the complex and often bi-directional relationship observed in a restricted number of high risk hospitalised patients may limit the causal interpretation of the observed association. We need to generate more data on cardiovascular comorbidities in COVID-19 patients and their likely impact on disease severity and survival for better management, future planning and resource allocation.