Covid-19: hypertension risk for severe illness

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A new study by researchers from Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center has alarmingly found that individuals with high blood pressure or hypertension have a higher risk of disease severity and getting hospitalized when infected with the various Omicron variants especially the new BA.5 variant and subvariants and also the BA.2.75, BA.2.77 and BA.2.78 variants, irrespective of vaccination status!

The early preliminary study findings were published in the peer reviewed journal: Hypertension (A Journal of the of the American Heart Association)
https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.122.19694
 

apid development of vaccines against SARS-CoV-2 led to substantial reductions in morbidity and mortal- ity early in the pandemic. Concerns regarding waning immunity and the risk of emerging new variants, including Omicron, prompted recommendations for a third booster vaccine dose after completion of a 2-dose mRNA vaccine regimen, given its efficacy at further reducing risk for severe illness by up to 70%.1

However, a proportion  of individuals who received 3 mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge. We sought to understand the characteristics associated with severe Omicron infection, necessitating hospitalization, despite having completed a full 3-dose mRNA vaccine regimen.

We conducted a retrospective cohort study of adults who received at least 3 mRNA vaccine doses but were subsequently treated for confirmed COVID-19 infection in our academic health care system during the Omicron surge onset  in  our  region  and  had  at  least  2 outpatient visits within the preceeding 2 years.

All laboratory testing for COVID-19 was performed using rtPCR of extracted RNA from nasopharyngeal  swabs. We obtained demographic (age, sex, and race/ethnicity), clinical, and outcomes data from the electronic health record and manually confirmed the validity  of key variables.

We used the International Classification of Diseases, Tenth Revision, diagnoses to identify spe- cific clinical characteristics previously associated with COVID-19 severity, including diabetes, chronic kidney disease (CKD), prior myocardial infarction (MI) or heart failure (HF), and prior chronic obstructive pulmonary disease or asthma. Hypertension was defined by the International Classification of Diseases, Tenth Revision, code or the prescription of antihypertensive pharma- cotherapy. Obesity was defined as a calculated body mass index of ³30 kg/m2.

Patients  with  missing  data on key variables were excluded. We also curated electronic health record data on ACE (angiotensin- converting enzyme) inhibitor, angiotensive receptor blocker, and statin use and days from the most recent SARS-CoV-2  vaccine  dose   to   confirmed   infection.  

In statistical analyses, we used multivariable logistic regression to  assess  for  associations  between  each  of the characteristics listed above and risk of hospi- talization. To minimize confounding by indication for ACE inhibitor/angiotensive receptor blocker use, we performed 2 separate sensitivity analyses: first, we removed ACE inhibitor/angiotensive receptor blocker from the multivariable analyses; second, we excluded individuals with a history of CKD, MI, or HF. All analyses were conducted using R v4.0.2, with a 2-tailed P<0.05 considered significant.

Overall, we identified a total of 912 individuals who received ³3 mRNA vaccine doses and were subsequently diagnosed with COVID-19 during the Omicron surge, of whom 145 (15.9%) required hospitalization. Demographic and clinical characteristics of the  cohort are shown in the Figure.

In multivariable analyses, factors significantly associated with risk of  hospitalization for Omicron infection included older age, hypertension, CKD, and MI or HF, as well as longer duration between the  last  vaccination  and  infection  (Figure). 

Notably, the presence of hypertension was associated with the greatest magnitude of risk, which remained significant in sensitivity analyses excluding  patients  with  a  history of CKD, MI, or HF. Results were similar when ACE inhibitor/angiotensive receptor blocker use was removed from the model.

Our findings reveal a persistent and marked association  between  hypertension  and  risk  for  severe COVID-19 illness, even among a fully vaccinated patient population. The Omicron variant  of  SARS-CoV-2  has led to overall less severe COVID-19 illness in most affected individuals when compared with prior variants—with morbidity and mortality even further reduced by receiving 3 doses of vaccine.

Our findings were con- sistent with prior studies demonstrating greater hos- pitalization risk with advanced age and time since the  last vaccine dose.2 Even when controlling for these and other clinical variables, the risk of hospitalization related to breakthrough Omicron infection was more than dou- bled by the presence of hypertension.

Recognizing that hypertension is quite prevalent in the setting of  high- risk conditions such as CKD, MI, and HF,  we  repeated our analyses excluding patients with these diagnoses  and found still substantial and significant risks associ- ated with hypertension. Our findings extend from prior reports of equivocal or potentially confounded asso- ciations of hypertension with COVID-19  illness  sever-  ity that were based on analyzing early pandemic and particularly pre-Omicron outcomes data.3

In the context of shifts in the risk factors associated with more severe forms of COVID-19 during the course of the pandemic,4 our  results  indicate  persistence  and  even accentuation of hypertension-related risk in  the  setting of a more transmissible albeit generally less virulent strain of SARS-CoV-2 and in the era of multidose vaccination.

Although the mechanism for hypertension- associated COVID-19 risk remains unclear,  prior  stud- ies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hyperten- sive patients, which may contribute to greater disease severity.5 Additional studies in separate cohorts are also needed to validate and assess  the  generalizability  of  our results.

Given that hypertension is one of the most prevalent chronic medical conditions, affecting individuals across the age spectrum, concordant findings would suggest  the  need  for  further  investigations  focused  on understanding the hypertension-specific risks from SARS-CoV-2 and on identifying individual- and popuation-level strategies for mitigating these risks as the pandemic transitions to an endemic.

Figure. Risk factors for Omicron infection requiring hospitalization, despite receiving prior booster vaccination.
A, Demographic and clinical characteristics. B, Multivariable-adjusted risk factors for hospitalization in the total cohort. C, Risk factors for hospitalization in the cohort without chronic kidney disease (CKD), myocardial infarction (MI), or heart failure (HF). All multivariable analyses are adjusted for the covariates displayed in addition to race/ethnicity. Age estimates shown are per 10 years of age. Time from vaccine to infection represents the interval (per 10 days) between the date of the last vaccine dose received (ie, booster) and the date of COVID-19 infection diagnosed during the Omicron surge period. ACE indicates angiotensin-converting enzyme inhibitor; ARB, angiotensive receptor blocker; and COPD, chronic obstructive pulmonary disease.

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