History of COVID-19 and Overall Survival Among Medicare Beneficiaries Hospitalized with Acute Ischemic Stroke, Medicare Cohort 2020-2021

    


    


    Figure 1: Overall Survival among AIS patients with and without history of COVID-19, Medicare 2020-2021.

    

Discussion

This study’s findings suggest significantly lower overall survival following AIS admissions among Medicare FFS beneficiaries aged 65 years or older with a history of COVID-19 diagnoses in the United States. Compared to AIS beneficiaries without COVID-19 diagnoses, the risk of mortality was 30% and 6% higher among beneficiaries with a history of hospitalized and non- hospitalized COVID-19, respectively.

The negative impact of COVID-19 on overall survival in this study is consistent with other studies [2,6–11]. Many studies assessed the incidence, risk factors, and outcomes of AIS in hospitalized patients with COVID-19, reporting an increased risk of AIS among COVID-19 patients and higher risk of in-hospital mortality [2,6,7]. A meta-analysis of observational cohort studies reported that stroke patients with COVID-19, had an almost 5-times higher probability of in-hospital mortality compared to their noninfected counterparts [8]. Several studies found that ischemic stroke patients with COVID-19 had more severe strokes and higher mortality than those without COVID-19 [3,9-11]. However, most studies focused on the outcomes among hospitalized patients with COVID-19; we are not aware of any study examining overall survival among AIS patients with history of COVID-19 by hospitalization status. Our study shows that the AIS Medicare FFS beneficiaries with a history of COVID-19 had significantly shorter mean overall survival (488 days and 587 days for hospitalized and non-hospitalized COVID-19) vs. 679 days without history of COVID-19. The corresponding adjusted 1-year overall survival was 62%, 67% and 69%, respectively.

Evidence indicates that acute cardiovascular complications represent an essential clinical manifestation of COVID-19, and COVID-19 appears to have both short-term and long-term effects on the risk of cardiovascular disease, including stroke [12-14]. Consistent with our findings, a study on the largest North American cohort of patients hospitalized with AIS and concurrent COVID-19 reported significantly higher mortality compared to historic non-COVID data indicating potentially poor outcomes associated with infection severity [13]. In addition, several studies suggested that the risk of ischemic stroke was significantly higher 28 days before and during after COVID-19 diagnosis as compared to the control periods, COVID-19 associated ischemic strokes were more severe, with worse functional outcomes and significantly higher mortality than non-COVID-19 associated ischemic strokes [2,12]. In our study, 32% and 13% of beneficiaries with history of hospitalized and non-hospitalized COVID-19, respectively, had AIS admissions within 30 days of the first COVID-19 diagnosis. The higher proportion of Medicare FFS beneficiaries with a history of hospitalized COVID-19 occurring =30 days before AIS hospitalization may partly explain the worse overall survival that we observed. However, we conducted sensitivity analyses by excluding the beneficiaries with =30 days interval from COVID-19 diagnosis to AIS hospitalization, and the association was slightly attenuated with adjusted mortality HRs of 1.26 (95% CI, 1.21-1.30), and 1.04 (95% CI, 1.01–1.08) for beneficiaries with hospitalized and non-hospitalized COVID-19, respectively.

Our study found the highest proportion of severe NIHSS, and comorbidities (except tobacco use), among the AIS Medicare FFS beneficiaries with history of hospitalized COVID-19. Subgroup analyses showed that the beneficiaries with history of COVID-19 hospitalizations had the worst overall survival as compared to those without COVID-19 across all age, sex, race/ethnicity, and SVI groups. The worse outcomes among the beneficiaries with history of hospitalized COVID-19 might be associated with more severe NIHSS, more baseline comorbidities, greater probability of ICU admissions, and longer length of stay during AIS admissions [15]. However, during the COVID-19 pandemic, studies reported that the overall quality of treatment and care for patients with AIS did not decline [16,17].

It is well documented that social inequities increase health disparities, and SVI data from CDC is a valuable tool for documenting the disparities in access to advanced stroke care [18,19]. In our study, we found more than 40% of AIS Medicare FFS beneficiaries lived in high SVI communities, and significantly more beneficiaries with a history of COVID-19 lived in high SVI communities, compared to their counterparts without COVID-19 diagnoses. Beneficiaries with a history of hospitalized COVID-19 living in high SVI communities had the worst 1-year overall survival, compared to those with a history of non-hospitalized COVID-19 and no COVID-19 diagnoses. Studies have reported that SVI is associated with cardiovascular risk factors and stroke mortality, and mortality rates attributable to stroke increased from lowest to highest SVI [20,21]. Among beneficiaries with hospitalized COVID-19, the 1-year adjusted overall survival of those living in moderate SVI communities was lowest. This might be due to the high risk of death among non-Hispanic White beneficiaries (we found the worst 1-year survival among non-Hispanic White beneficiaries with hospitalized COVID-19) who were more likely to live in low and moderate SVI areas [22]. Future studies are needed to explore the possible association between SVI and survival, and to identify risk factors associated with patients living in socially vulnerable communities.

This study’s findings may have important implications. A history of COVID-19, especially hospitalized COVID-19, was associated with significantly higher risk of all-cause mortality. Forty percent of AIS Medicare FFS beneficiaries lived in high SVI communities, and disproportionately higher numbers of such AIS beneficiaries had a history of COVID-19. These data may inform the future treatment and care for stroke patients to reduce long-term effects of COVID-19 and may highlight the disparities in stroke survival between those who lived in low and high socially vulnerable communities.

Our study has several limitations. First, AIS hospitalizations, COVID-19 diagnoses, and all-cause mortality were based on administrative records and limited to Medicare FFS beneficiaries aged 65 years or older. We may have omitted some beneficiaries with diagnosed COVID-19, diagnosed AIS, or incorrect diagnoses dates of COVID-19, due to our using preliminary Medicare monthly data. Second, NIHSS scores were based on ICD-10 codes, which may potentially be inaccurate. Third, although our analysis adjusted for several covariates and selected commodities, we cannot rule out the possibility that the beneficiaries with a history of hospitalized COVID-19 might have an overall worse health status and decreased survivals after AIS. However, the differences in survivals between non-hospitalized COVID-19 and no-COVID-19 stroke patients may be informative and more likely associated with history of COVID-19. Lastly, the findings based on FFS beneficiaries may not be generalizable to Medicare beneficiaries covered under health maintenance organization plans, due to possible differences in beneficiary characteristics with the two types of coverage.

Conclusions

Our findings suggest that a history of COVID-19 diagnoses, especially those with a history of severe COVID-19, is associated with significantly reduced survival among Medicare FFS beneficiaries hospitalized with AIS.

References

1. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al. Heart Disease and Stroke Statistics-2022 Update: a Report from the American Heart Association. Circulation. 2022; 145: e153–e639.
2. Yang Q, Tong X, George MG, Chang A, Merritt RK. COVID-19 and risk of acute ischemic stroke among Medicare beneficiaries aged 65 years or older: self-controlled case series study. Neurology. 2022; 98: e778–89.
3. Martí-Fàbregas J, Guisado-Alonso D, Delgado-Mederos R, Martínez-Domeño A, Prats-Sánchez L, Guasch-Jiménez M, et al. Impact of COVID-19 infection on the outcome of pateints with ischemic stroke. Stroke. 2021; 52: 3908–17.
4. CDC/ATSDR Social Vulnerability Index (SVI).
5. Centers for Medicare & Medicaid Services. Chronic conditoins data warehouse.
6. Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, et al. Risk, clinical course, and outcome of ischemic stroke in patients hospitalized with COVID-19: a multicenter cohort study. Stroke. 2021; 52: 3978–86.
7. Shakil SS, Emmons-Bell S, Rutan C, Walchok J, Navi B, Sharma R, et al. Stroke among patients hospitalized with COVID-19: results from the American Heart Assoication COVID-19 Cardiovascular Disease Registry. Stroke. 2022; 53: 800–07.
8. Katsanos AH, Palaiodimou L, Zand R, Yaghi S, Kamel H, Navi BB, et al. The impact of SARS-CoV-2 on stroke epidemiology and care: a meta-analysis. Ann Neurol. 2021; 89: 380–88.
9. Liu JL, Shah K, Marji A, Sareini R, Bhasin A, Rao S, et al. Descriptive analysis of acute ischemic stroke in COVID-19 patients through the course of the COVID-19 pandemic. Journal of Clinical Neuroscience. 2022; 96: 221–26.
10. Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: a systematic review and meta-analysis. International Journal of Stroke. 2021; 16: 137–49.
11. Srivastava PK, Zhang S, Xian Y, Xu H, Rutan C, Alger HM, et al. Acute ischemic stroke in patients with COVID-19: an analysis from Get with the Guidelines–Stroke. Stroke. 2021; 52: 1826–29.
12. Kastoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, Connolly AMF. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet. 2021; 398: 599–607.
13. Dmytriw AA, Dibas M, Phan K, Efendizade A, Johanna O, Schirmer C, et al. Acute ischemic stroke associated with SARS-CoV-2 infection in North America. Journal Neurol Neurosurg Psyschiatry. 2022; 93: 360-368.
14. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nature Medicine. 2022; 28: 583–90.
15. Amiri HA, Razavi AS, Cheraghmakani H, Baghbanian SM, Sedaghat-Chaijan M, Zarvani A, et al. The effects of COVID-19 on patients with acute ischemic and hemorrhagic stroke. Journal of Stroke and Cerebrovascular Disease. 2022; 31: 106512.
16. Myers LJ, Perkins AJ, Kilkenny MF, Bravata DM. Quality of care and outcomes for patients with acute ischemic stroke and transient ischemic attack duing the COVID-19 pandemic. Journal of Stroke and Cerebrovascular Disease. 2022; 31: 106455.
17. Tong X, Coleman King SM, Asaithambi G, Odom E, Yang Q, Yin X, et al. COVID-19 pandemic and quality of care and outocmes of acute stroke hospitalizations: the Paul Coverdell National Acute Stroke Program. Preventing Chronic Disease. 2021; 18: E82.
18. Arcaya MC, Arcaya AL, Subramanian SV. Inequalities in health: definitions, concepts, and theories. Global Health Action. 2015; 8: 27106.
19. Isenberg DL, Isenberg R, Henry KA, Kraus CK, Ackerman D, Sigal A, et al. Assessing disparities in access to advanced stroke care in 4 northeastern states using the social vulnerability index. Stroke Vasc Interv Neurol. 2023; 3: e000684.
20. Khan SU, Javed Z, Lone AN, Dani SS, Amin Z, Al-Kindi SG, et al. Social vulnerability and premature cardiovascular mortality among US counties, 2014 to 2018. Circulation. 2021; 144: 1272–79.
21. Bevan G, Pandey A, Griggs S, Dalton JE, Zidar D, Patel S, et al. Neighborhood-level social vulnerability and prevalence of cardiovascular risk factors and coronary heart disease. Current Problems in Cardiology. 2022; 48: 101182.
22. Rifai MA, Jain V, Khan SU, BK A, Mahar JH, Krittanawond C, et al. State-level social vulnerablitiy index and healthcare access: the Behavioral RIsk Factor Surveillance System Survey. American Journal of Preventive Medicine. 2022; 63: 403–09.