OHCA epidemiology in the era of the Omicron variant: Insights from Shanghai

The SARS-CoV-2 (COVID-19) pandemic has impacted the worldwide epidemiology of out-of-hospital cardiac arrest (OHCA) with multiple publications reporting increased incidence and worsened outcomes in communities.1Lai P.H. Lancet E.A. Weiden M.D. et al.Characteristics associated with out-of-hospital cardiac arrests and resuscitations during the novel coronavirus disease 2019 pandemic in New York City.JAMA Cardiol. 2020; 5: 1154-1163Crossref PubMed Scopus (181) Google Scholar, 2Baldi E. Sechi G.M. Mare C. et al.Out-of-hospital cardiac arrest during the COVID-19 outbreak in Italy.N Engl J Med. 2020; 383: 496-498Crossref PubMed Scopus (425) Google Scholar, 3Lim Z.J. Ponnapa Reddy M. Afroz A. et al.Incidence and outcome of out-of-hospital cardiac arrests in the COVID-19 era: A systematic review and meta-analysis.Resuscitation. 2020; 157: 248-258Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 4Chan P.S. Girotra S. Tang Y. Al-Araji R. Nallamothu B.K. McNally B. Outcomes for out-of-hospital cardiac arrest in the United States during the coronavirus disease 2019 pandemic.JAMA Cardiol. 2021; 6: 296-303Crossref PubMed Scopus (88) Google Scholar, 5Uy-Evanado A. Chugh H.S. Sargsyan A. et al.Out-of-hospital cardiac arrest response and outcomes during the COVID-19 pandemic.JACC Clin Electrophysiol. 2021; 7: 6-11Crossref PubMed Scopus (47) Google Scholar, 6Teoh S.E. Masuda Y. Tan D.J.H. et al.Impact of the COVID-19 pandemic on the epidemiology of out-of-hospital cardiac arrest: a systematic review and meta-analysis.Ann Intensive Care. 2021; 11: 169Crossref PubMed Scopus (32) Google Scholar Much of this epidemiology is derived from the early part of the pandemic when the circulating variants were highly virulent, and the population lacked immunity from either natural infection or vaccination. Since March 11, 2020, when COVID-19 was formally declared a pandemic by the World Health Organization, vaccines have been developed and widely distributed while the virus has simultaneously evolved to become less pathogenic but also more transmissible. The Omicron variant (B.1.1.529) which was first identified in southern Africa is the one most mutated circulating variants and has been shown to evade immunity induced by prior infection or vaccination.7Fan Y. Li X. Zhang L. Wan S. Zhang L. Zhou F. SARS-CoV-2 Omicron variant: recent progress and future perspectives.Signal Transduct Target Ther. 2022; 7: 141Crossref PubMed Scopus (114) Google Scholar Early studies investigating the worsened OHCA outcomes such as restoration of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge and the Utstein bystander survival highlighted multiple contributing factors.8Kovach C.P. Perman S.M. Impact of the COVID-19 pandemic on cardiac arrest systems of care.Curr Opin Crit Care. 2021; 27: 239-245Crossref PubMed Scopus (15) Google Scholar This included an increase in the number of OHCA caused by hypoxemic respiratory failure presenting with non-shockable initial rhythms which are inherently associated with worsened outcomes.3Lim Z.J. Ponnapa Reddy M. Afroz A. et al.Incidence and outcome of out-of-hospital cardiac arrests in the COVID-19 era: A systematic review and meta-analysis.Resuscitation. 2020; 157: 248-258Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 4Chan P.S. Girotra S. Tang Y. Al-Araji R. Nallamothu B.K. McNally B. Outcomes for out-of-hospital cardiac arrest in the United States during the coronavirus disease 2019 pandemic.JAMA Cardiol. 2021; 6: 296-303Crossref PubMed Scopus (88) Google Scholar, 6Teoh S.E. Masuda Y. Tan D.J.H. et al.Impact of the COVID-19 pandemic on the epidemiology of out-of-hospital cardiac arrest: a systematic review and meta-analysis.Ann Intensive Care. 2021; 11: 169Crossref PubMed Scopus (32) Google Scholar The restructuring of healthcare systems globally also played a role with decreased access for prevention and control of chronic diseases (e.g. hypertension, diabetes, hyperlipidemia, etc.) associated with OHCA risk and as well as decreased availability of early cardiovascular diagnostic testing in particular coronary artery cardiac catheterization.8Kovach C.P. Perman S.M. Impact of the COVID-19 pandemic on cardiac arrest systems of care.Curr Opin Crit Care. 2021; 27: 239-245Crossref PubMed Scopus (15) Google Scholar This was further compounded by the reluctance of patients to seek care for early warning symptoms of myocardial ischemia due to fears of contracting the virus.8Kovach C.P. Perman S.M. Impact of the COVID-19 pandemic on cardiac arrest systems of care.Curr Opin Crit Care. 2021; 27: 239-245Crossref PubMed Scopus (15) Google Scholar Another factor identified in early studies was the weakened chain of survival for OHCA.5Uy-Evanado A. Chugh H.S. Sargsyan A. et al.Out-of-hospital cardiac arrest response and outcomes during the COVID-19 pandemic.JACC Clin Electrophysiol. 2021; 7: 6-11Crossref PubMed Scopus (47) Google Scholar, 6Teoh S.E. Masuda Y. Tan D.J.H. et al.Impact of the COVID-19 pandemic on the epidemiology of out-of-hospital cardiac arrest: a systematic review and meta-analysis.Ann Intensive Care. 2021; 11: 169Crossref PubMed Scopus (32) Google Scholar, 8Kovach C.P. Perman S.M. Impact of the COVID-19 pandemic on cardiac arrest systems of care.Curr Opin Crit Care. 2021; 27: 239-245Crossref PubMed Scopus (15) Google Scholar This included less public location arrests due to social distancing mandates, lower bystander CPR rates and lower public AED use due to concerns of virus transmission, as well as longer EMS response times related to resource limitations as well the need for enhanced PPE. Of note, these impacts were noted in communities with both low and high mortality rates related to COVID-19 but higher in the latter communities.4Chan P.S. Girotra S. Tang Y. Al-Araji R. Nallamothu B.K. McNally B. Outcomes for out-of-hospital cardiac arrest in the United States during the coronavirus disease 2019 pandemic.JAMA Cardiol. 2021; 6: 296-303Crossref PubMed Scopus (88) Google Scholar, 5Uy-Evanado A. Chugh H.S. Sargsyan A. et al.Out-of-hospital cardiac arrest response and outcomes during the COVID-19 pandemic.JACC Clin Electrophysiol. 2021; 7: 6-11Crossref PubMed Scopus (47) Google Scholar Given the evolution of the virus as well as increasing natural and acquired immunity as well as the lifting of public health measures, one would anticipate that survival from OHCA will improve. It is challenging however to appreciate whether the changes in OHCA survival are related to the changes in the circulating virus strain, vaccination efforts or due to chain of survival influences related to event, patient, EMS, and hospital treatment factors. Indeed, little is known about the long term impact of SARS-CoV-2 on OHCA epidemiology. In this issue of resuscitation, Li et al.9Li G. Zhang W. Jia D. Rong J. Yu Z. Wu D. Epidemic of the SARS-CoV-2 Omicron variant in Shanghai, China in 2022: Transient and persistent effects on Out-of-hospital cardiac arrests.Resuscitation. 2023; 186: 109722Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar report on the impact of an Omicron variant outbreak on the incidence and outcomes from OHCA in Shanghai, China. This experience is valuable since the strict zero-COVID policy in China combined with their restrictive lockdown efforts that were implemented rapidly during outbreaks, provides unique short term as well as longer epidemiological insights not yet available from other registries. Li and colleagues retrospectively examine electronic health records of patients seen for OHCA by the Shanghai Emergency Medical Center (SEMC) during 5 periods from January 1, 2018, to September 30, 2022.9Li G. Zhang W. Jia D. Rong J. Yu Z. Wu D. Epidemic of the SARS-CoV-2 Omicron variant in Shanghai, China in 2022: Transient and persistent effects on Out-of-hospital cardiac arrests.Resuscitation. 2023; 186: 109722Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The focus was on the time frame when the BA.2 subvariant of Omicron entered the community resulting in a strict lockdown from March 28, 2022, through May 31, 2022. The SEMC provides an EMS physician response to OHCA for approximately 1/3 of the city population which is estimated to be 25 million. OHCA data is recorded using an Utstein-style template and includes outcome information as well as independent quality monitoring. Of note, cultural practices permit family members to accept natural death and refuse OHCA interventions such as CPR, defibrillation, or airway management from the SEMC. These authors found that the monthly number of OHCA doubled during the Omicron epidemic and this increase persisted through the early post-epidemic period before returning to the pre-epidemic levels. Not surprisingly ROSC rates also decreased during the outbreak and then slowly returned to pre-epidemic levels. Median response times were slower (21 min vs. 10 min) and more families declined SEMC resuscitation measures during the epidemic (22.2% vs 15.1%) compared to the pre-epidemic period. The OHCA patient demographics reported by Li et al. are markedly different than those previously reported by others.10Sayre M.R. Barnard L.M. Counts C.R. et al.Prevalence of COVID-19 in out-of-hospital cardiac arrest: Implications for bystander cardiopulmonary resuscitation.Circulation. 2020; 142: 507-509Crossref PubMed Scopus (54) Google Scholar The majority of patients were older elders (median age 84–85) and there was a nearly equal sex distribution. Many patients had significant underlying comorbidities, in particular hypertension, coronary artery disease, or stroke but interestingly only 0.6% of these OHCA were confirmed to be infected with SARS-CoV-2. This is not a surprise since similar findings have been previously reported.10Sayre M.R. Barnard L.M. Counts C.R. et al.Prevalence of COVID-19 in out-of-hospital cardiac arrest: Implications for bystander cardiopulmonary resuscitation.Circulation. 2020; 142: 507-509Crossref PubMed Scopus (54) Google Scholar Limitations of this study include its retrospective design, incomplete data capture, as well as a lack of information regarding how many of the OHCA patients had been vaccinated and received boosters given changes in the circulating variant. This is important to understand since vaccine hesitancy among older adults in China may have contributed to the increased mortality observed during the Omicron outbreak in Shanghai. In a recent paper from China, Wang et al. reported that individuals who were older than 70, female, unmarried, residing in urban areas, functionally dependent with chronic conditions were less likely to have received COVID-19 vaccines.11Wang G. Yao Y. Wang Y. et al.Determinants of COVID-19 vaccination status and hesitancy among older adults in China.Nat Med. 2023; (Jan 31: Epub ahead of print)Crossref Scopus (4) Google Scholar The authors also do not provide any specific details regarding how EMS protocols were modified during the epidemic which would help us better understand the increased response times since this can help with future epidemic planning.12Prezant D.J. Lancet E.A. Zeig-Owens R. et al.System impacts of the COVID-19 pandemic on New York City's emergency medical services.J Am Coll Emerg Physicians Open. 2020; 1: 1205-1213Crossref PubMed Scopus (17) Google Scholar The authors do note that most hospitals closed during the Omicron epidemic to prevent in-hospital transmission and that the EMS system was also responsible for transferring COVID-19 patients to designated shelter hospitals in Shanghai for observation and treatment. The authors hypothesize that chronic disease management may have been limited by reduced access and that movement restrictions as well as fear of acquiring infection from the healthcare system may have been contributing factors for the increased mortality. Unfortunately, we are not provided with additional system level data that would support these assertions although others have reported lower hospitalization rates of patients with STEMI and acute stroke during the pandemic.8Kovach C.P. Perman S.M. Impact of the COVID-19 pandemic on cardiac arrest systems of care.Curr Opin Crit Care. 2021; 27: 239-245Crossref PubMed Scopus (15) Google Scholar The findings reported by Li et al. resemble published studies examining the impact of influenza epidemics on the incidence and outcomes from OHCA.13Muller A. Dyson K. Bernard S. Smith K. Seasonal variation in out-of-hospital cardiac arrest in Victoria 2008–2017: Winter peak.Prehosp Emerg Care. 2020; 24: 769-777Crossref PubMed Scopus (11) Google Scholar, 14Suematsu Y. Kuwano T. Yamashita M. et al.Adult influenza epidemic is associated with out-of-hospital cardiac arrest: From the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational registry.Medicine. 2022; 17: 101Google Scholar, 15Onozuka D. Hagihara A. Extreme influenza epidemics and out-of-hospital cardiac arrest.Int J Cardiol. 2018; 263: 158-162Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar These studies reported increased in OHCA incidence as well worsened outcomes highlighting the importance of preventive public health measures such as vaccination. Older patients with underlying co-morbidities as well as less robust responses to vaccination appear to those at highest risk for such events.16Liu Y. Ge L. Fan S. Xu A. Wang X. et al.Disease progression of hospitalized elderly patients with Omicron BA.2 treated with Molnupiravir.Infect Dis Ther. 2022; 11: 2241-2251Crossref PubMed Scopus (3) Google Scholar, 17Zhong W. Yang X. Jiang X. et al.Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2.Front Public Health. 2023; 10: 1087800Crossref PubMed Scopus (2) Google Scholar Moreover, epidemics often result in less than optimal management of co-morbidities since existing resources are over-whelmed. Strategies are also needed to mitigate the effects of isolation, social distancing, and disenfranchisement from the healthcare system during these events. Access to health care is challenging for older patients since the traditional model of care requires that a patient travel to see their health care provider. It would be valuable to examine if some of the burden of OHCA observed during influenza epidemics could be mitigated by alternate models of care for vulnerable populations such as the in-person delivery of healthcare at home, telemedicine, remote physiological monitoring, point of care testing, and if available, the early initiation of therapy. The SARS-CoV-2 virus is now endemic and as the virus continues to evolve, it is important that we continue to actively track its impact of the epidemiology of OHCA in communities with a particular focus on older adults as well as those with underlying cardiovascular co-morbidities. Understanding OHCA epidemiology during epidemics provides us with a unique opportunity to examine population outcomes for other medical conditions as well as access to health care related issues. Dr. Daya receives grant support from the NIH and DoD and Dr. Jui receives grant support from the NIH. The authors report no other conflicts of interest.