SARS-CoV-2 Infection Concurrent with Acute Stroke: A Case Study of Aged People Partially Vaccinated Against COVID-19

Abstract

Background:

Elderly people have largely been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) because of their higher risk of coronavirus disease 2019 (COVID-19). Little is known about the efficacy of such vaccines in elderly people with cerebrovascular diseases.

Method:

Here, we present the preliminary results of serology (IgA and IgG) and molecular testing for SARS-CoV-2 in a case series of elderly patients who were admitted with an acute stroke and had received a single dose of the COVID-19 vaccine in a city of northeastern Brazil. Currently, we are enquiring from 11 Brazilian neurology centers for their data and openly inviting groups that are working in this field to collaborate.

Results:

Between January 28 and March 25, 14 patients with acute stroke and ages within the vaccine age ranges were admitted to our neurology center. Ten patients had received their first dose of the COVID-19 vaccine. Most patients were women over 80 years of age with vascular risk factors and ischemic stroke. Three patients aged >85 years had no anti-SARS-CoV-2 antibodies detectable. Three other patients had SARS-CoV-2 infection, among whom a man died a few days later.

Conclusion:

These cases exemplify how elderly people with cerebrovascular diseases and incomplete vaccination schemes can be susceptible to COVID-19.

Introduction

In March 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) as pandemic, leading to an urge to develop vaccines. The protocols of COVID-19 vaccine trials were mainly designed to detect, in a least amount of time, a 50% reduction in mild cases among adults.1 These protocols have underrepresented specific cohorts, such as older people, especially in low- and middle-income countries (LMIC).1 For instance, four large trials of the AstraZeneca COVID-19 vaccine included a Brazilian cohort of more than 3,000 participants, of which only 2% were over 70 years old.2

Since the end of 2020, elderly people have been vaccinated worldwide owing to their higher risk of COVID-19.1 A body of evidence indicates that elderly people have a higher risk of severe COVID-19, especially those with cardio or cerebrovascular diseases.3 –5 On the other hand, acute cerebrovascular events can complicate severe COVID-19.6 –10 However, there are a few data on the effect of COVID-19 vaccines on elderly people with cerebrovascular diseases, especially in LMIC.1,2,11 In Brazil, vaccination against COVID-19 was started on January 17, 2021.12 Since then, we have conducted a prospective case–control study at 11 Brazilian neurology centers (NeuroCOVID study) to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, COVID-19 vaccine status, and immune responses in 1,000 acute stroke cases.

Here, we preliminary report some challenging findings of 10 elderly patients who were enrolled in a singlecenter of the NeuroCOVID study. These patients had an acute stroke after receiving the first dose of the COVID-19 vaccine during the first 2 months of vaccination in a city at northeastern Brazil. We aim to show how elderly people with cerebrovascular diseases and incomplete vaccination schemes can be susceptible to COVID-19.

Materials and Methods

This study was supported by the Oswaldo Cruz Foundation-Fiocruz, the governmental research agency of the Ministry of Health of Brazil (Emergencial Fund to Combat COVID-19: Grant no. VPPCB-005-FIO-20-2-22). This study was approved by the Ethics Committee for Research on Human Beings of Aggeu Magalhães Institute-Fiocruz (approval no. CAAE36538320.9.0000.5190). All participants consented to participate and signed the consent form before being included in the study, and underwent clinical data and sample collection.

We selected elderly people who had already been vaccinated before study enrollment from among all patients from Recife, who were admitted with an acute stroke to the Hospital da Restauração, the main neurology center of our city (State of Pernambuco, northeastern Brazil). In the city of Recife, 125,000 elderly people aged 74–97 years were vaccinated between January 28 and March 22, 2021 (Table1).

Table1.

Data on the COVID-19 vaccine program of Recife, Brazil, January 28–March 22, 2021

Priority age ranges	Start of vaccination	No. of vaccinated people
>84 years old	January 28	18,487
80–84 years old	February 27	37,288
75–79 years old	March 6	30,874
70–74 years old	March 13	39,191
Total of vaccinated elderly people		125,840

Vaccination data from Recife/Pernambuco-Brazil available at https://conectarecife.recife.pe.gov.br/vacinometro/.

SARS-CoV-2 detection in the nasopharynx and serological anti-SARS-CoV-2 antibody testing were performed at baseline for all patients. Nasopharyngeal swabs for SARS-CoV-2 detection were repeated weekly in patients who remained in the hospital for more than a week. To detect SARS-CoV-2 in nasopharyngeal swabs, we used real-time polymerase chain reaction molecular methods: BIOMOL OneStep/COVID-19 kit (IBMP^©, Brazil) or 2019-nCoV RUO kit (IDT^©, Brazil). For serological testing, we used ELISA kits for anti-SARS-CoV-2 IgA and anti-SARS-CoV-2 IgG (Euroimmun^©, Germany).

Case Series Results

Between January 28 and March 25, 44 elderly patients from Recife were admitted with an acute stroke to the Hospital da Restauração. Fourteen patients were within the COVID-19 vaccine age range at admission, of which 10 patients had already received the first dose of COVID-19 vaccine a median of 10 days before the first neurologic symptoms (see case descriptions in Table2). These patients had received the chimpanzee adenoviral vectored vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca^©) or inactivated SARS-CoV-2 vaccine CoronaVac (Butantan-Sinovac^©).

Table2.

Case descriptions of patients admitted to a neurology emergency with an acute stroke after COVID-19 vaccines (Recife-Brazil, January 28–March 22, 2021)

Age and sex	Comorbidities	Acute clinical manifestation at admissiona	Brain CT images	Diagnostic	Outcomes	COVID-19 vaccine	Time from vaccine to stroke symptoms	SARS-CoV-2 RNA detection in swab	SARS-CoV-2 antibodies in serumb	Time from vaccine to serology
79 y/o female	Hypertension and diabetes	Alteration of the consciousness content with episodic delusional ideas during 7 days before	Hypodensity in left frontal lobe at admission	Acute lacunar stroke	Discharge at 2nd day without disability (mRS = 1)	ChAdOx1 nCoV-19 1st dose	8 days	Negative at 1st day of admission	IgA positive IgG positive	16 days
79 y/o male	Hypertension, dyslipidemia, and previous stroke	Dizziness, nausea, headache, dysarthria, and seizures	No brain acute damage at admission; bilateral subdural and subarachnoid hematomas, with compressive effect on the left side at 17th day (CT+MRI)	Acute hemorrhagic stroke	Discharge at 31st day with moderately severe disability (mRS = 4)	ChAdOx1 nCoV-19 1st dose	14 days	Negative at 5th and 8th day of admission	IgA positive IgG positive	25 days
81 y/o female	No known comorbidities	Dysarthria, reduction of consciousness, and right hemiplegia 2 days before	Hypodensity in left lentiform nucleus at admission	Acute lacunar stroke	Discharge at 6th day with mild disability (mRS = 2)	CoronaVac 1st dose	7 days	Negative at 2nd day of admission	IgA positive IgG negative	14 days
81 y/o female	Hypertension, dyslipidemia, coronary disease, previous stroke	Dysarthria plus right painful hemiparesis a day before	Hypodensity in left lentiform nucleus and external capsule at admission	Acute lacunar stroke	Discharge at 14th day with mild disability (mRS = 2)	CoronaVac 1st dose	8 days	Positive at 3rd day of admission	IgA positive IgG negative	12 days
82 y/o male	Dyslipidemia, hypertension, and diabetes	Reduction of consciousness and right hemiparesis a day before, SatO₂ 90%, high CRP, and neutrophil at admission	Hypodensity in left thalamus at admission; 25% of ground glass in both lungs at 4th day	Acute lacunar stroke and severe COVID-19	Death at 7th day (mRS = 6)	CoronaVac 1st and 2nd doses	23 days (1s dose); 0 day (2nd dose)	Positive at 4th day of admission	IgA positive IgG negative	28 days
83 y/o female	No known comorbidities	Dysarthria and right hemiparesis	Hypodensity in left peri-insular region, external capsule, and lentiform nucleus at admission	Acute lacunar stroke	Discharge at 9th day with mild disability (mRS = 2)	CoronaVac 1st dose	2 days	Negative at 8th day of admission	IgA positive IgG negative	10 days
86 y/o female	Hypertension and coronary disease	Dysarthria, left hemiplegia, and hemianesthesia 2 days before	Hypodensity in right media cerebral artery territory with compressive effect at admission	Acute large vessel ischemic stroke	Discharge at 18th day with moderate disability (mRS = 3)	ChAdOx1 nCoV-19 1st dose	48 days	Negative at 1st and positive at 10th day of admission	Not performed	51 days
87 y/o male	Hypertension, diabetes, previous coronary disease	Dysarthria and right hemiplegia	Hypodensity in the left corona radiata at admission	Acute lacunar stroke	Discharge at 3rd day with mild disability (mRS = 2)	ChAdOx1 nCoV-19 1st dose	7 days	Negative at 1st day of admission	IgA negative IgG negative	8 days
90 y/o female	Hypertension	Right hemiplegia and aphasia	No brain acute damage at admission	Acute lacunar stroke	Discharge at 7th day without disability (mRS = 1)	ChAdOx1 nCoV-19 1st dose	29 days	Negative at 1st day of admission	IgA negative IgG negative	30 days
97 y/o female	Hypertension	Right hemiplegia and reduction of consciousness	Hypodensity in left media cerebral artery territory at admission, and hematoma in lentiform nucleus with compressive effect	Acute hemorrhagic stroke	Death at 48th day (mRS = 6)	ChAdOx1 nCoV-19 1st dose	13 days	Negative at 2nd, 25th, 35th, and 42nd day of admission	IgA negative IgG negative	16 days

CT, computed tomography; y/o, year/old; mRS, modified Rankin Scale; ChAdOx1 nCoV-19, chimpanzee adenoviral vectored vaccine against COVID-19 (Oxford-AstraZeneca^©); CoronaVac, inactivated SARS-CoV-2 vaccine (Butantan-Sinovac^©); CRP, C-reactive protein; MRI, magnetic resonance imaging.

In patients without citations on the duration of the neurological picture, the symptoms started on the day of admission.

Tests performed at baseline (study enrollment).

Bold values indicate those patients who were susceptible to COVID-19.

The patients had a median age of 82 years (range 79–97 years); most of them were women (7/10) and presented with ischemic stroke (8/10). Only two patients over 80 years old had not known vascular risk factors, while most of cases had hypertension (8/10), isolated (2/10), or combined with diabetes (2/10), dyslipidemia (3/10), coronary disease (3/10), or previous stroke (2/10). Seven patients tested negative for SARS-CoV-2 in swabs. Among these swab-negative patients, two 79-year-old patients had IgA and IgG anti-SARS-CoV-2 antibodies detected, and two patients aged 81–83 years tested only IgA positive at the 3rd- or 4th-week postvaccine. Three other patients over 85 years of age had both IgA and IgG antibodies undetectable in serum at the 2nd-, 3rd-, and 5th-week postvaccine, respectively.

Three (3/10) patients had SARS-CoV-2 detected in their swabs during admission, at 12th-, 28th-, and 51st-day postvaccine, respectively. An 81-year-old asymptomatic woman probably became infected in the community (swab positive on the 3rd-day of admission), despite having IgA detected in her serum. A 86-year-old asymptomatic woman was found to be infected on the 10th day of admission, despite being at 51st-day after vaccination (serology was not performed). A 82-year-old man was admitted the first day of stroke and with symptoms of COVID-19 despite a positive IgA at 28th-day postvaccine. His swab yielded SARS-CoV-2 RNA on 4th-day of admission, a chest computed tomography showed 25% of ground glass in both lungs, and he died a few days later.

Discussion

In our hospital-based case series, elderly patients with stroke had a rate of primary vaccination against COVID-19 of 70% (10/14) during the first 2 months of the Brazilian National Planning of Vaccination against COVID-19.12 Among the vaccinated patients, six (60%) were susceptible to COVID-19 because they had no antibodies or were infected with SARS-CoV-2. An older patient died after being admitted with stroke concurrent with COVID-19. Curiously, all susceptible patients were >80 years of age.

Although both ChAdOx1 nCoV-19 and CoronaVac have two dose schemes to maximize efficacy, a single dose can be effective against mild disease in the general population and in healthy elderly individuals.2,11 In a CoronaVac trial with 349 healthy elderly participants in China, 54% had seroconverted by the 28th day after the first dose,11 which agrees with the serology results of our elderly patients. In turn, in a trial with single doses of ChAdOx1 nCoV-19 in the general population from the United Kingdom, Brazil, and South Africa, only 32/9,257 (0.35%) had SARS-CoV-2 infection by the 90th-day postvaccination.2 In these trials, there were no lethal COVID-19 cases among vaccinated individuals.2,11 Accordingly, in a Chilean prospective national cohort, there were only 0.16% of deaths for COVID-19 among 542,418 people who were partially vaccinated with CoronaVac.13

Evidence from retrospective studies worldwide, before the COVID-19 vaccination began, indicates a two-way risk association between stroke and severe COVID-19.14,15 However, whether SARS-CoV-2 infection is more frequent or lethal in partially vaccinated elderly people with cerebrovascular diseases remains unclear. Our study was conducted during the first phase of COVID-19 vaccination program, and, thus, we have no data on susceptibility of elderly patients after a booster dose. Nevertheless, we believe that the high frequency of SARS-CoV-2 infection (30%) in our small sample of elderly individuals with cerebrovascular disease is worthy of attention, especially because of the lethal COVID-19 case.

Conclusions

This paper is a preliminary report from the first prospective study on associations among stroke, subclinical SARS-CoV-2 infection, and COVID-19 vaccines (NeuroCOVID study). This case series reinforces the importance of the universal testing for SARS-CoV-2 in elderly people with acute stroke, as well point toward the old-aged people with cerebrovascular diseases as a priority for COVID-19 vaccine boosters. Eventually, we suggest closely monitoring such a population within the vaccination programs and to better examine the stroke-SARS-CoV-2 interrelations.

Authorship Confirmation/Contribution Statement: This article was conceptualized by CCBS, CNLM, MLBF, MFPMA, CB, SL, and TS. CCBS, CNLM, MLBF, JJFM, ERPA, and FFA investigated the cases and collected and verified the underlying data. CCBS and SL wrote the original draft of the article, and all other authors revised the final version.

Data Access Statement: All relevant data are within the paper.

Funding Statement: This study was supported by the Oswaldo Cruz Foundation, Ministry of Health of Brazil (Emergency Fund to Combat COVID-19 no. VPPCB-005-FIO-20-2-22).

Authors’ Disclosure: Dr. Bresani-Salvi is the principal investigator of the NeuroCOVID study. Dr. Solomon is a consultant in the Medicine Healthcare Products Regulatory Agency. Dr. Araújo is the superintendent of the Immunisations and Vaccine-Preventable Diseases Division of Pernambuco. All other authors declare no competing interest.

References

Doshi

COVID-19 vaccine trial protocols released. BMJ, 2020; 371: M4058. DOI: 10.1136/bmj.m4058

Voysey

, Clemens

SAC

, Madhi

, et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: A pooled analysis of four randomised trials. Lancet, 2021; 397(10277): 881–891. DOI: 10.1016/S0140-6736(21)00432-3

Aggarwal

, Lippi

, Michael Henry

Cerebrovascular disease is associated with an increased disease severity in patients with coronavirus disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke, 2020; 15(4): 385–389. DOI: 10.1177/1747493020921664

, Li

, Wang

, et al. Acute cerebrovascular disease following COVID-19: A single center, retrospective, observational study. Stroke Vasc Neurol, 2020; 5(3): 279–284. DOI: 10.1136/svn-2020-000431

Qin

, Zhou

, Hu

, et al. Clinical characteristics and outcomes of COVID-19 patients with a history of stroke in Wuhan, China. Stroke, 2020; 51(7): 2219–2223. DOI: 10.1161/STROKEAHA.120.030365

Favas

, Dev

, Chaurasia

, et al. Neurological manifestations of COVID-19: A systematic review and meta-analysis of proportions. Neurol Sci, 2020; 41(12): 3437–3470. DOI: 10.1007/s10072-020-04801-y

, Yang

, Zhao

, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID‐19 in China. Clin Res Cardiol, 2020; 109(5): 531–538. DOI: 10.1007/s00392-020-01626-9

Taquet

, Geddes

, Husain

, et al. 6-Month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. Lancet Psychiatry, 2021; 8(5): 416–427. DOI: 10.1016/S2215-0366(21)00084-5

Mao

, Jin

, Wang

, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol, 2020; 77(6): 683–690. DOI: 10.1001/jamaneurol.2020.1127

10.

Merkler

, Parikh

, Mir

, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol, 2020; 77(11): 1366. DOI: 10.1001/jamaneurol.2020.2730

11.

, Hu

, Xu

, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: A randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis, 2021; 21(2): 181–192. DOI: 10.1016/S1473-3099(20)30843-4

12.

Plano Nacional de Operacionalização da Vacinação contra COVID-19—Brazilian Ministry of Health. Available at www.gov.br/saude/pt-br/coronavirus/vacinas/plano-nacional-de-operacionalizacao-da-vacina-contra-a-covid-19. Accessed July 18, 2022.

13.

Jara

, Undurraga

, González

, et al. Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. N Engl J Med, 2021; 385(10): 875–884. DOI: 10.1056/NEJMoa2107715

14.

Chavda

, Chaurasia

, Fiorindi

, et al. Ischemic stroke and SARS-CoV-2 infection: The bidirectional pathology and risk morbidities. Neurol Int, 2022; 14(2): 391–405. DOI: 10.3390/neurolint14020032

15.

Di Carlo

, Montemurro

, Petrella

, et al. Exploring the clinical association between neurological symptoms and COVID‐19 pandemicoutbreak: A systematic review of current literature. JNeurol, 2021; 268(5): 1561–1569. DOI: 10.1007/s00415-020-09978-y