|Year : 2021 | Volume
| Issue : 3 | Page : 79-82
COVID-19 pneumonia with stroke: Is it a vascular phenomenon or thrombotic event?
Shital Patil1, Gajanan Gondhali2
1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
2 Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India
|Date of Submission||11-Mar-2021|
|Date of Acceptance||20-May-2021|
|Date of Web Publication||25-Sep-2021|
Dr. Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
Source of Support: None, Conflict of Interest: None
COVID-19 disease is known to cause pulmonary and extrapulmonary complications including effects on cardiovascular, gastrointestinal, renal, and neurovascular system. Ischemic stroke seems to be one of the most serious neurologic complications in patients with COVID-19 infection. In this case report, we have documented, 70-year-old male presented with acute respiratory syndrome with hypoxemia and neurological involvement as right hemiparesis with altered level of consciousness, COVID-19 real-time polymerase chain reaction positive, with abnormal laboratory parameters such as ferritin, lactate dehydrogenase, and D-dimer. Further investigations such as echocardiography documented cardiomyopathy and left heart dysfunction, high-resolution computed tomography thorax documented COVID pneumonia, and magnetic resonance imaging brain documented left frontoparietal and parieto-occipital lobe infarct. We have observed excellent clinical and radiological response to anticoagulation, antiplatelets, and steroids with other supportive care in critical care unit.
Keywords: Anticoagulation, COVID-19, left heart dysfunction, stroke
|How to cite this article:|
Patil S, Gondhali G. COVID-19 pneumonia with stroke: Is it a vascular phenomenon or thrombotic event?. J Appl Sci Clin Pract 2021;2:79-82
|How to cite this URL:|
Patil S, Gondhali G. COVID-19 pneumonia with stroke: Is it a vascular phenomenon or thrombotic event?. J Appl Sci Clin Pract [serial online] 2021 [cited 2021 Oct 28];2:79-82. Available from: http://www.jascp.com/text.asp?2021/2/3/79/326724
| Introduction|| |
The evidence from SARS-CoV-2 studies implies that the virus can have central nervous system involvement., Other reports suggest a prothrombotic state with COVID-19. Since the coronavirus pandemic in 2020, there has been an ever-growing evidence of neurologic complications associated with COVID-19. Retrospective study form China with 214 COVID-19 patients reported four ischemic strokes. The report suggests that the neurologic complications were seen in patients with severe COVID-19. Furthermore, abnormalities in liver enzyme, hemoglobin, lactate dehydrogenase (LDH), d-dimer, Cr, and lymphopenia were more common in patients with neurologic complications. Patients with COVID-19 tend to be in a prothrombotic state. On the other hand, increased prothrombin time, partial thromboplastin time, and decreased platelet counts are also reported in COVID-19, which may increase the risk of hemorrhagic incidents. This is especially important in patients with cerebrovascular diseases.
| Case Report|| |
A 70-year-old male, with no history of any tobacco or substance abuse, known case of ischemic heart disease, presented with acute onset respiratory syndrome having cough, fever, and fatigability and acute onset altered level of consciousness with right-sided hemiparesis.
On clinical examination, thin built gentleman, heart rate – 100/min respiratory rate – 28/min, blood pressure – 130/80 mmHg, oxygen saturation (SpO2) – 84% room air, 93% nasal canula oxygen supplementation at 3 L/min, respiratory system examination revealed - bilateral crepitations, central nervous system examination documented-altered consciousness, cranial nerves functions normal, obeys verbal commands, neurodeficit documented on the right side of body including right upper and lower limb, tone decreased, Grade 2 to Grade 3 power in right upper and lower limb, deep tendon reflexes were diminished on right upper and lower limbs. Plantar reflexes were extensor on right side and flexor on the left side.
Laboratory examination documented: Hemoglobin - 12 gm% Total white blood cell count – 12,900/mm3.
Viral markers: Australia antigen test-negative, ELISA for HIV negative.
COVID 19 real-time polymerase chain reaction (RT PCR)-positive, ECG suggestive of sinus tachycardia, echocardiography suggestive of left ventricular systolic function, dilated left ventricle, left ventricular diastolic dysfunction, and mild pulmonary hypertension.
Antinuclear antibody-negative, D-dimer-raised >10,000 ng/L, C-reactive protein (CRP)-raised 190 IU/L, Pro-BNP-normal, LDH-raised 1500 IU/L, Ferritin-raised >480 IU/L, homocystine-raised, liver functions-abnormal, kidney functions-normal, blood sugar level - 156 mg%.
Magnetic resonance imaging brain images were documented as acute infarct in left frontoparietal, parieto-occipital, and peritriagonal region pertaining to left middle cerebral artery, middle, and posterior cerebral artery watershed territory [Figure 1], [Figure 2], [Figure 3].
|Figure 1: MRI brain images showing acute infarct in left fronto-parietal, parieto-occipital region|
Click here to view
|Figure 2: MRI brain images were documented as acute infarct in parieto-occipital and peritriagonal region pertaining to left middle cerebral artery, middle and posterior cerebral artery watershed territory|
Click here to view
|Figure 3: MRI brain images were documented as acute infarct in parieto-occipital and peritriagonal region|
Click here to view
High-resolution computed tomography (HRCT) thorax documented abnormalities as – bilateral peripheral, subpleural to central airspace opacities in upper lobe, middle lobe, and lower lobe [Figure 4] and [Figure 5] suggestive COVID-19 pneumonia, require COVID-19 RT PCR for confirmation, CORAD-4, computed tomography severity score-12/25 [Figure 6].
|Figure 4: HRCT thorax showing bilateral peripheral, subpleural in middle lobe and lower lobe|
Click here to view
|Figure 5: HRCT thorax showing bilateral peripheral, subpleural to central airspace opacities in lower lobe|
Click here to view
|Figure 6: HRCT thorax showing abnormalities as-bilateral peripheral, subpleural to central airspace opacities in upper lobe, middle lobe and lower lobe|
Click here to view
We have started anticoagulation with low molecular weight heparin (LMW0 injection 60 units BID, injection methylprednisolone 40 mg IV TDS, injection remdesivir, oral formulations of Aspirin 75 mg OD, and oxygen supplementation with target SpO2 more than 95% and other supportive care in critical care unit. Clinical response documented after 14 days of treatment, with near complete neurological recovery, consciousness recovered, neurodeficit recovered, right upper limb and lower limb tone improved, Grade 4-Grade 5 power regained, deep tendon reflexes were normal, plantar reflexes documented flexor response. Respiratory system parameters were improved after 7 days of treatment, SpO2 marinating 95% at room air, fatigability decreased and able to perform breathing exercises and walk across room with minimal respiratory discomfort. We have discharged patient after neurological recovery and 6 min walk parameters are acceptable and having saturation more than 93% at room air.
| Discussion|| |
While details of the pathogenesis of ischemic stroke in COVID-19 are still emerging, current evidence suggests putative mechanisms. In the study of Mao et al., 5.7% of patients with severe infection developed cerebrovascular disease later in the course of illness. In a study by Li et al., the incidence of stroke in COVID-19 patients was about 5% with a median age of 71.6 years. These patients were associated with severe disease and had a higher incidence of risk factors such as hypertension, diabetes, coronary artery disease, and previous cerebrovascular disease. Average time of onset of stroke after COVID-19 diagnosis was 12 days. Elevated levels of CRP and D-dimer indicating a high inflammatory state and abnormalities with the coagulation cascade, respectively, might play a role in the pathophysiology of stroke in the setting of COVID-19 infection.
The SARS-CoV-2 virus is the seventh known variant of coronavirus that infects humans. SARS-CoV-2 is genetically similar to SARS-CoV-1. SARS-CoV-1 in 2003 affected about 8000 patients with few reports of neurological manifestations – mostly peripheral neuropathy and encephalitis. Similar to SARS-CoV-1, the current SARS-CoV-2 affects the neurological system in about 36.7% of patients as per Mao et al. Most coronaviruses are neurotropic, and others speculate that SARS-CoV-2 is neurotropic too. Furthermore, there are reports of SARS-CoV-2 being identified in cerebrospinal fluid by PCR. Angiotensin-converting enzyme-2 (ACE) receptors are the major entry points for SARS-Cov-2 and other coronaviruses. Although ACE-2 receptors are present in the nervous system, alternate pathways have been proposed to explain the entry of SARS-CoV-2 into the nervous system including direct injury to the blood and blood–brain barrier, hypoxic injury, and immune-related injury.,
Evidence of abnormal coagulation parameters associated with COVID-19 appeared in early reports from China. The first report of 99 hospitalized patients in Wuhan showed that inflammatory biomarkers of interleukin-6, erythrocyte sedimentation rate, CRP, D-dimer, and other coagulation parameters were increased or deranged. High levels of D-dimer were observed in the present review which might be due to COVID-19-associated inflammation and the consequent downstream triggering of coagulation cascade.
Higher age and CRP levels were observed among patients symptomatic for COVID-19 at the time of diagnosis of stroke. Reports elucidating differences between COVID-19 positive and COVID-19 negative strokes have also found higher levels of inflammatory biomarkers among the former.
Strokes in patients with COVID-19 may be due to usual causes such as atherosclerosis, hypertension, and atrial fibrillation. Three main mechanisms appear to be responsible for the occurrence of ischemic strokes in COVID-19. These include a hypercoagulable state, vasculitis, and cardiomyopathy.
All patients admitted to intensive care should receive prophylaxis against venous thrombosis, with at least LMW heparin. Tang et al. reported that anticoagulation reduced mortality in COVID-19 patients with coagulopathy. In reply, Asakura and Ogawa noted that some features of the coagulopathy in COVID-19 suggest Disseminated intravascular coagulation (DIC) and recommended a combination of heparin and nafamostat mesylate, a treatment used for DIC in Japan. Thachil et al. responded with a discussion of possible benefits of unfractionated heparin versus LMW heparin.
Beigel et al. reported that, in a randomized controlled trial in 1059 patients hospitalized for COVID-19, remdesivir was associated with a shorter median recovery time (11 days, 95% confidence interval [CI]: 9–12), compared with placebo (15 days, 95% CI: 13–19), and a lower 14-day mortality of 7.1% with remdesivir versus 11.9% with placebo (hazard ratio for death, 0.70; 95% CI: 0.47–1.04). Stroke was not mentioned in the report.
We have documented a significant role of anticoagulation, antiplatelets, remdesivir, and methylprednisolone.
Key learning points from this case report are:
- COVID 19 disease is known to cause pulmonary and extrapulmonary complications including effects on cardiovascular, gastrointestinal, renal, and neurovascular system
- Neurovascular complications such as stroke, venous thrombosis, encephalopathy, and vasculitis is documented in various studies
- We have documented, embolic stroke in this case in COVID-19 secondary to hypercoagulability and cardiomyopathy
- Early interventions such as anticoagulation and antiplatelets have a crucial role in early clinical recovery
- Timely steroid use has positive impact on both COVID pneumonia and stroke outcome
- We recommend, all cases with stroke should undergo HRCT thorax in current scenario as many of these cases may have less respiratory symptoms, and in stroke cases with SpO2 <95% warrants lung pathology to be ruled out to have satisfactory treatment outcome.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7.
Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK, et al
. Middle East Respiratory Syndrome. N Engl J Med 2017;376:584-94.
Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al
. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683-90. doi:10.1001/jamaneurol.2020.1127.
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al
. Clinical characteristics of 113 deceased patients with corona virus disease 2019: Retrospective study. BMJ 2020;368:m1091.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al
. Neurologic manifestations of hospitalized patients with corona virus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.
Li X, Zai J, Zhao Q, Nie Q, Li Y, Foley BT, et al
. Evolutionary history, potential intermediate Animal host, and cross-species analyses of SARS-CoV-2. J Med Virol 2020;92:602-11.
Corman VM, Lienau J, Witzenrath M. Corona viruses as the cause of respiratory infections. Internist (Berl) 2019;60:1136-45.
Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al
. Genome composition and divergence of the novel corona virus (2019-nCoV) originating in China. Cell Host Microbe 2020;27:325-8.
Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan 2005;14:113-9.
Steardo L, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol (Oxf.) 2020;229:e13473.
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al
. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-8.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al
. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al
. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, et al
. SARS-CoV-2 and stroke in a New York healthcare system. Stroke 2020;51:2002-11.
Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, et al
. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry 2020;91:889-91.
Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al
. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020;18:1023-6.
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094-9.
Asakura H, Ogawa H. Potential of heparin and nafamostat combination therapy for COVID-19. J Thromb Haemost 2020;18:1521-2.
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al
. Remdesivir for the treatment of COVID-19: Preliminary report. N Engl J Med 2020;383:1813-26.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]