key: cord-0936916-b45njsvp
authors: Finsterer, Josef; Wilfing, Astrid
title: Anticoagulated de novo atrial flutter complicated by transitory ischemic attack in fatal COVID‐19
date: 2022-01-20
journal: Clin Case Rep
DOI: 10.1002/ccr3.5246
sha: f30edcb0eb995dae1902d55d68a63393c37456ed
doc_id: 936916
cord_uid: b45njsvp

SARS‐CoV‐2 may not only manifest as pneumonia (COVID‐19) but also in other organs, including the brain (neuro‐COVID). One of the cerebral complications of SARS‐CoV‐2 is ischemic stroke. Transitory ischemic attack (TIA) in a SARS‐CoV‐2 positive has not been reported. A 78‐year‐old poly‐morbid male (diabetes, hypertension, and coronary heart disease), admitted for COVID‐19, developed atrial flutter on hospital day (hd) 2. Anticoagulation with enoxaparin was started. On hd5, he experienced a TIA despite sufficient anticoagulation. The patient expired on hd28 due to multi‐organ failure from sepsis due to superinfection with staphylococcus aureus. Infection with SARS‐CoV‐2 may be complicated by atrial flutter. Atrial flutter may be complicated by TIA despite sufficient anticoagulation, suggesting that standard anticoagulation may be insufficient to meet SARS‐CoV‐2‐associated hypercoagulability syndrome. Forced anticoagulation and adequate antibiosis in poly‐morbid SARS‐CoV‐2‐infected patients with hypercoagulability and cytokine storm are warranted.

anticoagulation with enoxaparin was begun. Though creatine-kinase was mildly elevated (Table 1) , myocardial infarction was excluded as the cause of atrial flutter upon ECG and absence of anginal chest pain. Endocarditis was not considered. On hd5, the patient developed sudden onset hemiparesis on the right side (NIHSS 7) with spontaneous, complete recovery within 24 h. As cerebral MRI was non-informative, including time-of-flight (TOF) angiography (Figure 1) , he was diagnosed with a TIA and anticoagulation was continued. As a self-limiting, non-convulsive epileptic state was considered as a differential diagnosis by the neurologist on duty, he additionally received levetiracetam (LEV) 2,000 mg/d. On hd7, the patient was tired but communicated verbally and was able to walk. Despite being seizure-free, LEV was increased to 3,000 mg/d. On hd8, the PCR for SARS-CoV-2 was still positive. On the following day, a superinfection with staphylococcus aureus was diagnosed for which he received cefazolin. Despite this regimen, inflammatory parameters further increased (Table 1) , why the antibiotic treatment was switched to tazonam. On hd11, he was again tested positive for SARS-CoV-2. PCR for SARS-CoV-2 became negative on hd15. Though EEG on hd20 only showed diffuse generalized slowing without epileptiform discharges and without ever having experienced a seizure, LEV was kept. Clinical neurologic examination on hd21 revealed somnolence, mutism, and reduced Achilles tendon reflexes. Meningitis was suspected. However, cerebro-spinal fluid (CSF) investigations on hd22 were non-informative, including cell count, culture, and viral screen. Sinus venous thrombosis was excluded on hd23. Blood sedimentation rate on hd23 was 120/1 h and interleukin-6 97.5 pg/ml (n, <7.0 pg/ml). Sepsis was diagnosed, and renal insufficiency developed during the following days. The patient died on hd28 from multi-organ failure. Autopsy was refused by the relatives because of religious concerns.

The patient is interesting for several aspects. First, the patient developed de novo atrial flutter during the infection with SARS-CoV-2. Atrial flutter in association with COVID-19 has been previously reported as a cardiac complication of COVID-19 and can be attributed to the cytokine storm, hypoxic myocardial injury, electrolyte abnormalities, plaque rupture, coronary spasm, microthrombi, or direct endothelial or direct myocardial injury by the virus. 4 Indications for a cytokine storm in the index patient were high IL6 and high blood sedimentation rate. Myocardial infarction as an alternative cause of atrial flutter was excluded. Endocarditis was not considered as causative for atrial flutter.

Second, the patient experienced a TIA. Though ischemic stroke is a well-known complication of COVID-19, 5 a TIA has, to our knowledge, not been reported in association with COVID-19. The cause of the TIA remained speculative but most likely it was due to newly detected atrial flutter or the hypercoagulability syndrome. 6 An indication for hypercoagulability in the index patient was the mildly elevated D-dimer (Table 1) . Fibrinogen values were normal throughout hospitalization. On the other hand, there are also indications for hyper-fibrinolysis in COVID-19. 7 Alternative causes of TIA could be cerebrovascular disease due to diabetes or arterial hypertension, a focal epileptic seizure, or a cerebral manifestation of the SARS-CoV-2 infection. However, cerebral MRI, CSF investigations, and EEG were non-informative.

Third, the patient developed a TIA despite sufficient anticoagulation with enoxaparin. Either the patient had a source of embolism other than atrial flutter or anticoagulation was too weak for SARS-CoV-2-associated hypercoagulability syndrome. Other sources of embolism could be a ventricular thrombus, 8 or low output failure. Unfortunately, the patient did not undergo echocardiography during hospitalization. Since the patient was aseptic at the time of the TIA, sepsis is rather unlikely to have been causative. A clinical implication of the case could be to broaden the therapeutic range of the anti-factor Xa values and increase the intensity of anticoagulation. Fourth, the patient developed superinfection with staphylococcus aureus and consecutively sepsis. Bacterial superinfection is common in COVID-19 9 and attributed to neutropenia due to sepsis or a weak humoral immune response. 10 DIC syndrome in the context of COVID-19 has been also attributed to sepsis. 10 

Infection with SARS-CoV-2 may be complicated by atrial flutter, which may cause TIA despite sufficient anticoagulation. SARS-CoV-2 infection may be complicated by superinfection, which may lead to sepsis, DIC syndrome, multi-organ failure, and death. SARS-CoV-2-associated sepsis may mimic meningitis. The combination of sepsisinduced DIC syndrome and SARS-CoV-2-associated hypercoagulability may require forced anticoagulation and appropriate antibiosis. F I G U R E 1 Cerebral MRI on hd5 without showing an acute lesion on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, perfusion-weighted imaging (PWI) time-to-peak, or time-of-flight angiography

The European academy of neurology COVID-19 registry (ENERGY): an international instrument for surveillance of neurological complications in patients with COVID-19

Incidence, characteristics and clinical relevance of acute stroke in old patients hospitalized with COVID-19

Systemic coagulopathy in hospitalized patients with coronavirus disease 2019: a systematic review and metaanalysis

Electrocardiographic manifestations of COVID-19

A case series of ischemic stroke with coronavirus disease 2019 in two Egyptian centers

Coronavirus disease 2019-associated coagulopathy

COVID-19-associated hyperfibrinolysis: mechanism and implementations

The role of anticoagulation in post-COVID-19 concomitant stroke, myocardial infarction, and left ventricular thrombus: a case report

Bacterial superinfection pneumonia in SARS-CoV-2 respiratory failure

Resolution of disseminated intravascular coagulation in a patient with COVID-19 and associated sepsis-induced neutropenia

None.

No conflict of interest declared.

JF: Design, literature search, discussion, first draft, critical comments, and final approval. AW: Data acquisition, literature search, discussion, and final approval. The study was approved by the institutional review board.

Statement of ethics was in accordance if ethical guidelines.

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Josef Finsterer https://orcid.org/0000-0003-2839-7305