A Young Female with SARS-CoV-2 Infection Presenting with Concurrent Neurological and Pulmonary Manifestations: A Case Report

Coronavirus disease 2019 (COVID-19), besides its well-known deleterious effects on the respiratory system, is also reported to affect the central nervous system (CNS), presenting with neurological manifestations, that are commoner among older patients with associated co-morbidities and in the critically ill with COVID pneumonia. Infective, cerebrovascular, and hypoxic-toxic-metabolic etiology have been implicated. Reported outcomes have been poor with persistent neurological deficits among the majority who have survived. We report a young lady who presented with neurological manifestations alongside moderately severe COVID-19 pneumonia. Diagnosed early and managed as severe encephalopathy after excluding infective and cerebrovascular aetiology. Responded well to conservative measures and made a complete recovery. Early recognition of neurological manifestations of COVID-19 disease followed by the institution of appropriate therapies improved the outcomes.


Introduction
COVID-19 is well known for its respiratory effects.Published data suggests that over 35% of COVID-19 patients may initially present with neurological manifestations due to diverse aetiologies and mechanisms. 1 CNS involvement is commoner among older patients (>50 years) with associated co-morbidities, and among the critically ill with COVID-19 posing difficulties in recognition and demanding a high degree of alertness for early recognition to commence appropriate therapies to improve outcomes. 1 report a patient who presented with neurological symptoms alongside moderately severe COVID-19 pneumonia managed as acute encephalopathy and made a full recovery within two weeks of hospital admission.

Case Report
An unvaccinated, 35-year-old lady with fever, cough, and loss of appetite for over two weeks was admitted to hospital on the 17 th day of illness, in respiratory distress, and tested positive for Rapid Antigen Test (RAT) for COVID-19.On admission, she was conscious but drowsy, tachypnoeic with a respiratory rate (RR) of 60/ minute and oxygen saturation (SpO2) of 84% onair.Treated with oxygen 15L/minute via Non-Rebreathing Mask (NRBM), intravenous (iv) dexamethasone 6 mg, subcutaneous (sc) enoxaparin 40 mg and iv ceftriaxone 2g.Stabilized and transferred on NRBM (SpO2 96%) to a COVID-ICU on the same day for further management.Other than for gestational diabetes mellitus, her past medical history was unremarkable.
On admission to the ICU, she was afebrile, drowsy, confused, GCS 14/15, pupils equal and reacting to light, and no neck stiffness or focal neurologic deficits; respiratory parameters were satisfactory on NRBM (RR of 35-40/min; SpO2 96%); slightly tachycardic but stable otherwise; random blood sugar (RBS) 500 mg/dl with ketone bodies present in urine.Respiratory supports and rehabilitation were continued and glycaemic control achieved with (iv) soluble insulin on a sliding scale.High-resolution CT (HRCT) -Chest showed moderate interstitial pneumonia and minimal ground-glass opacities with a CT severity score of 15/25.Since admission, the drowsiness, confusion, and agitation worsened and the NCCT Brain (noncontrast CT) showed slightly effaced ventricles with early cerebral oedema.As CSF was inconclusive of infection or inflammation, encephalopathy was suspected and empirically treated with (iv) dexamethasone 8mg 8 hourly for 48 hours and (iv) mannitol (20%) 250ml for 3 days.Acyclovir 500mg (iv) 8 hourly and vancomycin 1g (iv) 12 hourly were commenced to provide antiviral and antibacterial cover, respectively.MRI brain and EEG were not considered in the absence of localizing neurological features and convulsions respectively.
On Day 2 in ICU, respiratory parameters deteriorated due to sepsis however, improved

Case Discussion
Neurological manifestations occur in over onethird of hospitalized COVID-19 patients, and may present during the disease or as the initial or only presentation. 2,3he aetiological mechanisms of neurologic manifestations are multi-factorial; infective, toxic-metabolic (encephalopathy), cerebrovascular (thromboembolic or heamorrhagic stroke secondary to high blood pressure caused by dysfunction of ACE2 receptors), or immune dysfunction (inflammatory or cytokinesmediated). 4,5,6In a systematic review (n=407), reported incidences of neurological symptoms were headache (16.8%), dizziness (13.9%), altered consciousness (11.2%), and epilepsy (1.7%).Related aetiological factors were viral meningitis/encephalitis (25;6.1%),hypoxic encephalopathy (23;5.6%),acute cerebrovascular disease (6;1.4%), and encephalomyelitis (1;0.2%). 7Neurological manifestations were commonly reported in patients with severe COVID-19 disease who are elderly with co-morbidities. 7wever, our patient was a relatively young healthy lady who presented at the outset with moderately severe COVID-19 pneumonia along with severe and progressive CNS manifestations.Having ruled out the infective and cerebrovascular pathology, encephalopathy was considered the most likely cause of her CNS manifestations favoured by cerebral oedema on the NCCT.
Encephalopathy is characterized by diffuse brain dysfunction that typically manifests with altered consciousness, a hallmark feature ranging from confusion, and delirium progressing to deep coma, typically with no evidence of brain inflammation on CT/ MRI or on CSF analysis. 8n a cohort study (n=2088), 55% had delirium 9 and in another study among hospitalized patients (n=509), 31.8% had encephalopathy. 8e aetiology of encephalopathy can be multiple with direct neuronal injury caused by hypoxaemia, toxic-metabolic abnormalities, and inflammatory-immune-mediated mechanisms. 8,9ypoxaemia (PaO2 52 to 80 mmHg; SaO2 92-96%) and inflammatory mediators (indicated by raised markers of inflammation -CRP, LDH, ferritin) were likely causative factors in this lady.Other than the metabolic acidosis (base deficit -15) and ketonuria present at the time of admission but normalized within 24 hours, no other metabolic causes were evident as the renal and liver functions were satisfactory throughout.Presumably, over time the respiratory supports and other therapies would have helped reverse the causal factors and facilitated recovery from the encephalopathy.
Although the role of glucocorticoids or other immunomodulatory therapies in treating encephalopathy is uncertain, a case series have shown improvement of severe encephalopathy in a minority following the use of glucocorticoids with or without plasma exchange. 10Despite the conflicting evidence, (iv) dexamethasone was administered for 48 hours.Though encephalopathy was identified as a risk factor for poor outcomes, including longer lengths of hospital stays and functional/ cognitive impairments at discharge (5-80%), our patient made a full recovery within 3 weeks.

Conclusion
In a pandemic state of COVID-19, alertness on CNS manifestations of SARS-CoV-2 infection is beneficial for early diagnosis, and to commence specific and supportive therapies to facilitate recovery from the neurological manifestations.

Image 1 :
CT Pulmonary Angiogram (CTPA)with non-invasive supports (CPAP).PE was excluded by a CT-pulmonary angiogram (CTPA).Respiratory supports were stepped down gradually.Following complete recovery from CNS manifestations by Day 12 of ICU stay, discharged to the COVID ward on nasal oxygen 2L/ minute and sent home within a week.Image 2: High-Resolution CT -Chest (HRCT) showing moderately severe COVID-19 pneumonia (CT severity A score of 15/25) and segmental consolidation Image 3: Non-contrast CT Brain (NCCT) showing slightly effaced ventricles with early cerebral oedema

Table 1 :
Clinical details and Lab reports