How does COVID 19 affect Nervous System?
Covid 19, caused by SARS CoV2 virus, is a global pandemic, which has infected about 1.88 million people in about 200 countries, resulting in about 1,16,800 deaths. Covid 19 predominantly affects respiratory system. Common symptoms include fever, cough, breathing difficulty, fatigue and chest pain. Severe cases manifest with pneumonia, necessitating the use of mechanical ventilator in many of them. However, viral infections are known to result in multi-system involvement, and Covid 19 is no exception. In this article, we would focus on neurological manifestations of Covid 19.
Guillain Barre syndrome (GBS)
GBS is an immune-mediated polyradiculoneuropathy resulting in acute onset, rapidly progressive weakness of all 4 limbs. Weakness usually starts in lower limbs, and ascends upwards to involve upper limbs in a few days. Severe cases develop difficulty in swallowing & speaking and breathing difficulty. The diagnosis is confirmed by nerve conduction studies and CSF analysis. A case of GBS was reported from China.  What was interesting was that GBS was the presenting feature of Covid 19 (the patient had no typical symptoms of Covid 19 such as fever, cough or breathing difficulty). After admission, neurological symptoms worsened and only after a week, respiratory symptoms typical of Covid 19 developed. At that point, testing confirmed SARS CoV 2 infection. Patient responded to treatment with intravenous immunoglobulins.
- GBS can be a presenting symptom of Covid 19.
- Usually GBS is a post-infectious syndrome (symptoms of GBS begin about 2 weeks after the viral infection). In this case, however, symptoms of GBS and Covid 19 started together (so, the GBS was para-infectious).
- Usual treatment of GBS (IVIG) works in GBS related to Covid 19 also.
There have been a few reports of stroke in patients with SARS CoV2 infection. In a case reported from China, a 79-year old man was admitted with right hemiparesis and aphasia.  He also had low-grade fever and cough at admission. Investigations confirmed it to be a case of SARS CoV2 infection. CT brain showed lacunar infarction. The patient also had paroxysmal atrial fibrillation and hypertension. It was hypothesised that SARS-CoV-2 infection caused hypoxemia and excessive secretion of inflammatory cytokines, which induced acute ischemic stroke.
He was treated with clopidogrel and atorvastatin. For SARS CoV 2, he was given antivirals. Patient had significant improvement by day 12 of admission.
Another 72-year-old patient presented with symptoms of stroke and was admitted in Neurology ward at AIIMS, New Delhi, India. He had no symptoms of Covid 19 at admission, however, he complained of chest pain and breathing difficulty two days later. Investigations confirmed it to be a case of SARS CoV 2 infection. More details are awaited about this case.
In a recent case series, cerebrovascular diseases occurred in about 5.7% (5/88) patients with severe Covid 19. 
- Ischemic stroke can be the first manifestation of Covid 19.
- Treatment of ischemic stroke in Covid 19 is similar to the patients without Covid 19.
The first case of acute necrotising encephalopathy in Covid 19 was reported from the USA.  A 58-year-old woman presented with a 3-day history of fever, cough and altered mental status. A diagnosis of SARS CoV 2 was confirmed with a nasopharyngeal swab specimen. CT brain showed bilateral thalamic hpodensities. MRI brain showed symmetrical T2W/FLAIR hyperintense lesions involving thalami and medial temporal lobes. There was evidence of hemorrhages in the affected areas on SWI MRI. There was rim enhancement on post contrast MRI images. A diagnosis of acute nectrotizing encephalopathy (ANE) was made. ANE is a rare complication of influenza and other viral infections and has been related to intracranial cytokine storms, which result in blood-brain-barrier breakdown, but without direct viral invasion or parainfectious demyelination. Patient was treated with immunoglobulins. Steroids were avoided as it could worsen concomitant bacterial infection.
The first case of encephalitis (due to direct brain invasion by SARS CoV2 viruses) was reported from China.  The patient was 56-year old admitted with a diagnosis of Covid 19 encephalitis. On March 4, gene sequencing confirmed the presence of SARS-CoV-2 in the cerebrospinal fluid.
The first case of meningitis due to SARS CoV2 was also reported from China.  A 24 year old man developed headache, fatigue and fever. He was treated with antiviral and antipyretic by a nearby physician. On day 5, his symptoms worsened and he also developed cough. On day 9, he was found unconscious. He had a seizure on the way to hospital. He had neck stiffness on examination. SARS CoV2 RNA was not detected in nasopharyngeal swab, however, it was detected in CSF. MRI bran showed features of right lateral ventriculitis and encephalitis affecting right medial temporal lobe and hippocampus. CSF showed elevated opening pressure and mild pleocytosis.
Loss of smell (Anosmia) and taste (Dysgeusia)
The typical symptoms of Covid 19 are fever, cough and breathing difficulty. However, several cases have been reported, where patients presented with lack of smell and taste, who were later diagnosed to have Covid 19. Many of these patients had no respiratory symptoms suggestive of Covid 19, when they developed loss of smell and taste.
The mechanism of lack of smell seems to be the involvement of olfactory nerves and their brain connections by the SARS-CoV 2 virus. Lack of smell and taste are not permanent. As patients recover from Covid 19, smell and taste sensations also return to normal.
So, it is recommended that persons who develop new onset lack of smell and taste (without any common cold) should self-isolate themselves and if they develop symptoms suggestive of Covid 19 later, should present themselves for covid 19 testing.
The guidelines in this regard were published by American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) on 22nd march, 2020 
What are the different ways SARS CoV2 can affect nervous system?
- Direct hematogenous spread- viruses can travel from lungs to brain via blood, resulting in meningitis or encephalitis
- Spread via olfactory nerves- Viruses can enter via nose and then travel via olfactory nerves (through cribriform plate) into the brain. This can result in loss of smell and later encephalitis.
- Spread via neural synapses- viruses can travel from lungs via neural synapses to respiratory center located in medulla oblongata. This can result in respiratory failure.
- Cytokine storm syndrome- A group of COVID 19 patients present with cytokine storm syndrome resulting in release of inflammatory mediators. This can result in acute necrotising encephalopathy and stroke.
- Immune-mediated demyelination- Antibodies produced against SARS CoV2 viruses can result in demyelinating disorders such as GBS and acute disseminated encephalomyelitis (ADEM).
Covid 19 caused by SARS CoV2 virus can present with neurological diseases affecting central as well as peripheral nervous system. Common neurological symptoms include headache, fatigue and muscle pains. In more severe cases, there could be a decrease in alertness, loss of smell, seizures and focal neurological deficits. In many cases, neurological symptoms can be the first (presenting) symptom of Covid 19. Therefore, one should have a high index of suspicion to diagnose Covid 19 early. Universal precautions to prevent the spread and transmission of Covid 19 should be taken while dealing with neurology outpatients as well as inpatients.
- Lancet Neurology, April 1, 2020
- Infectious Diseases, March 31, 2020
- Economic Times newspaper, April 8, 2020
- MEDRXIV. Feb 25, 2020
- Radiology, March 31, 2020 (all CT and MRI images are from this reference)
- Travel Medicine and Infectious Disease, March 24, 2020
- International Journal of Infectious Diseases, March 25, 2020