presented by Dr. Rudra sen

1. Long COVID Syndrome
PRESENTER : Dr Rudra Sen ( PG-2)
MODERATOR : Dr Manisha B. Thakur (Consultant)

2. CONTENTS
• What is it ?
• Factors affecting severity
• Symptoms of Long COVID
• Pathogenesis of Long COVID
• Respiratory Manifestations
• Cardiac Manifestations
• Nephrological Manifestations
• Neurological Manifestations
• GI Manifestations
• Prevention and Treatment
• References

3. WHAT IS IT ?
• Persistent symptoms after acute COVID -19 Infection
• > 4 weeks
• Not explained by an alternative diagnosis
• “Post-COVID conditions, Post acute sequelae of SARS-CoV-2
infection, Post acute COVID-19, Chronic COVID-19 and Post-
COVID syndrome”.

5. FACTORS AFFECTING RECOVERY TIME COURSE FOLLOWING
COVID-19
• Severity of infection
• Hospitalization
• Complications of disease
• Females
• More than 40 years of age
• High BMI
• Prior obstructive airway disease
• Variant of virus

6. SYMPTOMS
Physical :
• Fatigue ( 13-87 %)
• Dyspnoea ( 10-71 %
• Chest Pain ( 12 – 44 % )
• Cough ( 17 – 34 % )
• Less Common : anosmia, headache
Psychological :
• PTSD ( 24 % )
• Memory problems ( 18%)
• Difficulty in Concentrating ( 16%)
• Anxiety ( 22 %)
• Depression ( 22 % )

7. PATHOGENESIS OF LONG COVID

8. LONG TERM RESPIRATORY EFFECTS OF COVID-19
• Symptoms :
• Shortness of Breath
• Dry Cough
• Chest Pain
• Abnormalities :
• Diffuse lung disease ( inflammatory or fibrotic )
• Respiratory muscle weakness
• Pulmonary Thromboembolism Sequelae
• Pulmonary infections including mycosis

9. PATIENTS AT HIGH RISK FOR PULMONARY SEQUELAE
• Age > 60 years
• Smoker
• Comorbidities – Diabetes/Hypertension/CAD
• Pre-existing respiratory disease – like asthma, ILD, COPD
• Requiring oxygen therapy at home
• Patient who required Mechanical Ventilation / NIV during acute COVID -19
illness

13. CHEST IMAGING
• Need
• Pulmonary infiltrate / New or worsening respiratory symptoms
– indicated
• Timing : - 12 weeks
• Type of Imaging
• Chest X Ray sufficient for most
• Abnormalities on imaging suggestive of another pathology – CT
Chest ( CECT – Malignancy , HRCT – ILD )

16. MANAGEMENT OF SPECIFIC SYMPTOMS
• Cough :
• Treat cause – infections , GERD, OAD.
• Rule out infections
• Breathlessness :
• According to underlying cause
• Oxygen therapy
• Domiciliary Oxygen :
• Resting or exertional spO2 < 90 %
• From oxygen concentrator or oxygen cylinder via nasal prongs
• Pulmonary Rehabilitation

17. M/m OF SPECIFIC POST COVID PULMONARY CONDITIONS
• Post COVID Diffuse Lung disease :
• Persistent inflammatory pathology or lung fibrosis.
• Usually managed along the lines of fibrotic ILDs
• Steroids for organizing pneumonia
• Pulmonary Embolism : Therapeutic anticoagulation - 3 months .
• Pulmonary Infections :
• Secondary bacterial pneumonias - oral/intravenous antibiotics
• Fungal infections like mucormycosis , aspergillosis should be ruled out

19. POST COVID CARDIOVASCULAR SEQUELAE
• Common cardiovascular sequalae
• Myocardial scarring or fibrosis
• Persistent left ventricular dysfunction
• Heart failure
• Arrythmias
• Autonomic dysfunctions
• more prone to complications :
• Diabetes
• Hypertension
• CKD
• Obesity
• Dyslipidemia

20. CLINICAL FEATURES
• Chest pain
• Palpitations - inappropriate sinus tachycardia /POTS/ ventricular
arrythmias consequent to myocardial scarring .
• Shortness of breath - acute coronary syndrome /pulmonary embolism
/myocarditis /tachyarrytmias
• Heart failure - in patients with heart disease
• Syncope

24. INVESTIGATIONS
• Basic
• Chest X ray
• ECG
• Cardiac biomarkers ( Troponins, NTproBNP )
• Advanced :
• Echocardiography
• Cardiac MRI
• Cardiopulmonary exercise testing
• Holter monitoring
• Chest CT
• Lower extremity doppler testing

25. MANAGEMENT
• Recommendation on Exercise :
• Post COVID symptoms - limit exercise to slow walking and increase rest
period if symptoms worsen .
• If symptoms like fatigue , cough , shortness of breath , fever persist -
activity limited to 60 % of maximum heart rate , until 2-3 week after
symptom resolution .
• Intense cardiovascular exercise should be avoided in all patients for 3
months
• Comorbidites like diabetes , hypertension , obesity , atrial fibrillation , prior MI
and heart failure - managed as per guidelines

26. HYPERCOAGULABILITY/THROMBOSES RELATED TO COVID-19
• Venous and arterial thromboses
• Seen particularly in the critically ill patients
• Anticoagulated for the hypercoagulable state during acute illness alone
• No evidence of arterial or venous thrombosis - not routinely anticoagulated on
discharge
• Duration of hypercoagulability of COVID-19 - unknown
• Documented venous thrombosis - anticoagulated for a minimum of 3
months
• Post discharge thromboprophylaxis - major prothrombotic risk factors (like
history of VTE , history of recent surgery or major trauma ) as long as bleeding
risk is not high .( MICHELLE trial 2021 )

27. POST COVID NEPHROLOGICAL SEQUELAE
Common kidney related complications following COVID-19 are :
• New onset AKI
• Rapid progression of pre-existing CKD
• Progression of CKD to ESKD.
• New onset glomerular disease manifesting as proteinuria , hematuria and
renal dysfunction
• New onset hypertension or worsening of hypertension.

28. MECHANISMS OF RENAL INJURY
• Multifactorial
• Viral tropism –the virus enters the cells by binding its spike protein to
membrane bound ACE-2
• Endothelial dysfunction , thrombotic microangiopathy, coagulopathy and
complement activation -kidney injury in COVID-19
• Indirect mechanisms contributing to renal injury include volume depletion
due to GI manifestation , insensible fluid losses due to hyperpyrexia , use
of nephrotoxic drugs .

29. INCIDENCE/PREVALENCE
• AKI - 46 % of severe COVID requiring ICU admissions of whom around 20 -30 %
require renal replacement therapy
• 1/3 patients with AKI – no recovery of kidney function within 3 weeks of discharge
from the hospital COVID-19 related AKI also leads to faster decline in pre-existing
kidney function
• Hematuria and proteinuria -15-25 % COVID-19 patients.
• COVID-19 related collapsing glomerulopathy - African patients.

30. • Incomplete AKI recovery at discharge - followed monthly for a minimum
period of 3 months to document late AKI recovery or to diagnose patients
going to CKD
• Patients with recovered AKI at discharge - followed up
• at least 14 % have been shown to develop kidney dysfunction
FOLLOW UP

32. COVID-19 NEUROLOGICAL SEQUELAE
• SARS-COV-2 virus - high affinity for human ACE-2 receptor .
• ACE-2 receptor - expressed in the neuron and glial cells -neurological
manifestations like olfactory neuropathy , peripheral neuropathy and brain
disorders .
• Prevalence of symptoms -10%- 87.4 % across various studies .

33. • Fatigue
• Changes in concentration
• Impaired memory (Brain fog)
• Persistent muscle ache/myalgia
• Headache
• Sleep disorders
• Dizziness
• Impairment in smell ( anosmia) and taste ( ageusia)
• New onset status epilepticus , stroke , acute inflammatory demyelinating
polyneuropathy , autonomic dysfunction
• Non-specific sensory complaints like paraesthesia, numbness and tingling
in the limbs
CLINICAL FEATURES

34. RISK FACTORS
Probable factors predicting long term symptoms
• Severe COVID-19 requiring hospital admission
• Older age
• Obesity
• More than 5 symptoms in the first week of acute COVID-19

35. FATIGUE
• Most commonly reported symptom
• If symptom persists for more than 6 months , CFS/ME ( Chronic Fatigue
Syndrome/Myalgic Encephelitis) criteria to be applied
• Managed by- self management and support
• Adequate rest , sleep and hydration are important
• Aerobic exercises

36. CHRONIC FATIGUE SYNDROME/MYALGIC ENCEPHALOMYELITIS

37. SMELLAND TASTE DISTURBANCES
• Infection with SARS-COV-2 - chemosensory symptoms like hyposmia/anosmia
and ageusia/dysgeusia
• Present in the period of acute COVID and may persist upto 30 days.
• Some amount of dysfunction may persist in 1/3rd patients

38. DYSAUTONOMIA
• Upto 12 % patients recovering from COVID-19
• Symptoms : dizziness , palpitations, exercise intolerance , chest tightness ,
presyncope , orthostatic hypotension.
• Symptoms > 3 months - possibility of POTS(Postural Orthostatic
Tachycardia Syndrome).
• Treatment - adequate fluid intake ( 2-3lt/day)
• salt supplementation ( 1 -2 tablespoon per day )
• compression garments
• drugs - midodrine or fludrocortisone
• Precipitating factors - coffee, alcohol , prolonged standing , hot humid
conditions , dehydration should be avoided

40. HEADACHE
• Upto 60 %
• Majority - tension type headache ; migraine type headache is less common
• Increase in frequency of migraine have been reported in those with pre-
existing migraine
• Managed like any other headache.

41. COGNITIVE IMPAIRMENT
• In 12- 50 % of patients
• May persist beyond 1 year
• Brain fog - deficits in attention, concentration, executive function and memory
.
• More frequently in patients who required ICU admission or mechanical
ventilation.

42. SLEEP DISORDERS
• In 18-30 % and may persist for beyond 1 year
• Insomnia, nightmares , excessive daytime sleepiness , post traumatic like
sleep dysfunction

43. NEUROMUSCULAR DISORDERS
• Skeletal muscle weakness in COVID-19 patients - commonly affect the
biceps or triceps muscles
• COVID-19 disease requiring ICU care /mechanical ventilation may cause
ICU acquired weakness. (Critical Illness Polyneuropathy / Critical Illness
Myopathy).

44. GUILLIAN BARRE SYNDROME ( AIDP)
• GBS may develop even weeks after infection.
• May be mild or may be associated with severe quadriparesis.
• Multiple cranial nerve involvement , Miller Fisher Syndrome also reported.
• Sometimes associated with a rapidly progressive course , may require ICU
admission / mechanical ventilation due to respiratory involvement.

45. STROKE
• Associated mechanisms - activation of the coagulation system , DIC ,
vascular complications manifesting as organ damage.
• Treated like any other stroke patient.

46. COVID-19 RELATED ENCEPHALOPATHY
• Devastating complication of acute SARS COV-2 infection.
• Hypoxic/metabolic changes - due to intense inflammatory response
against the virus and ARDS can result in encephalopathy.
• Presentation : altered sensorium - range from mild confusion, delirum
to deep coma. Symptoms like anosmia , ageusia would help
differentiate from other encephalopathies.
• Can lead to chronic neurological deficits.

47. GI MANIFESTATIONS OF COVID-19
• Common GI symptoms in acute infection :
• ageusia
• lack of appetite
• nausea/vomiting
• dyspepsia
• diarrhea
• abdominal pain
• elevated OT/PT levels
• Usually self limited.
• Occurs due to the presence of ACE-2 in the gut epithelium.

48. RISK FACTORS FOR DEVELOPING POST
COVID GI AND LIVER MANIFESTATIONS
• Severe disease
• Older age
• Admission to intensive care
• Respiratory tract infection
• Gut dysbiosis due to antivirals and antibiotics.
• Liver injury due to COVID-19 or medication intake.
• Polypharmacy.

49. HOW TO DIFFERENTIATE BETWEEN COVID-19
AND DRUG RELATED LIVER INJURY

50. DYSPEPSIA
• Post COVID-19 dyspepsia - reassurance , antacids and PPI
• Alarm symptoms - bleeding , weight loss , dysphagia , anemia
or vomiting upper GI endoscopy is indicated.
• Drugs – stop offending drug.
• Stool H.pylori / breath test - positive , Anti H.pylori treatment is
indicated.

51. DIARRHEA
• Diarrhea in the post covid period - pre-existing pathologies like IBS,
IBD, Celiac disease , Lactose intolerance
• Antibiotics used -diarrhea due to C.difficile infection
• Diarrhea associated with COVID-19 -reassurance , diet modification.

52. ABDOMINAL PAIN
• Post COVID-19 abdominal pain -covid related pancreatitis ,
cholecystitis or gastritis.
• Investigated by USG/CECT , S.Amylase , Lipase , LFT , Hemogram.
• Treated as per guidelines

53. ENDOCRINE SEQUELAE OF COVID-19
• After 3-6 months – new onset diabetes may occur rarely.
• Those with diabetes may become newly insulin dependent , increased insulin
dependency.
• Accelerated loss of bone mineral density following critical illness.
• Fatigue, myalgia , decreased appetite , weight loss , hypotension -evaluate for
adrenal insufficiency.

54. PREVENTION OF POST COVID SYMPTOMS
• Most effective way to prevent post COVID symptoms - prevent
COVID-19 infection.
• Vaccination, social distancing , masking , hand hygiene –important.
• Lower rates of post COVID symptoms in vaccinated individuals.

55. FOLLOW UP OF PATIENTS AFTER ACUTE COVID-19
• Mild-moderate symptoms following COVID-19 , recovering well -no
follow up required
• Severe COVID-19 requiring hospitalisation -follow up within 3 weeks
of discharge
• Persistent symptoms lasting below 12 weeks -managed in a specialized
COVID-19 recovery clinic
• If recovery clinics not available - managed by subspeciality clinic
relevant to the patients symptoms.

56. TREATMENT OF LONG COVID SYMPTOMS
• Breathing exercises , adequate sleep , rest -important
• Rehabilitation services like physical , occupational therapy , cardiac
and pulmonary rehabilitation.
• Rehabilitation as needed for critical illness neuropathy, pulmonary
recovery, exercise, nutrition.

57. REFERENCES
• UP TO DATE – Long COVID Syndrome
• Harrison’s Principles of Internal Medicine – 21st edition
• National Comprehensive Guidelines for Management OF Post COVID
Sequelae from Ministry of Health and Family Welfare
• Current Medical Diagnosis and Treatment 2023
• https://www.thelancet.com/journals/eclinm/article/PIIS2589-
5370(21)00299-6/fulltext
• https://casereports.bmj.com/content/14/4/e241485
• Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM,
Preston R, Thillai M, Dewar A, Molyneaux PL, West AG. Persistent Post-
COVID-19 Interstitial Lung Disease. An Observational Study of
Corticosteroid Treatment. Ann Am Thorac Soc. 2021 May;18(5):799-806.
doi: 10.1513/AnnalsATS.202008-1002OC. PMID: 33433263;

58. THANK YOU