Coronavirus

Coronavirus Disease (COVID-19): All you need to know as a Doctor

By Dr Daya

Posted on March 20, 2020

Coronavirus Disease 2019 (COVID-19): All you need to know as a Doctor

Updated on 28th May 2020. These materials are regularly updated based on new scientific findings as the pandemic evolves.

Coronaviruses

Introduction

Coronaviruses are a large family of viruses causing illness in animals or humans.
In human, they cause illness ranging from Common Cold to MERS, SARS & COVID-19.

Morphology

Enveloped
Shape: Carrying petal or club shaped or crown like peplomer spikes giving appearance of Solar Corona.
Size: Large (120-160 nm)
Symmetry: Helical
Genome: Linear, positive sense ss RNA (non- segmented genome)
(Note: Segmented Genome: BORA: Bunya, Orthomyxo, Reo, Astro)
SARS-CoV-2 Morphology

Classification

Human Coronaviruses which cause human infections. There are 7 recognised human coronaviruses:

Human coronavirus 229E
Human coronavirus NL63
Human coronavirus OC-43
Human coronavirus HKU1
SARS-CoV
MERS-CoV
SARS-CoV-2 (Novel coronavirus, Wuhan virus, China virus)

Most Human coronaviruses are widespread affecting most part of world. Except: SARS-CoV, MERS-CoV → Restricted, cause severe respiratory disease with higher mortality.

1. SARS-CoV

Origin: 2003, China
Discovered by WHO Physician Dr Carlo Vrbani in a business man
Later on, 8098 cases in 29 countries with over 774 deaths.
Source: Contracted from animals including monkeys, palm civets, rodents

2. MERS-CoV

Mortality: 30%
Between 2012-2018, about 2143 cases, 750 deaths from 27 different countries.

3. SARS-CoV-2

Source: Contracted from animals including bats, snakes

Coronavirus Disease (COVID-19)

Introduction

COVID-19 is the infectious disease caused by the most recently discovered coronavirus SARS-CoV-2.

Epidemiology

History

Origin: Wuhan, Hubei, China
31 Dec 2019: WHO China office reported cases of pneumonia of unknown etiology.
Timeline for COVID-19

Upto 28th May, 2020
Total cases: 5,813,418
Deaths: 357,896
Recoveries: 2,515,416
217 countries & territories involved
India reported first case in Kerala.

Epidemiological parameters

Causative agent: SARS-CoV-2
Source of infection: Cases
Mode of infection: Droplets, Contact & Fomites
Reproductive number (R0): 2- 2.5 (Number of secondary infections generated from one infected person)
Incubation Period: 2.2-11.5 days (Median Incubation Period: 5.1 days)
Age group affected: All age groups (Mostly 30+ age group)

Note: Influenza spreads faster than COVID-19.

Case fatality rate (CFR)

Overall CFR: 2.0-3.7% (0.2-15%)
>1% CFR in age 50+ years
>10% CFR in age 80+ years
CFR highest if co-existing morbidities (CVD, HTN, DM)

Epidemic Curve

More steeper the curve, More the requirements of ICU’s

WHO Risk Assessment (on 28th feb 2020)

China: Very High
Regional: Very High
Global: Very High

Definitions of case

1. Suspect Case

A. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease (e.g.,
cough, shortness of breath), AND with no other etiology that fully explains the clinical presentation AND a
history of travel to or residence in a country/area or territory reporting local transmission of COVID-19 disease during the 14 days prior to symptom onset.

B. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID19 case in the last 14 days prior to onset of symptoms;

C. A patient with severe acute respiratory infection (fever and at least one sign/symptom of respiratory disease (e.g., cough, shortness breath) AND requiring hospitalization AND with no other etiology that fully explains the clinical presentation.

2. Probable case

A suspect case for whom testing for COVID-19 is inconclusive. (Inconclusive being the result of the test reported by the laboratory).

3. Confirmed case

A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms.

Pathogenesis

Entry into host cell

⇓
Primarily causing infection of airway epithelial cells → Respiratory symptoms
Later on, additionally infect surrounding cells like macrophages, dendritic cells → Release of cytokines → Systemic symptoms

⇓

Spike molecules of virus interact with ACE-2 receptor on host cell

⇓

Virus particle uncoated

⇓

Genome enters cell cytoplasm

⇓

Coronavirus RNA Genome has a 5’ methylated cap & a 3’ polyadenylated tail which allows RNA to attach to Host cell ribosome for Translation

⇓

Coronavirus also have RNA-dependent RNA polymerase (RdRP) which allows viral genome to Transcribe into new RNA copies using Host cell machinery

⇓

RdRP is first protein to be made

⇓

After RdRP gene coding, Translation stops by Stop Codon called as Nested Transcript

Clinical features

For first 7 days

Fever, Cough, Shortness of breath (SOB)
±

Sore throat, Rhinorrhea, Diarrhoea

On 9-10th day

B/L Pneumonia (Consolidation) : MC & Severe manifestation

⇓

On Imaging- Ground Glass appearance of lungs

Features that are not seen

Pleural effusion
Lymphadenopathy
Cavitation
Pulmonary nodules
Pneumothorax (Rare)

Clinical spectrum

Severity of disease

Fraction of severe disease is more in COVID-19.

80% Mild to moderate
15% Severe (needs supplemental O2) e.g. severe pneumonia (Fever or suspected respiratory infection, plus one of – Respiratory rate >30 breaths/min, Severe respiratory distress, SpO2 <90% on room air)
5% Critical (requires ventilation) e.g. respiratory failure, septic shock, multiple organ dysfunction or failure

Factors determining the severity of disease

Age of individual (More severe in elderly)
Immunity of host (More severe in patient with Comorbid conditions, immunocompromising conditions, obesity)

High risk patients

Age > 60 years
Chronic artery disease (CAD)
Chronic kidney disease (CKD)
Chronic liver disease (CLD)
Chronic lung disease
Hypertension
Diabetes
Immunocompromised patients

Theoretically, patients who are at highest risk of being critically sick: Hypertensives taking ACE-2 Inhibitors as antihypertensives

Hypertension

↓

Prescription : ACE-2 Inhibitors

↓

Upgrade of ACE-2 receptors (More in number)

↓

More severe COVID-19

Lab diagnosis

Sample collection

Specimens: URT (Nasopharyngeal swabs NPS, Oropharyngeal swabs OPS & Sputum, LRT (BAL, Tracheal aspirate)
Location: In OPS, Tonsillar pillars & Posterior oropharynx
Specimen should be collected by Synthetic fiber swabs with plastic shafts (Should not use calcium alginate swabs with plastic shaft)
Specimen should be collected as soon as PUI (Person Under Identification) is identified.
Procedure: Tilt head → 90° parallel to palate
Precautions to be taken: Use PPE in place, Use purple nitrite latex free glove.

Investigations

1. rRT-PCR (Sensitivity-70% but Specific)

Genes: N, E, RdRP
Cost for rRT-PCR on NPS/OPS : 36-51 USD (∼3500 INR)

Genes E & N : For screening any bat associated beta coronavirus
Gene RdRP : Specific for SARS & SARS like (SARS-CoV-2)

If initial testing is negative but the suspicion for COVID-19 remains, the WHO recommends resampling & testing from multiple respiratory tract sites.

2. CT Scan chest (Sensitivity-95%, Specificity-Low)

Bilateral lung involvement on initial CT
Consolidative pattern in ICU patients
Predominanatly ground glass pattern in patients who were not in ICU
Multifocal ground glass opacities & consolidation with a peripheral lung predilection

Although the imaging features closely resemble the MERS & SARS, involvement of both lungs on initial CT likely to be seen with COVID-19; initial CT abnormalities in SARS & MERS are more frequently unilateral.

3. IgM-IgG Combo test (COVID-19 Rapid Test)

Current testing strategy

Strategy for COVID19 testing in India (Version 4, dated 09/04/2020, as per ICMR)

All symptomatic individuals who have undertaken international travel in the last 14 days
All symptomatic contacts of laboratory confirmed cases
All symptomatic health care workers
All patients with Severe Acute Respiratory Illness (fever AND cough and/or shortness of breath)
Asymptomatic direct and high-risk contacts of a confirmed case should be tested once between day 5 and day 14 of coming in his/her contact

In hotspots/cluster (as per MoHFW) and in large migration gatherings/ evacuees centres

All symptomatic ILI (fever, cough, sore throat, runny nose)
a. Within 7 days of illness – rRT-PCR
b. After 7 days of illness – Antibody test (If negative, confirmed by rRT-PCR)

Differential diagnosis (D/D)

H1N1
H5N1
Flu A & B
RSV
Rhinovirus
Parainfluenza
Allergy

Flu vaccine taken will reduce the diagnostic test & reduce list of D/D.

Complications

ARDS (M/C cause of death)

COVID-19

⇓

Hypoxia (unlike to COPD → hypercapnia) due to bilateral interstitial pneumonia

⇓

ARDS

⇓

paO2/FiO2 < 300
spO2/FiO2 < 315

Management

A. General guidelines

1. Symptomatic treatment

2. High flow nasal O2 / NIV Low volume ventilation (6 ml/kg)

3. Empirical antimicrobials

4. Lopinavir 200 mg / Ritonavir 50 mg (2 Tablets daily × 14 days) case to case basis as per following guideline:

Indicated in Lab confirmed symptomatic patients with any of the following

Hypoxia
Hypotension
New onset organ dysfunction (one or more)
↑↑ creatinine by 50% from baseline
GFR reduction by >25% from or Urine output of <0.5 ml/kg for 6 hours
↓ of GCS by 2 or more
Any other organ dysfunction
High risk patients

5. Lung protective ventilation strategy in ARDS

Methods

a. Mechanical ventilation (because of decrease in lung compliance, don’t use non-invasive methods): Indicated in obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma, or convulsions.

Rapid sequence intubation
Pre-oxygenate with 100% FiO2 for 5 minutes via bag mask
Low volume: Tidal volume of 6 ml/kg (predicted body weight)
Plateau airway pressure ≤ 30 cm H2O
Adequate PEEP for recruitment
NM Blockade for 24 hours to relax patient & facilitate ventilation
Prone positioning because improves ventilation of lungs. (Hazards: Spontaneous extubation, orthopedic injuries)

b. ECMO for most critically ill patients (refractory hypoxemia)

Aim

SpO2 ∼ 88-93%
pO2 ∼ 55-80 mm of Hg

When to stop

2 consecutive negative PCR reports at least 24 hours apart

With

Clinico-radiological improvement

B. Protocols

1. AIIMS Protocol

2. Other Protocol

a. Mild illness

Admit in isolation area
Symptomatic care
Oseltamivir
Antibiotics in high risk patients

b. Moderate to Severe

Admit in designated CCU
Start Empirical antibiotics as per CAP treatment guidelines
Oseltamivir
O2 support
Hydroxychloroquine (HCQ) 400 mg BD followed by 200 mg BD for 5 days
Consider Lopinavir/Ritonavir case to case basis

COVID with Hypoxia worsening or not improving

⇓

High flow nasal O2 / NIV Low volume ventilation (6 ml/kg)

↓worsening

IMV (Intubate)

↓worsening

ECMO

Avoid nebulisations (Spacer MDI preferred)

Steroids avoided. However, may be helpful in refractory shock, cytokine release syndrome.

C. Discharge policy

D. Recommendation for empirical use of Hydroxychloroquine (HCQ) for prophylaxis of SARS-CoV-2 infection

Eligible individuals

Asymptomatic health care workers involved in the care of suspected or confirmed cases of COVID-19
HCQ 400 mg BD on Day 1 followed by 400 mg once weekly for next 7 weeks
Asymptomatic household contacts of lab confirmed cases of COVID-19
HCQ 400 mg BD on Day 1 followed by 400 mg once weekly for next 3 weeks

HCQ not recommended if

Age < 15 years
Known retinopathy
Known hypersensitivity to HCQ
G6PD deficiency
Chronic heart disease, including propensity to/previous arrythmia

E. Drugs under Trial

1. RNA Polymerase inhibitor

Remdesivir
Favilavir

Both of these were developed for Ebola virus.

2. Chloroquine & Hydroxychloroquine

3. Oseltamivir

4. ARV Protease inhibitors

Lopinavir
Ritonavir

Recently, scientists are also trying to modify the components of protease inhibitors to improve efficiency.

5. TMPRSS2 inhibitors

6. Umifenovir

7. Ribavirin

8. Reverse transcriptase inhibitors

Emtricitabine
Tenofovir

9. Interferon

10. ASC09

11. Azvudine

12. Baloxavir marboxil

13. Favipiravir

Download: International Pulmonologist’s Consensus On Covid-19

COVID-19 in Pregnancy

Clinical features

Problems expected & seen in pregnant women’s

Cough
Fever
Shortness of breath
Severe symptoms e.g. pneumonia, marked hypoxia seen in the pregnant women’s with immunocomromised & long term conditions such as DM, Chronic lung disease, Cancer

Pregnant women do not appear to be more susceptible to the consequences of infection with COVID-19 than the general population.

Vertical transmission

Vertical transmission is unlikely (Amniotic fluid, Cord blood, Neonatal throat swabs & Breast milk samples from COVID-19 infected mothers were tested & all of them were negative.)
Transmission is therefore most likely to be as a neonate.

Intranatal transmission

Currently no evidence concerning transmission through genital fluids.

Effect on fetus

Currently there are no evidence for intrauterine fetal infection so unlikely that there will be congenital effects of virus on feta development
No data suggesting increased risk of miscarriage or early pregnancy loss.

Antenatal women

Be advised to self isolate, should stay indoors & not allow visitors.
Avoid contact with others.
Not go to work or public places.
Not use public transport
Ventilate the rooms where they are by opening a window
Separate themselves from other members of their household as far as possible, using their own towels, crockery & utensils and eating at different times.
Use friends, family or delivery services to run errands, but advise them to leave items outside.

Labor Management

Continuous electronic fetal monitoring using Cardiotopograph (CTG) in labour is currently recommended for all women with COVID-19.
Mode of delivery
-Should not be influenced by the presence of COVID-19, unless the women’s respiratory condition demands urgent delivery.
-Decision to do operative delivery is based on the obstetric requirements.
-Delayed cord clamping is still recommended following birth, provided that there are no other contraindications.

Neonate

All the newborns of women with suspected or confirmed COVID-19 need to also be tested for COVID-19.

Breastfeeding

Even if breastfeeding does not transmit the virus, it is best avoided as the baby is to be isolated from the mother.

Medico-legal perspective

Autopsy

No need to do autopsy in patient died due to COVID-19.

Pathological autopsy

Necessities

1. Consent from the legal guardian or relatives is necessary.

2. PPE’s

The following PPE should be worn at a minimum:

Wear non-sterile, nitrile gloves when handling potentially infectious materials.
To avoid the risk of cuts, puncture wounds, or other injuries that break the skin, wear heavy-duty gloves over the nitrile gloves.
Wear a clean, long-sleeved fluid-resistant or impermeable gown to protect skin and clothing.
Use a plastic face shield or a face mask and goggles to protect the face, eyes, nose, and mouth from splashes of potentially infectious bodily fluids.

The following PPE should be worn during autopsy procedures:-

Double surgical gloves interposed with a layer of cut proof synthetic mess gloves
Fluid resistant or impermeable gown
Waterproof apron
Goggles or face shield
Disposable N95 respirator or higher (Powered Air Purifying Respirators (PAPRs) with HEPA filters may provide increased worker comfort during extended autopsy procedures.)
When respirators are necessary to protect workers, employers must implement a comprehensive respiratory protection program in accordance with the OSHA Respiratory Protection standard that includes medical exams, fit-testing, and training.

3. During the procedure

Standard Precautions, Contact Precautions, and Airborne Precautions with eye protection (e.g., goggles or a face shield) should be followed during autopsy. e.g.

Do not use an oscillating bone saw for confirmed or suspected cases of COVID-19.
Consider using hand shears or oscillating saw attached to a vacuum shroud to contain aerosols.
Limit the number of personnel working in the autopsy suite at any given time to the minimum number of people necessary to safely conduct the autopsy.

Collection of Postmortem Specimens

Collection of Postmortem Clinical Specimens for SARS-CoV-2 Testing

Upper Respiratory Tract Specimen Collection: Nasopharyngeal Swab AND Oropharyngeal Swabs (NP swab, OP swab)
Nasopharyngeal swab: Insert a swab into the nostril parallel to the palate. Leave the swab in place for a few seconds to absorb secretions. Swab both nasopharyngeal areas with the same swab.
Oropharyngeal swab (e.g., throat swab): Swab the posterior pharynx, avoiding the tongue.
Lower respiratory tract: Lung swabs (Collect one swab from each lung).

Collection of Fixed Autopsy Tissue Specimens

The preferred specimens would be a minimum of eight blocks and fixed tissue specimens representing samples from the respiratory sites & major organs (including liver, spleen, kidney, heart, GI tract) and any other tissues showing significant gross pathology.
The recommended respiratory sites include:Trachea (proximal and distal)
Central (hilar) lung with segmental bronchi, right and left primary bronchi
Representative pulmonary parenchyma from right and left lung

Ethical aspects

1. No need to maintain professional secrecy.

2. Privileged communication

Doctor has to notify the public health authorities
Doctor is immune for the breach of professional secrecy.

3. Respect the patient privacy.

Can a doctor refuse to treat a patient of coronavirus?

INDIAN MEDICAL COUNCIL (Professional Conduct, Etiquette and Ethics) Regulations, 2002

5. DUTIES OF PHYSICIAN TO THE PUBLIC

5.2 Public and Community Health

Physicians, especially those engaged in public health work, should enlighten the public concerning quarantine regulations and measures for the prevention of epidemic and communicable diseases.
At all times the physician should notify the constituted public health authorities of every case of communicable disease under his care, in accordance with the laws, rules and regulations of the health authorities.
When an epidemic occurs a physician should not abandon his duty for fear of contracting the disease himself.

Duties of hospital

Duty to report
Duty for timely referral
Proper isolation of patient
Safety measures for the health care professionals
Should create awareness among general public.

The Epidemic Diseases Act

1. Titles & descriptions
2. Special Powers given to the central & state government to take special regulations to contain the spread of dangerous disease.

2A. Powers of Central Government.
It also includes the detention of people or any vessel that came from international shores and are seen potent to spread the epidemic in the country.
Section 271 IPC: Disobedience to quarantine rule

3. Punishment for violating the regulations: Any person disobeying any regulation or order made under this Act shall be deemed to have committed an offence punishable under section 188 of the Indian Penal Code

IPC Section 188: Disobedience to order duly promulgated by public servant.

4. Legal protection to the implementing persons (officers) acting under Act. No suit or other legal proceeding shall lie against any person for anything done or in good faith intended to be done under this Act.

What if a patient intentionally spreads the disease?

Section 269: Negligent act likely to spread infection of disease dangerous to life.
Section 270: Malignant act likely to spread infection of disease dangerous to life.

Prevention

Preventive measures

1. Hand washing

Wash often with soap and water for at least 20 seconds.
Use alcohol based hand sanitizer with ≥60% alcohol by volume.

2. Respiratory hygiene

Cover your mouth and nose with a tissue when you cough or sneeze (which should then be disposed of immediately) or use the inside of your elbow (with a sleeve).
Avoid touching your eyes, nose, and mouth with unwashed hands.
Surgical mask use by those who may be infected.

3. Self isolation and Self quarantine

Self isolation at home: Those diagnosed & those who suspect to have been infected.
Self quarantine: Those recently traveled to a country with widespread transmission or who have been in direct contact with someone diagnosed with COVID-19.

4. Social distancing

Definition: Infection control actions intended to stop or slow down the spread of a contagious disease by minimizing close contact between individuals.
Distance need to be maintained between 2 persons: 3-6 feet (1-2 meter)
Measures: Quarantine, travel restrictions, closing schools/workplaces/stadia/theatres/shopping centers/recreational facilities (community swimming pools, youth clubs, gymnasiums), limiting travel, avoiding crowded areas, & physically distancing themselves from sick individuals.

5. Use of Personal Protective Equipment (PPE) by healthcare providers

6. Vaccine research

Vaccine development ∼ 1 year
20-30 vaccine in development

Precautions that need to be taken by all the households

1. Wash milk bags/packets the moment you take it & wash your hands while you are at it.

2. Consider cancelling newspapers.

3. Keep a separate tray for couriers. Courier person can place the envelope/package in the tray and courier should be left untouched for at least 24 hours unless unless urgent to open.

4. Instruct maids not to touch main door. On entering the home, she has to immediately wash hands thoroughly, before touching other things . After that, wipe the calling-bell switch with a cleaning fluid.

5. Avoid getting food through swiggy, zomato etc as far as possible. If necessary, instruct to leave the packet at secure place of house as suggested by you over the call.

6. Wash all fruits and vegetables once you bring them home.

7. Remote, phone and keyboards are the most highly contaminated elements in our house. Clean them at least once a day using cleaning fluid.

8. Wash hands frequently when in house or in office. Once every hour at least. Follow 20 seconds rule while washing the hand.

9. Avoid public transport as far as possible. Even Ola and Uber may be used when absolutely unavoidable.

10. Avoid gyms, swimming pool and other exercise areas, where surface contact or air-borne contamination is inevitable.

11. Cancel tuition, dance/music classes, etc.

12. When you return home from office, shopping, etc. discard your clothes and wash your hands and feet thoroughly.

13. Most importantly, avoid touching hands anywhere on face. Inform children and parents.

14. Ask senior citizens to stop going for the routine walking exercise.

15. Use online payment methods to pay at outside Kirana stores, Dairy etc. As pieces of note you are getting as exchange may be contaminated.

16. Don’t visit hospital until unless very urgent. However if symptoms of #COVID-19 observed, essentially dial the helpline number with no delay.

Lets all be alert. Stay safe. Don’t panic.

Mnemonics

1. Practice WUHAN to prevent spread

W: Wash hands
U: Use mask properly
H: Have temperature checked regularly
A: Avoid large gatherings
N: Never touch your face with unclean hands

2. Practice CORONA VIRUS

C: Clean your hands
O: Omit raw meat
R: Remove germs from hand & face by wash.
O: Obey govt. guidelines
N: Neat & clean
A: Avoid crowded places
V: Verify not to touch any poles in public poles
I: Infection control
R: Regular healthy & hygienic diet
U: Use hand sanitizer & mask
S: Stay hydrated

Categorisation of Inbound Passengers – Airport screening

Category A: High-risk passengers

A passenger with fever, cough, shortness of breath and with a history of travel or contact with such persons from countries reporting local transmission of Covid-19 during the 14 days prior to onset of symptoms
Action: Segregate such cases from other passengers and send them for isolation in care facilities

Category B: Moderate risk

An asymptomatic passenger coming from 7 countries )China, Democratic republic of korea, France, Germany, Spain, Italy, Iran) And/OR elderly people (above 60 years) and/or hypertensive, diabetic, asthmatic, with cancer under immunosuppressive therapy, post-transplant patients or any other illness. A decision shall be taken after screening and risk profiling.
Action: To be shifted by state govt to a dedicated quarantine facility and will be monitored daily for the next 14 days. They should be isolated in tertiary care facilities if they develop symptoms

Category C: Low risk

An asymptomatic passenger coming from any Covid-19-affected country including passengers coming from the above seven countries and not falling under the above two categories.
Action: Kept under home quarantine and monitored by IDSP (Integrated Disease Surveillance Programme) network for 14 days. If they develop fever/cough/difficulty in breathing within 14 days after return, they should immediately call national helpline (011-23978046) for further management