COVID – 19
Useful links
COVID-19 UK dashboard
Dashboard from Johns Hopkins

Healthmap

Worldometer dashboard
WHO COVID-19 page
WHO COVID-19 daily sitrep
COVID-19 Dashboard (WHO)
PHE
COVID-19: guidance for health professionals
NHS.UK advise for the public
Health Protection Scotland COVID-19 page
India COVID-19 page
CDC COVID -19 page
Singapore COVID -19 page
ECDC COVID-19 page

Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition)

JAMA network COVID-19 page
IDSA COVID 19 resource centre
Journal of Antimicrobial Chemotherapy COVID-19 page
NEJM COVID-19 page
BMJ COVID-19 page
The Lancet COVID-19 page
Elsevier COVID -19 page
Uptodate COVID-19 page
Medscape COVID-19 page
Royal College of Obstetricians and Gynaecologists page
British Society for Rheumatology
British Transplant Society

A presentation on COVID -19

Coronavirus, the largest known RNA virus, derives its name from the ray-like projections on its surface giving it an appearance of a crown (Latin for the crown is a corona).

It is an enveloped virus making is more susceptible to disinfectants. It can be inactivated by alcohol.

This virus was discovered in 1965.

The Coronavirus belongs to the order Nidovirales.
The subfamily Coronavirinae is divided into four genera – alpha, beta, gamma and delta.

There is 7 known human coronavirus.
These belong to either beta or alpha coronavirus.

Amongst these – SARS, MERS and the COVID-19 (Wn CoV) are the newly discovered coronavirus believed to have jumped from animal hosts to the humans.

Other human coronaviruses are a common cause of seasonal cough and cold. They are
HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1.

Coronavirus is known to affect various animals – like bats, snakes, poultry, swine, goats, camels, beluga whales, palm civets etc.
In 2003, a new coronavirus – Severe Acute
Respiratory Syndrome Coronavirus (SARS CoV) was discovered in China. It was considered to have transferred to the humans from racoon dog or Asian palm civet.
Rodents have also been implicated. The host was considered to be bats.

Until now, 8098 cases were reported from 17 countries with 774 deaths—case fatality rate – 9.6%.

No new case has been reported since 2004.

(Ref: https://www.who.int/ith/diseases/sars/en/)

The Middle East Respiratory Syndrome -Coronavirus (MERS-CoV), another betacoronavirus started circulating in Saudi Arabia in 2012.

It has affected 2519 people in 27 countries with 866 deaths reported. The mortality rate is approximately 35%.

current scientific evidence suggests that dromedary camels especially juvenile camels are a major source. However, serological evidence of the virus has been found in bats and some other animals like goats.

The number of cases and the number of deaths has far exceeded that of SARS or MERS CoV. The case fatality rate of MERS CoV is about 35%, and that of SARS is 9.6%. 

It is difficult to estimate case fatality rate while the pandemic is ongoing, but it is certainly not as high as MERS CoV.

How does COVID-19 compared to Spanish flu – the deadliest pandemic of the 20th century?

How does the mortality compare with seasonal influenza?

(It shows the importance of the seasonal influenza vaccine – without which mortality expected to be higher)

 December 2019, a cluster of pneumonia cases was reported with an epidemiological link to Huanan wet market. The number of cases kept increasing thereafter.

This market is a wet market, which sells various animal meats/products.

The origin of the virus, although, has been questioned.

Two phylogenetic studies, by Forster et al and Zhang et al – traced the types of viruses and concluded that the earliest form of the virus (type I or type A), may not have any epidemiological link with Hainan market.

The SARS-CoV2 (COVID-19) virus has 96% similarity with a bat coronavirus (RaTG13). It has been proposed that the virus may have evolved as a result of natural selection [Anderson, Nature.com].

Anderson et al. (https://www.nature.com/articles/s41591-020-0820-9)
Zhang et al (https://www.medrxiv.org/content/10.1101/2020.02.25.20027953v1.full.pdf)
Forster et al (https://www.pnas.org/content/early/2020/04/07/2004999117)

 

The virus, based on phylogenetic studies has been classified into 3 central variants I, II, and III (or A, B, C according to Forster et al).

The variant I/A is closely related to the ancestor bat virus (BatCoV RaTG13). 

Type I can be divided into subclusters Ia and Ib. The Type Ib underwent mutation to form type II. This variant (type II/B) is more contagious than I/A and is associated with the Hainan market. This variant is the common variant is east Asia.

The variant II mutated to form variant III (or type C). Type III and I (C and A) are the predominant type of virus found in the Europeans and Americans.

To update yourself about the current situation check these dashboards and sitreps.
Check the current situation of COVID 19 from This Dashboard
WHO dashboard and situation report
A collection of dashboards
European Centre for Disease Prevention and Control data
Public Health England
COVID-19 India dashboard
Transmission

The knowledge about the transmission is still being investigated. Current understanding/recommendation:

Animal to Human transmission: Yes (this virus has likely to have come from an animal)

Human to Human (H2H) transmission: Yes.

Mode of H2H transmission:

Droplet: When an infected person cough or sneezes they generate droplets of fluid with the virus. The droplets are heavy and fall to the surface within 1-2 metres. This droplet may deposit on the face or body or upper respiratory tract and infect the person.

Fomite: When the droplets with the live virus get deposited on a surface. It may remain infective for a certain period of time depending on the nature of the surface.

Vertical transmission (From mother to the baby during pregnancy or immediately after delivery): Probable. More details on the RCOG website.

Airborne/aerosol spread:

This area is a matter of debate (Nature https://www.nature.com/articles/d41586-020-00974-w)

The current recommendation from WHO, CDC and PHE is that transmission via airborne route or aerosol is unlikely in normal circumstance.

However, there are procedures, performed in hospital or healthcare, which may generate aerosol artificially – like intubation. These procedures are called aerosol-generating procedures (AGPs). If anyone is performing these procedure additional protection must be used.

CDC: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Ftransmission.html

WHO – https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

PHE – https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/transmission-characteristics-and-principles-of-infection-prevention-and-control

Tellier et al, Recognition of aerosol transmission of infectious agents: a commentary, BMC Infectious Diseases volume 19, Article number: 101 (2019) .

Atkinson J, et al, Natural Ventilation for
Infection Control in Health-Care Settings, WHO Publication/Guidelines 2009 ISBN 978 92 4 154785 7 (Page 18, table 3.1)

A video of Sneezing.
This annotated series of shadowgraph video clips.

Video S2 from Tang J, Nicolle A, Pantelic J, Jiang M, Sekhr C, Cheong D, Tham K (2011).Qualitative Real-Time Schlieren and Shadowgraph Imaging of Human Exhaled Airflows: An Aid to Aerosol Infection Control“. PLOS ONEDOI:10.1371/journal.pone.0021392PMID 21731730PMC3120871.
This file is licensed under the Creative Commons Attribution 2.5 Generic license (taken from Wikipedia)

Clinical features

Incubation Period

Estimated median incubation time: 5.1 days

In most cases, symptoms appear by 11.5/12 days  (NEJM journal watch)(Lauer, Ann Intern Med).

PHE suggest a range of 1-11 days. CDC suggests 2-14 days.

Lauer et al – https://annals.org/aim/fullarticle/2762808/incubation-period-coronavirus-disease-2019-covid-19-from-publicly-reported

PHE – https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/873713/01-spi-m-o-consensus-statement-on-2019-novel-coronavirus-_covid-19_.pdf

CDC – https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

Infectious/Infectivity period

The infective period of a case is difficult to estimate. The widely used test method – PCR, detects a portion of the virus nucleic acid. Presence of this portion does not mean that the live virus is present.  Nucleic acid left from the dead virus could make the PCR positive.

It is also difficult to know if a person starts spreading the virus even before they develop a symptom as we wouldn’t test a person for the virus if (s)he is not unwell.

There are reports to suggest that PCR could be positive up to 20-21 days from the onset of symptoms [Xi He, Nature][Zhou, Lancet].
ECDC assessment found that
WHO fact-finding mission in China suggesting up to 2 weeks in severe cases and a paper from Singapore [Young] suggesting 24 days.

Xi He inferred that the infectivity starts 2-3 days before the onset of symptom and decline significantly 8 days after the symptom onset, although PCR could be positive up to 21 days or longer.
A similar finding was obtained from WHO fact-finding mission in China. SARS-CoV-2 virus can initially be detected 1–2 days prior to symptom onset in upper respiratory tract samples; the virus can persist for 7–12 days in moderate cases and up to 2 weeks in severe cases. (ECDC)
WHO is conducting further research.

Zhou – https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30566-3.pdf
Xi He – https://www.nature.com/articles/s41591-020-0869-5
ECDC –https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-Discharge-criteria.pdf

Clinical recovery

Mild cases = approximately 2 weeks

Severe or critical cases = 3-6 weeks.

Approximately

[PHE, UK]

Most cases are mild or asymptomatic. However, approx 20% may develop severe illness.

Major clinical features: [Guan et al, Huilan et al]

Fever (88.7%),
cough (67.8%),
fatigue (38.1%),
sputum production (33.7%),
shortness of breath (18.7%),
sore throat (13.9%),  
headache (13.6%),
vomiting (5%),
diarrhoea (3.8%)

lymphocytopenia (64.5%),

increase of CRP (44.3%),

increase of LDH (28.3%),

leukocytopenia (29.4%)

There are anecdotal reports of loss of smell and taste associated with COVID 19 (ENT UK. Lancet correspondence)

https://www.journalofinfection.com/article/S0163-4453(20)30222-X/pdf
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30293-0/fulltext

 

 

Case fatality rate:

A paper published in JAMA suggested that early cases had a case fatality rate of 2.3%
for confirmed cases (11/02/2020)

14.8% in patients aged ≥80 years (208 of 1408)

8.0% in patients aged 70-79 years (312 of 3918)

49.0% in critical cases (1023 of 2087)

————

Case fatality rate is difficult to calculate while a pandemic is ongoing. Also it is not standardised as every country have different test/dignostic criteria. 
For example – on 22/4/20
CFR in Italy is 13.39% and that of Germany is 3.5%.

 

Imaging: Chest X-ray

>>At the early stage: no abnormalities.
>>Advanced disease: localized or multisegmented bilateral interstitial opacities with peripheral predilection.
>>Severe case: multiple alveolar consolidations were seen in both lungs.
Critical disease: “white lung” with a small amount of pleural effusion.

Pleural effusion – approx 5% cases.

Chest radiographs have low sensitivity.
[Yi Lei 2020]

Imaging: CT scan

Sensitivity – 86-97%

Typical findings of COVID-19 infection on HRCT –

>>Ground-glass opacities, vascular dilation inside the lesion, “crazy-paving” pattern, and interlobular septal thickening, mostly bilateral with lower lobes predilection (66%).

>>It is unusual to find: single ground-glass nodules, cavitation, and combination of ground-glass opacities and alveolar consolidations. [Yi Lei, 2020]

In some cases, CT finding was reported to be present before the onset of symptoms [Heshui Shi, Lancet Infec. Dis.].

Detecting COVID 19

Real-time PCR:

Sensitivity – 66-80% (some PCR platforms claiming higher sensitivity) [Ai]

Specimen:
upper and lower respiratory specimens
(nasopharyngeal or oropharyngeal
swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) – The preferred specimen type should be suggested by your microbiology laboratory.

A positive result does not rule out infection by a 2nd organism (virus/bacteria) e.g influenza.
A negative result does not rule out COVID-19/ SARS-CoV-2. The false-negative result has been observed. A repeat test may be required based on clinical conditions. The local protocol must be followed.

Useful link: https://www.cdc.gov/coronavirus/2019-ncov/lab/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Flab%2Frt-pcr-detection-instructions.html

Here are some PCR; the list is not exhaustive.

Serology:

>>There is a lag period of antibody development – 7-14 days.
>> Point of care tests, including lateral flow device, have been developed, capable of detecting both IgG and IgM.
>> Sensitivity is quoted to be 90-100%, however if the test is done early (within 10 days) after the infection the sensitivity could be a dismal 13% (approx).
>>In the UK, the serology platforms being considered are Roche and Abbott. More platforms may be used in future.

Ref: https://sph.nus.edu.sg/wp-content/uploads/2020/03/COVID-19-Science-Report-Diagnostics-13-Mar.pdf
https://www.centerforhealthsecurity.org/resources/COVID-19/serology/Serology-based-tests-for-COVID-19.html

Other potential method:
Microfluidic lab-on-chip technologies

Other potential method:
CRISPR to isolate gene segments

Other potential method:
Whole-genome sequencing

Treatment

Experimental drugs – multiple RCTs are going on.

1. Remdesivir
(https://www.nih.gov/news-events/news-releases/nih-clinical-trial-remdesivir-treat-covid-19-begins)
2. Chloroquine (https://www.nature.com/articles/s41422-020-0282-0)
3. Lopinavir/ritonavir – no improvement over standard care
(Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282)
4. Chloroquine + Azithromycin  [Gautret, IJAA, in press] – small trial.
5. Tocilizumab – https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext?rss=yes
6. Darunavir
7. Sarilumab
8. Ribavirin
9. Nitazoxanide
10. Faviripavir
11. Monoclonal antibody, convalescent plasma

Ref: https://twitter.com/MayoClinicINFD/status/1241361095442542594

Some trials registered: https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=&cntry=&state=&city=&dist=

COVD-19 vaccine and treatment tracker – https://milkeninstitute.org/covid-19-tracker

 

 

Infection control
The principles being followed to control the spread of the virus are –

Hand hygiene.
Appropriate personal protective equipment.
Isolation of the patient.
Self-isolation for patient’s and family.
Social distancing.
Environmental decontamination.
Appropriate waste disposal.

The local policy must be followed.

5 Comments

  1. Anirban Chakraborty

    Excellent resource at a time when authentic information is getting submerged in a sea of misinformation. Well done Dr. Suryabrata Banerjee

    Reply
    • SB

      Thanks Anirban.

      Reply
  2. Dhara Shah

    Fantastic complication, precise and quite useful covering all important aspects

    Reply
    • SB

      Thanks, Dhara.

      Reply
  3. Dhara Shah

    Fantastic compilation, precise and quite useful covering all important aspects

    Reply

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