COVID-19: guidance for health professionals
Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition)
A presentation on COVID -19
It is an enveloped virus making is more susceptible to disinfectants. It can be inactivated by alcohol.
This virus was discovered in 1965.
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.
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.
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.
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.
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.
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 ONE. DOI:10.1371/journal.pone.0021392. PMID 21731730. PMC: 3120871.
This file is licensed under the Creative Commons Attribution 2.5 Generic license (taken from Wikipedia)
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.
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
Mild cases = approximately 2 weeks
Severe or critical cases = 3-6 weeks.
Most cases are mild or asymptomatic. However, approx 20% may develop severe illness.
Major clinical features: [Guan et al, Huilan et al]
increase of CRP (44.3%),
increase of LDH (28.3%),
There are anecdotal reports of loss of smell and taste associated with COVID 19 (ENT UK. Lancet correspondence)
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.].
Sensitivity – 66-80% (some PCR platforms claiming higher sensitivity) [Ai]
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
>>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.
Other potential method:
Microfluidic lab-on-chip technologies
Other potential method:
CRISPR to isolate gene segments
Other potential method:
Experimental drugs – multiple RCTs are going on.
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
11. Monoclonal antibody, convalescent plasma
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
Appropriate personal protective equipment.
Isolation of the patient.
Self-isolation for patient’s and family.
Appropriate waste disposal.
The local policy must be followed.