WUHAN CORONAVIRUS (2019-nCoV) : AN UPDATE
As the world steps into the 3rd decade of the new millennium, we are now faced with the 3rd instance of an outbreak due to a zoonotic coronavirus jumping across species to infect humans. As of March 11th, there were 118,326 confirmed cases with 4292 deaths. Having spread to every continent except Antarctica, the COVID-19 outbreak has officially been designated as a pandemic by the WHO.(1)
In comparison, the severe acute respiratory syndrome (SARS) outbreak of 2002-2003 lasted about six months, resulting in more than 8,000 cases and killing 774 people.(2) The Middle-East respiratory syndrome (MERS) was first identified in Saudi Arabia in Sep. 2012 and by June the following year, there were 55 laboratory-confirmed cases reported to WHO.(3) In 2015, there was a separate outbreak of MERS-CoV in South Korea. The first patient of the outbreak developed symptoms on May 11, 2015. WHO and the South Korean government estimated that the outbreak ended in July 2015, after about two months by which time, there were 186 confirmed cases and 38 deaths.(4)Ā
WHAT IS THE CORONAVIRUS?
Coronaviruses are enveloped non-segmented positive sense RNA viruses.(5) They belong to the subfamily Coronavirinae in the family of Coronaviridae of the order Nidovirales, and this subfamily includes four genera:(6)
They can infect respiratory, gastrointestinal, hepatic and central nervous system of human, livestock, avian, bat, mouse and many other wild animals.(6) Since the outbreaks of SARS in 2002 and MERS in 2012, the possibility of CoVs transmission from animals to human has been proved.(6)
Before 2019, there were only six CoVs that can infect humans and cause respiratory diseases:(6)Ā
- HCoV-229E, HCoV-OC43, HCoV-NL63 and HKU1 induce only mild upper respiratory disease, and in rare cases some of them can cause severe infection in infants, young and the elderly.(6)
- SARS-CoV and MERS-CoV can infect lower respiratory tract and cause severe respiratory syndrome in human.(6)
WHAT ABOUT THE NEW STRAIN?
Since the end of December 2019, an outbreak of mystery pneumonia in Wuhan has been drawing tremendous attention around the world. Chinese government and researchers have taken swift measures to control the outbreak and conduct the etiological studies.(6) The causative agent of the mystery pneumonia has been identified as a novel coronavirus by deep sequencing and etiological investigations by at least 5 independent laboratories of China. On 12 January 2020, the World Health Organization temporarily named the new virus as 2019 novel coronavirus (2019-nCoV). On 11 February 2020, the ICTV officially named the virus as SARS-CoV-2 and WHO announced a name for the new coronavirus disease: COVID-19.(7,8) To avoid confusion with the disease SARS, the WHO sometimes refers to the virus as “the virus responsible for COVID-19” in public health communications.(9)
The new coronavirus SARS-CoV-2, which belongs to betacoronaviruses according to the genome analysis, can also infect lower respiratory tract and cause pneumonia, but in general, the symptoms are milder than SARS and MERS.(6)Ā
SARS-CoV-2 is a positive-sense single-stranded RNA virus. From a taxonomic perspective SARS-CoV-2 is classified as a strain of the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV).(8)
SOURCE & TRANSMISSION OF THE VIRUS
The initial source of 2019-nCoV still remains unknown; there are many suspects but conclusive proof still evades us. Given its close similarity to bat coronaviruses, it may be likely that bats are the primary reservoir for the virus. SARS-CoV was transmitted to humans from exotic animals in wet markets, whereas MERS-CoV is transmitted from camels to humans. In both cases, the ancestral hosts were probably bats.(10,11)
COVID-19 is transmitted via droplets and fomites during close unprotected contact between an infector and infectee. Airborne spread has not been reported for COVID-19 and it is not believed to be a major driver of transmission based on available evidence.(12) Significant environmental contamination by patients with SARS-CoV-2 through respiratory droplets and fecal shedding suggests the environment as a potential medium of transmission and supports the need for strict adherence to environmental and hand hygiene.(13)
Fecal shedding has been demonstrated from some patients, and viable virus has been identified in a limited number of case reports. However, the fecal-oral route does not appear to be a driver of COVID-19 transmission; its role and significance for COVID-19 remains to be determined.(12)
Although risk of being infected by a patient with SARS-CoV-2 virus is highest after onset of symptoms, high viral load can be detected before patient is symptomatic. Since the viral loads of non-symptomatic patients are similar to that of symptomatic patients, there is a high risk of human to human transmission during non-symptomatic phase of disease.(14)
The reproduction number (the number of secondary cases induced by a single infected individual in a totally susceptible population) of the SARS-CoV-2 virus is estimated to be 2.6 (credibility interval: 2.1-5.1).(15)
The estimated risk of health care personnel being infected can be as high as 4%.(16)
CASE DEFINITIONS & TESTING
The WHO has updated the case definitions for testing for COVID-19 as follows:
A suspected case, who should be tested, is:(17)
- a patient with acute respiratory illness (that is, fever and at least one sign or symptom of respiratory disease, for example, cough or 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 that has reported local transmission of COVID-19 disease during the 14 days prior to symptom onset (for updated reporting, see the situation reports at https://www.who.int/emergencies/diseases/novelcoronavirus-2019/situation-reports/);
- a patient with any acute respiratory illness AND who has been a contact of a confirmed or probable case of COVID-19 disease during the 14 days prior to the onset of symptoms;
- a patient with severe acute respiratory infection (that is, fever and at least one sign or symptom of respiratory disease, for example, cough or shortness breath) AND who requires hospitalization AND who has no other etiology that fully explains the clinical presentation.
A probable case is a suspected case for whom the report from laboratory testing for the COVID-19 virus is inconclusive.(17)
A confirmed case is a person with laboratory confirmation of infection with the COVID-19 virus, irrespective of clinical signs and symptoms.(17)
A contact is a person that is involved in any of the following:(17,18)
- Providing direct care without proper personal protective equipment (PPE) for COVID-19 patients
- Staying in the same close environment of a COVID-19 patient (including workplace, classroom, household, gatherings).
- Traveling together in close proximity (1 m) with a symptomatic person who later tested positive for COVID-19.
- High Risk Contact:(18)
- Touched body fluids of the patient (Respiratory tract secretions, blood, vomit, saliva, urine, faeces)
- Had direct physical contact with the body of the patient including physical examination without PPE.
- Touched or cleaned the linens, clothes, or dishes of the patient.Ā
- Lives in the same household as the patient.
- Anyone in close proximity (within 3 ft) of the confirmed case without precautions.
- Passenger in close proximity (within 3 ft) of a conveyance with a symptomatic person who later tested positive for COVID-19 for more than 6 hours.
- Low Risk Contact:(18)
- Shared the same space (Same class for school/worked in same room/similar and not having a high risk exposure to confirmed or suspect case of COVID-19).
- Travelled in same environment (bus/train/flight/any mode of transit) but not havingĀ a high-risk exposure
Any suspected case should be tested for infection with the COVID-19 virus using a molecular test. Based on clinical judgment, clinicians may opt to order a test for the COVID-19 virus in a patient who does not strictly meet the case definition, for example, if there is acute respiratory illness among a cluster of health care workers or severe acute respiratory infection or pneumonia in families, workplaces or social networks.(17)
WHAT ARE THE SYMPTOMS & SIGNS OF COVID-19?
The symptoms, based on the analysis of 55924 laboratory confirmed cases were found to be:(12)Ā
- Fever (87.9%)
- Dry cough (67.7%)
- Fatigue (38.1%)
- Sputum production (33.4%)
- Shortness of breath (18.6%)
- Sore throat (13.9%)
- Headache (13.6%)
- Myalgia & arthralgia (14.8%)
- Chills (11.4%)
- Nausea or vomiting (5.0%)
- Nasal congestion (4.8%)
- Diarrhea (3.7%)
- Hemoptysis (0.9%)
- Conjunctival congestion (0.8%)
The incubation period varies between 2-14 days.(19)
AGE DISTRIBUTION OF INFECTED PATIENTS
The age distribution of infected patients is as follows (data from 44,672 patients laboratory confirmed cases):(16)
- <10 years: <1%
- 10-19 years: 1%
- 20-29 years: 8%
- 30-79 years: 87%
- ā„80 years: 3%
SEVERITY OF THE DISEASE
According to WHO, 80% of patients with COVID-19 have mild symptoms. Approximately 15% develop severe disease, and only 2-5% may become critically ill and need ICU admission.(16,20)
The case fatality rate in COVID-19 (as determined from 44,672 confirmed patients) is 2.3% (2-4%). This is lower than SARS (9.6%) and MERS (34.4%).(16,21)
LAB FINDINGS IN COVID-19
According to a recent literature review, the most frequent laboratory abnormalities encountered in patients with COVID-19 encompass:(22,23)
- Lymphopenia (35-83%)
- Thrombocytopenia (5-36%)
- Increased CRP (75-93%)
- Increased LDH (27-92%)
- Increased ESR (up to 85%)
- Increased D-dimer (36-43%)
- Decreased serum albumin (50-98%)
- Decreased Hb (41-50%).
Risk factors associated with higher odds of in-hospital death were:(24)
- Older age,
- D-dimer levels greater than 1 Ī¼g/mL
- Higher SOFA score on admission
Elevated levels of blood IL-6, high-sensitivity cardiac troponin I, lactate dehydrogenase, ALT and ferritin & lymphopenia were more commonly seen in severe COVID-19 illness.(24)Ā
Lymphopenia is one of the hallmarks of COVID-19 and is also an unfavourable prognostic indicator. In general, counts of peripheral CD4 and CD8 T cells are found to be substantially reduced. CD8 T cells are also found to contain a considerable number of cytotoxic granules.(25)
Increased high-sensitivity cardiac troponin I during hospitalisation was found in more than half of those who died.(24)
Although less than 20% of COVID-19 patients present with increased procalcitonin, results of a recent meta-analysis suggest that serial procalcitonin measurement may play a role for predicting evolution towards a more severe form of disease and for defining the risk of developing severe bacterial co-infections. Increased procalcitonin values are associated with a nearly 5-fold risk of more severe forms of COVID-19.(26)
In patients with severe COVID-19, histological examination of lung tissue shows diffuse alveolar damage characterized by the presence of cellular fibromyxoid exudates, desquamation of pneumocytes and hyaline membrane formation. This is consistent with ARDS.(25)
Chest radiographs may show bilateral infiltrates.(27) The most common patterns on chest CT were found to be ground-glass opacity (56.4%) and bilateral patchy shadowing (51.8%).(22)Ā
INFECTION PREVENTION AND CONTROL DURING HEALTHCARE
The following is a highly abridged version of the WHO document āInfection prevention and control during health care when novel coronavirus infection is suspected: Interim Guidanceā ā the complete document is available at:(28) https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125
- Ensure that all patients cover their nose and mouth with a tissue or elbow when coughing or sneezing;
- Offer a medical mask to patients with suspected infection while they are in waiting/public areas or in cohorting rooms;
- Perform hand hygiene after contact with respiratory secretions:
- Hand hygiene includes either cleansing hands with an alcohol-based hand rub (ABHR) or with soap and water;
- alcohol-based hand rubs are preferred if hands are not visibly soiled;
- wash hands with soap and water when they are visibly soiled.
- When dealing with suspected cases:
- Wear an N95 rated medical mask, eye protection (googles) or facial protection (face shield) to avoid contamination of mucous membranes; clean, non-sterile, long-sleeved gown and gloves.
- The use of boots, coverall and apron is not required during routine care.
- After patient care, appropriate doffing and disposal of all personal protective equipment (PPE) and hand hygiene should be carried out. A new set of PPEs is needed, when care is given to a different patient.
- Equipment should be either single-use and disposable or dedicated equipment (e.g., stethoscopes, blood pressure cuffs and thermometers). If equipment needs to be shared
among patients, clean and disinfect it between use for each individual patient (e.g., by using ethyl alcohol 70%). Refrain from touching eyes, nose or mouth with potentially contaminated gloved or barehands; avoid moving and transporting patients out of their room or area unless medically necessary.Ā
- Use designated portable X-ray equipment and/or other designated diagnostic equipment. If transport is required, use predetermined transport routes to minimize exposure for staff, other patients and visitors, and have the patient using a medical mask;
- Routinely clean and disinfect surfaces which the patient is in contact;
- Limit the number of health care workers, family members and visitors who are in contact with a suspected and confirmed case;
- Maintain a record of all persons entering the patientās room, including all staff and visitors.
The WHO has released detailed information on many other aspects of infection control, which can be viewed at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/infection-prevention-and-control
HOW AND WHEN SHOULD THE GENERAL PUBLIC USE MASKS?
Guidelines on use of a mask by the general public(29)
- Persons having no symptoms are not to use mask
- In asymptomatic patients, more effective measures are:
- Wash hands frequently with soap and water / alcohol-based hand sanitizer with 70% alcohol.
- While coughing or sneezing cover nose and mouth with handkerchief, paper tissue. If handkerchief or tissue paper is not available cough into the flexed elbow. Dispose of tissue immediately after use and wash hands.
- Refrain from touching face, mouth, nose and eyes.
- Stay at least a metre away from those coughing or sneezing.
- Monitor your body temperature.
- Apart from healthcare workers, masks can be used in the following situations:
- When a person develops cough or fever.
- While visiting a healthcare facility.
- When you are caring for an ill person.
- Close family contacts of such suspect/confirmed cases undergoing home care should also use Triple layer medical mask.
Duration for which a medical mask will remain effective:(29)
A medical mask, if properly worn, will be effective for 8 hours. If it gets wet in between, it needs to be changed immediately
Correct procedure of wearing triple layer mask:(29)
While wearing a medical mask, the steps given below needs to be followed. These steps are:
- Unfold the pleats; make sure that they are facing down.
- Place over nose, mouth and chin.
- Fit flexible nose piece (a metallic strip that can easily be located) over nose bridge.
- Secure with tie strings (upper string to be tied on top of head above the ears ā lower string at the back of the neck.)
- Ensure there are no gaps on either side of the mask, adjust to fit.
- While in use, avoid touching the mask.
- Do not let the mask hanging from the neck.
- Change the mask after six hours or as soon as they become wet.
- Disposable masks are never to be reused and should be disposed off.
- While removing the mask great care must be taken not to touch the potentially contaminated outer surface of the mask
- To remove mask first untie the string below and then the string above and handle the mask using the upper strings.
Disposal of used masks(29)
Used mask should be considered as potentially infected. Masks used by patients / care givers/ close contacts during home care should be disinfected using ordinary bleach solution (5%) or sodium hypochlorite solution (1%) and then disposed of either by burning or deep burial.
GUIDANCE ON SAMPLE COLLECTION
Rapid collection and testing of appropriate specimens from patients meeting the suspect case definition for COVID-19 is a priority for clinical management and outbreak control. Suspect cases should be screened for the virus with nucleic acid amplification tests (NAAT), such as RT-PCR.(30)Ā
In India, the ministry of health and family welfare and the ICMR have designated 52 testing centres and an additional 57 laboratories to assist in sample collection. All the designated centres and laboratories are higher level medical centers and medical colleges.(31) No private laboratory has been given permission to perform testing for COVID-19.
Given below is a table with the relevant details. The full WHO document is available at: https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117
|Specimen type||Collection materials||Transportation||Storage till testing||Comment|
|Dacron or polyester flocked|
swabs in viral transport medium
|2-8 Ā°C||ā¤5 days: 2-8 Ā°C|
>5 days: -70 Ā°C (dry ice)
|The nasopharyngeal and|
oropharyngeal swabs should be placed in the same tube to increase the viral load.
|sterile container||2-8 Ā°C||ā¤48 hours: 2-8 Ā°C|
>48 hours: ā70 Ā°C (dry ice)
|There may be some dilution|
of pathogen, but still a
aspirate or nasal wash
|sterile container||2-8 Ā°C||ā¤48 hours: 2-8 Ā°C|
>48 hours: ā70 Ā°C (dry ice)
|SputumĀ ||sterile containerĀ ||2-8 Ā°C||ā¤48 hours: 2-8 Ā°C|
>48 hours: ā70 Ā°C (dry ice)
|Ensure the material is from|
the lower respiratory tract
|Tissue from biopsy or|
with saline or VTM
|2-8 Ā°C||ā¤24 hours: 4 Ā°C|
>24 hours: ā70 Ā°C
TESTING AND DIAGNOSIS
Laboratory confirmation of COVID -19 is not possible at private laboratories. As mentioned earlier there are designated testing centres and laboratories for sample collection. The full list of laboratories which have been designated can be viewed at : https://www.icmr.nic.in/content/covid-19
The only testing methodologies validated at present are RT-PCR and viral culture (viral culture requires a biosafety level of BSL3).(32)
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