COVID-19 Test

COVID-19 TESTING : AN UPDATE

WHAT ARE THE SYMPTOMS & SIGNS?

The presenting symptoms resemble those of common ‘flu’. The frequency of the symptoms listed below are based on 55924 laboratory confirmed cases.(1)

  • 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%)

Incubation period : In one study published in the New England Journal of Medicine, the median incubation period was found to be 4 days (interquartile range, 2 to 7).(2)

Laboratory findings: Lymphopenia is one of the hallmarks of COVID-19 infection and is also an unfavourable prognostic indicator. Neutrophilic leukocytosis is also seen in many cases. 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. (3)

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.(3)

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.(4)

According to a recent literature review, the most frequent laboratory abnormalities encountered in patients with COVID-19 are lymphopenia (35-75%), increased CRP (75-93%), increased LDH (27-92%), increased ESR (up to 85%), increased d-dimer (36-43%), decreased serum albumin (50-98%) and decreased Hb (41-50%)(5). These laboratory parameters can be used for monitoring progression of the disease in moderately severe to severe cases of Covid 19 infection. Laboratory abnormalities predicting severe COVID-19 include increased WBC count, neutrophil count, LDH, AST, ALT, total bilirubin, creatinine, cardiac biomarkers, D-dimer, PT, procalcitonin, CRP & decreased lymphocyte count, albumin. A progressive increase in CRP, Procalcitonin, D-Dimer and LDH indicate progression of the disease and poor outcome.(5)

The coagulation parameters show evidence of a DIC-like syndrome without significant prolongation of prothrombin time and activated partial thromboplastin time. However, D-Dimer level is increased and high leves have been found to associated with rapid progression of the disease and high mortality.(5)

Radiological changes. Chest radiographs may show bilateral infiltrates.(6) The most common patterns on chest CT were found to be ground-glass opacity (56.4%) and bilateral patchy shadowing (51.8%). These changes suggest ARDS.(2)

Outcome: Clinical illness varies from mild to severe; about 25% of confirmed cases have been classified as severe, and there are increasing numbers of deaths. In early cases, mortality was associated with advanced age or comorbidities.(6)

LABORATORY TESTING FOR COVID-19

WHOM TO TEST?

As per the guidelines laid down by the ICMR on 20th March, 2020, the current testing strategy in India is as follows:(7)

  • 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 (HCWs).
  • All hospitalized 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

WHAT SAMPLES SHOULD BE COLLECTED?

The following types of respiratory material should be collected:(8)

  • Upper respiratory specimens: nasopharyngeal and oropharyngeal swabs in ambulatory patients, and/or,
  • Lower respiratory specimens: sputum (if produced) and/or endotracheal aspirate or bronchoalveolar lavage in patients with more severe respiratory disease. (Note high risk of aerosolization; adhere strictly to infection prevention and control procedures).

Upper respiratory tract swabs – Nasopharyngeal swab (NP) /oropharyngeal swab (OP)

Use only synthetic fiber (nylon/polyester/dacron) swabs with plastic shafts. Do not use natural fiber swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit PCR testing. The swabs should be immediately placed into sterile tubes containing 2-3 ml of viral transport media. If both swabs are used, NP and OP specimens should be combined at collection into a single vial. OP swabs remain an acceptable specimen type.

Lower respiratory samples – Bronchoalveolar lavage, tracheal aspirate

Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container.

Lower respiratory samples – Sputum

Have the patient rinse the mouth with water and then expectorate deep cough sputum directly into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container.

COVID-19 testing positivity rates based on sample type.(9)

COVID-19 Testing Positivity rates
Broncho-Alveolar Lavage Fluid93%
Sputum72%
Nasal swabs63%
Fibrobronchoscope brush biopsy46%
Pharyngeal swabs32%
Feces29%
Blood1%
Urine0%

COLLECTING AND HANDLING OF SPECIMENS FROM PATIENTS WITH SUSPECTED COVID-19(10)

All specimens collected for laboratory investigations should be regarded as potentially infectious. HCWs who collect, handle or transport clinical specimens should adhere rigorously to the following standard precaution measures and biosafety practices to minimize the possibility of exposure to pathogens.

  • Ensure that HCWs who collect specimens use appropriate PPE (i.e. eye protection, a medical mask, a long-sleeved gown, and gloves). If the specimen is collected during an aerosol-generating procedure, personnel should wear a particulate respirator at least as protective as a NIOSH-certified N95, an EU standard FFP2, or the equivalent.
  • Ensure that all personnel who transport specimens are trained in safe handling practices and spill decontamination procedures.
  • Place specimens for transport in leak-proof specimen bags (secondary containers) that have a separate sealable pocket for the specimen (a plastic biohazard specimen bag), with the patient’s label on the specimen container (the primary container), and a clearly written laboratory request form.
  • Ensure that laboratories in health care facilities adhere to appropriate biosafety practices and transport requirements, according to the type of organism being handled.
  • Deliver all specimens by hand whenever possible. DO NOT use pneumatic-tube systems to transport specimens.
  • Document clearly each patient’s full name, date of birth and “suspected COVID-19” on the laboratory request form.

TRANSPORT AND STORAGE OF SAMPLES (8)

Specimen typeCollection materialsStorage temperature till testingRecommended temperature for shipment according to expected shipment time
Nasopharyngeal and oropharyngeal swabDacron/Nylon/Polyester flocked swabs2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >5 days
BAL fluidSterile container2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >2 days
Endotracheal aspirateSterile container2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >2 days
SputumSterile container2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >2 days
Tissue from biopsy or autopsy including from lungSterile container with saline or Viral Transport Medium2-8 °C2-8 °C if ≤24 hours
-70 °C (dry ice) if >24 hours
SerumSerum separator tubes2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >5 days
StoolStool container2-8 °C2-8 °C if ≤5 days
-70 °C (dry ice) if >5 days

MODALITIES OF COVID TESTING

There are two main approved modalities of testing:

  • Molecular testing (NAAT)
    • Molecular testing is, at present, the recommended diagnostics method.
    • Very little data is available on the rates of false-positive and false-negative results for the various RT-PCR tests available; however, both have been reported. If a negative result is obtained from a patient with a high index of suspicion for COVID-19, additional specimens should be collected and tested, especially if only upper respiratory tract specimens were collected initially.(8,11)
    • Sensitivity and specificity of RT-PCR for diagnostic testing are unknown. Given the lack of a reference standard for diagnosing COVID-19, the sensitivity and specificity of diagnostic testing are unknown. In addition, inadequate sample collection may reduce test sensitivity.(12)
    • Collect nasopharyngeal swabs to rule out influenza and other respiratory infections according to local guidance. It is important to note that co-infections can occur, and a positive test for a non-COVID-19 pathogen does not rule out COVID-19.(11)
    • To diagnose COVID-19, it is recommended that there should be a positive NAAT result for at least two different targets on the COVID-19 virus genome, of which at least one target is preferably specific for COVID-19 virus using a validated assay.(8)
  • Antibody testing (IgM/IgG)
    • As per the WHO’s document on laboratory testing strategy in COVID-19, serological assays will play an important role in research and surveillance but are not currently recommended for case detection.(13)
    • As per the RCPA position statement on serology testing, COVID-19 IgG/IgM antibody rapid tests have no role to play in the acute diagnosis of COVID-19 virus infection, and most importantly rapid tests will miss patients in the early stages of disease when they are infectious to other people.(14)
    • Reliable detection of IgM antibodies early in infection is also problematic due to cross-reactions resulting in false-positive results. Most importantly from a public health perspective, COVID-positive patients are infectious to other people early in infection when the COVID-19 IgG/IgM tests give false-negative results. In low responders and non-responders the antibody response can take long time or can even be absent.(14)
    • According to a recent study, the median duration of IgM and IgA antibody detection was 5 days (IQR 3-6), while IgG was detected on 14 days (IQR 10-18) after the onset of symptom, with a positivity rate of 85.4%, 92.7% and 77.9% respectively. In confirmed and probable cases, the positivity rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR method after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when IgM ELISA assay is combined with PCR for each patient compare with a single qPCR test (51.9%).(15)
    • Serology has been particularly important for antibody detection in the diagnosis of cases of novel and emerging HCoVs, such SARS-CoV and MERS-CoV. In these situations, affected patients may not test positive for viral RNA, particularly in the early phase of disease, but retrospectively can be shown to have developed an immune response (16).
    • In the case of COVID-19, these antibody tests may have a place in detecting unrecognised past infection and immunity. However, that role needs to be rigorously evaluated.(14)

POINTS TO KEEP IN MIND WHEN INTERPRETING THE REPORT

  • Respiratory virus detection is highly dependent on the type of sample collected, the time of collection after the onset of clinical symptoms, the age of the patient, and the transport and storage of the sample prior to testing. Detection of respiratory viruses using a NAAT panel was significantly less sensitive with oropharyngeal swab specimens (54.2%) than with either nasopharyngeal swabs (73.3%) or nasopharyngeal wash specimens (84.9%).(17)
  • One or more negative results do not rule out the possibility of COVID-19 virus infection. A number of factors could lead to a negative result in an infected individual, including:(8)
    • poor quality of the specimen, containing little patient material (as a control, consider determining whether there is adequate human DNA in the sample by including a human target in the PCR testing).
    • the specimen was collected late or very early in the infection.
    • the specimen was not handled and shipped appropriately.
    • technical reasons inherent in the test, e.g. virus mutation or PCR inhibition.
  • If a negative result is obtained from a patient with a high index of suspicion for COVID-19 virus infection, particularly when only upper respiratory tract specimens were collected, additional specimens, including from the lower respiratory tract if possible, should be collected and tested (8).

INFECTION CONTROL

APPLYING STANDARD PRECAUTIONS FOR ALL PATIENTS

Standard precautions include hand and respiratory hygiene, the use of appropriate personal protective equipment (PPE) according to a risk assessment, injection safety practices, safe waste management, proper linens, environmental cleaning, and sterilization of patient-care equipment.(18)

Ensure that the following respiratory hygiene measures are used (18):

  • 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 COVID-19 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 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.

The rational, correct, and consistent use of PPE also helps reduce the spread of pathogens. PPE effectiveness depends strongly on adequate and regular supplies, adequate staff training, appropriate hand hygiene, and appropriate human behavior (18).

It is important to ensure that environmental cleaning and disinfection procedures are followed consistently and correctly. Thoroughly cleaning environmental surfaces with water and detergent and applying commonly used hospital level disinfectants (such as sodium hypochlorite) are effective and sufficient procedures (18).

CONTACT AND DROPLET PRECAUTIONS (10)

  • In addition to using standard precautions, all individuals, including family members, visitors and HCWs, should use contact and droplet precautions before entering the room of suspected or confirmed COVID-19 patients;
  • Patients should be placed in adequately ventilated single rooms;
  • When single rooms are not available, patients suspected of having COVID-19 should be grouped together;  (?)
  • All patients’ beds should be placed at least 1 metre apart regardless of whether they are suspected to have COVID-19;
  • Where possible, a team of HCWs should be designated to care exclusively for suspected or confirmed cases to reduce the risk of transmission;
  • HCWs should use a medical mask (medical masks are surgical or procedure masks that are flat or pleated (some are like cups); they are affixed to the head with straps);
  • HCWs should wear eye protection (goggles) or facial protection (face shield) to avoid contamination of mucous membranes;
  • HCWs should wear a clean, non-sterile, long-sleeved gown;
  • HCWs should also use gloves;
  • The use of boots, coverall, and apron is not required during routine care;
  • After patient care, appropriate doffing and disposal of all PPE and hand hygiene should be carried out. A new set of PPE 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%);
  • HCWs should refrain from touching eyes, nose, or mouth with potentially contaminated gloved or bare hands;
  • Avoid moving and transporting patients out of their room or area unless medically necessary. Use designated portable X-ray equipment 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 wear a medical mask;
  • Ensure that HCWs who are transporting patients perform hand hygiene and wear appropriate PPE;
  • Notify the area receiving the patient of any necessary precautions as early as possible before the patient’s arrival;
  • Routinely clean and disinfect surfaces with which the patient is in contact;
  • Limit the number of HCWs, family members, and visitors who are in contact with suspected or confirmed COVID-19 patients;
  • Maintain a record of all persons entering a patient’s room, including all staff and visitors.

AIRBORNE PRECAUTIONS FOR AEROSOL-GENERATING PROCEDURES (10)

Some aerosol-generating procedures, such as tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, and bronchoscopy, have been associated with an increased risk of transmission of coronaviruses. Ensure that HCWs performing aerosol-generating procedures:

  • Perform procedures in an adequately ventilated room – that is, natural ventilation with air flow of at least 160 L/s per patient or in negative- pressure rooms with at least 12 air changes per hour and controlled direction of air flow when using mechanical ventilation;
  • Use a particulate respirator at least as protective as a US National Institute for Occupational Safety and Health (NIOSH)-certified N95, European Union (EU) standard FFP2, or equivalent. When HCWs put on a disposable particulate respirator, they must always perform the seal check. Note that facial hair (e.g. a beard) may prevent a proper respirator fit;
  • Use eye protection (i.e. goggles or a face shield);
  • Wear a clean, non-sterile, long-sleeved gown and gloves. If gowns are not fluid-resistant, HCWs should use a waterproof apron for procedures expected to create high volumes of fluid that might penetrate the gown;
  • Limit the number of persons present in the room to the absolute minimum required for the patient’s care and support.

RECOMMENDATIONS FOR PPE AS PER THE WORLD HEALTH ORGANIZATION (WHO)(19)

SettingTarget personnelActivityType of PPE or procedure
Inpatient facilities
ScreeningHCWsPreliminary screening not involving direct contact
  • Maintain physical distance of at least 1 metre.
  • Ideally, build glass/plastic screens to create a barrier between health care workers and patients
  • No PPE required.
  • When physical distance is not feasible and yet no patient contact, use mask and eye protection.
Patients with symptoms suggestive of COVID-19Any
  • Maintain physical distance of at least 1 metre.
  • Provide medical mask if tolerated by patient.
  • Immediately move the patient to an isolation room or separate area away from others; if this is not feasible, ensure spatial distance of at least 1 metre from other patients.
  • Perform hand hygiene and have the patient perform hand hygiene
Patients without symptoms suggestive of COVID-19Any
  • No PPE required
  • Perform hand hygiene and have the patient perform hand hygiene
Patient room/wardHCWsProviding direct care to COVID-19 patients, in the absence of aerosol generating procedures
  • Medical mask
  • Gown
  • Gloves
  • Eye protection (goggles or face shield)
  • Perform hand hygiene
HCWsProviding direct care to COVID-19 patients in settings where aerosol generating procedures are frequently in place
  • Respirator N95 or FFP2 or FFP3 standard, or equivalent
  • Gown
  • Gloves
  • Eye protection
  • Apron
  • Perform hand hygiene
CleanersEntering the room of COVID-19 patients
  • Medical mask
  • Gown
  • Heavy-duty gloves
  • Eye protection (if risk of splash from organic material or chemicals is anticipated)
  • Closed work shoes
  • Perform hand hygiene
Areas of transit where patients are not allowed (e.g. cafeteria, corridors)VisitorsEntering the room of COVID-19 patients
  • Medical mask
  • Gown
  • Gloves
  • Eye protection (goggles or face shield)
  • Perform hand hygiene
All staff, including HCWsAny activity that does not involve contact with COVID-19 patients
  • Maintain physical distance of at least 1 metre
  • No PPE required
  • Perform hand hygiene
LaboratoryLab technicianSpecimen handling for molecular testing would require BSL-2 or equivalent facilities.
Handling and processing of specimens from cases with suspected or confirmed COVID-19 infection that are intended for additional laboratory tests, such as haematology or blood gas analysis, should apply standard precautions.
  • Maintain physical distance of at least 1 metre
  • Medical mask
  • Eye protection
  • Gown
  • Gloves
  • Perform hand hygiene
Administrative areasAll staff, including HCWsAdministrative tasks that do not involve contact with COVID-19 patients.
  • Maintain physical distance of at least 1 metre
  • No PPE required
  • Perform hand hygiene
Outpatient facilities
Screening/triageHCWsPreliminary screening not involving direct contact
  • Maintain physical distance of at least 1 metre.
  • Ideally, build a glass/plastic screen to create a barrier between health care workers and patients
  • No PPE required
  • When physical distance is not feasible and yet no patient contact, use mask and eye protection.
  • Perform hand hygiene
Patients with symptoms suggestive of COVID-19Any
  • Maintain spatial distance of at least 1 metre.
  • Provide medical mask if tolerated.
  • Perform hand hygiene
Patients without symptoms suggestive of COVID-19Any
  • No PPE required
  • Perform hand hygiene
Waiting roomPatients with symptoms suggestive of COVID-19Any
  • Provide medical mask if tolerated.
  • Immediately move the patient to an isolation room or separate area away from others; if this is not feasible, ensure spatial distance of at least 1 metre from other patients.
  • Have the patient perform hand hygiene
Patients without respiratory symptomsAny
  • No PPE required
  • Have the patient perform hand hygiene
Consultation roomHCWsPhysical examination of patient with symptoms suggestive of COVID-19
  • Medical mask
  • Gown
  • Gloves
  • Eye protection
  • Perform hand hygiene
HCWsPhysical examination of patient without symptoms suggestive of COVID-19
  • PPE according to standard precautions and risk assessment.
  • Perform hand hygiene
Patients with symptoms suggestive of COVID-19Any
  • Provide medical mask if tolerated.
  • Hand hygiene and respiratory etiquette
Patients without symptoms suggestive of COVID-19Any
  • No PPE required
  • Have the patient perform hand hygiene
CleanersAfter and between consultations with patients with respiratory symptoms
  • Medical mask
  • Gown
  • Heavy-duty gloves
  • Eye protection (if risk of splash from organic material or chemicals).
  • Closed work shoes
  • Perform hand hygiene
Administrative areasAll staff, including HCWsAdministrative tasks that do not involve contact with COVID-19 patients.
  • Maintain physical distance of at least 1 metre
  • No PPE required
  • Perform hand hygiene
Home care
HomePatients with symptoms suggestive of COVID-19Any
  • Maintain physical distance of at least 1 metre.
  • Provide medical mask if tolerated, except when sleeping.
  • Hand and respiratory hygiene
CaregiverEntering the patient’s room, but not providing direct care or assistance
  • Maintain physical distance of at least 1 metre
  • Medical mask
  • Perform hand hygiene
CaregiverProviding direct care or when handling stool, urine, or waste from COVID-19 patient being cared for at home
  • Gloves
  • Medical mask
  • Apron (if risk of splash is anticipated)
  • Perform hand hygiene
HCWsProviding direct care or assistance to a COVID-19 patient at home
  • Medical mask
  • Gown
  • Gloves
  • Eye protection

REFERENCES

  1. World Health Oragnization (WHO). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 2020.
  2. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28;NEJMoa2002032.
  3. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb;S221326002030076X.
  4. Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta. 2020 Jun;505:190–1.
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  8. World Health Organization (WHO). Laboratory testing for coronavirus disease (COVID-19) in suspected human cases [Internet]. Available from: https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117
  9. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA [Internet]. 2020 Mar 11 [cited 2020 Apr 8]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2762997
  10. Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected [Internet]. [cited 2020 Apr 8]. Available from: https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125
  11. British Medical Journal (BMJ). BMJ Best Practice: COVID-19.
  12. Omer SB, Malani P, del Rio C. The COVID-19 Pandemic in the US: A Clinical Update. JAMA [Internet]. 2020 Apr 6 [cited 2020 Apr 8]; Available from: https://jamanetwork.com/journals/jama/fullarticle/2764366
  13. World Health Organization (WHO). Laboratory testing strategy recommendations for COVID-19: Interim Guidance [Internet]. 2020 [cited 2020 Apr 4]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/laboratory-guidance
  14. Royal College of Pathologists of Australasia (RCPA). RCPA Position Statement: COVID19 IgG/IgM RAPID POCT TESTS [Internet]. [cited 2020 Apr 4]. Available from: https://www.rcpa.edu.au/getattachment/bf9c7996-6467-44e6-81f2-e2e0cd71a4c7/COVID19-IgG-IgM-RAPID-POCT-TESTS.aspx
  15. Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020 Mar 21;ciaa310.
  16. Loeffelholz MJ, Tang Y-W. Laboratory diagnosis of emerging human coronavirus infections – the state of the art. Emerg Microbes Infect. 2020 Jan 1;9(1):747–56.
  17. Ginocchio CC, McAdam AJ. Current Best Practices for Respiratory Virus Testing. J Clin Microbiol. 2011 Sep 1;49(9 Supplement):S44–8.
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  19. Rational use of personal protective equipment for coronavirus disease (COVID-19) and considerations during severe shortages [Internet]. [cited 2020 Apr 8]. Available from: https://www.who.int/publications-detail/rational-use-of-personal-protective-equipment-for-coronavirus-disease-(covid-19)-and-considerations-during-severe-shortages
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