Diagnosing Covid-19

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Identifying infected persons as well as their possibly infected contacts is a vital component in monitoring the extent of the contagious spread and strategizing on ways of mitigating its spread. This chapter focuses on the transmission of coronavirus disease 2019 (COVID-19), the disease’s signs and symptoms, and the tests needed to confirm if a person is infected or not.

Transmission

A infographic depicting the transmission of the COVID-19 virus and the ways people can protect themselves against infection. (Vibal Group graphic licensed under BY-SA-NC)

Unlike the Middle East respiratory syndrome coronavirus (MERS-CoV) and the original severe acute respiratory syndrome coronavirus (SARS-CoV), which are both communicated through fine respiratory droplets in the air, the transmission of COVID-19 occurs via large respiratory droplets.[1]

COVID-19 can be transmitted mainly in two ways: contact transmission and droplet transmission. Contact transmission occurs when the respiratory secretions are transferred directly through physical contact with an infected patient, (i.e., handshaking and touching) or indirectly by exposure to intermediate surfaces or objects that have been contaminated with the virus. Droplet transmission, on the other hand, happens when the virus is transferred by the respiratory secretions expelled by an infected individual onto another person’s mucosal surfaces, such as the mouth, eyes, and nose.[2]

An infographic depicting the identified signs and symptoms of COVID-19 infection. (Vibal Group graphic licensed as BY-SA-NC)

Large droplets settle quickly on the surface in which the secretions are generated. Thus, the risk is limited to about two meters or six feet from the patient.[3] There is no certain period of how long the COVID-19 virus can thrive on surfaces, but the COVID-19 virus behaves similarly to other coronaviruses. According to preliminary studies of coronaviruses, the virus may survive on surfaces for a few hours and even up to several days. This may vary under different conditions (i.e., the type of surface, temperature, or humidity of the environment.)[4] When someone infected with coronavirus coughs, he or she could emit large droplets that settle on surfaces in a room, thus creating a thin film of pathogens. A study by Neeltje Doremalen et al. concluded that SARS-CoV-2 may live for roughly four days. It also discovered that there are high viral loads in the upper respiratory tract and that an infected person can shed and transmit the virus while asymptomatic. These findings echoed studies that had been undertaken of the original SARS virus that was also associated with hospital-acquired infections and other super-spreading events.[5]

More than 114 million worldwide infections prove the highly contagious nature of human-to-human transmission of the coronavirus. However, the animal-human route of transmission, as well as the specific animal source of the new coronavirus strain, has not been confirmed by the World Health Organization. Moreover, there is no evidence that a dog, cat, or any pet can transmit COVID-19 to humans.[6] Officials in Hong Kong reported an isolated case of a dog, which initially tested as “weak positive” and subsequently died but was not autopsied as reported by Dr. Chuang Shuk-Kwan of the Communicable Branch of the Centre for Health Protection. See https://time.com/5805524/hong-kong-dog-dies-after-coronavirus-quarantine/?playlistVideoId=6136852484001.</ref> However, people with COVID-19 are cautioned to limit contact with their pets and other animals.However, some animals can contract the virus from humans.[7]

Currently, the known coronaviruses are zoonotic or transmissible from animals to humans. Many strains of coronaviruses commonly circulate in bats, specifically those of the Rhinolophus bat sub-species, which are widely present in Southern China, and across Asia, the Middle East, Africa, and Europe.[8]


Signs and symptoms

A person infected with COVID-19 virus may show different signs and symptoms, which may vary from one patient to another, and may also depend on the severity and progression of the disease. The most common symptoms are fever (defined as body temperature above 37.5 °C) and a dry cough.

In the first few days, a patient may show mild symptoms or none at all. The incubation period, or the time in which a patient catches the virus and the appearance of first symptoms, is estimated to be between five to six days.[9] This delay is explained by the clinical phenomenon in which the virus replicates inside the cells. At this stage, the immune system response occurs, but the body fails to contain the virus.[10] Most dangerously, an asymptomatic COVID-19 patient, although he/she appears well, is still considered a carrier and can transmit the virus during the incubation period.

As the disease advances and continuously spreads in the body, other respiratory and constitutional symptoms manifest. The COVID-19 patient may experience muscle pain (myalgia), fever, and headache as constitutional symptoms. Other respiratory symptoms may include nasal congestion (rhinorrhea), runny nose, sore throat, difficulty in breathing while at rest (which may lead to even dangerously low blood oxygen levels or hypoxemia), chest tightness, dry cough, or coughing of blood or blood-stained mucus (hemoptysis). There are also rare cases of gastrointestinal symptoms, such as nausea or vomiting and diarrhea.[11]

People of all ages are prone to COVID-19. However, older persons and persons with preexisting medical conditions, such as asthma, high blood pressure, heart disease, lung disease, cancer, or diabetes, are more susceptible to develop serious illnesses than others.[12]

Screening and testing for COVID-19

Infographic specifying which persons would be tested for COVID-19 (Vibal Group graphic licensed under BY-SA-NC)

A patient may only experience a mild fever and cough in the early onset of COVID-19, which are in fact common symptoms to other respiratory diseases and infections. Thus, the World Health Organization and public health agencies defined a set criteria for selecting which persons should be first investigated and isolated with a view to monitoring their symptoms in a timely manner and to break the further chain of transmission of the disease.

The key considerations include:

  1. Recent travel to affected areas—people who have been to areas with community-based transmission or with a high number of reported cases.
  2. Contact with anyone with known COVID-19—people who have been exposed for a prolonged period and with less than a two-meter or six-feet distance from an infected patient.
  3. Broader testing in the case of wider community transmission. Areas with a high number of confirmed COVID-19 cases need community testing to further evaluate persons with the symptoms of the coronavirus. In a time of rapidly emerging infections, alternative diagnoses may also be rolled out such as CT scanning, apart from deploying available testing kits. The assessment will also take into consideration certain extenuating circumstances such as if patients tested positive for influenza, it is would be less likely that they acquired the influenza and coronavirus at the same time.[13]

Quarantine versus isolation

People who may have been exposed to an infectious agent or disease may be subjected to quarantine, or a restriction of activities and a separation from healthy persons. A quarantine is done for the purpose of monitoring symptoms and detecting the disease earlier. Undergoing mandated or voluntary quarantine does not mean that the persons are infected.

Isolation, in contrast, is the separation of an ill person from others to prevent the spread of an infection or contamination. If a person has a travel history or was exposed to an infected person, and has symptoms of lower respiratory illness, then the person will be isolated in a private room and observed with regard to his or her clinical status.[14]

Testing and diagnosis

Testing is the method of identifying if a suspected person has COVID-19. It is also done to determine if a patient is cleared from the disease. First, a nose or throat swab is taken. Care is taken by the diagnostic staff to make sure that there is a sufficiently deep specimen. The test makes use of a molecular method that leverages a real-time reverse transcription polymerase chain reaction (rRT-PCR) along with nucleic acid tests to detect the genetic marker of the virus. One of the earliest PCR tests was developed at Charité in Berlin, Germany, in January 2020, and was the basis of 250,000 kits distributed by the World Health Organization.[15] Another WHO-certified PCR test was developed by South Korean Kogenebiotech on 28 January 2020. Several other Korean FDA-approved tests developed by Solgent and Seegene powered the South Korean government’s massive testing program,[16] which included drive-through and walk-in centers and guaranteed the most extensive testing ever conducted in any country.

China’s BGI Group received one of the first certifications from China’s National Medical Product Administration for another PCR-based kit.[17] In the United States, the Centers for Disease Control and Prevention sanctioned a genetic test from older versions of its approved test kits, which resulted in inconclusive results and created a huge bottleneck at the CDC lab in Atlanta. In March 2020, a leading American life sciences company LabCorp developed LabCorp 2019 Novel Coronavirus NAA test, which was certified by the US FDA. The test kit is purchased by hospitals for diagnosis. Specimens are sent back to LabCorp, which takes three to four days to turn around results.[18]

The current list of COVID-19 test kits approved by the Philippine FDA for commercial use, accessed 5 April 2020, https://drive.google. com/open?id=1Dk8KjbCzk8g92HydWDRvg8KATp7gBez.

In the Philippine testing specimens such as nose and throat swabs are done for free in public hospitals and other select testing areas. Members of PhilHealth Insurance may also avail of a health packages worth 514 000, 516 000, up to 532 000 depending on the severity of the developed pneumonia.[19] The only available test kits are those that were supplied by the WHO and are administered by the Research Institute of Tropical Medicine (RITM). To expedite diagnosis, the Philippine FDA sanctioned a locally developed COVID-19 testing kit, the COVID-19 Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) detection kit, commercially known as “GenAmplify,” developed by a team of experts from the University of the Philippines – National Institutes of Health and the Department of Science and Technology.[20] On April 3, this local test kit was approved by the Philippine Food and Drug Administration (FDA).[21]

Apart from its main lab of RITM, the Department of Health also designated five subnational laboratories and three other laboratories (UP National Institutes of Health, WCMC, and Bicol Public Health Laboratories) to conduct the PCR-based tests. The Philippine FDA has approved over 75 COVID-19 Test Kits based on the genetic PCR method for commercial use. It has also approved other rapid test kits, which detect antibodies present from blood extracted from a patient. The FDA advised that this should be used with caution because this minutes-long test only measures antibodies present in the bloodstream and not the viral load itself. This means that it may give a negative result for patients already infected but have not yet developed antibodies. Thus, rapid tests need to be confirmed with a PCR-based test.[22]

While nasal swab testThe Philippine FDA also encourages commercial importers to bring into the country other test kits that have been licensed in other countries, such as those approved by their FDA counterparts in the United States, Japan, Singapore, South Korea, and Germany, or those already sanctioned by the World Health Organization. On January 24, 2021, the government allowed the Philippine Red Cross to conduct after COVID-19 tests using saliva examples. receiving a go-signal from the national government, the Philippine Red Cross announced that they will start conducting COVID-19 tests using saliva samples.

The debate over CT scans

Presently, experts have different opinions regarding the diagnostic value of a computed tomography or CT scan[23] in diagnosing COVID-19. According to a study by Chinese scientists, a CT scan can complement the RT-PCR tests in the diagnosis of COVID-19.[24] They examined the results of the CT scan and RT-PCR tests done in patients in Wuhan, China, from 6 January to 6 February 2020 and based on their findings, they concluded that a CT scan of the chest has high sensitivity in diagnosing COVID-19[25] and can be used as a complementary test in detecting the disease. Due to a shortage of testing kits, Chinese doctors used CT findings as a primary diagnostic criterion since February 17.[26]

CT imaging of a patient with COVID-19 in the early and then rapid progression stage. Notice in the second scan the ground-glass patterned areas, which represent lesions. These findings were found in China on practically 50% of patients within the first two days of progression. Source: Military Medical Research. https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-020-0233-6.

However, other experts are firm that while a chest CT scan is helpful in determining and identifying abnormalities in the lungs, the results it generates are non-specific to COVID-19.[27] A study published in The Lancet Infectious Diseases concluded that there is more to discover about COVID-19 and the use of the CT scan in detecting the disease.[28] Furthermore, the Royal College of Radiologists (RCR) in the UK maintains that as of 12 March, the CT scan had no role in the diagnostic assessment of persons who are possibly COVID-19-positive.[29] Meanwhile, the American College of Radiology (ACR) has several recommendations to health professionals who would opt to use CT scan in diagnosing COVID-19:

  • CT scan should not be used to screen for or as a first-line test to diagnose COVID-19.
  • CT scan should be used sparingly and reserved for hospitalized, symptomatic patients with specific clinical indications for CT. Appropriate infection control procedures should be followed before scanning subsequent patients.
  • Facilities may consider deploying portable radiography units in ambulatory care facilities for use when CXRs are considered medically necessary. The surfaces of these machines can be easily cleaned, avoiding the need to bring patients into radiography rooms.
  • Radiologists should familiarize themselves with the CT scan appearance of COVID-19 infection in order to be able to identify findings consistent with infection in patients imaged for other reasons.[30]

The ACR cautioned those who use CT scan results in diagnosing COVID-19 that a normal CT scan result does not necessarily mean that a person is free from the infection, and an abnormal result is not specific for diagnosis of the disease.[31]

References

  1. Josh Farkas, “Transmission,” Emcrit Internet Book of Critical Care, accessed 5 April 2020, https:// emcrit.org/ibcc/covid19/#transmission.
  2. Shiu, et al., “Infection control for respiratory virus infections” and Shiu, et al., “Controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention,” Current Opinion in Infectious Diseases 32, 4 (2019): 373-374, https://emcrit.org/wp-content/uploads/2020/03/ tada2019.pdf; “Factsheet for health professionals on coronaviruses,” European Centre for Disease Prevention and Control, accessed 5 April 2020, https://www.ecdc.europa.eu/en/factsheet-health-professionals-coronaviruses.
  3. Josh Farkas, “Transmission,” Emcrit Internet Book of Critical Care, accessed 5 April 2020, https:// emcrit.org/ibcc/covid19/#transmission.
  4. “Q&A on Coronaviruses (COVID-19),” under “How long does the virus survive on surfaces?” World Health Organization, accessed 5 April 2020, https://www.who.int/news-room/q-a-detail/q-a-coronaviruses.
  5. Neeltje van Doremalen, Brenton Bushmaker, Dylan Morris, et al., “Aerosol and surface stability of SARS-CoV-2 as compared with SARS=CoV-1,” The New England Journal of Medicine, 17 March 2020, accessed 5 April 2020.
  6. World Health Organization, “Q&A on Coronaviruses (COVID-19),” under “Can I catch COVID-19 from my pet?”, accessed 5 April 2020, https://www.who.int/news-room/q-a-detail/q-a-coronaviruses.
  7. World Health Organization, "Transmission of SARS-CoV-2: implications for infection prevention precautions" (PDF), accessed 2 March 2020, https://www.who.int.
  8. “Novel Coronavirus (2019-nCoV) Situation Report-22,” under “Technical Focus: Zoonotic component of 2019-nCoV and human-animal interface,” World Health Organization, 11 February 2020, https:// www.who.int/docs/default-source/coronaviruse/situation-reports/20200211-sitrep-22-ncov.pdf?sfvrsn=fb6d49b1_2.
  9. “Coronavirus disease 2019 (COVID-19) Situation Report-46,” under “Subject Focus: Q&A: Similarities and differences – COVID 19 and Influenza,” World Health Organization, 6 March 2020, accessed 5 April 2020, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200306-sitrep-46-covid-19.pdf?sfvrsn=96b04adf_4.
  10. Josh Farkas, “Biology,” Emcrit Internet Book of Critical Care, accessed 5 April 2020, https://emcrit. org/ibcc/covid19/#biology.
  11. Josh Farkas, “Symptoms,” Emcrit Internet Book of Critical Care, accessed 5 April 2020, https://emcrit. org/ibcc/covid19/#symptoms; World Health Organization, “Q&A on Coronaviruses (COVID-19),” under “What are the symptoms of COVID-19?” accessed 5 April 2020, https://www.who.int/news-room/q-adetail/q-a-coronaviruses.
  12. “Q&A on Coronaviruses (COVID-19),” under “What are the symptoms of COVID-19?” World Health Organization, accessed 5 April 2020, https://www.who.int/news-room/q-a-detail/q-a-coronaviruses; WHO, “Coronavirus disease (COVID-19) advice for the public: Myth busters,” under “Does the new coronavirus affect older people, or are younger people also susceptible?”, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters.
  13. Josh Farkas, “Screening & Selection for Investigation,” Emcrit Internet Book of Critical Care, accessed 5 April 2020, https://emcrit.org/ibcc/covid19/#screening_&_selection_for _investigation.
  14. “Considerations for quarantine of individuals in the context of containment for coronavirus disease (COVID-19),” World Health Organization, accessed 5 April 2019, https://www.who.int/publications-detail/considerations-for-quarantine-of-individuals-in-the-context-of-containment-for-coronavirus-disease-(covid-19)
  15. Cormac Sheridan, “Coronavirus and the race to distribute reliable diagnostics,” Nature Biotechnology, 19 February 2020.
  16. Sei-im Jeong, “Korea approves 2 core COVID-19 detection kits for urgent use,” Korea Biomedical Review, 28 February 2020, accessed 5 April 2020, oreabiomed.com/news/articleView.html?idxno=7561.
  17. “BGI Sequencer, coronavirus molecular assays granted emergency use approval in China,” Genome Web, 30 January 2020, accessed 5 April 2020, https://www.genomeweb.com/regulatory-news-fda-approvals/bgi-sequencer-coronavirus-molecular-assays-granted-emergency-use#.XnNSPpMzYw9.
  18. “2019 Novel Coronavirus, NAA,” LabCorp, accessed 5 April 2020, https://www.labcorp.com/ tests/139900/2019-novel-coronavirus-covid-19-naa.
  19. “Testing for Coronavirus disease is free—Duque,” CNN Philippines, 11 March 2020, accessed 5 April 2020, https://www.cnnphilippines.com/news/2020/3/11/coronavirus-testing-free-.html.
  20. “FDA clarifies availability of COVID-19 test kits in the country,” Philippine Food and Drug Administration, 15 March 2020, accessed 5 April 2020, https://www.fda.gov.ph/fda-clarifies-availabilty-of-covid19-test-kits-in-the-country/.
  21. “FDA Allows Use of COVID-19 Test Kits Developed by Local Scientists,” Food and Drug Administration Philippines, 9 March 2020, accessed 5 April 2020, https://www.fda.gov.ph/fda-allows-use-ofcovid-19-test-kits-developed-by-local-scientists/; Khalil Ismael Michael G. Quilinguing, “The Philippine Genome Center: Stockpiling or COVID-19,” University of the Philippines, 10 March 2020, accessed 5 April 2020, https://pgc.up.edu.ph/the-philippine-genome-center-stockpiling-for-covid-19/.
  22. “FDA approves rapid antibody test kits for COVID-19,” Food and Drug Administration Philippines, 30 March 2020, accessed 5 April 2020, https://www.fda.gov.ph/fda-approves-rapid-antibody-test-kits-for-covid-19/.
  23. CT (computerized or computed tomography) scan is basically an X-ray procedure that “combines many X-ray images with the aid of a computer to generate cross-sectional views and, if needed, three-dimensional images of the internal organs and structures of the body,” Melissa Conrad Stöppler, MD, “CT Scan (Computed Tomography, CAT Scan),” MedicineNet, accessed 5 April 2020, https://www. medicinenet.com/cat_scan/article.htm#ct_scan_facts
  24. Tao Ai, et al., “Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: A report of 1014 cases,” Radiology, 26 February 2020, accessed 5 April 2020, https://pubs.rsna.org/doi/10.1148/radiol.2020200642?fbclid=IwAR1mDovBzWL38LwwVcbsSwhCVgx4Plaxrv6ci9WN9glV7DSzvSOARTtAfm4.
  25. It means that, based on their findings, a CT scan can detect COVID-19-positive patients with a higher percentage of probability.
  26. Radiological Society of North America, “CT outperforms lab diagnosis for coronavirus infection,” Healthcare-in-Europe, 28 February 2020, accessed 5 April 2020, https://healthcare-in-europe.com/en/ news/ct-outperforms-lab-diagnosis-for-coronavirus-infection.html.
  27. It means that it can detect damages in the lungs, like pneumonia, but it cannot not present clear and direct data that what it detects is COVID-19 and not other kinds of viral pneumonia.
  28. Elaine Y.P. Lee, Min-Yen Ng, and Pek-Lan Khong, “COVID-19 pneumonia: what has CT taught us?” The Lancet Infectious Diseases, 24 February 2020, accessed 5 April 2020, https://www.thelancet.com/ journals/laninf/article/PIIS1473-3099(20)30134-1/fulltext.
  29. “RCR position on the role of CT patients suspected with COVID-19 infection,” The Royal College of Radiologists, accessed 5 April 2020, https://www.rcr.ac.uk/college/coronavirus-covid-19-what-rcr-doing/ rcr-position-role-ct-patients-suspected-covid-19.
  30. “ACR Recommendations for the use of Chest Radiography and Computed Tomography (CT) for Suspected COVID-19 Infection,” American College of Radiology, 19 March 2020, accessed 5 April 2020, https:// www.acr.org/Advocacy-and-Economics/ACR-Position-Statements/Recommendations-for-Chest-Radiography-and-CT-for-Suspected-COVID19-Infection.
  31. Ibid.

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