Editorial

Covid-19: Testing Times

Reproduced from: https://www.indialegallive.com/special/covid-19-widespread-testing-is-crucial-95702, April 11, 2020.

Dr KK Aggarwal, President CMAAO and Past National President IMA

Various tests are being done to confirm if a patient has the disease, be it bronchoalveolar lavage, oropharyngeal or nasopharyngeal swabs or rapid antibody tests.

Hours after having advised “rapid antibody tests” in “hotspot areas” in an interim advisory, the Indian Council of Medical Research (ICMR) left the decision to states and put out a list of such tests that had been approved earlier. ICMR said: “Population in hotspot areas may be tested using rapid antibody test, and antibody positives to be confirmed by RT-PCR using throat/nasal swab. Antibody negatives to be quarantined at home.” Once it has been confirmed that Covid-19 is finally over, diagnostic criteria will change. We may no longer require diagnostic tests with 100 percent specificity.

But for now, everyone with cough, fever and breathlessness (influenza-like illness or severe acute respiratory illness) will need to be treated as a Covid-19 patient unless proved otherwise. Secondly, fever with loss of taste and smell will also be treated as Covid-19. Also, people with interstitial oedema on ultrasound, bilateral pneumonia on x-ray or ground glass appearance on chest CT will be treated as Covid-19. Also, those with low lymphocyte counts, high ESR or rise in C-reactive protein (found in blood plasma and whose concentrations rise during inflammation) in suspected viral fevers will also be tested.

Populations need to be classified rapidly in five groups:

Who is infected?

Who is presumed to be infected (i.e., persons with signs and symptoms consistent with infection who initially test negative)?

Who has been exposed?

Who is not known to have been exposed or infected?

Who has recovered from infection and is adequately immune?

Now rapid tests based on IgM and IgG antibodies will be done to test the patient’s immunity. Earlier done on dengue patients, they should be able to identify patients who have either current (IgM) or previous infection (IgG) as a screening test. “M” means I am there and “G” means I am gone.

In one study that included 58 patients suspected of Covid-19 but who were negative, an immunoglobulin (Ig) M ELISA test proved positive in 93 percent of the cases. Rapid tests are cheap and rapid and can triage a patient in no time. Co-infection with SARS-CoV-2 and other respiratory viruses, including influenza, have been reported. This may impact management decisions.

Those who require confirmation of Covid-19 will go for a nasopharyngeal (reaching the posterior part of the throat through the nose) swab specimen. An oropharyngeal (reaching the pharynx through the mouth) swab can be collected but is not essential. If collected, it should be placed in the same container as the nasopharyngeal specimen. Oropharyngeal, nasal mid-turbinate or nasal swabs are acceptable alternatives if nasopharyngeal swabs are unavailable. Expectorated sputum should be collected from patients with productive cough; induction of sputum is not recommended. A lower respiratory tract aspirate or bronchoalveolar lavage (a bronchoscope is passed through the mouth/nose into the lungs with a measured amount of fluid and then collected for examination) should be collected from patients who are intubated.

SARS-CoV-2 RNA is detected by reverse-transcription polymerase chain reaction (RT-PCR). A positive test for SARS-CoV-2 generally confirms the diagnosis of Covid-19, although false-positive tests are possible. False-negative tests from upper respiratory specimens have been documented. If initial testing is negative, but the suspicion of Covid-19 remains, repeating the test is suggested. In such cases, the WHO also recommends testing lower respiratory tract specimens, if possible. Negative RT-PCR tests on oropharyngeal swabs despite CT findings suggestive of viral pneumonia have been reported in some patients who ultimately tested positive for SARS-CoV-2. Lower respiratory tract specimens may have higher viral loads and are more likely to yield positive tests than upper respiratory tract specimens.

In a study of 205 patients with Co­vid-19, the highest rates of positive viral RNA tests were reported from bronchoalveolar lavage (95 percent) and sputum (72 percent) compared with oropharyngeal swab (32 percent). Data from this study suggested that viral RNA levels are higher and more frequently detected in nasal regions compared with oral specimens, although only eight nasal swabs were tested. Coming to the rapid test, ICMR issued an interim advisory on the use of serological tests in “hotspots”, before pulling it down hours later.

According to the Johns Hopkins Bloomberg School of Public Health, “Serology tests are blood-based tests that can be used to identify whether people have been exposed to a particular pathogen. Serology-based tests analyse the serum component of whole blood. The serum includes antibodies to specific components of pathogens, called antigens. These antigens are recognised by the immune system as foreign and are targeted by the immune response.”

The serological test screens the plasma for antibodies that the body develops against the virus. It takes less than 30 minutes. It is important to note, however, that the PCR test is capable of identifying infection at an earlier stage. Only after the antibodies have developed, which takes a week, can the serological test come in.

As recently as on March 28, the ICMR’s guidance document on these tests said that they “can be done on blood/serum/plasma samples; Test result is available within 30 minutes; Test comes positive after 7-10 days of infection; The test remains positive for several weeks after infection; Positive test indicates exposure to SARS-CoV-2; Negative test does not rule out COVID-19 infection” but are not recommended for diagnosis of the infection. “These tests are not recommended for diagnosis of Covid-19 infection,” before going on to list the 12 approved serological testing kits.

South Korea, which had shot up to the top of the Covid-19 chart in February, is now a success story in its containment by aggressively using mass testing, including with serological kits, to reduce the number of cases. The country had 9,976 cases and 169 deaths but managed to contain the virus without the kind of lockdown that several countries including India have now gone into.

These are the ways in which mass testing can help:

If done on all healthcare workers, we will be able to identify asymptomatic cases who have recovered and no more need PPE strictly as indicated

If all those exposed develop antibodies, it may mean that they have been cured because of asymptomatic infections

Epidemiological data will show recovered asymptomatic cases in the community

If positive patients at 14 days have antibodies, they can be classified as antigen-infective positives

If the elderly and at-risk population are antibodies positive, they may not require much restriction

All hotspots can have extensive tests done cheaply and quickly for the presence of IgM

IgM has become a standard strategy for dengue rather than NS1 and Elisa tests.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA