While the Polymerase Chain Reaction (PCR) was the only test that was being carried out in Pakistan, Getz Pharma introduced antibody screening in the country. There are different categories of antibodies test kits available, ranging from very poor to excellent quality. Getz Pharma purchased a US Food and Drug Administration-approved test kit, also marked CE (assessed for high safety, health, and environmental protection requirements) by the European Economic Area (EEA). This antibody testing kit has been imported by over 38 countries and is actively being used.
Antibody kits detect the prevalence (sero) of the disease (both past and current), so it can help throw up more than just the current number of infected cases, as the PCR method does. These test kits are designed to detect antibodies IgG and IgM. IgM is usually the first antibody produced by the immune system and a positive IgM test indicates that one may currently be infected, or have recently recovered from a Covid-19 infection. IgG antibodies develop in most patients within seven to 10 days after symptoms of Covid-19 begin and they remain in the blood after an infection has passed, hence they indicate a recent past exposure and may provide protection from future infection.
At this point, it is not known how much protection antibodies can provide against reinfection. However, antibody kits have the ability to detect asymptomatic carriers, who cannot be detected by a PCR test when the viral load is low. They are also able to tell whether a person was exposed in the past and has now recovered and/or has acquired immunity.
PCR testing can have high false negatives and may miss out people who do have the disease. Hence a lot of people who test negative on PCR are, in fact, positive and go around infecting others with the false assumption that they are safe, because the viral load in their body may be too little to be detected by the PCR tests.
As antibody kits depend upon detecting the response of the body rather than detecting the virus or antigen itself, they do not have the issue of low viral load. As pointed out, antibody kits can detect exposure to Covid-19 even in asymptomatic cases. Generally, antibody testing kits have a high level of accuracy, especially on sequential testing. The kit Getz Pharma has been using has a sensitivity (the ability to correctly detect positive cases) of 95.3% and specicity (the ability to correctly detect negative cases) of 98.7% for IgG, and the sensitivity is 86.48% and specicity is 95.18% for IgM.
An epidemiologist who oversaw Getz Pharma’s antibodies testing explains what their findings mean and how they can be used to move forward beyond a blindsided lockdown
Antibody kits have limitations also, as antibodies are only produced in the body after five to seven days of exposure to the infection. If anyone is tested in the initial five to seven days, antibody kits may not be able to detect the Covid-19 response. If the prevalence of Covid-19 is quite low in the population, say below 5%, and an antibody test can identify people who are truly negative with 95 percent reliability, half of the “positives” it yields will be false positives. In other words, half of the people the test says have antibodies would not actually have them.
However, this is true only for low prevalence. As soon as the prevalence is near 10%, an antibody test which has 95% accuracy will be able to detect the true positives up to 90% of the time. Hence, antibody kits are very useful tools when the prevalence is above 5% in a population.
Antibodies tests can also easily be used for mass screening at a population level even outside of hospitals to detect the asymptomatic carriers of Covid-19, which can help curtail the spread. Through the course of this study, Getz Pharma was approached by various private companies and hospitals whose employees we also tested using our antibody kits.
While our research is still ongoing — we plan to extend the number of subjects of this study to about 10,000 — we decided to share some of the initial results from testing asymptomatic employees and assessing their seroprevalence. We decided to do this not only because the findings present an important dataset about Covid-19 infections in Pakistan, but also because the Getz Pharma testing can be applied to work places, offices, manufacturing facilities etc. with similar demographics.
So far, a total of 2,174 people, across various industries’ head offices, banks, restaurants and hospitals, have been screened by Getz Pharma, including all of its own workers. The total positive cases were 8.6% in the general population. Most of these were ongoing infections at 7%, and only 1.5% had recovered.
In the high-risk frontline hospital workers, the seroprevalence of Covid-19 was assessed to be 11% (Getz Pharma plans to test 25,000 doctors and their families free of cost on a rolling basis). Families of positives contacts were also traced and their seroprevalence was found out to be 19%, making our secondary household attack rate at 19%, which is similar to what was found in studies in China, Taiwan and Spain.
Those who did not maintain social distancing measures at home and continued to ignore safety measures also had a prevalence of 19%. Increasing age (above 40), male gender, and high Body Mass Index (BMI >25) also had more seropositive, but the results were not statistically significant.
Interestingly, over 90% of those who tested positive did not have any symptoms or had only mild dizziness, fever and shortness of breath. But they were infective and were continuing to spread the virus to those around them. Because of their non-existent or mild symptoms, they had not reached out to a PCR testing facility to get tested for Covid-19, and were only incidentally picked out by the antibody test during the mass screening and testing campaign.
Based on the study findings and keeping in view its target age group (18-65 years), the urban setting and a sample revolving around office/factory workers, the following conclusions can be drawn:
The 8% prevalence can be extrapolated to the 1 million registered working population of Karachi, meaning at least 80,000 infected cases in Karachi alone, with 70,000 being currently infected, unaware and spreading infection to those around them. If the assumptions hold true for the rest of Pakistan, of its 61.7 million registered workers, at least 4.9 million could already be exposed and infected.
Of the 261,065 registered medical and dental practitioners in Pakistan who are on the frontline fighting Covid-19, at least 11% or 28,000 may currently be exposed to and infected with Covid-19, with no or only mild symptoms.
For the 41,151 officially confirmed cases of Covid-19 in Pakistan (as of May 17) and taking a family size of seven, at least 53,400 people are already infected with Covid-19, unaware of it and spreading it around.
The initial findings of the Getz Pharma census may be suggestive of an innate immunity in the Pakistani population that is preventing them from contracting a more severe form of the disease, but they themselves continue to spread the infection to others around them, unknowingly, as healthy carriers. So, unless we test at a massive scale, we will not be able to isolate the positive, asymptomatic cases and trace their contacts. Those who do develop a serious disease have the same mortality risk as that of other nations.
Based on the findings of this study, we suggest that mass level screening be conducted on the general population (outside of hospitals) to correctly determine the prevalence of the disease and take necessary steps towards the infected, quarantining them and tracing their contacts through antibody testing which is an easy, effective, rapid and a cost-effective Point of Care (near the patient and providing results quicker than when sent to laboratories) testing and screening procedure.
We suggest categorising the population into three groups: The immune, the infected and the negative.
For the immune: We endorse what the Journal of American Medical Association says in its recent publication on May 6, 2020. Antibody kits have the potential to give immunity-based licences to individuals who have been infected with Covid-19 and recovered, without worsening the situation of those who have not been infected, maximising benefits to individuals and society by allowing immune people to engage in economic activity, and protecting the least advantaged by allowing safer care for vulnerable populations.
For the infected: They should be isolated, their contacts traced and they should continue to follow medical treatment as and when required. Most of the infected are merely asymptomatic carriers, who themselves don’t have overt symptoms of the disease but continue to spread it to those around them, especially the weak and vulnerable. We need to adopt a selective lockdown strategy in which everyone above the age of 60, those who have low immunity or have any co-morbidities (additional conditions occurring simultaneous to the primary condition) should not be allowed back to work in order to protect them from the danger of contracting Covid-19 and growing into fulminant disease.
For the negative: They should be allowed back to work and continue to be tested every month as they can get exposed to Covid-19. This selective lockdown strategy should be considered and endorsed by the government for a safe working environment while protecting its vulnerable people, curtailing mortality as well as having a stable economy.
Similarly, the private sector should ease the government’s burden and prioritise compassion over commercial gains to pull the country out of this crisis. Getz Pharma continues to lobby with decision makers, policy analysts, epidemiologists and experts to help bring an informed policy change at a national level to start mass screening through the antibody kits, and to implement a selective, smart lockdown rather than an uncontrolled, blindsided lockdown.
The writer is an epidemiologist and head of public health and research at Getz Pharma
Published in Dawn, EOS, May 24th, 2020