Pakistan COVID19 Antibodies Study: 90% of Virus Carriers Have No Symptoms
Guest Post by Dr. Wajiha Javed
Head of Public Health and Research
Getz Pharma, Pakistan.
Key Findings:
• Survey revealed that 90% of the population who tested COVID-19 positive (screened via serologic test kits) were asymptomatic carriers of the disease, who would have otherwise not presented at a government-approved PCR testing facility.
• If the results of this study are extrapolated to the rest of the population with similar demographics, the total number of active COVID-19 infections in the country would go up to 4.11 million, which is 17.7 times higher than the current official number.
• While these findings are restricted to Pakistan’s urban, adult, working population in various metropolises, they still provide useful insights for guiding public health practices across the country.
• This is a groundbreaking research which can improve Pakistan’s public health response to COVID-19 by increasing testing capacity and ensuring that the true prevalence of the disease is captured via cost-effective methods, thereby reducing the burden on an already exhausted healthcare system.
Full Report:
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South Asia Investor Review
COVID19 in Pakistan: Test Positivity Rate and Deaths Declining
Pakistan's Pharma Industry Among World's Fastest Growing
Is Pakistan's Response to COVID19 Flawed?
Pakistan's Computer Services Exports Jump 26% Amid COVID19 Lockdown
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Pakistani-American Woman Featured in Netflix Documentary "Pandemic"
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Strikingly Similar Narratives of Donald Trump and Nawaz Sharif
Nawaz Sharif's Report Card
Riaz Haq's Youtube Channel
Head of Public Health and Research
Getz Pharma, Pakistan.
Key Findings:
• Survey revealed that 90% of the population who tested COVID-19 positive (screened via serologic test kits) were asymptomatic carriers of the disease, who would have otherwise not presented at a government-approved PCR testing facility.
• If the results of this study are extrapolated to the rest of the population with similar demographics, the total number of active COVID-19 infections in the country would go up to 4.11 million, which is 17.7 times higher than the current official number.
• While these findings are restricted to Pakistan’s urban, adult, working population in various metropolises, they still provide useful insights for guiding public health practices across the country.
• This is a groundbreaking research which can improve Pakistan’s public health response to COVID-19 by increasing testing capacity and ensuring that the true prevalence of the disease is captured via cost-effective methods, thereby reducing the burden on an already exhausted healthcare system.
 |
| Coronavirus Antibodies |
Full Report:
Pakistan has faced issues regarding limited testing per million population, a cost intensive, symptom-based testing methodology in hospital settings, which focuses exclusively on Polymerase Chain Reaction (PCR) swab tests. Alongside a limitation of funds, there is a dilemma that a majority of COVID-19 positive cases do not display overt symptoms, and for a large proportion of the population that does not have access to hospitals, a more efficient testing and screening approach is required to ascertain the true prevalence of COVID-19 in Pakistan.
One such approach has been provided by Getz Pharma, the largest branded generic pharmaceutical company in Pakistan, who followed a multi-pronged approach in combating the pandemic. They conducted the first, mass-level sero-prevalence study on general, low-risk population in Pakistan. The target population was 24,210 individuals from different workplaces of Karachi tested via serological kits, and the findings have been extrapolated to the rest of the urban, adult, working population of Pakistan. This is the first of its kind, large scale, groundbreaking census in urban areas of Pakistan, conducted on healthy, asymptomatic adults between 18 to 65 years of age and depicts the true extent of the spread of the disease at 4.11 million individuals, which is 17.7 times higher than the current, official figures of COVID-19 positive cases reported.
Summary:
Population-level serologic testing is a game-changer in monitoring the prevalence and case-fatality of COVID-19 within a population, and it provides valuable insights for developing an effective pandemic response plan. This approach has important implications in guiding public health policies by increasing testing capacity via cost-effective methods. In Pakistan, Getz Pharma conducted a 100% census sero-prevalence study on a sample of individuals with follow-up and sequential testing after every 15-20 days. The sample included an adult, working population between the ages of 18-65 years in urban workplaces of Karachi. This was the first ever large-scale, cross-sectional sero-prevalence study conducted on a low-risk population to assess the prevalence of COVID-19 in Pakistan. The results revealed the prevalence of COVID-19 amongst asymptomatic people using serologic test kits, which allow mass screening hence indicating the total numbers of the infected population which may be many folds higher than indicated by PCR tests which show that only 231,818 people are currently COVID-19 positive in Pakistan.[1]
Amongst the figures from ongoing testing by the government, the proportion tested positive from the total number of people tested is termed as the positivity rate[2] of COVID-19 infections, which is very different from the total prevalence of COVID-19 within a population. The positivity rate only considers the total number of positive cases amongst symptomatic individuals or contacts of COVID-19 positive cases tested divided by the total number of PCR tests conducted.[3] This is in itself a volunteer bias as those who present for PCR tests are the ones having symptoms. Hence, the positivity rate cannot be used to determine the true extent of the disease as it fails to capture the proportion of positive cases within the general, low-risk population including asymptomatic carriers, who can only incidentally be identified via a mass-screening model such as the one implemented by Getz Pharma.
According to Getz Pharma’s study, out of 24,210 individuals screened, 17.5% tested positive, with 7% IgM positive, 6.0% IgG positive and 4.5% combined IgM and IgG positive. These findings have then been extrapolated to the rest of the urban, adult, working population of Pakistan, and as of 6th July, 2020, 4.11 million people in Pakistan have been infected with COVID-19 as opposed to only 231,818 as per government PCR figures.[4]
Table 1: Seroprevalence study results and extrapolations
Getz Pharma has conducted a sero-prevalence 100% testing (census) of various workplaces in Karachi including factories, corporates, restaurants, media houses, schools, banks, healthcare providers in hospitals and families of positives using USFDA EUA and CE approved serologic test kits that have been used in 38 countries globally. Serologic tests are based on the qualitative detection of IgM and IgG generated by the body in response to a SARS-CoV-2 infection.[5] IgM is usually the first antibody type generated by the body in response to a COVID-19 infection, followed by IgG which then replaces IgM as the predominant antibody in the blood. IgM and IgG combat infections by targeting specific antigens on the surface of the virus.[6] The kits used by Getz Pharma have a sensitivity of 95.3% and specificity of 98.7% for IgG, and the sensitivity of 86.48% and specificity of 95.18% for IgM.[7]
Getz Pharma in its efforts to contribute back into the system is also testing 25,000 frontline healthcare providers and their families free of cost. In addition to this, we are also conducting a sequential serological testing every 15 days for all of our 1500 employees to keep our workplace COVID-19 free. More details of the initiative can be found at https://www.dawn.com/news/1559103/what-does-our-seroprevalence-study-tell-us
The results presented are from a sample of 24,210 individuals taken from different workplaces of Karachi. The numbers continue to grow on a daily basis as we continue to test and enroll more people in the study.
As this is a study sample from urban workplaces and not a multistage, cluster random household survey, the extrapolation of the data obtained through this census needs to keep the following statistical considerations in mind:
1. The study population included adults between 18-65 years of age. While extrapolating it to the general population of 220 million, 53% of the population in Pakistan which is under 18 years of age and 4.5% above 65 years[8] needs to be stratified and excluded, thus restricting the universe to 93 million.
2. The population setting of this census was a dense, urban population and excluded 64 percent of the rural population of Pakistan thus reducing the universe to 33 million people from the adult, urban population. It must be noted that the infectivity quotient (R0) is very different between densely urban and less crowded rural populations ranging from 1.4 to 3.9.[9] ,[10]
3. This is a cross-sectional sero-prevalence survey which also includes people who have had COVID-19, have recovered, and are now immune. 90% of those tested positivefrom various workplaces had asymptomatic individuals who would otherwise have never presented for a PCR testing at a government approved facility and would have continued to spread the infection had they not been incidentally tested by their workplaces.
4. Serological kits like the ones Getz Pharma used are FDA EUA approved, with a false positive rate ranging from 2% to a maximum of 7% (Stanford & Massachusetts study)[11] due to nonspecific immunity & nonspecific protection to COVID-19. There may be minimum cross-reactivity with other previous SARS virus. The antibodies can be general and nonspecific to COVID-19 but may be able to provide protection from COVID-19. Studies are still underway to prove this hypothesis (mainly through passive immunization from convalescent COVID-19 plasma which has both specific COVID-19 antibodies as well as nonspecific IVIG). According to a paper published in a peer-reviewed journal in JAMA, even the "gold standard" PCR kits can have an accuracy ranging from 32% (pharyngeal swab) to 63% (nasal swab) depending on the technique of sample collection, the site and the phase of the disease.[12]
5. The initial findings from the workplace census conducted by Getz Pharma show a high prevalence of humoral, adaptive immunity (specific to COVID-19 or cross reactivity to previous SARS) in the Pakistani population, which is different from innate immunity.[13] This is the first of its kind, large scale, groundbreaking census on healthy, urban adults between 18 to 65 years of age.
6. Caution must be applied before assuming that Pakistan is entering herd immunity as there are no studies available to date on our population which show what prevalence is needed in a population before herd immunity kicks in, for how long IgG remains in the blood, and whether or not the serological response is protective or not. The prevalence needed to achieve Herd Immunity Threshold (HIT) has been cited to be 29–74% in literature.[14] Additionally, for herd immunity to be successful, the recovered individuals must carry IgG in the blood for up to many months otherwise the immunity offered is temporary and not able to contribute to herd immunity or even protection from reinfection. Hence, Getz Pharma is conducting a sequential study on recovered individuals to assess the duration of IgG level in the blood.
7. Sero-prevalence studies can allow us to assess the prevalence of the disease rather than just the incidence as indicated through PCR testing of symptomatic individuals. Sero-prevalence studies provide us information about the extent of infections which may be many folds higher than what PCR reported cases indicate[15] [16]. The Santa Clara study[17] and the Iran study[18] showed similar results what Getz Pharma found in Pakistan - the sero-positivity prevalence of COVID-19 indicated that the asymptomatic infection is much higher than the number of confirmed cases of COVID-19. According to media reports sent to Punjab Chief Minister Usman Buzdar in June 2020, up to 670,000 persons could be infected in Lahore alone,[19] yet, a month later, Pakistan is still officially reporting only a total 231,818 PCR confirmed cases (as of 6th July, 2020)[20]. Hence the findings from the sero-prevalence study become even more significant given the context of Pakistan’s rising and under reported cases, as the official data severely under-estimates the true prevalence of infections.
8. Antibody surveys conducted in Germany, the Netherlands, and United States revealed that anywhere between 2% to 30% of certain populations have been infected with COVID-19[21], and the number of confirmed cases provided by government statistics are a much smaller fraction of the true number of people infected. According to Mark Perkins, a diagnostics expert at the World Health Organization, the current number of confirmed cases should have at least indicated 45-60% positive cases,[22] as it would have accurately demonstrated the true extent of silent transmission and possible immunity in the population. However, in reality, even the high numbers being reported are relatively small compared to the true prevalence of the virus. This means that widespread serologic testing is required to ensure that most of the population is screened for COVID-19, so the findings can then be used to better detect infection fatality rate and decide for public policy guidelines.
Like any other epidemiological survey, before it is conclusive, further studies are needed.
Study Results and Extrapolations:
1. So far, over 24,000 people across various industries’ head offices, banks, restaurants, hospitals, schools and media houses have been screened by Getz Pharma, including all of its own workers.
2. Out of the total sample size, the total positive cases were 17.5% in the workplace population. Most of these were ongoing infections at 11.5%, while 6% had recovered.
3. From a sample of 24,210 individuals recruited in the study, a total of 8,937 registered employees were screened from factories and corporate offices. Out of these, 15.2% tested positive. Specifically, 7.2% tested IgM positive, while 4.8% tested IgG positive and 3.2% were combined IgM and IgG positive. This prevalence can be extrapolated to the one million registered working population of Karachi, meaning at least 152,000 infected cases in Karachi alone, with 104,000 being currently infected, unaware and spreading infection to those around them.
4. These findings can be applied to the remaining urban workforce of Pakistan with similar demographics, between the ages of 18-65 years. By taking a base population of 61.7 million registered workers[23] between this age range in Pakistan, assuming that 36% live in urban areas with similar workplace dynamics (22.21 million), it can be extrapolated that 4,110,381 (4.11 million) from the working population are currently infected/exposed to COVID-19 as of 6th July, 2020.
5. From a total of 896 individuals screened from media houses and print media, 8.6% tested positive, with 4.7% IgM positive, 2.9% IgG positive and 1% with both. Taking a base population of 50,000 media individuals in Pakistan including mainstream media and print media, we can extrapolate that 4,297 individuals from the media industry of Pakistan are currently exposed to COVID-19.
6. Amongst 3,120 healthcare workers including doctors and paramedics from different metropoles in Pakistan (Karachi, Lahore, Multan, Peshawar, Quetta) 17% tested positive, with 4.1% currently infected and 4.6% IgG positive which meant that they had been infected in the past and now recovered. Taking a base population of 313,457 healthcare workers [24] across Pakistan as per WHO EMRO, we can extrapolate that 53,248 healthcare workers are currently exposed to COVID-19.
7. Out of a total of 7,857 individuals screened who were household contacts of a positive case, it was found that 15.9% individuals tested positive, with 4.2% IgM positive, 4.8% IgG positive and 6.8% had both. With 231,818 PCR cases being reported as of 6th July, 2020[25], taking an average Pakistani household size of 6.7[26], the base population on family members of positive cases is 1,553,181. Given a 15.9% secondary Household attack rate, we can extrapolate that 246,508 household members of positive cases are currently exposed to COVID-19.
8. Out of a total of 3,400 symptomatic individuals in the study, who requested for symptom-based testing at their households, 30% tested positive, with 16% IgM positive and 14% IgG positive. As of 6th July, 2020, there have been 1,420,623 [27] symptom-based COVID-19 tests across Pakistan. If the study was to be extrapolated to all tests done who presented with symptoms, given the false negativity of PCR especially when viral load is less, and given a 30% prevalence of test positivity in individuals who have symptoms, at least 426,187 people currently have COVID-19 in Pakistan.
9. Overall, from a sample of 24,210 individuals screened, 17.5% tested positive, with 7% IgM positive, 6.0% IgG positive and 4.5% combined IgM and IgG positive. Given the above extrapolations while keeping the study limitations in mind, we can extrapolate that as of 6th July, 2020, currently 4.11 million individuals in Pakistan have been infected with COVID-19 as opposed to 231,818 that the official figures of Pakistan are quoting.[28]
10. Interestingly, over 90% of those who tested COVID-19 positive did not have any symptoms. 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.
11. While the Getz Pharma study showed sero-prevalence of 17.5% at workplaces, the newly emergent cases at 6 weeks had an incidence rate of 7%. This means that on baseline, at least 17.5% of the Pakistani adult, working class population has COVID-19 at any given point in time, and every 6 weeks 7% more cases are added to the baseline pool.
12. We did not study people at high risk other than frontline healthcare providers. We targeted adults in the general population from all walks of life in the urban setting. Hence the findings cannot be extrapolated to rural populations.
13. We need a household, multistage, cluster random survey to find the true extent of the disease. This is what it looks like in a highly urban, dense, adult working class population.
Glossary:
Term
|
Definition
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Antibody
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A blood protein produced in response to and counteracting a specific antigen. Antibodies combine chemically with substances which the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood.
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Asymptomatic
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A condition producing or showing no symptoms.
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Case fatality
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A case fatality rate (CFR) is the proportion of deaths within a designated population due to a given medical condition (cases), of such cases over the course of the disease. A CFR is conventionally expressed as a percentage and represents a measure of risk.
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Immunity
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The ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells.
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Immunoglobulin G
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Immunoglobulin G is a type of antibody generated by the body in response to an antigen.
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Immunoglobulin M
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Immunoglobulin M is one of several isotypes of antibody that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen.
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Infectivity quotient
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In epidemiology, infectivity is the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission that is, how frequently it spreads among hosts that are not in a parent-child relationship.
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SARS-CoV-2
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic.
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Secondary household attack rate
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Secondary attack rate refers to the spread of disease in a family, household, dwelling unit, dormitory, or similar circumscribed group.
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Sensitivity
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The probability that a medical test will detect the condition being tested for in people who actually have the condition. A sensitive test is one that produces true positive results.
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Specificity
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The specificity of a test rules out someone who has not been exposed to the virus and has not developed antibodies, i.e. a true negative rate.
|
Serologic test
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Serologic tests are blood tests that look for antibodies in your blood. They can involve a number of laboratory techniques. Different types of serologic tests are used to diagnose various disease conditions. Serologic tests have one thing in common. They all focus on proteins made by your immune system.
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Seroprevalence
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The level of a pathogen in a population, as measured in blood serum.
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PCR
|
Polymerase chain reaction, or PCR, is a laboratory technique used to make multiple copies of a segment of DNA. PCR is very precise and can be used to amplify, or copy, a specific DNA target from a mixture of DNA molecules. It is used to detect the viral load of COVID-19 in the infected population.
|
References:
Adaptive immunity | Immune response (article) | Khan Academy [Internet]. Khan Academy. 2020. Available from: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/adaptive-immunity
Ahmed T, Ali SM. Characteristics of Households and Respondents. Pakistan Demographic and Health Survey. 1992 Jul;1:990-1.
Bendavid E, Mulaney B, Sood N, Shah S, Ling E, Bromley-Dulfano R, Lai C, Weissberg Z, Saavedra R, Tedrow J, Tversky D. COVID-19 Antibody Seroprevalence in Santa Clara County, California. MedRxiv. 2020 Jan 1.
COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations and Coordination [Internet]. Covid.gov.pk. 2020. Available from: http://covid.gov.pk/stats/pakistan
Davis C. How Do the COVID-19 Coronavirus Tests Work? [Internet]. MedicineNet. 2020. Available from: https://www.medicinenet.com/how_do_the_covid-19_coronavirus_tests_work/article.htm
Herd immunity [Internet]. En.wikipedia.org. 2020. Available from: https://en.wikipedia.org/wiki/Herd_immunity#cite_ref-53
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. (January 2020). "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia". The New England Journal of Medicine. 382 (13): 1199–1207. doi:10.1056/NEJMoa2001316. PMC 7121484. PMID 31995857.
Pakistan Demographics Profile 2019 [Internet]. Indexmundi.com. 2019. Available from: https://www.indexmundi.com/pakistan/demographics_profile.html
Pakistan Employed Persons | 1986-2018 Data | 2019-2020 Forecast | Historical | Chart [Internet]. Tradingeconomics.com. 2018. Available from: https://tradingeconomics.com/pakistan/employed-persons
Pakistan Medical & Dental Council > Statistics [Internet]. Pmdc.org.pk. 2019. Available from: http://www.pmdc.org.pk/statistics/tabid/103/default.aspx
Riou J, Althaus CL (January 2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveillance. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239. PMID 32019669.
Shaikh H. How can we protect contract and informal workers in Pakistan? [Internet]. DAWN.COM. 2019. Available from: https://www.dawn.com/news/1484090#
Shakiba M, Nazari SS, Mehrabian F, Rezvani SM, Ghasempour Z, Heidarzadeh A. Seroprevalence of COVID-19 virus infection in Guilan province, Iran. medRxiv. 2020 Jan 1.
Vogel G. Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable [Internet]. Science | AAAS. 2020. Available from: https://www.sciencemag.org/news/2020/04/antibody-surveys-suggesting-vast-undercount-coronavirus-infections-may-be-unreliable
Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in different types of clinical specimens. Jama. 2020 May 12;323(18):1843-4.
WHO EMRO | Health service delivery [Internet]. Emro.who.int. 2020. Available from: http://www.emro.who.int/pdf/pak/programmes/service-delivery.pdf?ua=1
Xu Wanzhou, Li Wei, He Xiaoyun, Zhang Caiqing, Mei Siqing, Li Congrong. Serum 2019 New coronavirus IgM and IgG antibodies jointly detect the diagnostic value of the new coronavirus infection .J/OL. Chinese Journal of Test Medicine. 2020;43. DOI: 10.3760/cma.j.cn114452-20200223-00109
[1] COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations and Coordination. Covid.gov.pk. 2020
[2] Geo.tv. 2020. Pakistan’s Positivity Rate Of COVID-19 'High', Finds WHO. [online] Available at: https://www.geo.tv/latest/293192-pakistans-positivity-rate-of-covid-19-high-finds-who
[3] Livengood, P., 2020. Austin's Positivity Rate Is The Highest In The Country. So What Does That Mean?. [online] www.kvue.com. Available at: https://www.kvue.com/article/news/health/coronavirus/coronavirus-austin-positivity-rate-covid19-texas-explainer/269-99f46ba3-e44f-4d3b-acbf-63216330a3b4
[4] COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations and Coordination.
[5] Davis, 2020. How Do the COVID-19 Coronavirus Tests Work? Available from: https://www.medicinenet.com/how_do_the_covid-19_coronavirus_tests_work/article.htm
[6] Davis, 2020
[7] Xu Wanzhou, Li Wei, He Xiaoyun, Zhang Caiqing, Mei Siqing, Li Congrong. Serum 2019 New coronavirus IgM and IgG antibodies jointly detect the diagnostic value of the new coronavirus infection .J/OL. Chinese Journal of Test Medicine. 2020;43.
[8] Pakistan Demographics Profile 2019. Indexmundi.com. 2019
[9] Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. (January 2020). "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia". The New England Journal of Medicine. 382 (13): 1199–1207. doi:10.1056/NEJMoa2001316. PMC 7121484. PMID 31995857.
[10] Riou J, Althaus CL (January 2020). "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020". Euro Surveillance. 25 (4). doi:10.2807/1560-7917.ES.2020.25.4.2000058. PMC 7001239. PMID 32019669.
[11] Bendavid et al., COVID-19 Antibody Seroprevalence in Santa Clara County, California. MedRxiv. 2020 Jan 1.
[12] Wang et al., Detection of SARS-CoV-2 in different types of clinical specimens. Jama. 2020
[13] Adaptive immunity | Immune response (article) | Khan Academy [Internet]. Khan Academy. 2020. Available from: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/adaptive-immunity
[14] Herd immunity [Internet]. En.wikipedia.org. 2020. Available from: https://en.wikipedia.org/wiki/Herd_immunity#cite_ref-53
[15] Bendavid et al., COVID-19 Antibody Seroprevalence in Santa Clara County, California. MedRxiv. 2020 Jan 1.
[16] Shakiba et al., Seroprevalence of COVID-19 virus infection in Guilan province, Iran. medRxiv. 2020 Jan 1.
[17] Bendavid et al., 2020
[18] Shakiba et al., 2020
[19] Junaidi I. Govt decides to hold Covid-19 prevalence survey [Internet]. DAWN.COM. 2020. Available from: https://www.dawn.com/news/1560956
[20] COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations and Coordination.
[21] Vogel G. Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable [Internet]. Science | AAAS. 2020. Available from: https://www.sciencemag.org/news/2020/04/antibody-surveys-suggesting-vast-undercount-coronavirus-infections-may-be-unreliable
[22] Vogel, 2020.
[23] Shaikh H. How can we protect contract and informal workers in Pakistan? [Internet]. DAWN.COM. 2019. Available from: https://www.dawn.com/news/1484090#
[24] WHO EMRO | Health service delivery [Internet]. Emro.who.int. 2020. Available from: http://www.emro.who.int/pdf/pak/programmes/service-delivery.pdf?ua=1
[25] COVID-19 Health Advisory Platform by Ministry of National Health Services Regulations and Coordination. Covid.gov.pk. 2020
[26] Ahmed T, Ali SM. Characteristics of Households and Respondents. Pakistan Demographic and Health Survey. 1992 Jul;1:990-1.
[27] COVID-19 Health Advisory Platform
[28] COVID-19 Health Advisory Platform
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Comments
A survey has suggested that around 300,000 persons have been infected with the novel coronavirus in Islamabad after which the city may be inching towards achieving “herd immunity”.
The study has also shown that a vast majority of the individuals exposed to the virus are asymptomatic, that is they are generally not showing symptoms of Covid-19 even after being infected with the dreaded virus.
During the last 24 hours, 2,276 new infections were detected, which took the country’s total caseload to 259,401. During the period, 48 people died from the virus, taking the death toll to 5,465. So far 178,737 people have recovered from the disease.
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The study — titled “Sero-Epidemio-logical Survey for Covid-19” — was carried out between June 1 and June 25 in the geographical limits of the Islamabad Capital Territory (ICT).
Most of the infected people are asymptomatic, says NIH chief
Dr Ikram said that after applying the standard techniques sample size required was found to be 4,328 for the survey. “A structured, pre-tested questionnaire was used to gather data relating to demography, clinical issues and exposure and risk factors from the community. Blood samples were collected from participants who were tested for immunoglobulins against Covid-19…. Throat or nasopharyngeal swabs were also collected from those having symptoms or a contact history with a positive case for PCR testing. All samples were tested at the virology lab of NIH,” he said.
A preliminary analysis showed a prevalence of 14.5 per 100 population for Covid-19, he said. “As for area-wise distribution of the disease, rural union councils were more affected. Out of all the union councils, Chattar was found to be the most affected, followed by the union councils of Muhrian and Tarlai Khurd.
“Considering the ages, the most affected group comprised people of between 41 and 50 years, followed by the 31-40 years group and 51-60 years group. PCR positivity rate was found to be 17pc,” he said.
“The calculated prevalence for Covid-19 in ICT is 14.5pc which translates into 290,000 individuals, who have been exposed to the SARS-CoV-2 virus and have developed immunoglobulins against the virus. This should be seen in the context that a vast majority of the individuals exposed to the virus are asymptomatic.”
In response to a question, Dr Ikram said the objective of the survey was to reveal the number of people who have already been exposed to the virus.
According to an official statement, an enhanced surveillance strategy that focuses on population-based methods is mandatory to understand the actual situation on the ground and then successfully control the pandemic.
“Asymptomatic/mild cases of Covid-19 are usually not picked up on routine surveillance and hinder estimation of the true population infection rate. Therefore, estimation of true population infection rate is mandatory to effectively guide public health interventions. To address the needs, following the WHO guidelines, a population-based, age-stratified, sero-epidemiological survey was conducted in Islamabad to determine the extent of infection among the population, age-specific attack rates and the fraction of asymptomatic or subclinical infections,” the statement said.
Dr Ikram said that as about 15pc of the population had developed antibodies for Covid-19, it could be said that about 300,000 people in the federal capital had been infected with the virus. “If 50pc of the population would be infected, the concept of herd immunity would kick in. Now we will hold similar studies in other cities,” he said.
Now comes a new paper in press at Nature. It confirms that convalescent patients from the current epidemic show T-cell responses (mostly CD4+ but some CD8+ as well) to various epitopes of the N (nucleocapsid) protein, which the earlier paper had identified as one of the main antigens as well (along with the Spike and M proteins, among others, with differences between the CD4+ and CD8+ responses as well). Turning to patients who had caught SARS back in 2003 and recovered, it is already known (and worried about) that their antibody responses faded within two or three years. But this paper shows that these patients still have (17 years later!) a robust T-cell response to the original SARS coronavirus’s N protein, which extends an earlier report of such responses going out to 11 years. This new work finds that these cross-react with the new SARS CoV-2 N protein as well. This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.
And turning to patients who have never been exposed to either SARS or the latest SARS CoV-2, this new work confirms that there are people who nonetheless have T cells that are reactive to protein antigens from the new virus. As in the earlier paper, these cells have a different pattern of reactivity compared to people who have recovered from the current pandemic (which also serves to confirm that they truly have not been infected this time around). Recognition of the nsp7 and nsp13 proteins is prominent, as well as the N protein. And when they looked at that nsp7 response, it turns out that the T cells are recognizing particular protein regions that have low homology to those found in the “common cold” coronaviruses – but do have very high homology to various animal coronaviruses.
Very interesting indeed! That would argue that there has been past zoonotic coronavirus transmission in humans, unknown viruses that apparently did not lead to serious disease, which have provided some people with a level of T-cell based protection to the current pandemic. This could potentially help to resolve another gap in our knowledge, as mentioned in that recent post: when antibody surveys come back saying that (say) 95% of a given population does not appear to have been exposed to the current virus, does that mean that all 95% of them are vulnerable – or not? I’ll reiterate the point of that post here: antibody profiling (while very important) is not the whole story, and we need to know what we’re missing.
There are still major gaps in our knowledge: how many people have such unknown-coronavirus-induced T-cells? How protective are they? How long-lasting is the T-cell response in people who have been infected with the current SARS CoV-2 virus, and how protective is it in the declining-antibody situation that seems to be common? What sorts of T cell responses will be induced by the various vaccine candidates? We just don’t know yet. But we’re going to find out.
The preliminary results of the country’s largest drug trial on the coronavirus — Pakistan Randomized and Observational Trial to Evaluate Coronavirus Treatment (PROTECT) — has not only established the safety of hydroxychloroquine, a drug generally used for malaria, in terms of mortality but has also shown significant recovery rates in Covid-19 patients when used in combination with two other drugs- azithromycin and oseltamivir.
The claims, as well as the results, were made public here at the University of Health Sciences (UHS), on Monday, in a ceremony, which was presided by Governor Chaudhry Muhammad Sarwar and attended by Punjab Minister for Higher Education Raja Yassir Humayun Sarfraz, vice chancellors of the medical universities, researchers and faculty members.
Releasing the results of the study, UHS Vice Chancellor Prof Javed Akram, who is also its principal investigator, clarified that it aimed at evaluating hydroxychloroquine alone and in various drug combinations as treatment of the coronavirus.
“It is a multicentre, multiarm, adaptive, randomized control drug trial aimed at newly diagnosed patients,” he informed the participants in the ceremony.
He said the study found that the coronavirus patients, who received the three drugs combined, had a recovery rate of 86pc.
UHS VC Prof Javed Akram told the participants that the drug trial was launched on April 30, after the approval from the Drug Regulatory Authority of Pakistan (DRAP) and the National Bioethics Committee (NBC).
He added that 12 centres, including 10 universities from eight cities, were included in the study. The study enrolled Covid patients over the age of 18 who were divided into eight groups. The patients included in the research were 60pc male and 40pc female. The three medicines were given to seven groups, each consisting of 60 to 65 patients, alone and in different combinations, while one control group was given nothing.
Prof Javed Akram disclosed that the rate of recovery from the combination of the three drugs was the highest at 86pc. The second highest recovery rate was 75pc from azithromycin. The overall recovery rate of the patients, who were given medicines, was 73.1pc while the rate of recovery without medicines was 67pc. The 27pc of patients remained Corona-positive even two weeks after taking the drug. Of the patients who were not given any medication, 33pc remained Corona-positive even after two weeks.
The UHS VC added that the recovery rate in the first week of research was 33.5pc while in the second week, it increased to 72.2pc.
Initially, the PCR test was used as a basis for research. He said a total of four deaths were reported during the study. Three deaths occurred in groups receiving single medicine, while one death occurred in the group receiving a combination of hydroxychloroquine and azithromycin.
Mr Akram made it clear that the study was still in progress and it would involve around 9,500 patients when completed. He added that Rs30m had been spent on research so far, which the university had collected from its own resources and through donations.
King Edward Medical University VC Prof Khalid Masood Gondal, in his address, said if the standard operating procedures (SOPs) were implemented on Eidul Azha, the coronavirus would be under control by September.
Paying a tribute to the front line health workers, Governor Chaudhry Muhammad Sarwar said the nation would always remember the valour with which the health workers fought against the virus.
“A memorial wall is being erected at the Governor House in recognition of the services of the health workers that would bear the names of all the front line soldiers,” he added.
The annual hajj that brings more than 2 million pilgrims to Saudi Arabia’s Mecca has been drastically scaled back this year due to the coronavirus pandemic, but virtual software developers are hoping to let Muslims experience what it’s like to worship at the city’s holy sites from far away.
Social-distancing measures by the Saudi government to fight the new coronavirus mean only a limited number of pilgrims already in the country can participate when this year’s hajj begins July 28. The decision is a blow for those hoping to fulfill their once-in-a-lifetime obligation to perform hajj in 2020.
Some see the news as a boon for virtual hajj software, but some Muslims question whether holy pilgrimages can be replicated virtually.
“Unfortunately, tech acceptance in the Islamic world has been a bit slower than our ambitions, with the result that specific segments of the population are unable to see the future benefit that virtual hajj can provide,” said Mohammed Alsherebi, founder of Centillion Inc., a company that advises companies expanding in the Middle East. “By focusing only on the inconvenience of the present moment, many of us are unable to see the incredible opportunity that lies ahead of us.”
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“We don’t believe there can be a substitute to an in-person hajj experience,” said Mr. Maqbool. “However, if we can bring some measure of spiritual and emotional peace to Muslims world-wide during these tough times, then we will have met our goals.”
Mr. Alhaddad, the iUmrah.World chief executive, said he is confident that a virtual hajj or umrah will one day be considered as legitimate as the real thing. The company, which Mr. Alhaddad hopes to take public in 2022, is also developing an iVatican product.
“Yes, it’s better to go yourself,” said Mr. Alhaddad. “But can you get the same experience or fulfillment by watching a pilgrimage being performed? Yes, I believe you can.”
https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html
Some of the nation’s leading public health experts are raising a new concern in the endless debate over coronavirus testing in the United States: The standard tests are diagnosing huge numbers of people who may be carrying relatively insignificant amounts of the virus.
Most of these people are not likely to be contagious, and identifying them may contribute to bottlenecks that prevent those who are contagious from being found in time. But researchers say the solution is not to test less, or to skip testing people without symptoms, as recently suggested by the Centers for Disease Control and Prevention.
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The PCR test amplifies genetic matter from the virus in cycles; the fewer cycles required, the greater the amount of virus, or viral load, in the sample. The greater the viral load, the more likely the patient is to be contagious.
This number of amplification cycles needed to find the virus, called the cycle threshold, is never included in the results sent to doctors and coronavirus patients, although it could tell them how infectious the patients are.
In three sets of testing data that include cycle thresholds, compiled by officials in Massachusetts, New York and Nevada, up to 90 percent of people testing positive carried barely any virus, a review by The Times found.
On Thursday, the United States recorded 45,604 new coronavirus cases, according to a database maintained by The Times. If the rates of contagiousness in Massachusetts and New York were to apply nationwide, then perhaps only 4,500 of those people may actually need to isolate and submit to contact tracing.
One solution would be to adjust the cycle threshold used now to decide that a patient is infected. Most tests set the limit at 40, a few at 37. This means that you are positive for the coronavirus if the test process required up to 40 cycles, or 37, to detect the virus.
Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk — akin to finding a hair in a room long after a person has left, Dr. Mina said.
Any test with a cycle threshold above 35 is too sensitive, agreed Juliet Morrison, a virologist at the University of California, Riverside. “I’m shocked that people would think that 40 could represent a positive,” she said.
A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he would set the figure at 30, or even less. Those changes would mean the amount of genetic material in a patient’s sample would have to be 100-fold to 1,000-fold that of the current standard for the test to return a positive result — at least, one worth acting on.
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Instead, new data underscore the need for more widespread use of rapid tests, even if they are less sensitive.
“The decision not to test asymptomatic people is just really backward,” said Dr. Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, referring to the C.D.C. recommendation.
“In fact, we should be ramping up testing of all different people,” he said, “but we have to do it through whole different mechanisms.”
In what may be a step in this direction, the Trump administration announced on Thursday that it would purchase 150 million rapid tests.
The most widely used diagnostic test for the new coronavirus, called a PCR test, provides a simple yes-no answer to the question of whether a patient is infected.
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But yes-no isn’t good enough, he added. It’s the amount of virus that should dictate the infected patient’s next steps. “It’s really irresponsible, I think, to forgo the recognition that this is a quantitative issue,” Dr. Mina said.
The vaccines made by Pfizer-BioNTech and Moderna set off a persistent immune reaction in the body that may protect against the coronavirus for years, scientists reported on Monday.
The findings add to growing evidence that most people immunized with the mRNA vaccines may not need boosters, so long as the virus and its variants do not evolve much beyond their current forms — which is not guaranteed. People who recovered from Covid-19 before being vaccinated may not need boosters even if the virus does make a significant transformation.
“It’s a good sign for how durable our immunity is from this vaccine,” said Ali Ellebedy, an immunologist at Washington University in St. Louis who led the study, which was published in the journal Nature.
The study did not consider the coronavirus vaccine made by Johnson & Johnson, but Dr. Ellebedy said he expected the immune response to be less durable than that produced by mRNA vaccines.
Dr. Ellebedy and his colleagues reported last month that in people who survived Covid-19, immune cells that recognize the virus lie quiescent in the bone marrow for at least eight months after infection. A study by another team indicated that so-called memory B cells continue to mature and strengthen for at least a year after infection.
Based on those findings, researchers suggested that immunity might last for years, possibly a lifetime, in people who were infected with the coronavirus and later vaccinated. But it was unclear whether vaccination alone might have a similarly long-lasting effect.
Dr. Ellebedy’s team sought to address that question by looking at the source of memory cells: the lymph nodes, where immune cells train to recognize and fight the virus.
After an infection or a vaccination, a specialized structure called the germinal center forms in lymph nodes. This structure is an elite school of sorts for B cells — a boot camp where they become increasingly sophisticated and learn to recognize a diverse set of viral genetic sequences.
The broader the range and the longer these cells have to practice, the more likely they are to be able to thwart variants of the virus that may emerge.