Improving Testing for COVID-19 for the Rural Southwestern American Indian Tribes

Arshia Chhabra¹

Varinn Sood²

Vanita Sood, MD³

Akshay Sood, MD, MPH^4,5

¹La Cueva High School, 7801 Wilshire Ave NE, Albuquerque, NM USA

²Albuquerque Academy, 6400 Wyoming Blvd. NE, Albuquerque, NM USA

³Andrew Weil Center for Integrative Medicine, University of Arizona, 655 N Alvernon Way, Tucson, AZ USA;

⁴Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM USA; ⁵Black Lung Program, Miners’ Colfax Medical Center, Raton, NM, USA.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome-related coronavirus-2 (SARS–CoV-2) infection. The United States (US) currently has more officially reported cases and deaths from COVID-19 than any other country in the world. The rural Southwestern American Indian (SAI) tribes are disproportionately affected, due to genetics, immunological naivety, social determinants of health, and high prevalence of concomitant comorbidities and co-exposures (1). On March 30, 2020, the New Mexico Governor, Michelle Lujan Grisham, informed the US President Donald Trump of the “incredible spikes” in cases of COVID-19 within the Navajo Nation in the rural Four Corners region of the American Southwest (2). The Governor warned that the disease “... could wipe out those tribal nations.”

Use of COVID-19 testing as an approach to combating the pandemic is supported by an Iceland-based epidemiological study, and endorsed by the World Health Organization (3). Rural states in the US rank higher in prevalence of COVID-19 risk factors (hypertension, obesity, and diabetes), but rank lower in overall testing rates (4). Notably, several Southwestern states such as Arizona, Texas and Oklahoma have among the lowest testing rates in the country (5). Taken together, these results suggest that the current COVID-19 surveillance does not effectively capture medically vulnerable rural populations in the Southwest (4). Testing in the SAI tribal communities is further limited by the following reasons: 1) misinformation on tests due to the lack of broadband Internet access; 2) inadequate access to test sites due to lack of transportation and long travel distances; 3) traditional mistrust of the healthcare system; 4) concern about mishandling of biological samples; 5) misunderstanding that molecular assays interpret the genetic structure of the virus and not their people; 6) difficulty paying for the tests; and 7) nationwide shortage of test kits. Buy-in from community leaders and traditional healers, utilizing culturally sensitive communications, and access to broadband Internet are crucial to improving effective testing-based surveillance in these communities.

A large number of molecular and serological tests for COVID-19 are currently available, many of which lack evaluation data. Molecular tests, useful for establishing a diagnosis, utilize respiratory tract specimens to assess for the presence of nucleic acid targets specific to SARS–CoV-2 using the reverse transcriptase-polymerase chain reaction (RT-PCR) or nucleic acid amplification assays. RT-PCR–based assays performed in the laboratory on nasopharyngeal swabs collected by trained professionals are currently the cornerstone of COVID-19 diagnostic testing. Most RT-PCR assays take a few hours to complete, but the Cepheid assay has shortened the test duration to 45 minutes (6). Recent molecular tests such as CRISPR-Case12-based lateral flow assay and Abbott ID Now™, utilizing isothermal nucleic acid amplification technology for the qualitative detection of viral RNA have shortened the turnaround time further (7). Unlike molecular tests, serological tests may be useful in public health surveillance and vaccine evaluation, but not as the sole test for diagnosing the acute stage of the disease (8). Performed on blood specimens, serological tests use formats such as enzyme-linked immunosorbent assay and rapid lateral flow immunoassay, to detect immunoglobulin M (IgM) and/or immunoglobulin G (IgG) antibodies, which are produced by the body at approximately 10 days and 20 days respectively following COVID-19 infection. Current molecular and serological tests are laboratory-based and not easily available in the SAI tribal settings.

Living far away from hospitals, rural SAI residents need easy access to sample collection venues.  Across the world, many different sample collection venues can serve as useful prototypes, which includes drive-through-, booth-, mobile laboratory-, and home-based approaches. The latter approach involves the use of self-test kits, which are ideal. The approach involves kits containing instructions for testees to self-collect nasal swabs (or possibly early morning salivary specimens (9)) for molecular tests, or finger-stick blood samples for serologic tests. The FDA recently granted emergency clearance to the first at-home molecular test, a nasal self-swab kit (Pixel, LabCorp, USA), with a mail-back to the company laboratory for conducting the PCR assay, with online access to the results (10).

Although not currently available, the ideal test for the SAI tribal settings is low cost, less complex, point of care, rapid (i.e., test turn-around time preferably within an hour), and able to be performed by non-laboratory professionals in low-infrastructure settings, such as homes. The test results could be potentially uploaded to a mobile app or be viewed over a telemedicine consultation to interpret the results and provide immediate counseling on the next step. Smartphone-based devices containing a cartridge-housed microfluidic chip, which carries out isothermal amplification of viral nucleic acids from nasal swab samples in 30 minutes, which are detected using the smartphone camera, may soon be available for home testing (11). Rapid point of care serologic tests, similar to finger-stick blood glucose tests, and home pregnancy tests with colorimetric reading, mal also soon become available for home testing (12).To take advantage of rapid point-of-care testing that will soon become available, improving access to smartphones and broadband Internet in SAI tribal communities is crucial.

The primary goal of the pandemic containment in the rural SAI tribal communities is to reduce the basic reproductive number (R0, the expected number of cases directly generated by one case) of the SARS–CoV-2 virus, thereby reducing disease transmission. Given the lack of effective vaccines or treatments, the only currently available levers to reduce SARS–CoV-2 transmission are to practice social isolation, universal masking, and hand hygiene, identify asymptomatic and symptomatic infected cases through ideal testing strategies, and isolate contagious persons (8). Although not currently available, the ideal test for SAI communities is point of care, rapid, and home-based and requires efforts to improve access to smartphones and broadband Internet. Testing can be popularized using community leaders and traditional indigenous care providers. Finally, policy solutions are needed to eliminate financial barriers for uninsured or underinsured patients, to help meet the goal of improving testing-based COVID-19 surveillance in the rural SAI tribal communities.

References

1. Kakol M, Upson D, Sood A. Susceptibility of southwestern american Indian tribes to coronavirus disease 2019 (COVID-19). J Rural Health. 2020. [CrossRef] [PubMed]
2. Faulders K, Rubin O. New Mexico's governor warns tribal nations could be 'wiped out' by coronavirus, https://abcnews.go.com/Politics/mexicos-governor-warns-tribal-nations-wiped-coronavirus, published March 30, 2020,  accessed on April 3, 2020: ABC news (online); 2020.
3. Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, et al. Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med. 2020 Apr 14.  [Epub ahead of print] [CrossRef] [PubMed]
4. Souch JM, Cossman JS. A commentary on rural-urban disparities in covid-19 testing rates per 100,000 and risk factors. J Rural Health. 2020 Apr 13. [Epub ahead of print] [CrossRef] [PubMed]
5. Monnat SM. Why coronavirus could hit rural areas harder. Available at https://lernercenter.syr.edu/2020/03/24/why-coronavirus-could-hit-rural-areas-harder/.  Printed March 24, 2020. Accessed March 26, 2020. Learner Center for Health Promotion.
6. Xpert®Xpress SARS-CoV-2. Available online: https://www.cepheid.com/coronavirus. March 21,2020. (accessed on 2 April 2020).
7. Abbott Launches Molecular Point-of-Care Test to Detect Novel Coronavirus in as Little as Five Minutes. Available online: https://abbott.mediaroom.com/2020-03-27-Abbott-Launches-Molecular-Point-of-Care-Test-to-Detect-Novel-Coronavirus-in-as-Little-as-Five-Minutes.  March 27, 2020. (accessed on 2 April 2020)
8. Cheng MP, Papenburg J, Desjardins M, Kanjilal S, Quach C, Libman M, et al. Diagnostic testing for severe acute respiratory syndrome-related coronavirus-2: a narrative review. Ann Intern Med. 2020 Apr 13. [Epub ahead of print] [CrossRef] [PubMed]
9. To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-74. [CrossRef] [PubMed]
10. LabCorp. Pixel by LabCorp, COVID-19 At-Home Kits. Available at https://www.pixel.labcorp.com/covid-19. Accessed April 23, 2020.
11. Sun F, Ganguli A, Nguyen J, Brisbin R, Shanmugam K, Hirschberg DL, et al. Smartphone-based multiplex 30-minute nucleic acid test of live virus from nasal swab extract. Lab Chip. 2020 May 5;20(9):1621-7. [CrossRef] [PubMed]
12. Vashist SK. In vitro diagnostic assays for covid-19: recent advances and emerging trends. Diagnostics (Basel). 2020 Apr 5;10(4). pii: E202. [CrossRef] [PubMed]

Cite as: Chhabra A, Sood V, Sood V, Sood A. Improving testing for COVID-19 for the rural Southwestern American Indian tribes. Southwest J Pulm Crit Care. 2020;20(5):175-8. doi: https://doi.org/10.13175/swjpcc037-20 PDF

Does the BCG Vaccine Offer Any Protection Against Coronavirus Disease 2019?

Mueez Rehman¹

Akshay Sood MD, MPH^2,3

¹University of New Mexico Main Campus, Albuquerque, NM, USA

²Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM USA

³Black Lung Program, Miners’ Colfax Medical Center, Raton, NM, USA

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-COV2), shares features with diseases caused by other coronaviruses such as influenza, the Severe Acute Respiratory Syndrome (SARS) outbreak of 2003, and the Middle East Respiratory syndrome (MERS) outbreak of 2012. COVID-19 has been a challenging and devastating pandemic, resulting in death rates of more than 1%, testing nations both rich and poor, and outlining the importance of strong public health programs. Social distancing, masking and hand washing have become the new norm. Healthcare professionals are on the front lines, risking their lives. Those with pre-existing health conditions or older individuals face a significant risk for complications.

As scientists race to understand this deadly virus and find a cure to protect millions, an unlikely ally may come in a vaccine created over 100 years ago. The Bacillus Calmette-Guérin or BCG vaccine was created in 1921 to protect against tuberculosis (TB). At the time, tuberculosis was widespread, and the BCG vaccine was quickly implemented globally. However, as tuberculosis rates declined, developed countries such as the United States and many European countries discontinued widespread BCG administration. This change in vaccination policy was due to the supply of the vaccine and concerns for its efficacy. On the other hand, countries such as India, Pakistan, Indonesia, Vietnam, Russia, Ethiopia, and many others have continued widespread administration of the BCG vaccine. Many of these countries still have high rates of tuberculosis infections, as well as a large percentage of their population live in poverty (1). When COVID-19 started to emerge as a pandemic, global leaders and public health officials feared this pandemic would have catastrophic effects on these countries, overwhelming their healthcare systems, and killing millions. Interestingly, the opposite outcome was observed as these countries reported low rates of COVID-19. Instead, Europe became the world’s first epicenter outside of mainland China, followed by the United States, both of which reported large infection rates and death tolls due to COVID-19. The hardest hit countries had a similarity in that, they did not require widespread neonatal BCG vaccination. Ultimately, it is possible that the key difference between rates of COVID-19 infections in nations lies in neonatal BCG immunization rates amongst the populations. However, these conclusions are subject to confounding variables, such as the strength of the public health programs, and testing and reporting rates for COVID-19. An interesting outlier is Iran, which implemented a nationwide BCG vaccination program late in 1984, for children less than 6 years of age, using the Pasteur strain (2). With the high rates of COVID-19 cases in Iran, further research needs to examine this outlier, to see if there is any association with the type of vaccine used, administration at a later age, or the fact that currently middle-aged and elderly Iranians are not universally vaccinated.

Another interesting observation comes from the COVID-19 racial/ethnic distribution in the United States. The Centers for Disease Control and Prevention (CDC) released the race/ethnicity data for 580 lab-confirmed COVID-19, hospitalized patients on April 8, 2020 (3). In this data, African Americans constituted 33% of patients (when compared to 18% in the catchment populations) while Asians constituted 5.5% of the patients (proportion of Asians in the catchment population was not described). In certain states, Asian American populations showed higher disease and death rates for COVID-19, when compared to the general population (4). Interpretation of this data is, however, subject to confounding variables. The racial category for the Asian population is reported differently throughout the nation. Many states have differing definitions for the Asian race, certain states fail to divide the Asian population into different subgroups, and others combine Asian populations with ‘other’ racial groups (5). Furthermore, because the US does not have a widespread COVID-19 testing program, certain communities lack access to tests, and disparities for groups may be hidden. Once comprehensive data is available, it would be interesting to examine if the Asian subgroups consisting of individuals who received the BCG vaccine from a BCG administering country, before immigrating to the US show better outcomes against COVID-19, when compared to other Asian American subgroups.

The BCG vaccine was created by Albert Calmette and Camille Guérin against a live attenuated strain of Mycobacterium bovis, a mycobacterium that is similar to the one that causes tuberculosis. The vaccine creates both specific immunity to that mycobacterium, as well as nonspecific immunity against other pathogens that cause respiratory tract infections. In a study conducted on mice, researchers found that when subjecting mice to infectious viruses such as the A0 and A2 influenza viruses, herpes simplex virus, as well as other highly infectious viruses, mice inoculated with BCG were found to exhibit a significantly higher resistance to these infections compared to control mice (6). An explanation for this finding may lie in the fact that the BCG vaccine results in innate immune memory in the host. This trained immunity works by reprogramming a host’s bone marrow hematopoietic stem cells and multipotent progenitors through epigenetic/metabolic changes, resulting in greater variability of the differentiated innate immune cells response following a pathogen (7). Ultimately, this may result in the host’s immune system being able to successfully fight off large numbers of respiratory tract infections, including possibly SARS-CoV-2.

The World Health Organization (WHO) stands firm on the stance that there is no scientific evidence as to whether the BCG vaccine actually protects against COVID-19. Furthermore, WHO mentions that BCG vaccination is particularly important for children in countries with high prevalence of tuberculosis, and if local supplies are diverted, these children will face an increase in disease and death from tuberculosis (8).

As more scientific research is being conducted, the preliminary findings may indicate BCG as a potential safeguard against COVID-19. This may be explained through the lower rates of infection in countries with widespread neonatal BCG vaccination policies. Furthermore, immigrants who come from BCG administering countries may also have this advantage against COVID-19. Currently, the US Government is working to release a racial/ethnic breakdown of COVID-19 cases. As more data is published on race and ethnicities, it will be useful to examine if fewer COVID-19 cases and deaths occur amongst immigrant populations from BCG-administering parent countries, after adjusting for confounders.

References

1. Zwerling A, Behr MA, Verma A, et al. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices. PLoS Med. 2011 Mar;8(3):e1001012. [CrossRef] [PubMed]
2. Fallah F, Nasiri MJ, Pormohammad A. Bacillus Calmette-Guerin (BCG) vaccine in Iran. J Clin Tuberc Other Mycobact Dis. 2018;11:22. [CrossRef] [PubMed]
3. Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 States, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69.458-64. [CrossRef] [PubMed]
4. NYC Health. Age-adjusted rates of lab confirmed COVID-19 non-hospitalized cases, estimated non-fatal hospitalized cases, and patients known to have died 100,000 by race/ethnicity group as of April 16, 2020. Available at https://www1.nyc.gov/assets/doh/downloads/pdf/imm/covid-19-deaths-race-ethnicity-04162020-1.pdf; Printed April 16, 2020. Accessed May 1, 2020.
5. Growing Data Underscore that Communities of Color are Being Harder Hit by COVID-19 | The Henry J. Kaiser Family Foundation. https://www.kff.org/coronavirus-policy-watch/growing-data-underscore-communities-color-harder-hit-covid-19/?utm_source=sfmc&utm_medium=email&utm_campaign=covidexternal&utm_content=newsletter. Accessed April 24, 2020.
6. Floc’h F, Werner GH. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guérin). Ann Immunol (Paris). 1976;127(2):173-86. [PubMed]
7. Gursel M, Gursel I. Is global BCG vaccination coverage relevant to the progression of SARS-CoV-2 Pandemic? Allergy. 2020 Apr 27. [CrossRef] [PubMed]
8. World Health Organization. Bacille Calmette-Guérin (BCG) vaccination and COVID-19. https://www.who.int/news-room/commentaries/detail/bacille-calmette-guérin-(bcg)-vaccination-and-covid-19. Accessed April 14, 2020.

Cite as: Rehman M, Sood A. Does the BCG vaccine offer any protection against coronavirus disease 2019? Southwest J Pulm Crit Care. 2020;20(5):170-2. doi: https://doi.org/10.13175/swjpcc035-20 PDF