Appendix 2 - Scientific Evidence for Asymptomatic Transmission

Articles Used By BYU report - Scientific Evidence Of Asymptomatic Covid-19 Transmission

Laura Sanger, Ph.D.

A selection bias seems to be evident in the studies chosen by the BYU researchers.  For example, there are a number of studies they selected that are problematic because the conclusions were drawn not from statistical significance, but rather from estimations and modeling (Studies #36-38).  I will simply include the title of these studies to demonstrate the problem with using them as scientific evidence of the asymptomatic transmission of COVID-19.

Study #37) Nishiura, H. et al. (2020). Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). medRxiv 2020.02.03.20020248.

Study #38) Bai, Y. et al. (2020) Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA (323), 1406–1407.

Study #39) Ganyani, T. et al. (March, 2020). Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data.  Euro Surveill, 25.

Study #29) Qian, G. et al (2020.)  COVID-19 Transmission Within a Family Cluster by Presymptomatic Carriers in China. Clinical Infectious Diseases. doi:10.1093/cid/ciaa316.

• N = 9.  All 9 were family members from three households.
• Methods - Index 1, a 58 y.o. woman developed fever, fatigue and headache on Jan 24 and was hospitalized on Jan 26.  She was diagnosed with COVID-19 on Jan 29.  Index 2, her 60 y.o. husband, was without symptoms and remained asymptomatic even after he tested positive.  Cases 1-4 were daughter, son-in-law and grandchildren of Index 1 & 2.  Cases 1-4 stayed in the home with Index 1 & 2 from Jan 20 – 23.  It’s important to note that during that time, Index 1 had not shown any symptoms yet.  On Jan 23, before Index 1 showed any symptoms, Cases 1-4 visited Case 2’s mother (Case 5), father (Case 6) and grandmother (Case 7).  After Index 1 tested positive, the other 8 family members were all hospitalized because they were under investigation.  It’s unclear when the testing occurred for each case, but it happened following their hospitalization.  For example, Index 2 was hospitalized on Jan 29 and tested positive 2 days later.  
• Results - The only family member that did not test positive was a 6 y.o. grandchild.  The other grandchild, 13-month-old, tested positive but remained asymptomatic. 
• Conclusions – “although the family members were from 3 households, they all were infected directly or indirectly from the same 2 index patients…this cluster demonstrated that COVID-19 is transmittable during the incubation period, as the daughter and her family caught the disease during the incubation period of index 1 and index 2…Given that Zou et al. found that the viral load of symptomatic and asymptomatic patients were similar, asymptomatic patients can still infect others.  These “silent patients” may remain undiagnosed and be able to spread the disease to large numbers of people.”
• Limitations – Unfortunately, the researchers did not make clear the hospital protocol for the family members that were admitted for observation prior to testing.  Were they placed on COVID-19 units and possibly exposed while in the hospital?  If hospital acquired pneumonia (HAP) occurs in up to 29% of patients admitted to the ICU, it’s reasonable to consider that cases 1-7 may have been infected with COVID-19 while in the hospital.  In light of the practices of Elmhurst Hospital in Queens, NY in which they placed non-COVID-19 patients on the same floor, and even in the same room with COVID-19 patients (documented by Erin Marie Olszewski, nurse working on COVID-19 unit for 1 month at Elmhurst Hospital), one has to consider that these practices could be happening elsewhere, especially in China.  Qian et al. rely too heavily upon the findings from Zou et al. that only tested 1 asymptomatic patient when they make the statement that “silent patients may remain undiagnosed and be able to spread the disease to large numbers of people.”
• BYU Report – 
  • “While much is still being learned about this disease, it appears that the main way the virus is spread is through small droplets of moisture that are produced when a person exhales, talks, coughs, or sneezes”.  The above study did not address the method of transmission, but simply documented that transmission had occurred. 
  • “Infected individuals are most contagious during the day before first symptoms and in the few days after onset, meaning that people who feel completely healthy can spread the virus to loved ones and strangers.”  It appears, from the findings, that Case 2 was the only family member that showed symptoms, other than Index 1, prior to being hospitalized.  The rest may have contracted COVID-19 as a result of being hospitalized, we have no way of knowing.

Study # 70) Lau, E. (2020, March 15). Temporal dynamics in viral shedding and transmissibility of COVID-19. 16.

• N = 94 lab confirmed COVID-19 patients, 0 asymptomatic or pre-symptomatic patients
• Methods - Throat swabs were collected from the day of illness onset up to 32 days after onset.  Researchers state “we did not have data on viral shedding before symptom onset for COVID-19”.  This means they had no data regarding the viral load of asymptomatic or pre-symptomatic people.  Researchers collected information of transmission pairs that were extracted from publicly available sources such as “government health agencies and media reports in mainland China and countries/regions outside of China.”  Given their sources of data collection for transmission pairs, the accuracy of the data is suspect.  The data includes “age, sex, location, date of symptom onset, type of relationship between the pair cases, and time of contact of the cases” of transmission pairs.
• Results - “We found that viral shedding of laboratory-confirmed COVID-19 patients peaked on or before symptom onset, and a substantial proportion of transmissions likely occurred before first symptoms in the index case.”  The researchers admit that they did not use the viral load data collected to influence their estimation of infectiousness.  The researchers state “we found substantial transmission potential for patients who have not yet shown symptoms, with 44% of transmission prior to symptom onset.”
• Conclusions - “Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.”
• Limitations –  It’s important to keep in mind that the inference (“the infectiousness profile was inferred from infector-infectee pairs”) the researchers make regarding the transmission of COVID-19 from asymptomatic or pre-symptomatic patients is based on data from transmission pairs with questionable accuracy.  They did not collect the data themselves and provided no assurances that they took measures to confirm the accuracy of the data.  The researchers draw conclusions that cannot be supported by statistically significant findings, largely because they didn’t provide any statistically significant findings.  Instead the researchers “infer”, “assume”, “estimate”, “presume”, “simulate”, and use “modeling analysis” to draw their conclusions. The researchers state “we found substantial transmission potential for patients who have not yet shown symptoms, with 44% of transmission prior to symptom onset.”  I would like to draw your attention to how the researchers arrived at 44% transmission rate prior to symptom onset, “assuming an incubation period…we inferred infectiousness started from 2.5 days before symptom onset” (emphasis mine).  The researchers have acted irresponsibly by stating a substantial proportion of the transmission (44%) is likely from pre-symptomatic or asymptomatic people given that their actual data cannot support this claim.  Instead they provide assumptions, estimations, modeling, inferences, and presumptions.  In other words, they are simply stating their opinion, but in a way that the general public and public officials could view as scientific proof.  I would argue that this is borderline unethical.
• BYU Report – 
  • “Research into COVID-19 has shown that asymptomatic carriers of the disease have a similar viral load (amount of virus in an organism) as those experiencing severe symptoms.”  This statement is cannot be supported by this study.  The researchers did not collect viral load data on asymptomatic carriers.

Study #71) Liu, Y. et al. Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases 20, 656–657 (2020).

• N = 76 confirmed COVID-19 patients; 46 mild cases, 30 severe cases.
• Methods – Nasal swabs were collected from both right and left nasal cavities.  Severe cases were classified as any of the following symptoms: “respiratory distress, oxygen saturation at rest ≤ 93%, ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤ 300 mm Hg, or severe disease complications (respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure).”
• Results - The mean viral load was approximately 60 times higher in severe cases than in mild cases suggesting that higher viral loads are associated with more severe outcomes.  Mild cases had early viral clearance with 90% of mild cases testing negative by 10 days after onset.  Whereas, all severe cases tested positive 10 days after onset.  
• Conclusions - Their findings suggested that severe COVID-19 patients “tend to have a high viral load and a long virus-shedding period”.
• BYU report 
  • “Research into COVID-19 has shown that asymptomatic carriers of the disease have a similar viral load (amount of virus in an organism) as those experiencing severe symptoms.This study cannot be used to support that statement for several reasons.  First, researchers did not distinguish the mild cases as being asymptomatic.  Second, the mild cases showed significantly less viral load as the severe cases, so this is in opposition to the statement the BYU report made.  This is further evidence that bias in support of mask efficacy may have been present among the team of BYU researchers.

Study #73) Zou, L. et al. (March 19, 2020). SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. New England Journal of Medicine 382, 1177–1179.

• N = 18; 9 female, 9 male.  Median age = 59.  17 patients were symptomatic, 1 patient asymptomatic (Pt. Z)
• Methods – Performed nasal and throat swabs of COVID-19 patients after symptom onset and one patient with no symptoms.
• Results - Higher viral loads were detected soon after symptom onset and similar viral loads were detected in the asymptomatic patient.
• Conclusions - “The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients.” 
• Limitations – they only had 1 asymptomatic patient so the findings are weakened by the small sample size.
• BYU report states – 
  • “This means that there is a high risk of transmission from asymptomatic carriers” and they reference this study as their only source of information for that statement.  There clearly is a discrepancy between “potential risk” and “high risk” which points to a bias in support of mask usage from the BYU researchers.
  • It seems that this study is referenced by numerous other articles used within the BYU report regarding the transmission of COVID-19 – Qian et al. (2020), Cheng et al. (2020), Howard et. al (2020).  Many have used the findings of this study to conclude that asymptomatic people can transmit the disease similar to that of a symptomatic person.  In fact, as of 9/3/20, this article has been cited by other scientific studies/articles 982 times.  Why hasn’t the study conducted by Gao et al (2020) been cited to this degree?  Gao et al. (2020) tested 455 contacts of one 22 yr old asymptomatic COVID-19 patient and they found that NONE of the 455 people that came in contact with this asymptomatic person tested positive for COVID-19. (Gao, M. (2020, May 13).  A Study of Infectivity of Asymptomatic SARS-CoV-2 Carriers.  Respiratory Medicine.  Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219423/)  Gao et al. (2020) state “Earlier research revealed that the viral load of respiratory tract samples in an asymptomatic patient was similar to that in the symptomatic patients [Zou et al. (2020)].  However, a single sample is difficult to be representative.  Moreover, although pathogenic nucleic acids can be detected in respiratory tract samples from asymptomatic carriers, the opportunity of transmission is less than that in symptomatic patient owing to the absence of the way expelling pathogen via cough and sneezing…This finding implicates that there is not needful to worry unduly for asymptomatic or mild patients during the ongoing COVID-19 pandemic.”  
  • The BYU group committed an egregious error and omission.  First, they embellished the findings of Zou et al. study by saying there is a “high risk” for transmission rather than “potential" risk.  Second, they omitted the Gao study that demonstrates that 455 contacts of an asymptomatic person all tested negative for COVID-19.  These two taken together demonstrate a clear and intentional bias among the BYU group.  Their behavior is irresponsible, especially considering the weight given to their report by policy makers to enforce the K-12 mask mandate for the entire state.