Tags
COVID-19 asymptomatic is when an RT-PCR test detects SARS-CoV-2 virus somewhere in the body or in bodily secretions (typically nose or throat swab, saliva, sputum or more rarely stool) without clinical symptoms of an infection.
- Asymptomatic COVID-19 is a snapshot in that someone SARS-CoV-2 virus positive by RT-PCR without clinical symptoms in the here and now could develop clinical symptoms later.
- Clinical symptoms and not symptoms because the clinical judgment of a healthcare professional is critical for the accurate diagnosis of COVID-19 asymptomatics.
Lay persons would vary considerably in their ability to self-report symptoms.
- For one, symptoms such as a mild fever or sore throat might engage the full attention of one person while another person might disregard them.
- For another, COVID-19 is a new infection and some might have disregarded symptoms such as a dry cough that they wouldn’t normally associate with the common cold or the flu. Unfortunately these two infections have become the most common comparators to COVID-19 in the popular imagination even though mounting evidence suggests this infection is very different from them.
This is why clinical judgment that deems a person asymptomatic should be the gold standard whereas with self-reported COVID-19 asymptomatics, the question of failing to report mild or subclinical symptoms would remain open.
As things stand then, an unknown number of self-reported COVID-19 asymptomatics might more accurately be mildly symptomatic (paucisymptomatic) and someone COVID-19 asymptomatic now could actually be either a ‘true’ asymptomatic or a presymptomatic,
- A ‘true’ COVID-19 asymptomatic shouldn’t show clinical symptoms for the entire duration they were RT-PCR positive for SARS-CoV-2.
- A COVID-19 presymptomatic would display obvious clinical symptoms at some point after testing RT-PCR positive for SARS-CoV-2.
It follows from such considerations that ‘true’ COVID-19 asymptomatics would need to fulfill the following criteria,
- RT-PCR positive clinical symptom negative at initial presentation to a healthcare professional.
- RT-PCR positive clinical symptom negative for initial duration of observation by a healthcare professional.
- RT-PCR negative clinical symptom negative for subsequent duration of observation by a healthcare professional.
These criteria in turn require that a COVID-19 asymptomatic
- Be clinically monitored for some duration. This could be for several days or even weeks.
- Be repeatedly RT-PCR tested for SARS-CoV-2 over that duration.
- Continue to be monitored until they become repeat RT-PCR negative for SARS-CoV-2 for some length of time.
These requirements set a pretty high bar in terms of investment of resources, personnel and time and they mandate careful, methodical studies to fully flesh out the ‘true’ asymptomatic phenotype in COVID-19 in terms of numbers, duration and infectiousness.
Though thin on the ground, several studies published thus far on COVID-19 asymptomatics can be separated into at least 3 different piles,
- Observational studies that closely monitored and repeatedly tested patients for SARS-CoV-2 virus over several days. Rich clinical and epidemiological details in such studies give insights into the types of close contact necessary to catch and spread SARS-CoV-2. They also reveal the sheer range of clinical outcomes across close social circles.
- For example, in one case, a secondary contact of a COVID-19 asymptomatic became so ill, they were admitted to the ICU even as the index case themselves remained asymptomatic.
- In another, similarly aged spouses presumably caught the infection simultaneously, i.e., they likely got similar exposure dose, yet only one developed symptoms such as fever, headache and fatigue while the other remained asymptomatic.
- Similar observational studies except they also treated all the patients with anti-virals such as ritonavir/lopinavir. Since anti-viral treatment would interfere with the intrinsic ability of an asymptomatic to spread the virus and to clear it by themselves, this answer ignores such studies.
- More analytical studies that also monitored and tested patients for several days but that also compared and reported viral loads between symptomatic and asymptomatic COVID-19 cases.
Some of this evidence suggests that
- COVID-19 asymptomatics likely infected others including close contacts who subsequently became symptomatic even as they themselves remained asymptomatic.
- COVID-19 asymptomatics had similar viral loads by RT-PCR to symptomatics.
Here are some illustrative examples of such studies.
Studies Where Asymptomatics Remained COVID-19 Asymptomatic Even As Their Close Contacts Became Symptomatic
9 family members. Index cases were spouses who got infected with SARS-CoV-2. They apparently infected their daughter and her family who came to visit them. They in turn apparently infected the son-in-law’s parents when they went to visit them. Length of observation period not clear. One index case, the 60 year old husband, and a 13-month old granddaughter remained asymptomatic, the other 6 year old granddaughter even remained uninfected even as the son-in-law’s 57 year old father became sick enough to require admission to the ICU (below from 1).
An infected couple apparently passed on SARS-CoV-2 to their son, daughter in law and 2 grandchildren who lived with them. They in turn apparently passed the infection on to the daughter in law’s mother and brother while the son apparently also passed it on to one of his workers who apparently passed it on to his daughter. The daughter in law, her mother and the worker’s daughter remained asymptomatic even as the worker remained paucisymptomatic for at least 8 to 13 days and then they all became RT-PCR negative (below from 2).
29 year old index case presumably had dinner with a SARS-CoV-2 infected visitor from Wuhan. Subsequently his 28 year old wife and 21 year old sister who lived with them became RT-PCR positive. Index case’s 42 year old colleague and family (41 year old wife and 12 year old son) also became RT-PCR positive. The sister in the 1st household and wife and son in the 2nd household remained asymptomatic for at least 5 to 10 days while the son remained RT-PCR positive till the end of the observation period (below from 3).
20 year old index case presumably infected 5 of her relatives with SARS-CoV-2 even as she remained asymptomatic and RT-PCR-positive for at least 7 days and then tested negative twice in a row. In order to explain how her relatives developed symptoms and tested RT-PCR positive before she did, authors speculate that her initial RT-PCR test could have been false-positive (below from 4).
Studies That Found Similar Viral Loads By RT-PCR Between Symptomatics & ‘True’ Asymptomatics
Outbreaks in a long term skilled nursing and a care facility that each found 3 asymptomatics who remained asymptomatic for at least 7 days in one study and where the viral loads by RT-PCR of asymptomatics in both studies overlapped with those of symptomatics (below from 5, 6).
Lastly, the most extensive study of them all, it sampled practically everyone in the town of Vo’ in Italy, not once but twice, 14 days apart. Out of a total population of 3275, 2812 (85.9%) were sampled the 1st time, 2343 (75.9%) the 2nd time (below from 7).
- 73 RT-PCR positive the 1st time, 30 asymptomatic (41.1%).
- 29 RT-PCR positive the 2nd time, 13 asymptomatic (44.8%).
- ~68% of RT-PCR positives from the 1st survey, symptomatic and asymptomatic both, had cleared the infection by the 2nd survey.
- Viral loads were similar between symptomatics and asymptomatics.
The immunological conundrum of ‘true’ COVID-19 asymptomatics
‘True’ COVID-19 asymptomatics are an immunological conundrum. Here’s a virus that the human population hadn’t encountered until a few months back. Theoretically, no one should be immune to it. Has to replicate within asymptomatics to attain levels high enough to be detected by RT-PCR and presumably for them to be able to infect others. How then could they not display symptoms? A few possibilities come to mind.
- Low exposure dose. Only a few viruses lodged in their upper respiratory tract and replicated enough to get picked up by RT-PCR but they didn’t represent the quorum necessary to set up a productive infection.
- Colonization resistance. Their commensal microbiota may have left no unoccupied niche among those in the human body that SARS-CoV-2 prefers. This would create a hostile environment for it when it tries to lodge.
- Genetics polymorphism(s). They may harbor immune gene polymorphism(s) that impede fully productive SARS-CoV-2 infection.
- SARS-CoV-2 acts like a pathobiont rather than as a pathogen within the bodies of ‘true’ COVID-19 asymptomatics and maybe this allows its innocuous carriage. This could be a corollary of the genetic polymorphism idea except it would allow the host to carry the virus without producing pathology. Such hosts would be more accurately characterized as carriers, akin to Typhoid Mary.
- Have pre-existing cross-reactive immunity. They got exposed in the past to pathogens such as related coronaviruses and developed effective immunity. Overlapping (cross-reactive) antigens with SARS-CoV-2 would engage and trigger such cross-reactive memory cells to prevent productive infection even as it allowed for initial carriage and replication.
Some possibilities such as genetic polymorphism and carriage would apply to a handful and not all asymptomatics. These possibilities also aren’t equivalent when it comes to the all important issue of whether COVID-19 asymptomatics develop robust, effective, long-lasting immunological memory against SARS-CoV-2. Only the last option of pre-existing cross-reactive immunity allows for that possibility and hints are emerging within the published literature that it could be a real one.
Bibliography
1. Qian, G., et al. “A COVID-19 Transmission within a family cluster by presymptomatic infectors in China.” Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America (2020). COVID-19 Transmission Within a Family Cluster by Presymptomatic Carriers in China
3. Tong, Z. D., et al. “Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020.” Emerging infectious diseases 26.5 (2020). https://wwwnc.cdc.gov/eid/article/26/5/pdfs/20-0198.pdf
4. Bai, Yan, et al. “Presumed asymptomatic carrier transmission of COVID-19.” Jama (2020). Presumed Asymptomatic Carrier Transmission of COVID-19
5. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility | NEJM
6. COVID-19 in a Long-Term Care Facility — King County, Washington…
7. Lavezzo, Enrico, et al. “Suppression of COVID-19 outbreak in the municipality of Vo, Italy.” medRxiv (2020). Suppression of COVID-19 outbreak in the municipality of Vo, Italy