As we begin to move toward a new normal while still in the midst of an ongoing pandemic, we are faced with the question of how to protect ourselves from an initial infection, and a possible reinfection of the virus known as COVID-19. We know little about the novel coronavirus that has impacted the world, many questions remain on how long viral shedding lasts, when someone is most infectious, and if a person can recover completely and then become re-infected with the virus. Research is currently being done to determine if those who are found to be positive after an initial recovery are due to reinfection, or if reactivation of the virus is occurring.
There have been reports of patients testing positive a second or even third time after recovering from an initial COVID-19 infection. A recent retrospective study examined a case series in the U.S. consisting of 11 virologically confirmed patients, who were experiencing a second acute COVID-19 episode. Reinfection and reactivation were contemplated as the cause as individuals were closely examined for outcomes. In these cases, the second confirmed case occurred on average, >21 days from the first infection. The median duration of symptoms in the first episodes were 18 days, and 10 days for the second episode. Four health care workers in this group had mild cases and complete recovery, 3 were re-exposed at work and one at home. All had a clinical relapse after a median symptom-free interval of 9 days. Of the seven additional patients, two died from ARDS and one from heart failure. All patients had a second confirmed test from respiratory samples after a complete recovery period. During the second episode, four of the seven older adults had worsening CT scans. In this study, reinfection was suspected among the healthcare workers due to the exposure to COVID-19 in their workplace. Among the older patient population, viral reactivation is suspected due to the chronic comorbidities experienced by the group in addition to suboptimal treatment during the infection, allowing for viral replication.
A small study of 9 patient’s revealed greater clinical severity produced higher antibody titers in these individuals, however, this was not always correlated with clinical improvement. The viral burden peaked early on in the illness and then declined as the body responded to antibody production and the viral load decreased. This study proposed that detection of viral RNA weeks after recovery does not likely relate to a meaningful risk in the absence of symptoms. Most importantly, this study used other coronaviruses as a model for relevance and understanding. In the other coronaviruses, IgG remained high over 4-5 months while slowly declining over time (2-3 years), which concludes that detection of antibodies is not indicative of durable immunity. Although no evidence of post recovery transmission was discovered, it may not be ruled out.
One study out of China examined 37 patients in the Wanzhou district who had confirmed RT-PCR testing and no relevant symptoms in the 14 days prior to hospitalization. In this group, the median duration of viral shedding was 19 days. Surprisingly, the asymptomatic patients had a significantly longer duration of viral shedding when compared to the group who were symptomatic. Asymptomatic individuals had a reduced IgG and neutralizing antibody level when compared to symptomatic patients, and overall have a weaker immune response to the virus. This information is relevant to the topic as it lends information to how long viral shedding may take place during an initial infection. This study insinuates that a person may have viral shedding for longer than originally anticipated. Current recommendations suggest that a positive individual isolate/quarantine for 14 days under the time-based strategy. This study suggests that the viral shedding period lasts approximately 5 days longer than the current recommended quarantine period of 14 days. In addition, asymptomatic carriers are shedding longer than those who are symptomatic which indicates they may be exposing a much greater number of individuals prior to receiving a positive COVID-19 test. Of course, further research would be needed for this to be solidified by evidence. This could greatly influence an asymptomatic individual’s ability to re-infect and/or re-expose others.
Although the literature is lacking solid evidence that reinfection is possible, there are several mentions of the possibility among the current research:
In one report out of Guangong Province: 14% of discharged/recovered patients were tested positive. For example, one woman specifically discussed tested positive after a hospital discharge although she had two prior consecutive negative tests at day 26 and 28 (Kang, Wang, Tong, et al, 2020).
Another retrospective study evaluated one patient whom was hospitalized three times during 108 day timeframe. The viral shedding in this individual lasted 65 days. The time from symptom onset to disappearance was 95 days. Throughout the duration of this observation period, the patient had abnormal erythrocyte indicators, abnormal liver function and serum lipid metabolism. In this patient’s case, viral shedding lasts far longer than what is typically discussed in the current literature. If others have prolonged viral shedding, this may influence the results of a retest, may increase risks of exposure to another individual, and may increase the infection rates in an area.
The CDC states that many recovered individuals do not have detectable levels of SARS-CoV-2 RNA in their URT specimens, but after two negative tests, end up testing positive later. We know that viral RNA can be detected for weeks in some individuals, however, studies have not proven how long a person remains infectious to others. Typically, after the onset of illness, detectable viral burden declines over time. After a week or more, anti-SARS-CoV-2 immunoglobulin is detectable and antibody titers increase (CDC, 2020). Studies to isolate live virus from URT specimens have been unsuccessful when the infection is >10 days from onset. No solid evidence exists to prove that antibody titers are successful in protecting a patient from reinfection. If a patient tests positive for COVID-19 after an initial recovery, they should again be quarantined until further studies determine if a person with detectable antibodies are immune to reinfection. Once again, further investigation and robust studies are needed to support the likelihood of re-infection or viral reactivation after an initial COVID-19 recovery.
References
Batisse, D., Benech, N, Botelho-Nevers, E., et al. (2020). Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection, or inflammatory rebound? Journal of Infection (2020). Doi: https://doi.org/10.1016/j.jinf.2020.06.073
CDC. (2020). Clinical Questions about COVID-19: Questions and Answers. Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#:~:text=The%20immune%20response%2C%20including,is%20not%20yet%20understood.
CDC. (2020). Test for Past Infection. Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/testing/serology-overview.html
Kang, H., Wang, Y., Tong, Z., and Liu, X. (2020). Retest positive for SARS-Co-2 RNA of “recovered” patients with COVID-19: Persistence, sampling issues, or re-infection? DOI: 10.1002/jmv.26114
Kirkcaldy, R., King, B., & Brooks, J. (2020). COVID-19 and Postinfection Immunity: Limited evidence, many remaining questions. doi:10.1001/jama.2020.7869
Liu, F., Cai, Z., Huang, J., et al. (2020). Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: Dynamic results from 108 days of follow-up. Doi: 10.1093/femspd/ftaa031
Long, Q., Tang, X., Shi, Q., et al. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. https://doi.org/10.1038/s41591-020-0965-6
Okhuese, A., (2020). Estimation of the Probability of Reinfection with COVID-19 by the Susceptible-Exposed-Infectious-Removed-Undetectable-Susceptible Model. https://publichealth.jmir.org/2020/2/e19097/
