One In 10 People With COVID-19 Could Still Be Infectious Beyond 10 Days

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The U.S. CDC has recently changed its guidelines on isolation and quarantine periods especially with the emergence of the Omicron variant despite not having any real published medical data to substantiate its policies.
 
The U.S. CDC had announced that people with COVID will only need to isolate for five days.

UK adopted the same policy with the additional clause of needing two negative lateral flow tests by day six.

Meanwhile, a new study by UK researchers have shown that one in 10 people may have clinically relevant levels of potentially infectious SARS-CoV-2 past the older 10-day quarantine period and in some, the virus could be present in the infectious state for as long as two months!
 
The U.K. researchers utilized a new test that could detect whether the SARS-CoV-2 coronavirus was potentially still active. They used it to analyze samples from 176 people who had tested positive on standard PCR tests.
 
Shockingly after 10 days, 13% of the people still had levels of active virus, indicating they could potentially still be infectious. These levels continued in some for as long as two months (68 days)!
 
The study findings were published in the peer reviewed International Journal of Infectious Diseases. https://www.sciencedirect.com/science/article/pii/S1201971221012066

Ongoing transmission of SARS-CoV-2 remains a problem worldwide. Patchy vaccination coverage in multiple parts of the world, vaccine hesitancy in vulnerable groups, and differences in the efficiency of available vaccines mean that virus transmission remains a problem in community and clinical settings, and in long-term care of older people. While opportunities for unfettered transmission remain, selection pressures on the evolving virus raise the risk of producing variants that significantly increase transmissibility, morbidity, or mortality, or have the ability to evade the host immune response produced by previous infection or vaccination.

The impact of more transmissible variants of SARS-CoV-2 has been observed: the B.1.1.7 Kent variant, which has elevated infectivity (Leung et al., 2021), was implicated as a crucial factor in the second wave of infections in the UK (Volz et al., 2021), while variants carrying similar genetic changes were linked with the emergence of a third wave in Europe and South America (Claro et al., 2021).

Regions of Brazil retained very high rates of new infection, despite their existing population-wide seropositivity of over 76% (Sabino et al., 2021).

Similarly, India experienced a catastrophic second wave, despite an estimated 50% of citizens in the largest cities having had prior exposure (Mallapaty, 2021).

Reaching a ‘zero Covid’ situation globally in the near term seems unlikely, so there remains a need for strategies to contain transmission of SARS-CoV-2 for the foreseeable future.

A key component of the prevention of SARS-CoV-2 transmission is the identification and isolation of infected individuals. A better understanding of who is likely to present an extended infectious period, and for how long, would greatly inform strategies to more effectively limit transmission. Limited findings suggest that most COVID-19 transmission occurs in the early stages of the disease, or before the onset of symptoms (He et al., 2020; Lauer et al., 2020; Shrestha et al., 2020; Xu et al., 2020; Yang et al., 2020).

Most evidence suggests that replication-competent virus cannot usually be recovered from individuals with mild-to-moderate COVID-19 disease beyond 10 days of symptom onset (Arons et al., 2020; Bullard et al., 2020). Other studies have suggested that whilst the shedding of viral fragments may be prolonged, the duration of viable virus is relatively short-lived (Cevik et al., 2021) and prolonged transmission potential may only be evident in individuals with severe disease (van Kampen et al., 2021) or in severely immunocompromised patients (Aydillo et al., 2020; Avanzato et al., 2020; Choi et al., 2020).

However, assessments of longer-term shedding of infectious virus in otherwise clinically unremarkable people are lacking because the widely available tests assess only the presence of viral fragments, not replicating viral genomes. Individuals frequently test positive for viral fragments beyond 6 weeks of onset of symptoms, in a fluctuating positive/negative pattern (Jang et al., 2021).

Moreover, a positive result as detected by quantitative real-time PCR (RT-qPCR) for viral genomic sequences does not represent the presence of replication-competent virus, since viral fragments may remain after viral clearance (Arons et al., 2020; Bullard et al., 2020; Lu et al., 2020). The gold standard for determining infectious potential is viral culture.

However, this is not a process suitable for rapid upscaling and high throughput. Moreover, it carries an obvious infective risk to staff and few diagnostics laboratories have the facilities to undertake the necessary culture.

A better measure of infectious potential may be the assessment of subgenomic RNAs (Wolfel et al., 2020). Subgenomic RNAs are produced by the discontinuous transcription of virion structural genes during active replication, and result in the formation of rearranged template sequences that are not found in juxtaposition in the native RNA genome of the virus (Wu and White, 2007).

Although the correlation between infectivity and E-gene-derived sgRNA positivity is not always well conserved (van Kampen et al., 2021; Alexandersen et al., 2020), it may be a better proxy than E-gene viral load for replication, and better suited for assessment of archival clinical samples than other techniques, such as viral culture.

Our study aimed to evaluate the relationship between genomic SARS-CoV-2 E-gene sequences, E-gene-derived sgRNA SARS-CoV-2 viral sequences, disease severity, and duration of infectious period in a retrospective collection of swab RNA samples from 265 clinically confirmed COVID-19 cases from the South West of the UK during the first wave of infection, between March 17, 2020 and November 29, 2020.

Conclusion

Our results suggest that, in some individuals, E-sgRNAs — a proxy for active virus — can be detected for extended durations following infection, and that these individuals may be clinically unremarkable. Although this does not indicate absolutely the presence of active and replication-competent virus, it suggests that, in some cases, the infectious period may extend beyond the 10-day quarantine period currently imposed.

Given the obvious potential for onward transmission that these cases may possess, more targeted studies to detect and examine secondary cases with transmission beyond 10 days should now be undertaken in these populations. These results also suggest that, in situations such as hospital inpatient care or patients returning to long-term care facilities following hospital discharge, where onward transmission would be especially problematic, it may be prudent to obtain molecular evidence of remission to protect vulnerable populations.

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