Children’s Hospital Los Angeles Led Study Alarmingly Shows SARS-CoV-2 Causing Viral Persistence In Children And Young Adults With Cancer!
A new study led by researchers from the Children’s Hospital Los Angeles along with scientists from New York Medical College, University of Southern California, Stanford University School of Medicine and Johns Hopkins Bloomberg School of Public Health has found alarmingly found that the new SARS-CoV-2 variants are causing viral persistence
in pediatric patients especially those with immunocompromised medical conditions.
Already with the case of the B.1.1.7 variant that emerged most probably from a immunocompromised patient that exhibited viral persistence hence giving the virus an environment to mutate rapidly, there is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses.
The study team here details three clinical case reports
of patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape.
The study team
found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. The study findings reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape.
The study findings highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.02.27.21252099v1
Typically RT-PCR or real-time polymerase chain reaction tests are used to detect SARS-CoV-2 infections and researchers have found that commonly the viral load peaks with the onset of symptoms and gradually wanes off by the third week, after the development of antibodies.
The U.S. CDC (Centers for Disease Control and Prevention) advocates isolation for 14 days following exposure to COVID-19.
However, several studies have recently indicated that for some patients, the infectivity persists for several weeks. These studies have suggested that the infection timeline varies from person to person due to the difference in age, immunity, and disease severity.
Very often infectivity does not persist beyond 10 days of the onset of COVID-19 symptoms. This is confirmed by RT-PCR, where no trace of total RNA or subgenomic RNA are detected after the above-stated period.
In rare cases that involve immunocompromised adults, prolonged infectivity has been reported.
Further detailed research on how SARS-CoV-2 affects this vulnerable population is extremely vital. More specifically, the sequential dynamics of viral infectivity and the development of SARS-CoV-2 variants in immunocompromised patients, especially children, is an area that is under-researched.
This study reports the effect of prolonged SARS-CoV-2 infection in immunocompromised children and young adults.
For this study, multiple nasopharyngeal samples from three patients were obtained from the Children's Hospital Los Angeles (CHLA) between May 7 and November 21, 2020. All three patients, including two children and one young adult, were diagnosed with B-cell acute lymphoblastic leukemia (ALL). Their brief case histories are mentioned below:
-Patient 1=female under 5 years of age. She was diagnosed with B-cell ALL and was treated with chemotherapy. She consistently tested SARS-CoV-2 positive RT-PCR for an extended period.
-Patient 2=male between 20-25 years of age. He was diagnosed with B cell ALL six months before his first SARS-CoV-2 positive RT-PCR. He was hospitalized multiple times with extremely severe health conditions. For several weeks he showed positive SARS-CoV-2 RT-PCR with consistently high viral loads. He remained SARS-CoV-2 RT-PCR positive even at the time of the publication of the research.
-Patient 3=male under 5 years of age. He was diagnosed with high-risk B-cell ALL 7 months before SARS-CoV-2 infection. He underwent an array of treatments for both diseases over a long period of time. He tested RT-PCR negative on the 196th day.
The study team reported that among these patients, two showed significant intra-host SARS-CoV-2 mutational accumulation and host immune responses that may have contributed to the course of their disease. They also found virus replication in patient 2 (up to 144 days) and patient 3 (up to 162 days). The subgenomic RNA was also easily detected during the period of infection. Therefore, it is vital to regularly monitor immunocompromised patients who are SARS-CoV-2 positive for a more extended period. Such studies could help us predict the ability of the virus to replicate and develop new variants continuously.
Researchers are mainly intrigued by the SARS-CoV-2 B.1.1.7 variant owing to its high level of infectivity.
When compared to the reference SARS-CoV-2 sequence, B.1.1.7 has acquired 17 mutations, 8 of which are in the spike gene. Such reports raise concerns because long-term replication within an immunocompromised host could develop more infective variants.
The study team in this study found mutations in several regions within the spike gene. They observed a V70P mutation in patient 3 (day 162), which coincides with B.1.1.7 variant. Similar mutations in the spike gene (N440D, E484A, and E484K) were also reported in other persistently infected, immunocompromised patients.
The detailed analysis of the patients' antibody responses were conducted, where, patient 1 with limited active replication of the virus showed high levels of ACE2-RBD blocking antibodies. However, both patients 2 and 3 showed poor antibody responses associated with prolonged replication of SARS-CoV-2 in the host.
Interestingly, all three patients had higher levels of antibodies targeting RBD and subgenomic transcripts S1 were more than N.
The study team concluded that immunocompromised children and young adult patients are a highly vulnerable group. This group can develop many virulent variants owing to their prolonged period of infection. It is, therefore, essential to monitor such immunocompromised groups to prevent further development of infectious variants that could prolong the pandemic.
Further research is needed to understand the influence of the host in viral clearance and mutation and the study could be conducted using a larger group of infected individuals.
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