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\begin{document}

\title{Covid19 Reinfection in Two Children with Cancer}



\author[1]{Satya Yadav}%
\author[1]{Teena Wadhwa}%
\author[1]{Dhwanee Thakkar}%
\author[1]{Rohit Kapoor}%
\author[1]{Neha Rastogi}%
\author[1]{Smita Sarma}%
\affil[1]{Medanta The Medicity}%


\vspace{-1em}



  
  \date{May 08, 2024}


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\begin{abstract}
Reinfection after getting covid19 once was thought not to happen as
patient would have developed immunity against the virus. But recently a
case has been reported from Hongkong where the second episode of
asymptomatic infection occurred 142 days after the first symptomatic
episode in an apparently immunocompetent patient. Epidemiological,
clinical, serological and genomic analyses confirmed that the patient
had re-infection with another strain of SARSCOV2 virus instead of
persistent viral shedding from first infection. Here we report two
children who got re-infected with SARSCOV2 after recovering fully and
developing IgG antibodies it.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Covid19 pandemic has affected \textgreater{}25 million people globally.
It's very rare in children and mostly non-fatal. In children with blood
and cancer disorders so far published data suggests most children are
either asymptomatic or get mild disease (1,2). Reinfection after getting
covid19 once was thought not to happen as patient would have developed
immunity against the virus. But recently a case has been reported from
Hongkong where the second episode of asymptomatic infection occurred 142
days after the first symptomatic episode in an apparently
immunocompetent patient. Epidemiological, clinical, serological and
genomic analyses confirmed that the patient had re-infection with
another strain of SARSCOV2 virus instead of persistent viral shedding
from first infection (3). Here we report two children who got
re-infected with SARSCOV2 after recovering fully and developing IgG
antibodies it. Whole genome sequencing could not be performed for two
episodes. Laboratory results, including RT-PCR Ct values and serum
SARS-CoV-2 IgG, were analyzed.

\textbf{Case 1}

14-year-old boy with T-cell acute lymphoblastic leukemia was being
treated as per BFM95 protocol for standard risk disease. He was in
complete remission after end of induction. In the
3\textsuperscript{rd}week of consolidation phase, he was found to be
SARSCOV2 positive by PCR (run on Thermofisher TaqPath kit) performed on
nasopharyngeal \& throat swab (Ct values; N-32.52 ORF-32, S-34.66) on
screening test prior to giving chemotherapy. He was asymptomatic and his
total leukocyte count (TLC) was low 1580/mm\textsuperscript{3}, Absolute
neutrophil count (ANC) -140/mm\textsuperscript{3} and absolute
lymphocyte count (ALC) was- 990/mm\textsuperscript{3}. As he was
asymptomatic so no specific treatment was given and he was isolated at
home for next 2 weeks. After 2 weeks his SARSCOV2 PCR was negative. He
was restarted on chemotherapy as per protocol and finished
consolidation. Later he was given a course of high dose methotrexate (5
g/m2) and oral 6-mercaptopurine 25 mg/m2 daily for central nervous
system prophylaxis which he tolerated well. Two weeks later he was again
screened for SARSCOV2 prior to next chemotherapy and his PCR was
positive (Ct values; N-19.25, ORF-18.7, S-18.02). This was 71 days after
the first infection. This time his TLC was 7450/mm\textsuperscript{3}
and ANC was 3500/mm\textsuperscript{3}and ALC
2200/mm\textsuperscript{3}. He was asymptomatic so again he was isolated
at home for 2 weeks and chemotherapy was stopped. After 2 weeks we
rechecked his PCR and it was still positive (Ct values; N-31.25,
ORF-31.57, S-30.48) so we treated him with tablet hydroxychloroquine 200
mg orally twice daily for 5 days and retested PCR and it became
negative. His IgG antibody (qualitative test by Orthoclinical diagnostic
kit) against SARSCO2 was positive (1.75 cutoff value for positive
\textgreater{}1)). He was given further chemotherapy as per protocol.

\textbf{Case 2}

A 3-year-old child with stage 4 neuroblastoma was being treated as per
OPEC/OJEC protocol. After 4 cycles of chemotherapy he underwent surgical
resection of primary right suprarenal tumor. He achieved very good
partial remission. Two weeks after surgery on screening for SARSCOV2
prior to chemotherapy PCR test came positive (Ct values N-14.59
ORF-16.84 S-17.48). As he was asymptomatic so he was isolated at home
for 2 weeks and chemotherapy was postponed. His TLC was
9630/mm\textsuperscript{3} and ANC -7400/ mm\textsuperscript{3} and
ALC-970/ mm\textsuperscript{3}. Two weeks later repeat PCR test (using
Siemens FTD SARSCOV2 RTPCR kit) was still positive (Ct value-32.39). We
repeated test again after 1 week and it came negative. Child was given
next course of chemotherapy OJEC. Three weeks later prior to next
chemotherapy PCR (using Siemens Labgun exofast RTPCR kit) was again
positive (Ct values, N-22.37 RdRp-22.15) and IgG antibody (quantitative
assay by CLIA technology for quantitative determination of anti S1 and
anti S2 specific IgG against SARSCOV2) was positive 306 AU/ml. Gap
between first and second infection was 42 days. He was isolated at home
for another 2 weeks and after that repeat PCR was negative. Child was
restarted chemotherapy as per protocol.

\textbf{Discussion}

So, in these two patients as we did not perform sequencing of the virus
in each episode so we can't prove that it's a reinfection from another
strain of the virus. But both patients had IgG antibodies present when
they got second infection so ideally, they should not have got
reinfected. Immune suppression due to chemotherapy may have reactivated
the virus but there are no reports of the same in the literature. Same
infection may have persisted but we have no proof of that as in between
two episodes virus was negative by PCR. Ct values in first case at first
diagnosis were high \textgreater{}30 so was it a false positive? At the
time of second infection Ct values were low \textless{}20. But patient
had IgG antibodies against SARSCOV2 present when he had second infection
suggesting first infection was real infection. In second patient Ct
values are low in both infection episodes and also, he had IgG antibody
against SARSCOV2 at onset of second infection suggesting first infection
was real and second infection is also real and possibly because of
another strain. Most neutralizing antibodies target the spike protein
(4). Several mutations in the spike protein receptor binding domain and
N-terminal domain have been shown to confer reduced susceptibility to
neutralizing antibodies (5). Both our patients had IgG antibodies
against SARSCOV2 at the time of onset of second infection so only way
new infection could have happened is if they got infection from a new
strain of virus which could escape these antibodies.

Our two cases raise more questions then give answers. More data is
needed to confirm this phenomenon of reinfection in Covid19.

\textbf{Disclosure} -- All authors have nothing to declare. All authors
have contributed to the manuscript.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Yadav SP. COVID-19 in Children with Blood and Cancer Disorders: What
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\item
  Boulad F, Kamboj M, Bouvier N, Maureen A, Kung AL. COVID-19 in
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  doi:10.1001/jamaoncol.2020.2028.
\item
  To KK, Hung IF, Ip JD, Chu AW, Chan W, Tam AR et al. COVID-19
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  confirmed by whole genome sequencing.~\emph{Clinical Infectious
  Diseases} , ciaa1275,~https://doi.org/10.1093/cid/ciaa1275
\item
  Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, et al. Potent
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\item
  Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi JCC, et
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\end{enumerate}

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