Treatment
with a JAK inhibitor has been indicated, but it has not yet been
possible to start it.
In April 2020, the child was once again admitted to hospital,
complaining of dyspnea and chest pain for three days. His mother and
sister had fever and anosmia for a week, with positive RT-PCR for
SARS-CoV-2. He had no fever, cough or other respiratory symptoms.
Laboratory results showed leukopenia (3.280/µL) and positive RT-PCR for
SARS-CoV-2.
He was treated with inhaled salbutamol 800mcg/day, oral prednisolone
1mg/Kg/day, oral azithromycin 250mg/day and oral levofloxacin 250mg/day.
Oxygen saturation was above 95% throughout the hospital stay, and
glycemic level was satisfactory with human insulin and strict monitoring
of a pediatric endocrinologist. Intraconazole prophylaxis was
maintained. After ten days of hospitalization, white blood cell count
went up to 9.710/uL. In addition, he presented D-dimer and interleukin 6
in the normal range (this last was 2.5, reference value less than 3.4
pg/mL). Chest CT did not show ground-glass opacities. Viral RNA load
determined by cell culture was present on the seventh day of symptoms.
At that same period, IgM against the novel virus was identified.
His nasopharyngeal swab for SARS-CoV-2
was still positive on the 13th day of symptoms and
became negative on the 16th day, when antibodies that potentially
neutralize SARS-CoV-2 were identified. During all this period, he
remained hospitalized, afebrile, with no complaints and without
supplemental oxygen.
SARS-CoV-2 is part of a large family of enveloped, single
positive-strand RNA viruses2. When it enters the cell,
its RNA is recognized by the Toll-like-receptors (TLRs): 7/8 and 9 TLR.
The result is the activation of different signaling pathways and
transcription factors, resulting in the expression of genes, which
products are essential for antiviral and inflammatory responses. The 7/8
and 9 TLRs engage the MyD88 adapter leading to activation of the
transcription factor NFkB, which induces inflammatory responses. They
also signal via the TRIF adapter (TIR domain-containing adapter inducing
IFN-β), that activates the interferon regulatory factor, which promotes
the production of type 1 interferons (IFN-α / β), important for innate
antiviral immune responses4.
Signal transducers and activators of transcription (STATs) are proteins
present in different cell types, involved in multiple functions of the
immune system 4,5. Mutations that lead to the gain of
function in STAT1 (STAT1-GOF) increase the uncontrolled phosphorylation
of this protein by impairing nuclear dephosphorylation. Thus, there is
greater production of STAT-dependent cytokines, such as type 1
interferon (IFN-α / β) and interferon γ (IFN-γ). As already mentioned,
the first one has the role in virus defense, and the second helps to
fight mycobacteria. In addition, there is greater inhibitory effect on
the IL17 pathway4.
Therefore, we have the hypothesis that despite the genetic
dysregulation, this patient may present some degree of protection
against a more severe form of COVID-19. Nonetheless, so far, there are
no reports of patients with STAT1-GOF infected with the novel
coronavirus in the world, which emphasizes the importance of continuing
research on this inflammatory syndrome, as well as on SARS-CoV-2
infection. The patient and his legal responsible consented to the case
report.
References
- Shaker M, Oppenheimer J, Grayson M et al. COVID-19: Pandemic
Contingency Planning for the Allergy and Immunology Clinic. The
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- Reference G. STAT1 gene. Genetics Home Reference.
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7, 2020.
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