Phosphoinositide 3-kinase disease (PI3K) disease is a rare disorder that causes severe
impairment of the immune system, and its ability to fight both bacterial and viral
infections
1
. PI3K disease can be caused by a mutation in the PIK3R1 gene. PIK3R1 gene encodes
the regulatory subunit of phosphoinositide 3-kinase holoenzyme, activating the pathway
involved in modulation of cell proliferation and growth
2
. It is characterized by recurrent ear, nose, throat, and respiratory tract infections,
that can lead to progressive airway damage
1
. Patients have also been found to suffer with recurrent staphylococcus aureus, Epstein-Barr
virus (EBV), and cytomegalovirus (CMV) infections
1
. PIK3R1 mutations have been seen to lead to impaired and dysregulated immunity
2
. Clinical phenotypes can also include chronic lymphoproliferation, growth restriction,
mild neurodevelopmental delay, and malignant disease (mostly B-cell lymphomas)
2
. Patients at the time of diagnosis can present with decreased serum immunoglobulin
A (IgA) and immunoglobulin G (IgG) levels, and increased immunoglobulin M (IgM) levels
2
. Majority of these patients require treatment with immunoglobulin replacement. We
describe a case of a patient with heterozygous pathogenic variant of PIK3R1 splice
site mutation presenting with COVID-19 infection following vaccination with 2 doses
of BNT 162b2 mRNA COVID-19 vaccination (Pfizer BioNTech COVID-19 vaccine). Our case
demonstrates both the safety and efficacy of the BNT 162b2 mRNA COVID-19 vaccination,
along with the need for vaccination in this subset of the patient population.
A 30-year-old Caucasian female born at term without complications with genetic testing
remarkable for heterozygous pathogenic variant of PIK3R1, c.1425+IG>A splice donor,
and SHORT syndrome (Table 1
). Prior to her diagnosis she had presented with a history of recurrent ear, sinus,
throat, and bronchopulmonary infections. Infections resolved while being maintained
on intravenous immunoglobulin (IVIG) 900 mg/kg every 3 weeks. She received the initial
dose of the BNT 162b2 mRNA COVID-19 vaccine on March 8, 2021, and second dose subsequently
on March 28, 2021, at the age of 30 years-old. Following the initial dose of the vaccination,
the patient had one day of generalized headache and no significant symptoms with the
second dose of the vaccination. On September 11, 2021, the patient's mother, and close
contact, developed sinus pressure and fatigue. The following day the patient also
developed symptoms consisting of sinus pressure, runny nose, sneezing, subjective
fever, nausea, ageusia, anosmia, and dry cough. Symptoms persisted for 48 hours and
were associated with progressive fatigue. A rapid COVID-19 antigen test done on September
12, 2021, resulted as positive for both the patient and mother. COVID-19 polymerase
chain reaction (PCR) test 5 days later was also positive for both the mother and the
patient. Patient experienced resolution of all symptoms within 1.5 weeks, except for
her dry cough which lingered for over 3-weeks from initial infection. Following the
infection SARS-CoV-2 nucleocapsid antibody IgG was found to be positive, and SARS-CoV-2
spike total antibody was reactive 10-days after initial positive test. Ultimately,
our patient did not require hospitalization following acute infection with COVID-19
after receiving the BNT 162b2 mRNA COVID-19 vaccine.
Table 1
Shows physical characteristics supportive of PI3K disease diagnosis presented in this
case.
Table 1
Physical Examination Findings
Lymphadenopathy (LAD)
Cervical LAD bilaterally
SHORT Syndrome Features
Short stature, deep-set eyes, micrognathia, prominent forehead and ears, down-turned
corners of the mouth
Patients with inborn errors of immunity (IEI) represent a subset of the high-risk
population at risk for viral and bacterial illnesses
3
. Although PIK3RI mutation disease is rare, it is of importance to note the need to
vaccinate in this and other immunodeficient populations. Though COVID-19 vaccines
have shown efficacy in the general population, it is not well known how efficacious
these vaccines are in the immunocompromised patients
3
. While small scale studies have shown evidence of both cellular and humoral response
in cases of patients with IEI, this has not been demonstrated in patients with PIK3RI
mutation disease
4
. There are currently no other known cases/case reports of patients with PIK3R1 mutation
disease and efficacy of the COVID-19 vaccinations in patients with an acute COVID-19
infection. Our case demonstrates both the safety and efficacy of the BNT 162b2 mRNA
COVID-19 vaccination in PIK3RI mutation disease patients with acute COVID-19 infection,
and the ability to prevent severe disease or need for hospitalization.
Author Contribution
Sandeep Sarkaria. MD: Preparation and revision of case report.
Amanpreet Kalkat. MD: Preparation and revision of case report
Robert Hostoffer. DO: Conception of study, preparation, and revision of case report
Declaration of Competing Interest
None