ABSTRACT
Background/Objectives: We previously demonstrated that carrying a single pathogenic CFTR allele increases the risk for COVID-19 severity and mortality rate. We now aim to clarify the role of several uncharacterized rare alleles, including complex (cis) alleles, and in trans combinations. Method(s): LASSO logistic regression was used for the association of sets of variants, stratified by MAF, with severity. Immortalized cystic fibrosis bronchial epithelial cell lines and Fischer Rat Thyroid cells were transfected by plasmid carrying specific CFTR mutations. YFP-based assays were used to measure CFTR activity. Result(s): Here we functionally demonstrate that the rare (MAF=0.007) complex G576V/R668C allelemitigates the disease by a gain of function mechanism. Several novel CFTR ultra-rare (MAF <0.001) alleles were proved to have a reduced function;they are associated with disease severity either alone (single or complex alleles) or with another hypomorphic allele in the second chromosome, with a global reduction of CFTR activity between 40 to 72%. Conclusion(s): CFTR is a bidirectional modulator of COVID-19 outcome. At-risk subjects do not have open cystic fibrosis before viral infection and therefore are not easily recognisable in the general population unless a genetic analysis is performed. As the CFTR activity is partially retained, CFTR potentiator drugs could be an option as add-on therapy for at-risk patients.
ABSTRACT
Introduction: Subacute thyroiditis is a self-limiting post-viral inflammatory disorder occurring in 3 phases (hyper-, hypo-, and euthyroidism) Post-vaccine thyroiditis has also been reported, but is rare. Case Description: A 36-year-old Emirati female presented to our clinic with generalized fatigue, mild to moderate vague neck pain, intermittent palpitations, and loss of appetite 2 weeks after receiving her first dose of Pfizer-BioNTech mRNA vaccine against COVID-19. Clinical examination findings and laboratory test results were consistent with subacute thyroiditis. Patient is a mother of 5 healthy children, youngest is breast-fed infant (11 months old). There was no history suggestive of postpartum thyroiditis and no family history of thyroid dysfunction. Physical examination at initial visit showed mild tachycardia, and a normal blood pressure. She weighed 66 kg. Thyroid function tests revealed a suppressed TSH of 0.011 muIU/mL, high Free T4 of >100 pmol/l), and Free T3 FT3 of 29.6 pmol/L. Both TSH receptor antibodies, and Thyroid antibodies (TPO) were negative. Thyroid scintigraphy showed decreased uptake in both lobes. Thyroid ultrasound showed hypoechoic heterogeneous echotexture of the thyroid gland with vascular conglomerate and micro-calcification, along with normal sized reactive lymph nodes at sternal angle. Symptoms aggravated through the next week;patient dropped 3kg of her body weight and her palpitations increased, with a recorded resting heart rate between 120-130 beats/min. TSH decreased to 0.001muIU/mL while FT4 remained high, with an improvement to 90 pmol/L. Subsequently, the patient started to regain weight. Palpitations improved within a month. She developed a biochemically hypothyroid picture followed by clinical and biochemical euthyroidism after one more month. Second dose of the vaccine was uneventful. Last evaluation was 10 months later;TSH, FT3 and FT4 were all in normal range, acute-phase reactants were completely normal and in complete remission. Discussion(s): The exact mechanism for post-vaccination subacute thyroiditis remains unknown, vaccine adjuvants may induce diverse autoimmune and inflammatory reaction. Subacute thyroiditis has rarely been reported with other COVID-19 vaccines contains no Polyethylene glycol (PEG). A possible cross-reactivity between thyroid cell antigens and spike protein of the coronavirus produced by mRNA vaccines might be responsible. Further research is needed to investigate the incidence of subacute thyroiditis in COVID-19 pandemic days.Copyright © 2023
ABSTRACT
Background: Subacute thyroiditis is being frequently seen after Covid infection as the cases of many other viral infections. Patients classically complain of symptoms of thyrotoxicosis mainly palpitations and sweating but with associated tenderness in neck with or without fever. Subacute thyroiditis has seldom been seen after viral vaccinations. We present a case series of subacute thyroiditis which presented after administration of the COVID-19 vaccine. Material(s) and Method(s): Case 1: A 28-year-old female without previous medical problems, presented to the clinic for sore throat, palpitations and dizziness . No recent history of any upper respiratory tract infection or pregnancy. The patient received her second dose of Pfizer/BioNTech mRNA vaccine for COVID-19 2 weeks earlier. Thyroid function testing was done and revealed TSH 0.001, fT4 3.29, fT3 6.8. Her TPO antibody, thyroglobulin antibodies and Trab were negative. Technetium-99m pertechnetate scan revealed diffuse thyroiditis. The patient was prescribed prednisone 20 mg daily. She reports rapid improvement of her symptoms and prednisone treatment was given for 3 weeks then stopped. Repeated tests showed normal TSH 10 days after stopping steroids. Case 2: A 49-year-old female with the history of V Leiden mutation and repetitive abortions presented to the clinics on May 25, 2021 for the complaint of unintentional weight loss of 6 kg in 20 days and palpitations, preceded by fever and neck pain at the end of April. The patient noted that she was vaccinated with her second dose of Sinopharm vaccine on the 6th of April 2021. Thyroid function test revealed a thyrotoxic profile TSH 0.005, fT4: 42, fT3 9,02. With negative thyroglobulin antibody, TRAb. CRP 60 , . Thyroid Ultrasound showed a diffuse heterogenous echtexture of the thyroid. A fever work up was done to rule out other infectious causes including Salmonella and Brucella, all were negative. The patient was prescribed prednisone 40 mg daily and propranolol 10 three times daily, gradually tapered over one months. Her Symptoms resolved and her follow up tests showed normal tsh and CRP Result(s): Discussion: Subacute thyroiditis is usually associated with upper respiratory tract infections including Covid -19 infection. This can be explained by T cells cross reacting between the virus and the thyroid cells. Moreover, De Quervain thyroiditis following viral vaccines has been reported influenza vaccines. Thyroiditis has not been described until now as a frequent side effect of Covid vaccine. So we presented the cases of a 28 and 49- year-old females who has presented with cases of subacute thyroiditis after receiving respectively the Pfizer mRNA vaccine and Sinopharm vaccine for COVID-19. Conclusion(s): Conclusion: Subacute thyroiditis after Covid-19 vaccine is rare but may be underreported. Further investigations are required to evaluate predisposing factors to De Quervain thyroiditis following Covid-19 vaccine.