Thyroid Inconveniences With Vaccination Against SARS-CoV-2: The Size of the Matter. A Systematic Review.

After the beginning of COVID-19 vaccination campaigns, several reports of thyroid disease possibly related to the COVID-19 vaccination progressively appeared in the literature, raising the question of whether the thyroid disorder might be a SARS-CoV-2 vaccine complication. The aim of this study was to analyze the data about COVID-19 vaccination and thyroid disease, evaluate the size and quality of related literature, assess the type of these events, and investigate their timing of onset with respect the vaccination. Pubmed/MEDLINE and Cochrane were systematically reviewed until February 2022 to retrieve the largest number of original papers, case reports, and case series articles reporting thyroid disease after SARS-CoV-2 vaccination. Forty-six articles were included with a total of 99 patients aged from 26 to 73 years were described, of whom 74.75% female. Regarding the vaccination received, 49.49% of patients received Comirnaty (Pfizer/BioNTech), 14.14% CoronaVac (Sinovac), 12.12% Vaxzevria (Oxford/Astrazeneca), 11.11% Spikevax (Moderna), 3.03% Ad26.COV2.S (Janssen, Johnson & Johnson), one patient Covaxin (Bharat Biotech) and one patient Convidecia (Cansino). In 7 cases the thyroid disorder developed after the third dose with a combination of different vaccines. Regarding the type of thyroid disorder, 59 were subacute thyroiditis (SAT), 29 Graves' disease (GD), 2 co-occurrence of SAT and GD, 6 painless thyroiditis (PT), and single cases of thyroid eye disease and hypothyroidism associated with mixedema. The timeline between vaccination and thyroid disorder ranged between 0.5 to 60 days, with an average of 10.96 days. Considering the limited follow-up time, a complete remission was reported in most of SAT and PT cases while a persistence was observed in GD. In conclusion, both size and quality of published data about thyroid inconveniences after COVID-19 vaccination are limited; thyroid disorders may occur within 2 months after COVID-19 vaccination; among all thyroid diseases after COVID-19 vaccination, GD and SAT seem to be more frequent.

COVID-19-Associated Subacute Thyroiditis: Evidence-Based Data From a Systematic Review.

Subacute thyroiditis (SAT) is a thyroid disease of viral or post-viral origin. Whether SAT represents a complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still unclear. Our aim was to systematically review the literature to 1) explore the size of the literature about SAT in COVID-19 and 2) evaluate the clinical characteristics of SAT. PubMed/MEDLINE, Embase, and Scopus were searched until April 20, 2021. Original papers, case reports, and case series reporting SAT in COVID-19 patients were included. Authors and their country, journal, year of publication, COVID-19 and SAT clinical presentation, thyroid function, therapy, and follow-up data were extracted. Nineteen papers (17 case reports and 2 case series) were included, describing 27 patients, 74.1% females, aged 18 to 69 years. COVID-19 was diagnosed by nasopharyngeal swab in 66.7% cases and required hospitalization in 11.1%. In 83.3% cases, SAT occurred after COVID-19. Neck pain was present in 92.6% cases and fever in 74.1%. Median TSH, fT3, and fT4 were 0.01 mU/l, 10.79 pmol/l, and 27.2 pmol/l, respectively. C-reactive-protein and erythrocyte sedimentation rate were elevated in 96% of cases. Typical ultrasonographic characteristics of SAT were observed in 83.3% of cases. Steroids were the most frequent SAT therapy. Complete remission of SAT was recorded in most cases. In conclusion, the size and quality of published data of SAT in COVID-19 patients are poor, with only case reports and case series being available. SAT clinical presentation in COVID-19 patients seems to be similar to what is generally expected.

Thyroid sequelae of COVID-19: a systematic review of reviews.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to cause multi-organ effects including endocrine disorders. The impact of COVID-19 on the thyroid gland has been described but several aspects have to be clarified. The systematic review was conceived to achieve more solid information about: 1) which thyroid disease or dysfunction should be expected in COVID-19 patients; 2) whether thyroid patients have a higher risk of SARS-CoV-2 infection; 3) whether the management has to be adapted in thyroid patient when infected. The literature was searched by two authors independently. A 5-step search strategy was a priori adopted. Only reviews focused on the relationship between thyroid and COVID-19 were included. The last search was performed on February 21st 2021. Two-hundred-forty-seven records was initially found and nine reviews were finally included. The reviews identified several potential thyroid consequences in COVID-19 patients, such as thyrotoxicosis, low-T3 syndrome and subacute thyroiditis, while no relevant data were found regarding the potential impact of COVID-19 on the management of patients on thyroid treatment. The present systematic review of reviews found that: 1) patients diagnosed with COVID-19 can develop thyroid dysfunction, frequently non-thyroidal illness syndrome when hospitalized in intensive care unit, 2) having a thyroid disease does not increase the risk for SARS-CoV-2 infection, 3) thyroid patients do not need a COVID-19-adapted follow-up. Anyway, several factors, such as critical illness and medications, could affect thyroid laboratory tests.

Subacute Thyroiditis during the COVID-19 Pandemic: Searching for a Clinical Association with SARS-CoV-2.

PURPOSE: To search for a clinical potential link between subacute thyroiditis (SAT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a series of patients diagnosed with SAT during the COVID-19 pandemic, by retrospective evaluation of (1) clinical symptoms and (2) contact tracing. METHODS: SAT patients diagnosed from March to December 2020 were enrolled. The presence of typical clinical presentation of SARS-CoV-2, diagnostic tests for SARS-CoV-2, and contact with other individuals proven to be positive for SARS-CoV-2 were searched. RESULTS: Ten SAT cases were included. Fever was recorded in four patients. Cough, dyspnea, and headache were rarely reported. No patient had diagnosis of pneumonia. Two patients had moderate to severe fatigue after SAT. One patient experienced loss of smell and taste and had persistent fatigue over the following five months. No patient had positive SARS-CoV-2 diagnostic tests. At contact-tracing evaluation, only one patient had a contact with people who were diagnosed with SARS-CoV-2. CONCLUSIONS: Patients diagnosed with SAT during COVID-19 pandemic rarely experienced SARS-CoV-2-related symptomatology. The contact tracing did not show close contact with SARS-CoV-2 individuals in 9/10 cases.

Impact of COVID-19 on the thyroid gland: an update.

Coronavirus disease 2019 (COVID-19) is the pandemic of the new millennium. COVID-19 can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. Data on the relationship between COVID-19 and thyroid have been emerging, and rapidly increasing since March 2020. The thyroid gland and the virus infection with its associated inflammatory-immune responses are known to be engaged in complex interplay. SARS-CoV-2 uses ACE2 combined with the transmembrane protease serine 2 (TMPRSS2) as the key molecular complex to infect the host cells. Interestingly, ACE2 and TMPRSS2 expression levels are high in the thyroid gland and more than in the lungs. Our literature search provided greater evidence that the thyroid gland and the entire hypothalamic-pituitary-thyroid (HPT) axis could be relevant targets of damage by SARS-CoV-2. Specifically, COVID-19-related thyroid disorders include thyrotoxicosis, hypothyroidism, as well as nonthyroidal illness syndrome. Moreover, we noticed that treatment plans for thyroid cancer are considerably changing in the direction of more teleconsultations and less diagnostic and therapeutical procedures. The current review includes findings that could be changed soon by new results on the topic, considering the rapidity of worldwide research on COVID-19.

SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients.

BACKGROUND: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. METHODS: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms' onset and date of sampling. RESULTS: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13-12.64, p = 0.03). CONCLUSIONS: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients.

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5-28) days since symptoms' onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06-3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11-0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.