The emerging osteo-metabolic phenotype of COVID-19: clinical and pathophysiological aspects

Filippo, Luigi di; Frara, Stefano; Giustina, Andrea

doi:10.1038/s41574-021-00516-y

Cited by 34 publications

(27 citation statements)

References 10 publications

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“…Furthermore, linear regression analyses showed a positive correlation between VD and calcium levels. These findings suggest that hypocalcemia in COVID-19 patients may be an epiphenomenon of the widespread hypovitaminosis D which can in turn represent the link between hypocalcemia and negative outcomes in this clinical context [1,18,35].…”

Section: Discussionmentioning

confidence: 90%

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Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response

et al. 2021

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Background Hypocalcemia has been identified as a major distinctive feature of COVID-19, predicting poor clinical outcomes. Among the mechanisms underlying this biochemical finding, high prevalence of vitamin D (VD) deficiency in COVID-19 patients reported so far in several studies was advocated. However, robust data in favor of this hypothesis are still lacking. Therefore, aim of our study was to investigate the role of hypovitaminosis D and parathyroid hormone (PTH) levels in the development of hypocalcemia in COVID-19 patients. Methods Patients admitted to IRCCS Ospedale San Raffaele for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing calcium and VD metabolism. Serum levels of total calcium (tCa), ionized calcium (Ca 2+ ), 25-OH-VD, and PTH were evaluated at admission. We defined VD deficiency as VD below 20 ng/mL, hypocalcemia as tCa below 2.2 mmol/L or as Ca 2+ below 1.18 mmol/L, and hyperparathyroidism as PTH above 65 pg/mL. Results A total of 78 patients were included in the study. Median tCa and Ca 2+ levels were 2.15 and 1.15 mmol/L, respectively. Total and ionized hypocalcemia were observed in 53 (67.9%) and 55 (70.5%) patients, respectively. VD deficiency was found in 67.9% of patients, but secondary hyperparathyroidism was detected in 20.5% of them, only. tCa levels were significantly lower in patients with VD deficiency and regression analyses showed a positive correlation between VD and tCa. Conclusions In conclusion, we confirmed a high prevalence of hypocalcemia in COVID-19 patients and we showed for the first time that it occurred largely in the context of marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism.

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Section: Discussionmentioning

confidence: 90%

“…An emerging osteo-metabolic phenotype [35] characterized by low calcium and VD levels as well as by increased risk of vertebral fractures was recently reported among the most prominent endocrine and metabolic conditions in COVID-19 [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response

et al. 2021

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“…Lastly, while circulating calcium and the parathyroid hormone were not assessed in the present trial, it is important to mention their influence on COVID-19 severity. Calcium in particular plays important roles in virus entry and gene expression [48], with hypocalcemia being commonly observed as a common biochemical abnormality among patients with severe COVID-19 manifestations [49,50], which, in combination with vitamin D deficiency, contributes to a unique osteo-metabolic phenotype [51]. Therefore, vitamin D correction, which controls the entire body's calcium homeostasis, may further benefit COVID-19 patients with suboptimal 25(OH)D levels by maintaining calcium balance, consequently decreasing risk of COVID-19 severity.…”

Section: Discussionmentioning

confidence: 99%

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial

et al. 2021

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Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan–Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

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“…Today, an osteo-metabolic phenotype of COVID-19 has been characterized, including hypocalcemia, chronic hypovitaminosis D, and a high prevalence of bone fragility. This phenotype is associated with a more severe form of the disease and higher mortality [ 10 , 11 , 12 ]. It was originally categorized as an endocrine/metabolic phenotype, since a link between COVID-19 and endocrine organs and tissues was easily established after observing a higher mortality in patients suffering metabolic diseases, such as diabetes or obesity.…”

Section: Covid-19 and Musculoskeletal Dysfunctionmentioning

confidence: 99%

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

Lauwers

Yuan

et al. 2022

IJMS

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COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

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The emerging osteo-metabolic phenotype of COVID-19: clinical and pathophysiological aspects

Cited by 34 publications

References 10 publications

Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response

Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

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