Causal relationships between COVID-19 and osteoporosis: a two-sample Mendelian randomization study in European population

Abstract

IntroductionThe causal relationship between Coronavirus disease 2019 (COVID-19) and osteoporosis (OP) remains uncertain. We aimed to assess the effect of COVID-19 severity (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and severe COVID-19) on OP by a two-sample Mendelian randomization (MR) study.MethodsWe conducted a two-sample MR analysis using publicly available genome-wide association study (GWAS) data. Inverse variance weighting (IVW) was used as the main analysis method. Four complementary methods were used for our MR analysis, which included the MR–Egger regression method, the weighted median method, the simple mode method, and the weighted mode method. We utilized the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test to identify the presence of horizontal pleiotropy. Cochran’s Q statistics were employed to assess the existence of instrument heterogeneity. We conducted a sensitivity analysis using the leave-one-out method.ResultsThe primary results of IVW showed that COVID-19 severity was not statistically related to OP (SARS-CoV-2 infection: OR (95% CI) = 0.998 (0.995 ~ 1.001), p = 0.201403; COVID-19 hospitalization: OR (95% CI) =1.001 (0.999 ~ 1.003), p = 0.504735; severe COVID-19: OR (95% CI) = 1.000 (0.998 ~ 1.001), p = 0.965383). In addition, the MR-Egger regression, weighted median, simple mode and weighted mode methods showed consistent results. The results were robust under all sensitivity analyses.ConclusionThe results of the MR analysis provide preliminary evidence that a genetic causal link between the severity of COVID-19 and OP may be absent.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…Another aspect of canonical inflammation in LC, which was not included in the aims and objectives of our study, is considering LC as a risk factor for the onset of various inflammatory diseases or the progression of existing inflammatory diseases [ 323 , 324 , 325 , 326 , 327 ]. This primarily concerns immune-dependent diseases, whose association has been established, namely various allergic, autoimmune, and infectious diseases, but also should be taken into account in other pathological conditions as well [ 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 ,…”

“…Moreover, the long-term use of glucocorticoids during acute COVID-19 and disturbances in the intestinal microbiome may exacerbate this pathological process [ 271 ]. To date, Mendelian randomization has not confirmed a direct link between osteoporosis and the severity of acute COVID-19 in European populations [ 273 ]; however, the risk of osteoporosis in LC might be significantly linked to even mild cases of COVID-19.…”

No Causal Association Between Cholelithiasis and COVID-19: A Bidirectional Mendelian Randomization Study

“…COVID-19 hospitalization was de ned as rst hospital admission between 7days before and 15days after the rst COVID-19 positive date. Severe COVID-19 was de ned as dyspnea, respiratory rate≤30/min, SpO2 ≤93%, PaO2/FiO2 <300mmHg, or more than 50% in ltration of the lung elds [17].…”

“…GWAS summary statistics of SARS-CoV-2 infection, COVID-19 hospitalization and severe COVID-19 were all extracted from the COVID-19 Host Genetic Initiative (HGI) (Round 5) [17] (Table 1). Cholecystectomy, cholecystitis and cholelithiasis were all obtained from FinnGen consortium (https://r9.…”