Research question Whether SARS-CoV-2 infection has effects on ovarian reserve, sex hormone and menstruation of women of child-bearing age. Design This is a retrospective, cross-sectional study. Clinical and laboratory data from 237 women of child-bearing age diagnosed with COVID-19 were retrospectively reviewed. Menstrual data from 177 patients were analyzed. Blood samples from the early follicular phase were tested for sex hormones and Anti-mullerian hormone (AMH). Results Among 237 patients confirmed with COVID-19, severely ill patients had more comorbidities than mildly ill patients (34% vs 8%), especially for patients with diabetes, hepatic disease and malignant tumors. Among 177 patients with menstrual records, 45 (25%) patients presented with menstrual volume changes, and 50 (28%) patients had menstrual cycle changes, mainly a decreased volume (21%) and a prolonged cycle (19%). The average sex hormone and AMH levels of women of child-bearing age with COVID-19 were not different from those of age-matched controls. Conclusions Average sex hormone levels and ovarian reserve did not change significantly in COVID-19 women of child-bearing age. Nearly one-fifth of patients exhibited a menstrual volume decrease or cycle prolongation. The menstruation changes of these patients might be the consequence of transient sex hormone change cause by suppression of ovarian function that soon resumed after recovery.

ADAMTS13 limits platelet-rich thrombosis by cleaving von Willebrand factor at the Tyr1605 -Met 1606 bond. Previous studies showed that ADAMTS13 truncated after spacer domain remains proteolytically active or hyperactive. However, the relative contribution of each domain within the proximal carboxyl terminus of AD-AMTS13 in substrate recognition and specificity is not known. We showed that a metalloprotease domain alone was unable to cleave the Tyr-Met bond of glutathione S-transferase (GST)-VWF73-H substrate in 3 h, but it did cleave the substrate at a site other than the Tyr-Met bond after 16 -24 h of incubation. Remarkably, the addition of even one or several proximal carboxyl-terminal domains of ADAMTS13 restored substrate specificity. Full proteolytic activity, however, was not achieved until all of the proximal carboxyl-terminal domains were added. The addition of TSP1 2-8 repeats and two CUB domains did not further increase proteolytic activity. ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) (1-6) cleaves von Willebrand factor (VWF) 1 at the Tyr 1605 -Met 1606 bond of the central A2 subunit (7,8). Inability to cleave newly synthesized and released "unusually large" VWF multimers from endothelial cells or platelets due to deficiency of ADAMTS13 proteolytic activity may result in an accumulation of the unusually large VWF multimers (9), leading to formation of disseminated platelet-rich microthrombi in small arteries, a characteristic pathologic feature of thrombotic thrombocytopenic purpura. For purposes of discussion, ADAMTS13 may be divided arbitrarily into four functionally distinct regions: the metalloprotease, the proximal, the middle, and the distal carboxyl-terminal regions. The metalloprotease domain is the catalytic center, containing a characteristic HEXXHXXGXXHD sequence that coordinates Zn 2ϩ or Ca 2ϩ binding (1-6, 10). The proximal carboxyl-terminal region consists of a disintegrin domain, a first thrombospondin type 1 (TSP1) repeat, a Cys-rich domain, and a spacer domain. The middle and distal carboxyl-terminal regions of ADAMTS13 have seven additional TSP1 repeats and two CUB (C1r/C1s, urinary epidermal growth factor, bone morphogenetic protein) domains (3, 6, 10, 11).Studies have shown that ADAMTS13 truncated after the spacer domain remains proteolytically active toward plasma VWF in the presence of 1.5 M urea and low ionic strength (12, 13) and appears to be hyperactive toward unusually large VWF that are newly released from cultured endothelial cells under flow conditions (14). In addition, the autoantibodies identified in patients with idiopathic thrombotic thrombocytopenic purpura all react with the Cys-rich domain and spacer domain (15,16). These data suggest a critical role of the proximal C terminus of ADAMTS13 in substrate recognition in vivo. However, the relative contribution of each domain within the proximal carboxyl-terminal region of ADAMTS13 to substrate recognition and enzymatic activity remains unclear, as the assays using plasma VWF in the pr...

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