Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 , with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.

Abstract Background Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. Objectives To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. Methods Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. Results We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. Conclusions We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.

Background The disease caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) was named Coronavirus Disease 19 (COVID-19) and classified as a global public health emergency. The evidence related to the impact of COVID-19 on pregnancy are limited to the second and the third trimester of pregnancy, while data on the first trimester are scant. Many viral infections can be harmful to the fetus during the first trimester of pregnancy, and whether SARS-CoV-2 is one of them is still unknown. Objective(s) With this study we evaluated SARS-CoV-2 infection as a risk factor for early pregnancy loss in first trimester of pregnancy. Furthermore, COVID-19 course in the first trimester was assessed. Study design Between February 22 and May 21, 2020, we conducted a case-control study at S. Anna Hospital, Turin, among first trimester pregnant women, paired for last menstruation. The cumulative incidence of COVID-19 was compared between women with spontaneous abortion (case group, n=100) and those with ongoing pregnancy (control group, n=125). Current or past infection was determined by detection of SARS-CoV-2 from nasopharingeal swab and SARS-CoV-2 IgG/IgM antibodies in blood sample. Patient demographics, COVID-19-related symptoms, and the main risk factors for abortion were collected. Results Twenty-three of the 225 women (23/225, 10.2%) tested positive for COVID-19 infection. There was no difference in the cumulative incidence of COVID-19 between the cases (11/100, 11%) and the controls (12/125, 9.6%) (p=0.73). Logistic regression analysis confirmed that COVID-19 was not an independent predictor of early pregnancy loss (Odd Ratio 1.28, confidence interval 0.53-3.08). COVID-19 related symptoms in the first trimester were fever, anosmia, ageusia, cough, arthralgia and diarrhea; no pneumonia or Hospital admission due to COVID-19-related symptoms were recorded. No difference in the incidence of symptoms was noted between the two groups. Conclusion(s) SARS-CoV-2 infection during the first trimester of pregnancy does not appear to predispose to early pregnancy loss; its cumulative incidence did not differ between women with spontaneous abortion and women with ongoing pregnancy. COVID-19 appears to have a favorable maternal course at the beginning of pregnancy, consistent with what has been observed during the second and the third trimester.