Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial.

Background: To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. Methods: CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200 µg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models. Results: Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70-1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0-16.0) and 14.0 (12.0-16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively. Conclusion: In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test. Clinical Trial Registration: ClinicalTrials.gov, NCT04703205.

Management of regional bone bank during declaration of a state of emergency concerning the COVID-19 in Japan.

Bone banks are necessary for providing biological allografts for a series of orthopedic procedures. As nations cope with new realities driven by the 2019 coronavirus disease (COVID-19) pandemic, health-care providers, institutions, and patients share a particular concern about the effect of COVID-19 on organ donation and transplantation. Here, we describe the management of the Kitasato University Bone Bank during the state of emergency declared in response to COVID-19. Living donors received pre-operative screening by PCR, and allograft bone from COVID-19-negative donors was cryopreserved as transplantable tissues. The weekly rate of infection gradually increased from February 2-9 to April 5-11 in the dead donor-derived allograft bone-harvesting region covered by the Bank. It is becoming clear that the virus can be transmitted by asymptomatic patients, and that this route may have facilitated the spread of COVID-19. Therefore, the Bank stopped dead donor donation to consider the safety of medical staff. Three recipients received bone allografts following pre-operative COVID-19 screening by PCR. All patients were asymptomatic after bone allograft. Our experience may provide helpful information for the management of tissue banks.

Experience of an Orthopaedic Surgery Department Early During the COVID-19 Outbreak in Japan Including Real-Time Polymerase Chain Reaction Assay Results for SARS-CoV-2.

Introduction The coronavirus disease 2019 (COVID-19) epidemic beginning December 2019 in China has now become a worldwide pandemic. With the need to develop an approach to manage orthopaedic surgeries, we aimed to evaluate the most current data on all the surgical cases in our department including the results of the reverse-transcriptase polymerase chain reaction (RT-PCR) assay for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods The monthly number of surgical cases from 2016 were reviewed, and compared the numbers of surgical cases both in elective and emergency surgery during the pandemic with the pre-pandemic period. The results of RT-PCR for SARS-CoV-2 in 94 orthopaedic surgery cases from May 13 to June 30, 2020, and clinical signs/symptoms, and laboratory data of 48 consecutive cases within a month from May 13 were also evaluated. Results The mean monthly number of surgeries from January to May 2020 was significantly lower than the mean number in 2019 (73.8 vs 121.9, respectively, p=0.01). The proportion of emergency surgeries in all surgeries performed in May 2020 was 35.5%, which is significantly more than the mean rate of 20.4% in 2019 (p=0.04). Hip arthroplasties and spine surgeries showed the greatest reduction, at greater than 80% and 65%, respectively. Although none of the 94 patients were positive for SARS-CoV-2, 66.7% showed signs/symptoms typical of COVID-19. The most frequent signs/symptoms were production of nasal mucus (25.5%), followed by dry cough (19.1%); and fatigue, headache, and dizziness (17.0% each). The incidence of abnormal values, which are commonly noted in COVID-19 patients, were eosinopaenia 37.5%; lymphopaenia 18.8%; thrombocytopaenia 8.3%; and elevated prothrombin time 10.4%. Conclusions Our results show that our RT-PCR negative patients showed signs/symptoms and abnormal laboratory values typical of COVID-19, indicating surgeons should be aware of these abnormalities in patients and the need to rule out COVID-19 before proceeding with surgery.

Short-Term Impact of Staying Home on Bone Health in Patients With Osteoporosis During a State of Emergency Declaration Due to COVID-19 in Kanagawa, Japan.

Background On April 16, 2020, the Japanese government declared a state of emergency due to the spread of COVID-19 infection, leading prefectural governors to announce a stay-at-home order for 39 days until May 25, 2020. As physical inactivity is a risk factor for osteoporosis, we investigated the short-term impact of the stay-at-home order on bone health among patients with osteoporosis in our hospital in Kanagawa prefecture. Methods Thirty patients with osteoporosis with no delays in their regular medication who received care at our hospital's osteoporosis outpatient clinic within one month after the end of the state of emergency were included. Lumbar spine and femur proximal bone mineral density (BMD) were measured at the last follow-up date (May 25 to June 30, 2020; 0M) and six (6M) and 12 months (12M) before the last follow-up using dual-energy X-ray absorptiometry. Bone alkaline phosphatase (BAP), Tartrate-resistant Acid Phosphatase 5b (TRACP5b), calcium and phosphorus were assessed at the same time points. Results Serum BAP concentrations were significantly lower at 0M than 12M (p=0.040), but were comparable between 0M and 6M (p=0.527). Serum TRACP5b was significantly lower at 6M than 12M (p=0.009), but was similar between 0M and 6M (p=1.000). Serum calcium and phosphorus did not differ among the time points (p=0.516 and p=0.358, respectively). Similarly, lumbar spine and femoral neck BMD were comparable (p=0.679 and p=0.076, respectively). Conclusion Bone health in patients with osteoporosis was maintained during the short-term COVID-19 stay-at-home order among patients who experienced no delays in medication. However, larger and long-term studies are needed.

Loop-Mediated Isothermal Amplification Screening for COVID-19 in Asymptomatic Preoperative Orthopedic Patients in a General Hospital in Kanagawa, Japan.

The global coronavirus disease 2019 (COVID-19) pandemic has caused several million infections and hundreds of thousands of deaths. A large number of healthcare workers have died as a result of infection with this virus. Therefore, elective surgery was markedly reduced or stopped in our hospital's orthopedic department. The detection of asymptomatic COVID-19-positive patients became key to reducing the infection risk to physicians and staff to allow orthopedic surgery to be performed. A total of 21 patients were scheduled to undergo orthopedic surgery, including elective surgery, in Shonantobu General Hospital, Chigasaki City, Kanagawa, Japan. All 21 patients gave permission to undergo loop-mediated isothermal amplification (LAMP) screening the day before surgery. None of the 21 patients we tested was positive for COVID-19. All patients remained asymptomatic during the two to four weeks of postoperative follow-up. No physicians or medical staff developed COVID-19 symptoms. This was a very small study in a city with a relatively low incidence of COVID-19. We found that LAMP screening was accurate, in terms of its negative predictive value. Larger studies are needed.