key: cord-0863756-gzao2fo6
authors: Yuan, Xiaolin; Yi, Wanrong; Liu, Baoyi; Tian, Simiao; Cao, Fang; Wang, Ruoyu; Qi, Baiwen; Lu, Faqiang; Fang, Meiyun; Pei, Fuyang; Chen, Ming; Zhang, Lichuan; Zhang, Yong; Zhang, Xiuzhi; Pan, Zhenyu; Zhao, Dewei; Yu, Aixi
title: Pulmonary radiological change of COVID-19 patients with 99mTc-MDP treatment
date: 2020-04-14
journal: nan
DOI: 10.1101/2020.04.07.20054767
sha: 825207cd9dc06484fd84231e0c45fa172b161e3e
doc_id: 863756
cord_uid: gzao2fo6

Background: As increasing cases of COVID-19 around world, urgent need for effective COVID-19-specific therapeutic drugs is necessary; therefore, we conducted a pilot randomized-controlled study to evaluate the efficacy of 99mTc-MDP for COVID-19 therapeutic treatment. Methods: A total of 21 mild patients with COVID-19 were enrolled in this pilot RCT from February 2020 through March 2020, and then were assigned, in a 1:1 ratio, into control (11 patients) and 99mTc-MDP group (10 patients). Patients in the control group received routine treatment and patients assigned to the 99mTc-MDP group received a combination of routine treatment and an administration of 99mTc-MDP injection of 5ml/day. Both of the patients in the control and 99mTc-MDP groups were treated for 7 days with the primary end point of CT-based radiological pulmonary changes during 7-day follow-up. Findings: From baseline to the day 7, 8 (80%) of 10 mild patients in the 99mTc-MDP group had a significant radiological improvement in lung and a decline in inflammatory infiltration, whereas only 1 (9.1%) of 11 patients in the control group had a radiological improvement in lung. None of the patients in the 99mTc-MDP group had disease progression from mild to severe, as well as an inflammatory cytokine storm, and 2 mild patients (18.2%) in the control group developed severe. During days 7 through 14, the number of patients with radiological improvement in the 99mTc-MDP group remained consistent, and only 1 additional case (22%) in the control group were reported. Conclusion: In this randomized pilot study, 99mTc-MDP had an effective inhibitory effect on the inflammatory disease progression for the therapy of COVID-19, and it can accelerate the absorption of pulmonary inflammation in a short period of time during the process of treatment.

Background: As increasing cases of COVID-19 around world, urgent need for effective COVID-19-specific therapeutic drugs is necessary; therefore, we conducted a pilot randomized-controlled study to evaluate the efficacy of 99m Tc-MDP for COVID-19 therapeutic treatment.

Methods: A total of 21 mild patients with COVID-19 were enrolled in this pilot RCT from February 2020 through March 2020, and then were assigned, in a 1:1 ratio, into control (11 patients) and 99m Tc-MDP group (10 patients). Patients in the control group received routine treatment and patients assigned to the 99m Tc-MDP group received a combination of routine treatment and an administration of 99m Tc-MDP injection of 5ml/day. Both of the patients in the control and 99m Tc-MDP groups were treated for 7 days with the primary end point of CT-based radiological pulmonary changes during 7-day follow-up.

Findings: From baseline to the day 7, 8 (80%) of 10 mild patients in the 99m Tc-MDP group had a significant radiological improvement in lung and a decline in inflammatory infiltration, whereas only 1 (9.1%) of 11 patients in the control group had a radiological improvement in lung. None of the patients in the 99m Tc-MDP group had disease progression from mild to severe, as well as an inflammatory cytokine storm, and 2 mild patients (18.2%) in the control group developed severe. During days 7 through 14, the number of patients with radiological improvement in the 99m Tc-MDP group remained consistent, and only 1 additional case (22%) in the control group were reported.

In this randomized pilot study, 99m Tc-MDP had an effective inhibitory effect on the inflammatory disease progression for the therapy of COVID-19, and it can accelerate the absorption of pulmonary inflammation in a short period of time during the process of treatment.

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint .

The recent outbreak of the novel coronavirus (2019-nCoV) is currently beginning spread to many countries around the world, and is becoming a pandemic according to World Health Organization (WHO). 1 The increasing cases and fatality highlight the urgent need for effective COVID-19-specific therapeutic drugs, which would prevent the progression of the disease, especially for decreasing the deterioration rate of respiratory and pulmonary infection. In the process of COVID-19, the cytokine storm is trigged by excessive inflammatory response and macrophage activation, which lead to multiple organ damages and even fatality; author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.04.07.20054767 doi: medRxiv preprint treated for 7 days. The primary end point was the CT-based radiological pulmonary changes from baseline to 7 days. The secondary end points were disease progression from mild to severe on the day 7, as well as radiological pulmonary changes during 7 days to 14 days after treatment.

Demographic characteristics were similar in the two groups except that patients in the control group were older than those in the 99m Tc-MDP group (median age, 62 years vs. 57 years), there were fewer women in the control group than in the 99m Tc-MDP group (55 % vs. 60%) ( Table 1) (Table 1 ).

In conclusion, in this randomized pilot study, the clinical drug, 99m Tc-MDP had an effective inhibitory effect on the inflammatory disease progression from mild to severe for the therapy of COVID-19, and it can accelerate the absorption of pulmonary inflammation in a short period of time during the process of treatment.

Besides, there were no serious adverse events including body immunity during the clinical use of 99m Tc-MDP. Additional potential advantage for application of 99m Tc-MDP is to avoid excessive use of glucocorticoids in the treatment of severe COVID-19 patients, in order to prevent further incidence of some glucocorticoids caused complications such as osteonecrosis of femoral head. 4 Limited by the small sample size, larger and longer trials are warranted to determine the efficacy of 99m Tc-MDP in the treatment of COVID-19.

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . Figure 1 : Computed Tomography (CT)-based radiographs of the patients' lung. On the top, shown are pulmonary radiographs for one patient in the 99m Tc-MDP group at admission (A), at day 7 (B) and at day 14 (C); on the bottom, shown are pulmonary radiographs for one patient in control group at admission (D), at day 7 (E) and at day 14 (F).

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.04.07.20054767 doi: medRxiv preprint

Technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro

Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance

Osteonecrosis of the femoral head in SARS patients: seven years later