Background: The rst case of a corona virus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a Naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19 positive patients. Methods/design: This is a placebo-controlled, randomized, clinical trial carried out in the Naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with con rmed COVID-19 infection but test negative for the virus on reverse, real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo, and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus for 14 days. Discussion: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a con ned area among otherwise healthy adults, at a relatively early stage of its spread.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by activation through removal of the propeptide domain from their latent zymogen form. MMPs are often secreted in an inactive proMMP form, which is cleaved to the active form by various proteinases including other MMPs. MMPs degrade various protein substrates in ECM including collagen and elastin. MMPs could also influence endothelial cell function as well as VSM cell migration, proliferation, Ca signaling, and contraction. MMPs play a role in vascular tissue remodeling during various biological processes such as angiogenesis, embryogenesis, morphogenesis, and wound repair. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension, preeclampsia, atherosclerosis, aneurysm formation, as well as excessive venous dilation and lower extremity venous disease. MMPs are often regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs may serve as biomarkers and potential therapeutic targets for certain vascular disorders.

Our results demonstrated a promising antitumour activity and a manageable safety profile of SHR-1210, displayed an explicit PK evidence of the feasibility of fixed dose, and established the foundation for further exploration.