See Related Article, page 412 The onslaught of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?associated disease that developed in 2019, COVID-19, has gripped the world in a pandemic and challenged the culture, economy, and healthcare infrastructure of its population. fatality rate of 2.3%, a small sub-group of 5% presented with respiratory failure, septic shock, and multiorgan dysfunction, resulting in fatality in 50% of such cases, a finding that suggests that it is within this group that the opportunity for life saving measures may be most pertinent.1 Once the disease is manifest, supportive measures are initiated with quarantines; however, a systematic disease modifying therapeutic approach remains empirical. Pharmacotherapy targeted against the virus holds the greatest promise when applied early in the course of the illness, but its usefulness in advanced stages may be doubtful.2 , 3 Similarly, usage of anti-inflammatory therapy applied prematurily . may possibly not be necessary and may actually provoke viral replication, such as for example in the entire case of corticosteroids.4 It appears that you can find 2 distinct but overlapping pathologic subsets; the first activated by the pathogen itself and the next by the sponsor response. Whether in indigenous state, immunoquiescent condition as with older people, or immunosuppressed condition as with heart transplantation, the condition will present and follow these 2 stages, albeit in various levels of intensity. The early reviews in center transplantation claim that sign expression through the phase of establishment of infection are PXD101 reversible enzyme inhibition similar to non-immunosuppressed individuals; however, in limited series, the second wave determined by the host inflammatory response seems to be milder, possibly owing to the concomitant use of immunomodulatory drugs.5 , 6 Similarly, an epidemiologic study from Wuhan, China, in a cohort of 87 patients suggests that precautionary measures of social distancing, sanitization, and general hygiene allow heart transplant recipients to experience a low rate of COVID-19 illness.7 Of course, we do not know whether they are asymptomatic carriers because in this survey-based study, universal testing during the early 3 months was not employed. One interesting fact in this study was that many heart transplant recipients have hematologic changes of lymphopenia because of the effects of immunosuppressive therapy, which may obfuscate the laboratory interpretation of infection in such patients, should they get infected. Much confusion abounds in the therapeutic tactics employed in COVID-19. It is imperative that a structured approach to clinical phenotyping be undertaken to distinguish the phase where the PXD101 reversible enzyme inhibition viral pathogenicity is dominant versus when the host inflammatory response overtakes the pathology. In this Rabbit Polyclonal to CAF1B editorial, we propose a clinical staging system to establish a standardized nomenclature for uniform evaluation and reporting of this disease to facilitate therapeutic application and evaluate response. We propose the use of a 3-stage classification system, recognizing that COVID-19 illness exhibits 3 grades of increasing severity, which correspond with distinct clinical findings, response to therapy, and clinical outcome (Figure 1 ). Open in a separate window Figure 1 Classification of COVID-19 disease states and potential therapeutic targets. The figure illustrates 3 escalating phases of COVID-19 disease progression, with associated signs, symptoms, and potential phase-specific therapies. ARDS, acute respiratory distress syndrome; CRP, C-reactive protein; JAK, janus kinase; LDH, lactate dehydrogenase; NT-proBNP, N-terminal pro B-type natriuretic peptide; SIRS, systemic inflammatory response syndrome; GM-CSF, Granulocyte Macrophage Colony Stimulating Factor. ? Stage I (mild)early infection The initial stage occurs at the time of inoculation and early establishment of disease. For most people, this involves an incubation period associated with mild and non-specific symptoms frequently, such as for example malaise, fever, and a dried out cough. During this time period, SARS-CoV-2 multiplies and establishes home in the web host, concentrating on the the respiratory system primarily. Just like its older comparative, SARS-CoV (in charge of the PXD101 reversible enzyme inhibition 2002C2003 SARS outbreak), SARS-CoV-2 binds to its focus on using the angiotensin-converting enzyme 2 receptor on individual cells.8 These receptors are PXD101 reversible enzyme inhibition abundantly present on individual lung and little intestine epithelium as well as the vascular endothelium. As a complete consequence of the airborne approach to transmitting and affinity for pulmonary angiotensin-converting enzyme 2 receptors, chlamydia presents with minor respiratory and systemic symptoms generally. Diagnosis at this time includes respiratory test polymerase chain response, serum tests for SARS-CoV-2.