key: cord-0968159-5rtvtcu2 authors: Griffin, Daniel O.; Jensen, Alexandra; Khan, Mushmoom; Chin, Jessica; Chin, Kelly; Saad, Jennifer; Parnell, Ryan; Awwad, Christopher; Patel, Darshan title: Cytokine storm of a different flavor: the different cytokine signature of SARS-CoV2 the cause of COVID-19 from the original SARS outbreak date: 2020-11-23 journal: J Glob Antimicrob Resist DOI: 10.1016/j.jgar.2020.11.005 sha: 4fb6dcc77119abe3dc65179ccfa595a693ff8f66 doc_id: 968159 cord_uid: 5rtvtcu2 We present a case series of three patients with COVID-19 who had a cytokine panel which revealed elevation of interleukin-6 (IL-6), but normal levels of interleukin-10 (IL-10), interferon-gamma (INF-γ) and interleukin-8 (IL-8) in contrast to the cytokine signature described in Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS). We also documented evidence of a compromised T-cell IFN-gamma response in two of these patients. We present a case series of three patients with COVID-19 who had a cytokine panel which revealed elevation of interleukin-6 (IL-6), but normal levels of interleukin-10 (IL-10), interferon-gamma (INF-and interleukin-8 in contrast to the cytokine signature described in Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS). We also documented evidence of a compromised T-cell IFN-gamma response in two of these patients. The clinical disease course of COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), can progress to involve significant complications that may be driven by a cytokine storm occurring during the second week of illness.(1, 2) Decompensation and increasing oxygen requirement during the second week is associated with elevated interleukin-6 (IL-6) levels. (3) This cytokine storm appears to be different than that described for Severe Acute Respiratory During what was assumed to be the cytokine storm phase, based on laboratory parameters and a rising oxygen requirement, the patients received intravenous steroids (methylprednisolone 1-2 mg/kg per day x 5-8 days) and the IL-6 receptor antagonist tocilizumab 400mg intravenously x1. All three patients had elevated levels of IL-6 but low levels of other cytokines including IFN- and IL-13 (table 1). Two of these patients also underwent testing with an interferon release assay to assess for latent tuberculosis and were observed to have a compromised T-cell IFN- response as assessed by mitogen challenge (table 1). Case 1: A 53-year-old male with no significant past medical history presented with 5 days of fever, malaise and difficulty breathing. On admission heart rate-96 beats per minute (bpm), respiratory rate-14 breaths per minute (BPM), temperature 39.3 0 C, blood pressure-122/51 mmHg and oxygen saturation on room air was 85%. He was admitted and treated with methylprednisolone 1mg/kg intravenously daily but with increasing oxygen requirements an IL-6 level was drawn and the patient was treated with tocilizumab 400mg intravenously x1. He improved and oxygen therapy was able to be de-escalated. Case 2: A 50-year-old male with past medical history of hypertension, gastroesophageal disease, and hyperlipidemia was admitted with fatigue and hypoxemia. On admission heart rate-114 bpm, respiratory rate-18 BPM, temperature-38 0 C, blood pressure--122/78 mmHg and oxygen saturation on room air was 86%. He was admitted and treated with methylprednisolone 1mg/kg intravenously daily but with increasing oxygen requirements an IL-6 level was drawn and the patient was treated with tocilizumab 400mg intravenously x1. He did not improve and was intubated and placed on mechanical ventilation. Case 3: A 45-year-old male with past medical history of asthma, gastroesophageal reflux, hyperlipidemia and lumbago was brought in by ambulance with cough, fever, difficulty breathing and hypoxemia. On admission heart rate-115 bpm, respiratory rate-22 BPM, temperature-38.8 0 C, blood pressure-124/86 mmHg and oxygen saturation on room air was 88%. He was admitted and treated with methylprednisolone 1mg/kg intravenously daily but with increasing oxygen requirements an IL-6 level was drawn and the patient was treated with tocilizumab 400mg intravenously x1. He improved and oxygen therapy was able to be de-escalated. Pt was ultimately discharged on supplemental oxygen and steroid taper. The cytokine storm associated with SARS-CoV2 appears to be distinct from that seen in the and if interventions to address the hyperinflammatory state such as steroids or IL-6 receptor inhibition could lead to persistent viral replication. (11) J o u r n a l P r e -p r o o f Clinical Characteristics of Coronavirus Disease 2019 in China COVID-19: consider cytokine storm syndromes and immunosuppression The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality An interferon-gamma-related cytokine storm in SARS patients Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome Interleukin-6: designing specific therapeutics for a complex cytokine Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms Virological assessment of hospitalized patients with COVID-2019 Virological assessment of SARS-CoV-2 Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia