High levels of mid-regional proadrenomedullin in ARDS COVID-19 patients: the experience of a single, Italian Center.

OBJECTIVE: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores. PATIENTS AND METHODS: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score). RESULTS: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%. CONCLUSIONS: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.

Case report of COVID-19 in an elderly patient: could SARS-CoV2 trigger myositis?

Though the exact etiology of autoimmune diseases still remains not completely known, there are various factors which are known to contribute to be trigger of autoimmune diseases. Viral infection is known to be among the other. It is known as the infection from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) can be an autoimmune trigger, so, we suppose that SARS-Coronavirus (SARS-CoV-2) could be as well. Several authors have highlighted the temporal consequence between SARS-CoV-2 and autoimmune diseases. In this case report we described a patient admitted for COVID-19 pneumonia with completely negative autoimmunity at admission who developed major pulmonary interstitial disease. During the hospitalization the weaning difficulties from oxygen led us to the repetition of autoimmunity pattern which became positive (both during hospitalization then after two months from dismission) with marked positivity for specific antibodies for myositis even after the patient's infectious healing. In the follow-up, the patient continued to have asthenia and muscle weakness despite steroid therapy. She is still in follow-up and will be further evaluated over time. Can we therefore think that in this case the development of autoimmunity can persist beyond the infectious phase and determine over time the development of a real autoimmune myositis?

Isolated immune thrombocytopenic purpura in a young adult Covid-19 patient.

OBJECTIVE: Patients with Covid-19 can have different symptoms, ranging from asymptomatic patients to various grades of respiratory failure, caused by typical interstitial pneumonia, cardiac involvement or neurological symptoms. PATIENTS AND METHODS: In April 2020, we focused our attention on a young woman with diffused purpura on her lower extremities, with no respiratory, cardiac or neurological symptoms. A complete blood analysis showed us a severe thrombocytopenia. We excluded other possible causes of thrombocytopenic purpura such as hematological (lymphocyte subsets), hepatological disease or splenomegaly. On autoimmune screening, we found Isolated immune thrombocytopenic purpura in a young adult Covid-19 patient positivity of anti-nuclear antibody (ANA) with a centrosome pattern and extractable nuclear antigens (ENA) and connective tissue disease screen resulted positive but none of the included specific antigens results positive, probably due to an aspecific antibody reaction. The wide variability of COVID disease presentation may be due to a personal different immune response to the virus. CONCLUSIONS: The immune response against the virus is crucial in the evolution and understanding of COVID-19 disease but it has still to be fully understood.

The first case of systemic lupus erythematosus (SLE) triggered by COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, SARS-CoV-2. The acute phase may be followed by a second phase actually not yet completely understood but probably associated to an autoimmune activation. At the moment is not possible to clearly define an association between immunological findings and pathological symptoms, however, this case report describes the case of a patient who following COVID-19 infection development autoimmune antibodies who persist in time longer than viral phase. Those antibodies can be responsible for the multi pathological clinical picture showed from our patient that, according to EULAR 2019 criteria, could be classified as systemic lupus erythematosus (SLE). SLE is probably one of the possible chronic rheumatologic diseases triggers by COVID-19 and this is the first case of SLE with vasculitis actually described in literature.

Severe acute dried gangrene in COVID-19 infection: a case report.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) related coagulopathy may be the first clinical manifestation even in non-vasculopathic patients and is often associated with worse clinical outcomes. CASE PRESENTATION: A 78 years old woman was admitted to the Emergency Unit with respiratory symptoms, confusion and cyanosis at the extremity, in particular at the nose area, hands and feet fingers. A nasal swab for COVID-19 was performed, which resulted positive, and so therapy with doxycycline, hydroxychloroquine and antiviral agents was started. At admission, the patient was hemodynamically unstable requiring circulatory support with liquids and norepinephrine; laboratory tests showed disseminated intravascular coagulation (DIC). During hospitalization, the clinical condition worsened and the cyanosis of the nose, fingers, and toes rapidly increased and became dried gangrene in three days. Subsequently, the neurological state deteriorated into a coma and the patient died. DISCUSSION: In severe cases, COVID-19 could be complicated by acute respiratory disease syndrome, septic shock, and multi-organ failure. This case report shows the quick development of dried gangrene in a non-vasculopathic patient, as a consequence of COVID-19's coagulopathy and DIC. CONCLUSIONS: In our patient, COVID-19 related coagulopathy was associated with poor prognosis.

Association between red cell distribution width and response to methotrexate in rheumatoid arthritis.

Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p<0.0001). The increase of RDW was greater among patients with good EULAR response, becoming progressively smaller in cases with moderate and poor response (1.0% [0.4-1.4] vs. 0.7 [0.1-2.0] vs. 0.3 [-0.1-0.8]; p=0.03). RDW is a strong predictor of early response to MTX in RA. RDW significantly increases after MTX initiation in parallel to treatment response, suggesting a role as a marker of MTX effectiveness.

Inflammatory markers predict insulin sensitivity in active rheumatoid arthritis but not in psoriatic arthritis.

Whether the insulin resistance commonly observed in patients with inflammatory arthritis is a disease-specific feature and/or is limited to a disease phase (i.e., it occurs only during phases of high disease activity) is unknown. Fifty-three rheumatoid arthritis (RA) and 44 psoriatic arthritis (PsA) patients were recruited consecutively along with 194 controls matched for age, sex and body mass index for a case-control study. All underwent an oral glucose tolerance test, the results of which were analysed to derive the following indexes: homeostatic model of insulin resistance (HOMA-IR), insulin sensitivity index (ISI) and early insulin sensitivity index (EISI). These data were related to anthropometric, clinical and laboratory findings. Metabolic parameters of patients and controls were similar. Neither inflammatory markers nor disease activity scores were related to glucose metabolism for the generality of RA and PsA patients; however, by restricting the analysis to the subset of RA patients with residual disease activity, an association emerged between erythrocyte sedimentation rate, on the one hand, and fasting insulin (ß=0.46, p=0.047) and HOMA-IR (ß=0.44, p=0.02), on the other. Moreover, C-reactive protein (CRP) levels were associated with plasma glucose and insulin levels measured 120 min after the glucose load (ß=0.91, p=0.0003 and ß=0.77, p=0.0006, respectively); ISI and EISI were predicted by CRP (ß=-0.79, p=0.0006; ß=-0.80, p=0.0001, respectively). The same did not hold true for PsA patients. The association between systemic inflammation and insulin resistance indexes is a feature of RA with residual disease activity, not a universal feature of inflammatory arthritides.