What can autopsy say about COVID-19? A case series of 60 autopsies.

INTRODUCTION: Autopsies in SARS-CoV-2 infected cadavers are mainly performed to distinguish patients who died with SARS-CoV-2 infection from those who died of COVID-19. The aim of the current study is to assess the most frequent autopsy findings in patients who died of COVID-19 and to establish an association with clinical records. MATERIALS AND METHODS: 60 patients died between April 2020 and March 2021 after SARS-CoV-2 infection underwent a full autopsy performed at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome). Ante-mortem diagnosis of SARS-CoV-2 infection was microbiologically confirmed. RESULTS: 55 (92%) of cases had at least a comorbidity. At microscopic examination, 40 (67%) of the patients presented pulmonary intravascular coagulation with an inflammatory pattern. Pulmonary microangiopathy was a rare finding (n = 8; 13%). Myocardiosclerosis was the main heart finding (n = 44; 73%). Liver involvement with congestion and hypotrophy was found in 33 (55%) of cadavers. Renal tubular epithelial exfoliation (n = 12; 20%) and intravascular coagulation (n = 4; 7%) were frequent observations. During hospitalization 31% of patients (n = 19) developed acute kidney injury (AKI). CONCLUSIONS: Lungs and kidneys have been shown to play a pivotal role in COVID-19. The gradual worsening of renal function and AKI might be the result of the progressive collapse of cardiopulmonary system.

Effect of COVID-19 Vaccination on the In-Hospital Prognosis of Patients Admitted during Delta and Omicron Waves in Italy.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 ± 18 years [range 18-100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over ¾ with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2-3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3-2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Current Evidence on Vaccinations in Pediatric and Adult Patients with Systemic Autoinflammatory Diseases.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.

Sarilumab use in severe SARS-CoV-2 pneumonia.

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and prognosis of hypertensive patients hospitalised with COVID-19.

BACKGROUND: Among hypertensive patients, the association between treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) and the clinical severity of COVID-19, remains uncertain. AIMS: To determine whether hypertensive patients hospitalised with COVID-19 are at risk of worse outcomes if on treatment with ACEI or ARB compared to other anti-hypertensive medications. METHODS: This is a retrospective study conducted at a single academic medical centre (Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy) from 1 to 31 March 2020. We compared patients on treatment with an ACEI/ARB (ACEI/ARB group) to patients receiving other anti-hypertensive medications (No-ACEI/ARB group). The end-points of the study were the all-cause in-hospital death and the combination of in-hospital death or need for intensive care unit (ICU) admission. RESULTS: The sample included 166 COVID-19 patients; median age was 74 years and 109 (66%) were men. Overall, 111 (67%) patients were taking an ACEI or ARB. Twenty-nine (17%) patients died during the hospital stay, and 51 (31%) met the combined end-point. After adjustment for comorbidities, age and degree of severity at the presentation, ACEI or ARB treatment was an independent predictor neither of in-hospital death nor of the combination of in-hospital death/need for ICU. No differences were documented between treatment with ACEI compared to ARB. CONCLUSIONS: Among hypertensive patients hospitalised for COVID-19, treatment with ACEI or ARB is not associated with an increased risk of in-hospital death.