Coagulation Abnormalities in Patients with COVID-19

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction, and coagulation activation have been described as key features of severe COVID-19. Fibrinogen and D-dimer are typically increased. Moreover, the risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit, often despite prophylactic-dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased. Bleeding is less common than thrombosis but can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. All inpatients should receive thromboprophylaxis unless contraindicated. In hospitalized patients with COVID-19, prophylactic dosing rather than more intensive (intermediate or therapeutic) dosing are suggested. On the other hand, therapeutic dose of anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Desensitization protocol for anti-SARS- CoV- 2 vaccines in allergic patients: A case series

Background: Vaccination has proven to be the best viable tool for preventing the spread of SarsCov2 infection. The fear of adverse events represents one of the limits of this vaccination campaign. As Allergists, we had a fundamental role evaluating the allergological risks and performing specific tests. The only absolute contraindication to SARS-CoV- 2 vaccination is hypersensitivity to its components. When an individual is allergic to an indispensable medication, it is possible to resort to desensitization. Given the lack of a standardized scheme, the aim of our study is to propose a desensitization protocol for anti-SARS- CoV- 2 vaccines. Method(s): The desensitization protocol we developed consists in the fractioned administration of the entire vaccine dose into 5 separate injections of increasing quantity, through a 2-hour period. Premedication with antihistamines and chromones was administrated. Between January 2021 and January 2022, 23 patients referred to our Unit were deemed with a high risk of hypersensitivity reactions to the vaccines and underwent the desensitization protocol. We here describe 23 consecutive cases of patients who underwent desensitization to anti-SARS- CoV- 2 vaccine. Result(s): 4/23 had positive allergy skin test to Polysorbate and underwent desensitization for their entire vaccination cycle. 19/23 had a previous hypersensitivity reaction to an anti-SARS- CoV- 2 vaccine (18 after the first dose and 1 after the second one). Among 4 patients with sensitization to Polysorbate none developed hypersensitivity reactions after fractionated administration of BNT162b2 vaccine. Among 19 patients that underwent desensitization because of hypersensitivity reactions after I or II dose of vaccine, 15 experienced a reaction following vaccination with BNT162b2, 4 with mRNA-1273 and 4 with ChAdOx1-S recombinant. Furthermore, we categorized their reactions according to WAO score per systemic reactions: 15/19 (79%) grade1, 2/19 (10.5%) grade2, 2/19 (10.5%) grade3. No severe late hypersensitivity reactions were observed. All but one of this 19 patients had no hypersensitivity reactions after vaccination through the desensitization protocol. 1 patient experienced anaphylaxis during desensitization with BNT162b2 vaccine (WAO grade4). No late hypersensitivity reactions were observed. Overall, 22/23 (95.6%) patients that underwent anti-SARS- CoV- 2 vaccination through the desensitization protocol did not experience hypersensitivity reactions. Conclusion(s): Our results suggest that desensitization can be implemented to extend the vaccination to currently ineligible individuals. Larger studies are needed to prove the safety and efficacy of this approach.

Duration of noninvasive continuous positive airway pressure as a risk factor for mortality in patients with COVID-19 acute respiratory failure

Introduction: Recent experiences suggest that noninvasive continuous positive airway pressure (CPAP) ventilation may be an effective alternative to mechanical ventilation in COVID-19 respiratory failure. However, in patients who failed CPAP, delayed intubation may increase the risk of mortality. We made a comparison between the patients admitted during the first and the second wave of the pandemic who failed CPAP and required mechanical ventilation. Methods: We retrospectively included all consecutive patients admitted to one of the four participating hospitals from March 1st to April 15th, 2020, and from November 1st to December 15th, 2020, with the following inclusion criteria: (1) age ≥ 18 years, (2) diagnosis of moderate to severe COVID-19 pneumonia treated with CPAP outside ICU, (3) intubation after CPAP failure. Patients who received post-extubation CPAP were excluded. We collected data about CPAP duration prior intubation, hospital length of stay and in-hospital mortality. Results: A total of 193 COVID-19 patients received intubation after CPAP failure during the first (n = 127) and the second (n = 66) wave. During the second wave, CPAP treatment was longer (4 (2-8) vs. 3 (2-5) days;p < 0.05) as well as hospital length of stay (20 (15-29) vs. 12 (6-30) days;p < 0.05) with an increased in-hospital mortality (62% vs. 35%;p < 0.001). The univariable analysis showed that CPAP duration was a risk factor for mortality in patients failing CPAP during the second wave and in the overall population [HR 1.080 (95% C.I. 1.007- 1.159) and HR 1.071 (95% C.I. 1.032-1.112), respectively. The multivariable model adjusted for centre, wave, age, gender, comorbidity, white blood cell count, and creatinine confirmed this results HR 1.117 (95% C.I. 1.029-1.214) during the second wave, and HR 1.077 (95% C.I. 1.025-1.131) in the overall patients. Conclusions: Our results confirmed that in COVID-19 patients failing CPAP performed outside ICU the risk of death increased with the days spent on noninvasive ventilation.

Successful allergological risk-assessment protocol and SARS-CoV-2 vaccination: The experience of a large Italian University Hospital

Background: Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been recently approved, and public concern regarding the risk of anaphylactic reactions arised after few cases during the first days of mass-vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions. We describe the allergy work-up protocol implemented for the vaccination campaign in our Center, aiming to allow the greatest number of people to be vaccinated safely. Method: The protocol included the self-report of a history of suspected drug or vaccine allergies, and subsequent teleconsultation and allergometric tests for PEG and Polysorbate 80 (PS80). A desensitizing protocol of vaccine administration was applied to patients sensitized only to PS80, and to those with a suspect allergic reaction after the first vaccine dose. Results: 10.2% (414 out of 4042) of the entire vaccine population have been screened: only one patient resulted allergic to PEG and therefore excluded from the vaccination. Another patient was sensitized to PS80 only and safely vaccinated applying the desensitizing protocol. Seven subjects without a previous history of allergic disease experienced suspect hypersensitivity reactions to the first administered dose: one of them resulted allergic to PEG and was excluded from the second dose, while the others safely completed the vaccination with the desensitizing protocol. Conclusion: A careful allergological risk-assessment protocol significantly reduces the number of patients who would have avoided SARS-CoV-2 vaccination for their allergies and to effectively identify and manage those rare patients with sensitization to PEGs and/or PS80.

Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure.

BACKGROUND: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure. METHODS: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data. RESULTS: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2), PaO2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO2/FiO2 or PaO2 and FiO2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO2/FiO2 are predictors of intubation. CONCLUSIONS: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO2/FiO2 after starting CPAP are predictors of intubation.

Venous thromboembolism in critically ill patients affected by ARDS related to COVID-19 in Northern-West Italy.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. An association between increased venous thromboembolism in patients with pneumonia-related to COVID-19 has not yet been well described. PATIENTS AND METHODS: We aimed to illustrate cases of pulmonary thromboembolism in patients with acute respiratory distress syndrome related to COVID-19 treated in our intensive care unit. The medical records of patients affected by COVID-19 with acute respiratory distress syndrome in our institute from 1/3/2020 to 31/3/2020 were retrospectively reviewed. RESULTS: Our center registered a high prevalence of thromboembolic events among 62 patients affected by acute respiratory distress syndrome related to COVID-19 despite a regular antithrombotic prophylaxis. Out of these, 32 patients were transferred to other hospitals, and 30 were treated in our center. Venous thromboembolism was registered in 12 (19.3%) cases. In particular, 11 diagnoses of pulmonary embolism and 1 diagnosis of deep vein thrombosis were formulated. We described a case series of venous thromboembolism in nine patients treated in our Intensive Care Unit (ICU). Main pulmonary arteries were always involved in these patients. None of them died. CONCLUSIONS: In conclusion, critically ill patients with ARDS related to COVID-19 may have an increased risk of VTE that could be a leading cause of mortality. These patients require a high index of clinical suspicion and an accurate diagnostic approach, in order to immediately start an appropriate anticoagulant treatment.