Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Detection of Platelet-Activating Antibodies Associated with Vaccine-Induced Thrombotic Thrombocytopenia by Flow Cytometry: An Italian Experience.

Rare cases of thrombocytopenia and thrombosis after anti-COVID-19 adenovirus-associated mRNA vaccines (VITT) due to platelet-activating anti-platelet-factor 4 (PF4)/polyanion antibodies have been reported. VITT laboratory diagnosis, similarly to heparin-induced thrombocytopenia (HIT) diagnosis, requires immunoassays for anti-PF4/polyanion antibodies identification, such as ELISA assays and platelet-activating functional tests, such as heparin-induced platelet activation test (HIPA), to confirm their pathogenicity. We compared the flow cytometry (FC) measurement of platelet p-selectin exposure to the gold standard functional test HIPA for diagnosis confirmation in 13 patients with a clinical VITT syndrome (6M/7F; median age 56 (33-78)) who resulted positive to anti-PF4/polyanion antibodies ELISA assays (12/13). FC and HIPA similarly identified three different patterns: (1) a typical non-heparin-dependent VITT pattern (seven and six patients by FC and HIPA, respectively); (2) low/no platelet activation in patients under IvIg therapy (five out of five and two out of four patients by FC and HIPA, respectively); (3) a HIT pattern. Antibodies investigated by FC became negative after 7, 17, and 24 days of therapy in three patients. FC measurement of P-selectin exposure was as sensitive as HIPA but simpler to detect anti-PF4/polyanion antibodies in VITT patients. FC could reliably discriminate VITT from HIT, thus helping for the choice of the anticoagulant.

Detection of Platelet-Activating Antibodies Associated with Vaccine-Induced Thrombotic Thrombocytopenia by Flow Cytometry: An Italian Experience

Rare cases of thrombocytopenia and thrombosis after anti-COVID-19 adenovirus-associated mRNA vaccines (VITT) due to platelet-activating anti-platelet-factor 4 (PF4)/polyanion antibodies have been reported. VITT laboratory diagnosis, similarly to heparin-induced thrombocytopenia (HIT) diagnosis, requires immunoassays for anti-PF4/polyanion antibodies identification, such as ELISA assays and platelet-activating functional tests, such as heparin-induced platelet activation test (HIPA), to confirm their pathogenicity. We compared the flow cytometry (FC) measurement of platelet p-selectin exposure to the gold standard functional test HIPA for diagnosis confirmation in 13 patients with a clinical VITT syndrome (6M/7F;median age 56 (33–78)) who resulted positive to anti-PF4/polyanion antibodies ELISA assays (12/13). FC and HIPA similarly identified three different patterns: (1) a typical non-heparin-dependent VITT pattern (seven and six patients by FC and HIPA, respectively);(2) low/no platelet activation in patients under IvIg therapy (five out of five and two out of four patients by FC and HIPA, respectively);(3) a HIT pattern. Antibodies investigated by FC became negative after 7, 17, and 24 days of therapy in three patients. FC measurement of P-selectin exposure was as sensitive as HIPA but simpler to detect anti-PF4/polyanion antibodies in VITT patients. FC could reliably discriminate VITT from HIT, thus helping for the choice of the anticoagulant.

Diffuse prothrombotic syndrome after ChAdOx1 nCoV-19 vaccine administration: a case report.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia is emerging as one of the most relevant side effects of adenoviral-based vaccines against coronavirus disease 2019. Given the novelty of this disease, the medical community is seeking new evidence and clinical experiences on the management of these patients. CASE PRESENTATION: In this article, we describe the case of a 73-year-old Caucasian woman who presented with diffuse prothrombotic syndrome, both in the arterial and venous districts, following the first dose administration of ChAdOx1 CoV-19 vaccine. The main thrombotic sites included the brain, with both a cortical ischemic lesion and thromboses of the left transverse and sigmoid sinuses and the lower limbs, with deep venous thrombosis accompanied by subsegmental pulmonary thromboembolism. The deep venous thrombosis progressively evolved into acute limb ischemia, requiring surgical intervention with thromboendoarterectomy. Anticoagulation was maintained throughout the whole hospitalization period and continued in the outpatient setting using vitamin K antagonists for a recommended period of 6 months. CONCLUSIONS: This case describes the management of vaccine-induced immune thrombotic thrombocytopenia in a complicated clinical scenario, including multisite arterial and venous thromboses. Given the complexity of the patient presentation, this case may implement the comprehension of the mechanisms and clinical features of this disease; it also provides a picture of the challenges related to the management, often requiring a multidisciplinary approach.