No abstract

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Introduction: Immunization of patients with chronic lymphocytic leukemia (CLL) with vaccines against several infectious diseases has proven insufficient. Data on seroconversion of patients with CLL after vaccination against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are still young, but accumulating evidence shows low seroconversion rates. Methods: We conducted a prospective, noninterventional study evaluating the safety and immunogenicity of two doses of the BNT162b2 mRNA Covid-19 vaccine, administered 21 days apart in consecutive adult patients with CLL. Patients vaccinated with other vaccines against SARS-CoV-2, with a history of confirmed Coronavirus Disease 19 (COVID-19), with known human immunodeficiency virus infection, or with an inability to provide written informed consent were excluded. Sera were tested before the first and after the second dose of the vaccine for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD), using the Abbott SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA), with a cutoff value for seroconversion at 50 AU/ml. Results: Sixty-one patients (28 males/33 females) with CLL, with a median age of 61 years, were included in the study. The majority of the patients (82.0%) were lower (0–2) stage per the RAI staging system. The seroconversion rate at 14 days after the second dose was 45% and was correlated with RAI stage (0–2 versus 3–4; 51.0% versus 18.3%, p = 0.047), the treatment status (treatment naïve, previously treated, or actively treated patients; 63.0% versus 40.0% versus 26.1%, respectively, p = 0.031), the number of previous treatment lines (0–2 versus >2; 55.3% versus 8.3%, p = 0.004), and the platelet count of the patients (over or under 100 × 109/L; 52.9% versus 10.0%, p = 0.015). Moreover, there was a positive linear relationship between the antibody titers and the gamma-globulin levels ( r = 0.182, p = 0.046) and platelet count ( r = 0.277, p = 0.002). Finally, patients actively treated with venetoclax had higher antibody titers than those treated with ibrutinib (15.8 AU/ml versus 0.0 AU/ml, p = 0.047). No safety issues were identified while the emergence of adverse events was not correlated with immunogenicity. Discussion: This study confirms results from previous studies on the low seroconversion rates in patients with CLL vaccinated with the BNT162b2 mRNA Covid-19 vaccine and on the detrimental effect of advanced disease and multiple treatment lines on seroconversion, while it is suggested that treatment with venetoclax may offer a chance for higher antibody titers, suggesting a treatment strategy change during the pandemic provided that this result is confirmed by larger studies specifically designed to address this issue.

Immune checkpoint inhibitors (ICI) have altered the prognosis of patients with melanoma over the past few years, with immune-related adverse effects (irAEs) being the only factor limiting their use. Neurologic and cardiac irAEs are rare, but usually severe. We reviewed the files of patients with melanoma treated with ICIs in one center to retrieve data from patients with neurologic irAEs. Patients with a combination of neurologic and cardiac manifestations were further analyzed. We also reviewed the literature for similar syndromes. Five out of 482 (1.01%) patients developed a neurologic syndrome and we present three patients with a constellation of neurologic and cardiac irAEs. A 66-year-old woman and a 68-year-old man presented with a constellation of findings after being treated with ipilimumab and nivolumab, respectively, for melanoma in the adjuvant setting and were eventually diagnosed with myasthenia gravis with cardiac involvement. An 80-year-old woman developed diffuse asymmetric muscle weakness, bilateral ptosis and asymptomatic high serum troponin levels after adjuvant treatment with nivolumab and ipilimumab for a stage IIIB melanoma. After excluding ischemic heart disease, she was diagnosed with axonal polyradiculoneuropathy and myocarditis. Neurologic or cardiac irAEs in patients treated with ICIs are uncommon (<1%), but usually severe, with high rates of morbidity and fatality. The co-development of neurologic and cardiac irAEs is even more rare and can arise soon after exposure to ICIs and escalate rapidly. Since more and more patients are now treated with ICIs in the adjuvant setting, prompt identification and management are essential to avoid serious complications or death.

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes.

No abstract

The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV stigma, are considered a vulnerable population at high risk. In this review, we report what is currently known in the available literature with regards to the clinical implications of the overlap of the two epidemics. PWH share the same risk factors for severe COVID-19 as the general population (age, comorbidities), but virological and immunological status also plays an important role. Clinical presentation does not differ significantly, but there are some opportunistic infections that can mimic or co-exist with COVID-19. PWH should be prime candidates for preventative COVID-19 treatments when they are available, but in the setting of resistant strains, this might be not easy. When considering small-molecule medications, physicians need to always remember to address potential interactions with ART, and when considering immunosuppressants, they need to be aware of potential risks for opportunistic infections. COVID-19 shares similarities with HIV in how the public perceives patients—with fear of the unknown and prejudice. There are opportunities for HIV treatment hidden in COVID-19 research with the leaps gained in both monoclonal antibody and vaccine development.

The mRNA vaccine BNT162b2 has proven highly effective and currently many millions are being vaccinated. There are limited and conflicting data from immunogenicity studies on the effects of age, gender, vaccination side effects (VSE), risk factors for severe COVID-19 (RFS-COV), obesity (BMI) and previous SARS-CoV-2 (Pr-CoV) Moreover, immunogenicity data from COVID-19 patients comparing various disease categories of natural infection i.e. asymptomatic vs mild vs moderate vs severe infection are sparse, and include limited number of individuals. This study included 871 vaccinated health care workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by a quantative assay measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD) and anti-SARS-CoV-2 against nucleocapsid protein (anti-N). Samples were collected 1-2 weeks after completion of the 2nd dose in the vaccinated HCWs and 15-59 days post symptoms onset in patients with natural infection. The concentration of anti-RBD in vaccinated individuals after multivariable analysis was significantly associated with age, gender, VSE and Pr-CoV. Specifically, anti-RBD median levels (95% CI) were lower by 2,466 (651-5,583), 6,228 (3,254-9,203) and 7,651 (4,479-10,823) AU/ml in 35-44, 45-54, 55-70 yrs respectively, compared with 18-34 yrs group. In females, median levels of anti-RBD were higher by 2,823 (859-4,787) compared with males, in individuals with VSE were higher by 5,024 (3,122-6,926) compared with no VSE, and in HCWs with Pr-CoV were higher by 9,971 (5,158-14,783) AU/ml compared with HCWs without Pr-CoV. Among individuals with natural infection, the median anti-RBD levels were 14.8 times higher in patients with critical COVID-19 infection compared with non-hospitalized individuals. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 up to 19.4 according to the clinical subgroup of natural infection. This study proves the high immunogenicity of BNT162b2 vaccine although its sustainability remains to be seen. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection may facilitate early decisions for vaccine evaluation in clinical trials.