Impact of prior infection status on antibody response to the BNT162b2 mRNA COVID-19 vaccine in healthcare workers at a COVID-19 referral hospital in Milan, Italy.

In Italy, SARS-CoV-2 vaccination campaign prioritized healthcare workers (HCWs) to receive two doses of BNT162b2 vaccine, irrespective of a previous SARS-CoV-2 infection. In this real-life study, we compared the humoral response to BNT162b2 vaccine in HCWs with and without a previous SARS-CoV-2 infection. Of the 407 HCWs enrolled, 334 (82.1%) were SARS-CoV-2-naive and 73 (17.9%) SARS-CoV-2-experienced. Post-vaccine humoral response was detectable in more than 98% of HCWs. Overall, the median level of anti-S IgG in SARS-COV-2-experienced HCWs was twice as high as those of SARS-CoV-2-naive subjects (24641.0 AU/mL [IQR: 15273.0->40000.0] versus 13053.8 [IQR: 7303.3-20105.8]; p < .001), irrespective of the time elapsed from SARS-CoV-2 previous infection. In a subgroup of SARS-CoV-2-naive and -experienced subjects who received only one dose of the vaccine, the latter showed 32 times higher levels of anti-S IgG compared to the former. Although no serious adverse events have been reported, mild to moderate side effects occurred more frequently after the first dose in the SARS-CoV-2-experienced than in naive subjects (67% versus 42%, respectively; p < .001). Notably, post-vaccination anti-SARS-CoV-2 spike IgG levels ≥20,000 AU/mL were independently associated with the risk of fever ≥38°C (adjusted odds ratio [aOR] 5.122, 95% CI 2.368-11.080, p < .0001).Our study showed high responsiveness of BNT162b2 vaccine and a relationship between levels of antibody response and reactogenicity. It suggests that a single dose of mRNA vaccine might evoke effective protection in SARS-CoV-2-experienced subjects.

Invasive Fungal Infections Complicating COVID-19: A Narrative Review.

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium.

Preventing COVID-19 in assisted living facilities: An impossible task pending vaccination roll out.

Here, we aimed to describe the clinical outcomes of the residents of a long-term care facility during its closure to visitors and suppliers in response to the first COVID-19 pandemic from February 23 to June 22, 2020, and the results of the facility-wide SARS-CoV-2 testing of residents and staff in June 2020 before its partially reopening. Seventy-four residents and 53 members of staff were included in the present study. The staff underwent nasopharyngeal swab tests for SARS-CoV-2, and both the staff and residents underwent serological tests to detect IgG antibodies against SARS-CoV-2. The results of all of the tests were negative. Conversely, 94% of residents and 38% members of the staff were tested positive to the nasopharyngeal swab tests during the second COVID-19 pandemic wave (data collected from November 1 to November 30, 2020). Our experience suggests that, in the presence of a life-threatening pandemic such as SARS-CoV-2 infection, the prompt use of restrictive procedures can prevent the spread and progression of disease in assisted living facilities in the short term but may fail in the long term, especially when the prevalence of the COVID-19 greatly increased outside the facility enhancing the risk of import the disease from outside. SARS-CoV-2 vaccination of residents and staff members would contribute to control/limit the prevalence and the spread of the virus.

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

Drug-Drug Interactions and Prescription Appropriateness at Hospital Discharge: Experience with COVID-19 Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) are often elderly, with comorbidities, and receiving polypharmacy, all of which are known factors for potentially severe drug-drug interactions (DDIs) and the prescription of potentially inappropriate medications (PIMs). OBJECTIVE: The aim of this study was to assess the risk of DDIs and PIMs in COVID-19 patients at hospital discharge. METHOD: Patients with a proven diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were hospitalized between 21 February and 30 April 2020, treated with at least two drugs, and with available information regarding pharmacological treatments upon admission and at discharge were considered. The appropriateness of drug prescriptions was assessed using INTERcheck®. RESULTS: A significant increase in the prescription of proton pump inhibitors and heparins was found when comparing admission with hospital discharge (from 24 to 33% [p < 0.05] and from 1 to 17% [p < 0.01], respectively). The increased prescription of heparins at discharge resulted in a highly significant increase in the potentially severe DDIs mediated by this class of drugs. 51% of COVID-19 patients aged > 65 years had at least one PIM upon admission, with an insignificant increment at discharge (58%). CONCLUSION: An increased number of prescribed drugs was observed in COVID-19 patients discharged from our hospital. The addition of heparins is appropriate according to the current literature, while the use of proton pump inhibitors is more controversial. Particular attention should be paid to the risk of bleeding complications linked to heparin-based DDIs.

Immune deficiency is a risk factor for severe COVID-19 in people living with HIV.

OBJECTIVES: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce. METHODS: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe. RESULTS: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26-6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. CONCLUSIONS: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

Drug-Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy.

BACKGROUND: Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. OBJECTIVE: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. METHODS: We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15-99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. RESULTS: Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. CONCLUSIONS: Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.

COVID-19 trials in Italy: A call for simplicity, top standards and global pooling.

The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective treatments for rapid transfer to clinical practice. Unfortunately, just few studies have a sufficiently valid design to provide reliable information for clinical practice.