Oral anti-viral therapy for early COVID-19 infection in patients with haematological malignancies: A multicentre prospective cohort.

High rates of lung failure have been reported in haematological patients after SARS-CoV2 infection. An early administration of monoclonal antibodies or anti-virals may improve the prognosis. Oral anti-virals may have a wider use independently of the genetic variations of the virus. Prospective data on anti-virals in haematological malignancies (HMs) are still lacking. Outpatients diagnosed with HM and early COVID-19 infection were prospectively treated with the oral anti-virals nirmatrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse events was analysed. Long-term outcome at third month was evaluated. Eighty-two outpatients were evaluable for the study objectives. All patients had been treated for their HM within 12 months. COVID-19-related lung failure was 23.1%. Active HM (aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted independent predictors of severe infection. The vaccination with three to four doses (aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protective. COVID-19-related deaths at 28 days were 6.1%. All-cause mortality at 90-day follow-up was 13.4% (n. 11) and included opportunistic infections and cardiovascular events. In conclusion, this approach reduced the incidence of lung failure and specific mortality compared to previous cohorts, but patients remain at high risk of further complications.

Efficacy of Remdesivir and Neutralizing Monoclonal Antibodies in Monotherapy or Combination Therapy in Reducing the Risk of Disease Progression in Elderly or Immunocompromised Hosts Hospitalized for COVID-19: A Single Center Retrospective Study.

INTRODUCTION: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. METHODS: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate-multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. RESULTS: Overall, 331 subjects were included; their median (q1-q3) age was 71 (51-80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3-11%) and 14% (95%CI = 3-25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02-0.77) when compared with monotherapy. CONCLUSIONS: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.

Impact of a Pro-Active Infectious Disease Consultation on the Management of a Multidrug-Resistant Organisms Outbreak in a COVID-19 Hospital: A Three-Months Quasi-Experimental Study.

BACKGROUND: Antimicrobial and diagnostic stewardship (AS/DS) principles are crucial for the management of multidrug-resistant organisms (MDROs) infections. We evaluated the impact of a pro-active Infectious Disease (ID) consultation on the mortality risk of patients during an MDROs outbreak in a COVID-19 hospital. METHODS: A quasi-experimental study was performed in a dedicated COVID-19 hospital, including patients with suspected/confirmed infection and/or colonization by MDROs, which were managed as follows: (i) according to the standard of care during the pre-phase and (ii) in collaboration with a dedicated ID team performing a pro-active bedside evaluation every 48-72 h in the post-phase. RESULTS: Overall, 112 patients were included (pre-phase = 89 and post-phase = 45). The AS interventions included the following: therapy optimization (33%), de-escalation to narrow the spectrum (24%) or to lessen toxic drugs (20%), and discontinuation of antimicrobials (64%). DS included the request of additional microbiologic tests (82%) and instrumental exams (16%). With the Cox model, after adjusting for age, sex, COVID-19 severity, infection source, etiological agents, and post-phase attendance, only age predicted an increased risk of mortality, while attendance in the post-phase resulted in a decreased risk of mortality. CONCLUSIONS: Implementation of AS and DS intervention through a pro-active ID consultation may reduce the risk of 28-day mortality of COVID-19 patients with MDROs infections.

Lung Ultrasound Is Useful for Evaluating Lung Damage in COVID-19 Patients Treated with Bamlanivimab and Etesevimab: A Single-Center Pilot Study.

Background and Objectives: COVID-19 induces massive systemic inflammation. Researchers have spent much time and effort finding an excellent and rapid image tool to evaluate COVID-19 patients. Since the pandemic's beginning, lung ultrasound (LUS) has been identified for this purpose. Monoclonal antibodies (mAb) were used to treat mild patients and prevent respiratory disease worsening. Materials and Methods: We evaluated 15 Caucasian patients with mild COVID-19 who did not require home oxygen, treated with Bamlanivimab and Etesevimab (Group 1). A molecular nose-throat swab test confirmed the diagnosis. All were office patients, and nobody was affected by respiratory failure. They were admitted to receive the single-day infusion of mAb treatment in agreement with the Italian Drug Agency (AIFA) rules for approval. LUS was performed before the drug administration (T0) and after three months (T1). We compared LUS at T1 in other outpatients who came for follow-up and were overlapping at the time of diagnosis for admittance criteria to receive mAb (Group 2). Results: Our COVID-19 outpatients reported no hospitalization in a follow-up visit after recovery. All patients became SARS-CoV-2 negative within one month since T0. LUS score at T0 was 8.23 ± 6.46. At T1 we found a significant decrease in Group 1 LUS score (5.18 ± 4.74; p < 0.05). We also found a significant decrease in the LUS score of Group 1 T1 compared to Group2 T1 (5.18 ± 4.74 vs 7.82 ± 5.21; p < 0.05). Conclusion: Early treatment of the SARS-CoV-2 virus effectively achieves a better recovery from disease and reduces lung involvement after three months as evaluated with LUS. Despite extrapolation to the general population may be done with caution, based on our data this ultrasound method is also effective for evaluating and following lung involvement in COVID-19 patients.

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years;48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2–61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients.

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

Prompt and Appropriate Antimicrobial Therapy Improves Outcomes of NDM-Producing and KPC-Producing Klebsiella pneumoniae Bloodstream Infections in Patients Hospitalized for COVID-19: A Comparative Retrospective Case-Series.

Secondary bloodstream infections (BSIs) caused by KPC- and NDM-producing Klebsiella pneumoniae (K.p.) during the course of COVID-19 infections lead to significant mortality. Herein, a comparative retrospective case series of KPC- or NDM-K.p. BSIs occurring in COVID-19 subjects treated with Ceftazidime/Avibactam (CAZ/AVI) for KPC-K.p., or CAZ/AVI+ Aztreonam (ATM) for NDM-K.p is reported. All patients hospitalized for COVID-19 in two Italian hospitals with a BSI between March and September 2021 were included. The main outcome was 14-day mortality. Overall, 44 patients were included: 23 with KPC-K.p. and 21 with NDM-K.p. BSIs. The median (q1-q3) age was 67 (57-75) years, and 32 (72%) were males. The two groups were similar in terms of baseline comorbidity, or severity of COVID-19. Notably, 14-day mortality of KPC-K.p. BSIs and NDM-K.p. BSIs (26% vs. 38%, p = 0.521) and 28-day mortality (35% vs. 48%, p = 0.541) were similar. A Cox regression model of delayed initiation of an appropriate antibiotic therapy after the onset of symptoms independently predicted mortality: initiation between 24 and 72 h (aHR = 12.03; 95% CI = 1.10-130, p = 0.041); and initiation after 72h (aHR = 36.9, 95% CI = 3.22-424, p = 0.004). Moreover, a trend towards an increased risk of mortality was observed for polymicrobial infections (aHR = 3.73, 95% CI = 0.87-15.8, p = 0.074), while a protective effect was observed for a beta-lactam loading dose at the start of treatment (aHR = 0.16, 95% CI = 0.02-1.10, p = 0.064). The high mortality of KPC and NDM-K.p. BSIs in COVID-19 patients may be reduced by an early and appropriate antibiotic therapy. Further efforts should be made to develop antimicrobial stewardship and infection control programs in COVID-19 wards.

Cefiderocol-Based Combination Therapy for "Difficult-to-Treat" Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives.

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as "rescue" treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.