In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

Background Organ transplant recipients (OTR) are less protected from vaccination than immunocompetent hosts. Additional vaccine doses have shown increased immunogenicity. Few studies assessed their clinical efficacy, particularly against Omicron variants, since most included patients from earlier phases of the pandemic, with higher base mortality rates. Methods We studied adult OTR who had COVID-19 between 12/15/21 and 5/25/22. We compared clinical outcomes between those who had received 2 or ≥3 doses of an mRNA vaccine and concurrent unvaccinated controls. Results Among 103 OTR, vaccination was associated with lower 90-day mortality (unvaccinated vs. 2 vs. ≥3 doses: 25% vs. 7% vs. 3%, P = 0.003), hospital (unvaccinated vs. 2 vs. ≥3 doses: 56% vs. 37% vs. 27%, P = 0.018) or ICU (unvaccinated vs. 2 vs. ≥3 doses: 25% vs. 15% vs. 3%, P = 0.001) admission rates, and peak O2 requirements (ordinal scale Kendall’s tau b=-0.309 [lower scores, i.e., O2 requirements with more vaccine doses], P = 0.003). Age (&gt;60 years adjusted hazard ratio [aHR] 7.73, P = 0.016), administration of anti-spike monoclonal antibody (aHR 0.17, P = 0.042) and vaccination, especially with ≥3 doses (aHR 0.105, P = 0.01), were independently associated with 90-day mortality. Black (P = 0.021) or Hispanic (P = 0.016) OTR were underrepresented among the vaccinated, especially in the ≥3 dose group. Conclusions Despite lower mRNA vaccine efficacy in OTR and against Omicron variants, vaccination protects this vulnerable patient population from severe COVID-19 and death. Ethnic and racial disparities in healthcare have been exacerbated by the COVID-19 pandemic and warrant better community outreach efforts.

Laboratory tests to assess cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI), such as the QuantiFERON ®-CMV assay

Patients with cancer have many comorbidities that increase their risk of death from Coronavirus disease 2019 (COVID-19). Anti-spike monoclonal antibodies (mAbs) reduce the risk of hospitalization or death from COVID-19 in the general population. To our knowledge, no studies have focused on the clinical efficacy of mAbs compared to no outpatient treatment exclusively among patients with solid tumors and hematologic malignancies, who are often excluded from clinical trials. We studied patients with cancer who had COVID-19 between 11.9.2020 and 7.21.2022 and received mAbs in an outpatient setting. We compared hospitalization and mortality rates to those of patients with cancer concurrently diagnosed with COVID-19, who were eligible for mAbs, but did not receive any outpatient treatment. 63 patients received mAbs and 89 no outpatient treatment. Administration of mAbs was associated with lower 90-day hospitalization (20.6% vs. 60.7%, p <0.001), all-cause (6.3% vs. 19.1%, p 0.025) and COVID-19-attributed (3.2% vs. 14.6%, p 0.019) mortality rates, and lower peak O 2 requirements (ordinal Odds Ratio [OR] = 0.33, 95% Confidence Intervals [CI] = 0.20–0.53). Administration of mAbs (aHR 0.21, p <0.001), age (≥ 60 years, adjusted Hazard Ratio [aHR] 1.86, p =0.033), and metastases (aHR 0.41, p 0.007) were independently associated with hospitalization. mAb treatment remained significantly associated with all-cause (aHR 0.27, p 0.019) and COVID-19-attributed (aHR 0.19, p 0.031) mortality, after adjustment for other factors. mAb administration was associated with improved clinical outcomes among vulnerable patients with cancer and COVID-19. With no mAbs approved currently for treatment against the prevalent circulating variants, the development of new mAbs should be a research priority.

Background The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. Methods MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. Discussion This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. Systematic review registration Open Science Framework (OSF) registration DOI: 10.17605/osf.io/4n9d7.

Introduction: Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia. Our institution adopted low-dose valganciclovir prophylaxis for intermediate-risk (seropositive) kidney transplant recipients in January 2018. Research Question: To analyze the efficacy (CMV DNAemia), safety (BK virus DNAemia, neutropenia, graft loss, and death), and cost savings associated with this change. Design: We retrospectively compared the above outcomes between CMV-seropositive kidney transplant recipients who received low-dose and standard-dose valganciclovir, transplanted within our institution, between 1/19/2014 and 7/15/2019, using propensity score-adjusted competing risk analyses. We also compared cost estimates between the two dosing regimens, for 3 months of prophylaxis, and for different percentage of patient-weeks with normal renal function, using the current average wholesale price of valganciclovir. Results: We studied 179 CMV-seropositive kidney transplant recipients, of whom 55 received low-dose and 124 standard-dose valganciclovir. The majority received nonlymphocyte depleting induction (basiliximab). Low-dose valganciclovir was at least as effective and safe as, and more cost-saving than standard-dose valganciclovir. Conclusion: This single-center study contributes to mounting evidence for future guidelines to be adjusted in favor of low-dose valganciclovir prophylaxis in CMV-seropositive kidney transplant recipients.

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