Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year.

BACKGROUND: Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated. METHODS: We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression. RESULTS: A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64). CONCLUSIONS: This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.

Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis.

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review and 5 were included in the meta-analysis. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2%-48.5%) after 2 doses of messenger RNA (mRNA) COVID-19 vaccines. The average antispike antibody response rates (range) were 42.7% (20.8%-88.5%) and 78.2% (55.8%-94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3%-68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pooled odds ratios of 0.36 (95% confidence interval [95% CI], 0.18, 0.69), I2 = 0% and 0.42 (95% CI, 0.22, 0.79), I2 = 14%, respectively. Patients who were not on active MM treatment were more likely to respond with pooled odds ratio of 2.42 (95% CI, 1.10, 5.33), I2 = 7%. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population.

Characteristics of COVID-19 Breakthrough Infections among Vaccinated Individuals and Associated Risk Factors: A Systematic Review.

We sought to assess breakthrough SARS-CoV-2 infections in vaccinated individuals by variant distribution and to identify the common risk associations. The PubMed, Web of Science, ProQuest, and Embase databases were searched from 2019 to 30 January 2022. The outcome of interest was breakthrough infections (BTIs) in individuals who had completed a primary COVID-19 vaccination series. Thirty-three papers were included in the review. BTIs were more common among variants of concern (VOC) of which Delta accounted for the largest number of BTIs (96%), followed by Alpha (0.94%). In addition, 90% of patients with BTIs recovered, 11.6% were hospitalized with mechanical ventilation, and 0.6% resulted in mortality. BTIs were more common in healthcare workers (HCWs) and immunodeficient individuals with a small percentage found in fully vaccinated healthy individuals. VOC mutations were the primary cause of BTIs. Continued mitigation approaches (e.g., wearing masks and social distancing) are warranted even in fully vaccinated individuals to prevent transmission. Further studies utilizing genomic surveillance and heterologous vaccine regimens to boost the immune response are needed to better understand and control BTIs.

Characteristics of COVID-19 Breakthrough Infections among Vaccinated Individuals and Associated Risk Factors: A Systematic Review

We sought to assess breakthrough SARS-CoV-2 infections in vaccinated individuals by variant distribution and to identify the common risk associations. The PubMed, Web of Science, ProQuest, and Embase databases were searched from 2019 to 30 January 2022. The outcome of interest was breakthrough infections (BTIs) in individuals who had completed a primary COVID-19 vaccination series. Thirty-three papers were included in the review. BTIs were more common among variants of concern (VOC) of which Delta accounted for the largest number of BTIs (96%), followed by Alpha (0.94%). In addition, 90% of patients with BTIs recovered, 11.6% were hospitalized with mechanical ventilation, and 0.6% resulted in mortality. BTIs were more common in healthcare workers (HCWs) and immunodeficient individuals with a small percentage found in fully vaccinated healthy individuals. VOC mutations were the primary cause of BTIs. Continued mitigation approaches (e.g., wearing masks and social distancing) are warranted even in fully vaccinated individuals to prevent transmission. Further studies utilizing genomic surveillance and heterologous vaccine regimens to boost the immune response are needed to better understand and control BTIs.