What behaviors and disparities in health resources are associated with the spread of COVID-19 in predominantly Black and Hispanic communities?In this survey study of adults living in a large US city, consistent masking was associated with a decrease in SARS-CoV-2 acquisition; however, Hispanic individuals were at higher risk for infection, more often worked outside the home, and were less likely to have received economic aid through stimulus checks or unemployment benefits.These results suggest public health messaging may have improved preventive behaviors over time but should be customized for Hispanic communities. This survey study examines associations of mitigating behaviors and receipt of economic aid with SARS-CoV-2 infection among a group of predominately Black and Hispanic adults tested for SARS-CoV-2 during the first surge of the COVID-19 pandemic in spring 2020. COVID-19, caused by SARS-CoV-2 virus, has disproportionately affected Black and Hispanic communities in the US, which can be attributed to social factors including inconsistent public health messaging and suboptimal adoption of prevention efforts.To identify behaviors and evaluate trends in COVID-19–mitigating practices in a predominantly Black and Hispanic population, to identify differences in practices by self-reported ethnicity, and to evaluate whether federal emergency financial assistance was associated with SARS-CoV-2 acquisition.This survey study was conducted by telephone from July 1 through August 30, 2020, on a random sample of adults who underwent SARS-CoV-2 testing at a safety-net health care system in Chicago during the surge in COVID-19 cases in the spring of 2020. Behaviors and receipt of a stimulus check were compared between participants testing positive and negative for SARS-CoV-2. Differences in behaviors and temporal trends were assessed by race and ethnicity.SARS-CoV-2 infection was assessed using nasopharyngeal quantitative reverse transcriptase–polymerase chain reaction testing. Mitigating behaviors and federal emergency financial assistance were assessed by survey. Race and ethnicity data were collected from electronic health records.Of 750 randomly sampled individuals, 314 (41.9%) consented to participate (169 [53.8%] women). Of those, 159 (51%) self-reported as Hispanic and 155 (49%) as non-Hispanic (120 [38.2%] Black), of whom 133 (84%) and 76 (49%) tested positive for SARS-CoV-2, respectively. For all participants, consistent mask use  and hand sanitizer use  were associated with lower odds of infection. During 3 sampled weeks, mitigation practices were less frequent among Hispanic compared with non-Hispanic participants . Hispanic participants were at high risk of infection  and more likely to work outside the home  compared with non-Hispanic participants, possibly because of limited receipt of stimulus checks  or unemployment benefits .In this survey study of adults in a large US city, public health messaging improved preventive behaviors over time but lagged among Hispanic participants; messaging tailored to Hispanic communities, especially for mask use, should be prioritized. Hispanic individuals were at higher risk for infection, more often worked outside the home, and were less likely to have received a stimulus check; this suggests larger studies are needed to evaluate the provision of economic support on SARS-CoV-2 transmission dynamics in low-income populations. In an effort to counter the economic effects of COVID-19, Congress approved emergency financial assistance to qualifying US citizens under the Coronavirus Aid, Recovery, and Economic Security (CARES) Act in late March 2020.14 Although the goal was to provide economic relief to individuals with reduced income, whether financial assistance was associated with SARS-CoV-2 transmission dynamics has not been evaluated.Prevention efforts such as shelter-in-place, mask use, and physical distancing have been shown to mitigate the spread of SARS-CoV-2.16In this study, we sought to identify individual behaviors hypothesized to contribute to or mitigate the spread of COVID-19 in predominantly Black and Hispanic populations residing in Cook County, Illinois, during the spring surge of 2020. We also evaluated the association of receiving financial safety-net assistance with the likelihood of SARS-CoV-2 positivity. Lastly, to understand the effectiveness of public health messaging during the early months of the pandemic and to inform future interventions to reduce transmission of SARS-CoV-2 in these populations, we analyzed differences in mitigating behaviors between Hispanic and non-Hispanic participants as well as changes in said behaviors across time. Given the identification of SARS-CoV-2 variants with the potential for increased transmissibility and concerns about vaccine uptake, there is an urgent need to improve nonpharmacologic prevention efforts continuously—before, during, and after wide-scale vaccination distribution.17 On April 3, 2020, the Chicago Department of Public Health recommended face coverings in public settings where social distancing measures were difficult to maintain, avoidance of interactions with people who do not live in the household, social distancing when outside of the home, and frequent hand washing in line with CDC guidance. Statewide mask mandates were issued on May 1, 2020.Cook County Health (CCH) is the largest safety-net health care system in Chicago, Illinois, serving a predominantly low-income racial and ethnic minority population. CCH detected its first case of COVID-19 infection in mid-March 2020. A rapid and dramatic increase in cases followed, culminating in peak rates of case detection during April and May 2020. Statewide shelter-in-place orders were initiated on March 21, 2020, with a nadir in individual mobility at the end of March 2020.Based on high rates of SARS-CoV-2 test positivity rates in our health system’s population, we selected 3 discrete calendar weeks  to evaluate exposures, mitigating behaviors, and temporal trends in behaviors among adults aged 18 years or older, with the goal of analyzing differences by race and ethnicity. We identified patients who underwent nasopharyngeal quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) testing at any CCH clinical location within the system’s integrated electronic health record. We excluded individuals who resided outside of Cook County, lived in congregate settings , were undomiciled at the time of testing, or were known to have died at the time of data collection. Then we used simple randomization to select 250 adults from each of the chosen calendar weeks with a ratio of participants testing SARS-CoV-2 positive  to SARS-CoV-2 negative (the control group) of 2:1; our final sample was 500 cases and 250 controls.18 All survey data were collected and managed using REDCap software version 11.1.2 hosted at CCH.19 Participants were offered a $20 gift card in compensation for their time. The CCH institutional review board reviewed and approved the study with a waiver of informed consent as the study did not involve more than minimal risk to participants.Study personnel contacted potential participants by telephone for a wellness check call since testing for COVID-19 and were then invited to participate in a structured survey by verbal consent. Three phone calls per participant were attempted, and efforts were made to schedule the survey call at participants’ convenience. The survey was developed by the study team through an iterative review process. Spanish translation was performed by research personnel with experience in English-to-Spanish translation. The survey translation was pilot tested on native Spanish speakers to assess for language validity and cross-cultural understanding. Surveys were conducted in English or Spanish depending on patient preference over 8 weeks from July 1 to August 30, 2020. Demographic data  of respondents were collected from the electronic health record.14 Responses for most questions used either a 3-point Likert scale  or were dichotomized as yes/no (eAppendix in the AAPOR) reporting guideline.The 36-item survey assessed baseline socioeconomic characteristics and putative COVID-19 exposures at home, work, social situations, and in the community. Baseline socioeconomic characteristics included preferred language at home, college education, occupation at the time of testing, access to employer-based insurance, and access to health care. Specific items included symptomatology at time of testing, mitigating behaviors , participation in social gatherings with 10 or more people who were not all household members, use of public transportation, education, occupation, household characteristics, and receipt of safety-net financial benefits (unemployment benefits and stimulus checks under the CARES Act) in the 14 days before SARS-CoV-2 testing.The primary objective was to compare exposures and mitigating behaviors between participants testing positive and negative for SARS-CoV-2. The secondary objectives were to compare responses by Hispanic vs non-Hispanic ethnicity and to evaluate temporal trends in behaviors as an indicator of the effectiveness of public health messaging. For analysis of Likert scale responses, we dichotomized the responses as always or sometimes vs never.We constructed logistic regression models to assess the association of SARS-CoV-2 test positivity with dichotomized survey responses for each response. To adjust for potential confounding by participant age and testing week, we retained these 2 variables in all models. We adjusted for sampling probability using survey weighting for each test week, as both factors may have influenced behaviors. The Mantel-Haenszel test of homogeneity was performed for data across racial and ethnic groups to determine whether a single adjusted odds ratio (aOR) for a variable could be presented. For the lone variable that revealed significant heterogeneity in its association with SARS-CoV-2 positivity , separate logistic regression models for Hispanic and non-Hispanic participants were constructed. To compare differences in survey responses by ethnic groups, we calculated ORs with their respective 2-sided confidence intervals. Graphic visualizations were used to display temporal trends on selected behaviors, and we tested for statistical significance of the trends in mitigating exposures by racial and ethnic groups using the nonparametric test for trend. All statistical analyses were conducted using Stata software version 14.2 (StataCorp).During the 3 study weeks, 1682 adults were tested for SARS-CoV-2 at CCH facilities. Most tests were obtained from individuals who self-reported as Hispanic (740 [44.0%]) or Black (715 [42.5%]). The distribution of cases from each week of sampling was as follows: 250 (46%) on week 1, 250 (42%) on week 2, and 250 (21%) on week 3. Of 750 individuals randomly selected, 314 (41.9%) participated in the telephone survey (169 [53.8%] women). Of these, 159 (50.6%) participants self-reported as Hispanic and 155 (49.4%) self-reported as non-Hispanic, of whom 120 (77.4%) self-reported as Black, 23 (14.8%) as White, and 12 (7.7%) did not report or were unknown. Reasons for not participating in the study for 436 (58.1%) individuals included inability to reach after 3 phone call attempts, wrong phone number listed in the electronic health record, or disinterest in the survey.Baseline characteristics of survey participants by SARS-CoV-2 status are shown in The association between testing positive for SARS-CoV-2 with self-reported exposure risks and mitigation practices for each response is shown in Significant differences were noted in exposure risks, mitigating behaviors, and receipt of safety-net benefits across ethnic groups in the 2 weeks before SARS-CoV-2 testing . CompareWith regards to mitigation practices, rates of mask use in public settings  and rates of hand sanitizer use  were significantly higher among non-Hispanic participants. There was no difference in reported hand washing or ability to maintain physical distance during work hours between groups. However, Hispanic participants reported less ability to maintain physical distance during work breaks . Lastly, non-Hispanic participants were more likely to have received a stimulus check  and unemployment benefits  compared with Hispanic participants in the 14 days before SARS-CoV-2 testing . Statistically significant differences between Hispanic and non-Hispanic participants for exposure risks, mitigating practices, and safety-net benefits remained unchanged when only participants who tested positive for SARS-CoV-2 were included in the analysis.P < .001), during work , or on public transport  across the 3 test weeks. Attending social gatherings appeared to increase during the second test week and then decrease. The percentage of Hispanic participants who reported consistent mask use in public settings remained lower across all 3 time points compared with non-Hispanic participants; attendance of social gatherings remained higher at all 3 time points. These differences remained unchanged when only participants who tested positive for SARS-CoV-2 were considered in the analysis, making recall bias less likely (data not shown).Four modifiable behaviors that could be influenced by public health messaging were evaluated for temporal trends across testing weeks . OverallIn this survey study of adults in a large US city, we found that the likelihood of SARS-CoV-2 positivity was associated with having known household or work contact exposures and Hispanic ethnicity. Individual adherence to public health messaging directing consistent mask and hand sanitizer use appeared protective against infection. When comparing exposure risks and mitigating practices among racial and ethnic groups, Hispanic participants were more likely to delay implementing preventive behaviors including mask use, physically distancing, and hand hygiene compared with non-Hispanic participants during each sampled week. Only 1 in 10 Hispanic participants reported receiving economic support through a CARES Act stimulus check compared with 3 out of every 4 non-Hispanic participants.14 In this study, Hispanic participants were significantly less likely to have received a stimulus check compared with non-Hispanic participants. Immigration status was not collected in this survey, but could be inferred from census tract demographics and preference for the Spanish language, and may explain the lower accessibility to economic aid for many participants.9 Financial aid might offer protection from SARS-CoV-2 transmission in the workplace, as immigrant populations often work in overcrowded industries that do not offer job stability, employment protections, or sick time.22 Larger epidemiological studies are needed to corroborate our findings, but if economic aid offers a modicum of protection against SARS-CoV-2 infection, income-based universal aid may merit consideration as an additional tool in the fight against COVID-19. The American Rescue Plan Act of 2021 as a follow-up to the CARES Act provides an opportunity to assess this in more detail.23To our knowledge, this is the first study that has evaluated receipt of a stimulus check across Hispanic and non-Hispanic communities. Our finding that it was uncommon for Hispanic participants to receive financial support, which might have contributed to continued workplace exposures, is important and deserves further scrutiny. Eligibility for stimulus checks included US citizens who met income thresholds; however, non-US citizens and mixed immigration status individuals were not eligible. Additionally, individuals who met income requirements but did not file taxes in 2018-2019 or did not use direct deposit for past tax refunds may have experienced a delay in receiving the stimulus check.24 We found that common community exposures such as social gatherings, use of public transportation, and work outside of the home did not increase the likelihood of SARS-CoV-2 positivity, apart from on-site dining, which was not assessed in this study but reported by Fischer et al.25 Importantly, and of value for public messaging, we corroborated that for our population consistent mask use was associated with a lower likelihood of test positivity.9 A novel finding in our study is the protective effect of hand sanitizers, suggesting their use may serve as a marker for enhanced SARS-CoV-2 preventive behaviors.As reported in previous studies, we found an increased risk of SARS-CoV-2 transmission from known household and work contacts, attributed to high-density living environments, shared workspaces, and prolonged workplace contact.26 Further studies are needed to explore the barriers to wearing a face mask in the Hispanic population, which could inform public health measures and messaging. Additionally, Hispanic respondents reported more participation in social gatherings compared with non-Hispanic respondents, possibly from a lower perceived risk of COVID-19 among family and friends.27 The cultural tendency to gather in groups may partially explain the discrepancy in not maintaining physical distancing during work breaks as during work hours, in addition to potentially small workplace environments. Indeed, close family units, multi-generational households, and social cohesion are characteristics associated with the Hispanic culture and are often credited with countering health inequities.29 Lastly, this study demonstrated significant improvements in mask adherence and a curtailment in social gatherings over a 6-week time period in both Hispanic and non-Hispanic groups, although Hispanic groups delayed implementing mitigation strategies at all 3 time points. This underscores the need for more intensive and repeated messaging and community outreach to improve preventive behaviors in the Hispanic community.Interestingly, we found considerable differences in SARS-CoV-2 prevention measures between racial and ethnic groups. Hispanic participants reported significantly lower rates of mask use during work and on work breaks, on public transportation, while running errands, and at social gatherings. Possible barriers to mask use have been proposed, including mask availability, financial constraints, confusion and misinformation, poor penetration of public health messaging to non-English speaking populations, lower perceived susceptibility to COVID-19, physical and social discomfort, and perceptions of identity and autonomy.30 Sixth, as Hispanic participants were overrepresented among cases, this may have confounded the strength of our findings. Nonetheless, this study identified behaviors which likely can be modified through public health interventions including workplace modifications.This study has several limitations. First, the survey was conducted on a relatively small sample size, and those who declined to participate may have different exposure risks and behaviors not measured. Additionally, the small sample size may not be sufficiently powered to show measurable differences between racial and/or ethnic groups. Second, although participant awareness of results at the time of the survey may have influenced responses, our findings stratified by race and ethnicity remained statistically significant when restricted to those who tested positive for SARS-CoV-2. Third, surveys were conducted up to 8 weeks after SARS-CoV-2 testing was obtained, which may have amplified recall bias. Fourth, social desirability response bias may have overestimated self-reported adherence to preventive behaviors. Fifth, reliance on electronic health record–derived demographic data may have resulted in unforeseen misclassifications of race, ethnicity, and language preference.Substantial changes in public policy are urgently needed while this pandemic still roils in order to address the social, economic, and health care disparities driving COVID-19 in Black and Hispanic communities. Based on the results of this survey study, public health messaging that is culturally adapted for and resonates with vulnerable populations, particularly Hispanic communities, must stress consistent mask use, enhanced hand hygiene, and physical distancing to stem the spread of SARS-CoV-2 and its variants while mass vaccination programs are rolled out. Larger studies are needed to evaluate the association of economic aid packages on SARS-CoV-2 transmission dynamics for all residents who meet income thresholds as a means to ease the burden of the pandemic and also lessen the risk for the general public.


In addition, the results of the pleiotropy test demonstrated that instrument SNPs were less likely to affect COVID-19 severity via approaches other than lung adenocarcinoma cancer susceptibility (p = 0.96). Leave-one-out analysis showed no outliers in instrument SNPs, whose elimination rendered alterations in statistical significance, which further supported the reliability of the MR results. Broad mutation and differential expression of these genes were also found in cancers, which may provide valuable information for developing new treatment modalities for patients with both cancer and COVID-19. For example, ERAP2, a risk factor for COVID-19-associated death, is upregulated in lung squamous cancer and negatively associated with patient prognosis. Hence, ERAP2-targeted treatment may simultaneously reduce COVID-19 disease severity and restrain cancer progression. Our results highlighted the importance of strengthening medical surveillance for COVID-19 deterioration in patients with lung adenocarcinoma by showing their causal genetic association. For these patients, a delay in anticancer treatment, such as chemotherapy and surgery, should be considered.The clinical management of patients with COVID-19 and cancer is a Gordian knot that has been discussed widely but has not reached a consensus. We introduced two-sample Mendelian randomization to investigate the causal association between a genetic predisposition to cancers and COVID-19 susceptibility and severity. Moreover, we also explored the mutation landscape, expression pattern, and prognostic implications of genes involved with COVID-19 in distinct cancers. Among all of the cancer types we analyzed, only the genetic predisposition to lung adenocarcinoma was causally associated with increased COVID-19 severity (OR = 2.93, β = 1.074, se = 0.411,  Coronavirus disease 2019 (COVID-19), which arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can result in severe illnesses such as acute respiratory distress syndrome, multiorgan dysfunction syndrome, and consequent death, and it has become a public health emergency of international concern .During the COVID-19 pandemic, the clinical management of patients with cancer is a Gordian knot that has been discussed broadly but has not reached a consensus . Two obsThese different findings revealed the close relationship between cancer and COVID-19 susceptibility and severity, and it is difficult to speculate on their causal relationship given the unavoidable bias derived from unmeasured confounding factors in traditional observational studies. Hence, we introduced Mendelian randomization (MR) to investigate the causal association between cancers and COVID-19 susceptibility and severity.MR is an increasingly acknowledged statistical method that uses genetic variants to determine whether an observational association between a risk factor and an outcome is consistent with a causal effect . IndividThe present study investigated the causal association between cancer and COVID-19 susceptibility and severity using two-sample MR analysis. Moreover, we also explored the mutation landscape, expression pattern, and prognostic implications of genes involved with COVID-19 in distinct cancers.A systematic retrieval of studies pertaining to COVID-19 and cancers was conducted using the following terms: (COVID-19[Title/Abstract] OR COVID-19[Title/Abstract] OR SARS-CoV-2[Title/Abstract]) AND .https://www.evalue-calculator.com/), and it could be calculated for an observed risk ratio (denoted RR) by E-value = RR + √[RR*(RR − 1)]. If the original risk ratio is below 1, then one first takes the inverse before applying the E-value formula  . Then, we identified the SNPs that were significantly associated with each cancer with the threshold value k/gwas/) . SNPs wihttps://www.covid19hg.org/) (Release 4)  . The phep-value will be retained. We pruned all SNPs in LD using the default cutoff value recommended by the “MR-base” platform. The clumping distance (kb) was set as 10,000 kb and R2 was 0.01. By default, if a particular requested SNP is not found in the outcome GWAS, then a SNP (proxy) in the LD with the requested SNP (target) will be searched for instead. Once the exposure and outcome data are obtained, the next step is to harmonize the effects of the instrumental variants, which refers to the effect of a SNP on the exposure, and the effect of that SNP on the outcome must correspond to the same allele. For inferable palindromic SNPs, we tried to infer the forward strand alleles using allele frequency information. Noninferable palindromic SNPs referring to the allele frequency no longer provide information about the strand. Such SNPs would be discarded. This is done for any palindromic SNPs that have minor allele frequencies above 0.42.For standard two-sample MR, it is important to ensure that the instruments for the exposure are independent. Among those SNPs that have linkage disequilibrium (LD) R-squares above the specified threshold, only the SNP with the lowest Once the exposure and outcome data were harmonized, the effects and standard errors for each instrument SNP were available for the exposure and outcome traits. Such information could be utilized to perform MR analysis. Inverse-variance weighted (IVW) estimation is a classic method to pool the MR effects of each instrument SNP.The variance term was calculated as e effect . A mediae effect . MR–Eggee effect . Hence, x-axis and the inverse standard error  for the association was represented on the y-axis. Asymmetry about the vertical line is indicative of the heterogeneity.Heterogeneity in the causal effects among instruments is a marker of the potential violations of instrumental variants’ assumptions. Heterogeneity could be assessed for the IVW and Egger estimates, and this can be used to navigate between models of horizontal pleiotropy . In addip-value of 0.05 by the number of testing methods .To evaluate the robustness of the MR effect estimates and identify any potential outliers, each instrument SNP was sequentially eliminated from the analysis . If the precision and direction of the association between the cancer-predicting SNPs and COVID-19 susceptibility and severity remained largely unaltered, then the results were probably not driven by any outliers. All analyses were performed using the R package “TwoSampleMR” (version 0.5.5). Bonferroni correction was performed by dividing the https://www.cancer.gov/). The whole exome sequencing (WES) and copy number variation (CNV) data of each cancer were integrated and processed through cBioPortal  . The core code for performing the MR analysis is attached in the The omics and clinical data of cancers derived from the primary organs that were the same as the cancer types investigated in the MR analysis were collected from The Cancer Genome Atlas (TCGA)  . Given tMany studies have investigated the clinical characteristics of COVID-19 patients with cancer . HoweverA total of 258 GWASs associated with the effect of SNPs on 10 cancers were included for screening instrumental variables . A totalp = 0.005). No obvious heterogeneity was detected by Q statistics . No obvious heterogeneity was detected by Q statistics . To test whether the heterogeneity was derived from the differences among the cohorts, we performed subgroup analysis by only using the SNPs in the study by p = 0.002) without any obvious heterogeneity or horizontal pleiotropy . To further support our conclusion, we performed MR analysis based on hospitalized and non-hospitalized COVID-19 cohort and found a similar conclusion .Then, we further analyzed the causal association between genetic predisposition to cancers and COVID-19 severity. Among all of the cancer types we analyzed, only genetic susceptibility to lung adenocarcinoma was causally associated with COVID-19 severity ; Table 2APOE and SLC6A20) were associated with COVID-19 susceptibility, 6 genes  were related to COVID-19 severity, 4 genes  were associated with COVID-19 mortality, and 5 genes  were detected in SARS-CoV-2 receptors (BRF2 was the most frequently mutated gene and it mainly had amplification mutations (p = 0.02)  . Mutual  = 0.02) . Mutatioelopment .APOE transcript was upregulated in 6 cancers, while the expression of ANPEP was downregulated in seven cancers, and it may have oncogenic and antitumor effects. To further evaluate the correlation between the expression level of these genes and the patient prognosis, we divided patients into two groups according to the median transcript level and conducted survival analysis. Many genes were associated with patient overall and disease-free survival , suggesting that increased surveillance for severe COVID-19-associated complications should be conducted among hospitalized patients with lung adenocarcinoma. To avoid the unexpected bias from weak instruments, we calculated the F-statistic for SNPs used in the MR analysis. The results showed that all SNPs were qualified with the F-statistic larger than 10 (p = 0.005). However, such a small β effect may not have valuable clinical implications, and the β value mainly reflects the causal association between a genetic predisposition to colorectal cancer and COVID-19 susceptibility, while many hospitalized patients with colorectal cancer have received either cytotoxic chemotherapy or surgery, which theoretically increases the risk of succumbing to COVID-19.MR is an effective tool to assess the causal relationship between exposure factors and the outcome . Here, w than 10 . InteresERAP2 is a risk factor for COVID-19-related death and it is upregulated in lung squamous cancer but is negatively associated with the patient prognosis. Therefore, targeting ERAP2 might be a potential treatment target to both relieve COVID-19 severity and restrain cancer progression.We also evaluated the mutation landscape, expression pattern, and prognostic implications of genes involved with COVID-19 in distinct cancers to explore whether novel targeted treatment could be applied for patients with both cancer and COVID-19. For instance, To the best of our knowledge, this study is the first MR analysis to report the causal association between a genetic predisposition to lung adenocarcinoma and an increased risk for severe COVID-19, such as closer and positive surveillance to be applied to such patients in clinical practice. Specifically, for patients with lung adenocarcinoma, considering its causal association with COVID-19 severity, we suggest that chemotherapy or surgery could be postponed until they recover from COVID-19. Drugs that may exacerbate cytokine storms or lung injury should also be avoided. In addition, we explored potential molecular targets concurrently for the treatment of patients with both cancer and COVID-19, which may optimize clinical decisions precisely for such patients.Certainly, the present study has some limitations. First, due to the inaccessibility of primary data, we cannot adjust for some key confounding factors; for example, the ethnic percentage of patients across cohorts was difficult to assess and adjust. Statistical heterogeneity and subgroup analysis were performed to minimize such unavoidable bias. Second, although our data showed no causal association between a genetic predisposition to most cancers and COVID-19 susceptibility and severity, it should not be mistaken that medical surveillance management for all of these patients could be reduced to the same level as that applied to the general population. Third, the cancer state is a binary exposure that could introduce unexpected bias, which may mitigate the causal association between the genetic predisposition to lung adenocarcinoma and increased COVID-19 severity. For patients undergoing cytotoxic chemotherapy or experienced surgery, intensified management and surveillance for COVID-19 infection and deterioration are still significant.The management of cancer patients with COVID-19 is a knotty problem whose resolution requires wisdom and a joint effort by researchers around the world. Our results highlighted the importance of strengthening medical surveillance for COVID-19 deterioration in patients with lung adenocarcinoma by showing their genetic causal association. For these patients, a delay of anticancer treatment, such as chemotherapy and surgery, should be considered.


ALK) have been discovered as a novel driver mutation in patients with non–small-cell lung cancer (NSCLC). Patients’ responses to ALK tyrosine kinase inhibitors (TKIs) may vary depending on the variations of ALK rearrangements they have. It is imperative for clinicians to identify druggable ALK fusions in routine practice.Rearrangements of Anaplastic lymphoma kinase (ALK rearrangement type (SDK1–ALK) in a Chinese lung adenocarcinoma patient who responded well to ALK inhibitor SAF-189s. The positive expression of ALK in lung biopsy tissue was verified by IHC analysis. A new SDK1-ALK fusion was discovered using NGS. The patient was treated with SAF-189s (160 mg per day) as a first-line therapy and went into continuous remission, with a 12 months progression-free survival at the last follow-up.In this study, we discovered a rare SDK1-ALK fusion with an excellent response to an ALK inhibitor, which will provide better understanding of ALK-TKI applications for NSCLC patients with ALK fusion in the future.This is the first case of  ALK) rearrangements account for approximately 5% of patients with non-small-cell lung cancer (NSCLC) and represent as a critical therapeutic target in clinical practice  provide a marked objective response rate (ORR) and impressive clinical benefit for patients with ALK-rearranged lung cancer. The first-generation ALK inhibitor was crizotinib, developed after the discovery of chromosomal rearrangement involving the ALK and echinoderm microtubule-associated protein like 4 (EML4) genes in NSCLC in 2007. Second-generation inhibitors including ceritinib, alectinib, and brigatinib, were authorized for treatment in ALK-positive patients after then. As third-generation inhibitors, lorlatinib and ensartinib have been developed for the treatment of NSCLC patients who have acquired resistance to prior ALK inhibitor treatment , KIF5B (1.6%), and other variants (4.7%), have been identified with the rapid development and application of next-generation sequencing (NGS)  in a lung adenocarcinoma patient who exhibited a remarkable response to SAF-189s.Numerous SDK1 Exon36-ALK Exon20 fusion variant (abundance: 9.2%)  scan revealed a mass in the left lower lobe measuring 8.1 × 6.1 cm, multiple enlarged lymph nodes in left hilum and mediastinum, obstructive pneumonia in the left lung, and left pleural effusion. Radionuclide bone scan and magnetic resonance imaging revealed no evidence of bone or brain metastasis. His medical history was not remarkable. The pathology of this patient’s lung cancer was verified through a CT-guided percutaneous fine-needle lung biopsy. According to the American Joint Committee on Cancer Staging Manual, 8th edition, he was finally diagnosed with stage IV lung adenocarcinoma (cT4N2M1). The biopsy specimen was subjected to next-generation sequencing (NGS), which revealed a hitherto unknown It is well known that ALK inhibitors, such as Crizotinib and alectinib, are pricey. If the patient had maintained his treatment, he would have been in serious financial trouble. SAF-189s is a new selective ALK inhibitor, and the patient satisfied all of the criteria for clinical trial inclusion. He provided informed permission. On January 13, 2021, the patient was then enrolled onto a phase I/II clinical trial evaluating SAF-189s in NSCLC after a thorough enrollment assessment and began with oral administration of SAF-189s at a dose of 160 mg per day. After 10 days of medication, his symptoms considerably improved. On February, 2021, done 2 months after treatment initiation, a chest CT scan revealed a partial response (42 percent reduction in the sum of the target lesion’s longest diameters per RECIST 1.1)  mutations that were frequently found in female and adenocarcinoma patients, ALK gene aberrations are routinely found in patients with adenocarcinoma histological subtype. Remarkably, brain metastases are more likely to be found in this subset of patients . Many reividuals , 8. Secoin situ or liquid biopsy samples. According to the KWAY Italian multicenter cost evaluation research, the implementation of NGS saves personnel time spent to testing activities and lowers the overall cost of testing per patient . The understanding of biological mechanisms underlying immune-targeted combinations still need further clinical investigations and NGS will be a valid tool in future decision-making .SDK1-ALK fusion detected in a Chinese patient with advanced lung adenocarcinoma by using NGS-based cancer genomic DNA profiling in the clinic. In this case, the SDK1-ALK-rearranged lung cancer in this patient is susceptible to treatment with a new ALK inhibitor SAF-189s, which is now being studied in a clinical trial. Thus, our study provides a new druggable target for NSCLC driver mutation in routine practice.In summary, this is the first case report involving The datasets for this article are not publicly available due to concerns regarding participant/patient anonymity. Requests to access the datasets should be directed to the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of The First Affiliated Hospital of Shandong First Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.LM: Data curation, Writing- Original draft preparation. JX: Writing - review & editing. TG: Visualization, Investigation. DW: Software. JW: Supervision. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (Grant No. 81572875), CSCO-MSD Cancer Research Foundation (Grant No. Y-MSD2020-0350), CSCO-PILOT Cancer Research Foundation (Grant No. Y-2019AZMS-0440), Wu Jieping Medical Foundation for Clinical Scientific Research (Grant No. 320.6750.2020-12-16), and the Natural Science Foundation of Shandong Province (Grant No. ZR202102190539).DW and TG are employees of YuceBio Technology Co., Ltd Shenzhen.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


For locally advanced rectal cancer, what is the economic implication of short-course radiotherapy and total neoadjuvant therapy followed by total mesorectal excision compared with conventional long-course chemoradiotherapy followed by total mesorectal excision?This decision analytical model found that compared with conventional long-course chemoradiotherapy with or without adjuvant chemotherapy, short-course radiotherapy and total neoadjuvant therapy were associated with cost savings without diminishment in quality-adjusted life-years.The findings of this study support short-course radiotherapy and total neoadjuvant therapy as a new treatment paradigm in the management of locally advanced rectal cancer. This decision analytical model compares the cost-effectiveness of short-course total neoadjuvant therapy vs conventional long-course chemoradiotherapy among patients with locally advanced colorectal cancer. Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy.To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer.A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma treated with SCRT-TNT or LCCRT. Markov modeling was used to model disease progression and patient survival after treatment in 3-month cycles. Data on probabilities and utilities were extracted from the literature. Costs were evaluated from the Medicare payer’s perspective in 2020 US dollars. Sensitivity analyses were performed for key variables. Data were collected from October 3, 2020, to January 20, 2021, and analyzed from November 15, 2020, to April 25, 2021.Two treatment strategies, SCRT-TNT vs LCCRT with adjuvant chemotherapy, were compared.Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefits. Effectiveness was defined as quality-adjusted life-years (QALYs). Both costs and QALYs were discounted at 3% annually. Willingness-to-pay threshold was set at $50 000/QALY.During the 5-year horizon, the total cost was $41 355 and QALYs were 2.21 for SCRT-TNT; for LCCRT, the total cost was $54 827 and QALYs were 2.12, resulting in a negative incremental cost-effectiveness ratio (−$141 256.77). The net monetary benefit was $69 300 for SCRT-TNT and $51 060 for LCCRT. Sensitivity analyses using willingness to pay at $100 000/QALY and $150 000/QALY demonstrated the same conclusion.These findings suggest that SCRT-TNT followed by TME incurs lower cost and improved QALYs compared with conventional LCCRT followed by TME and adjuvant chemotherapy. These data offer further rationale to support SCRT-TNT as a novel cost-saving treatment paradigm in the management of locally advanced rectal cancer. Previous cost-effectiveness analyses of treatment paradigms for locally advanced rectal cancer have compared conventional LCCRT with SCRT alone,18 SCRT with a short duration of consolidation chemotherapy,19 and long-course TNT.20 However, there are no economic evaluations comparing conventional LCCRT with SCRT-TNT. Therefore, we performed a cost-effectiveness analysis of SCRT-TNT vs conventional LCCRT using data from the RAPIDO trial16 and other published data. Data were collected from October 3, 2020, to January 20, 2021.Although SCRT-TNT has shown oncologic promise and is recommended by the National Comprehensive Cancer Network,CHEERS) reporting guidelines for economic evaluations developed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).21This study was deemed exempt from review by the Washington University School of Medicine in St Louis Institutional Review Board owing to the use of deidentified data. This report follows the Consolidated Health Economic Evaluation Reporting Standards  adenocarcinoma of the rectum using TreeAge Pro software, version 2020 R2.1  A. This t24 We defined SCRT-TNT as neoadjuvant SCRT followed by consolidation chemotherapy with the modified FOLFOX regimen  for 9 cycles25 or the CAPOX regimen  for 6 cycles.27 We defined LCCRT as 50.4 Gy in 28 fractions for 28 treatment days with concurrent capecitabine.28 Subsequently, TME was performed with either abdominoperineal resection and a permanent colostomy29 or low anterior resection with a temporary defunctioning ileostomy and planned reversal.31 The base model included adjuvant chemotherapy after LCCRT per the National Comprehensive Cancer Network guideline,32 although the delivery of such treatment was at the discretion of the treating hospitals in the RAPIDO trial.16 After treatment with either SCRT-TNT or LCCRT, Markov models were constructed to describe disease progression and patient survival.We defined SCRT as 25 Gy in 5 fractions for 5 treatment days with 3-dimensional techniques.The Markov model as illustrated by the transition state diagram was characterized by 5 health states: no evidence of disease (NED), resectable locoregional recurrence (LRR), unresectable LRR, distant metastatic disease, and all-cause death (absorbing state) B. Furthe33 A proportion of patients with LRR were assumed to have resectable disease and underwent additional salvage abdominoperineal resection or pelvic exenteration.34 For patients with unresectable LRR or distant metastatic disease, the patients were assumed to have received palliative chemotherapy with capecitabine for 1 year. For patients with unresectable LRR, it was assumed that the patients could stay in the unresectable LRR state or transition to death.After TME, all patients entered the NED state of the Markov model. In the next cycle, they could remain in this state or transition to LRR, distant metastatic disease, or death. All patients with LRR were assumed to have received a second course of radiotherapy using the previously established hyperfractionated accelerated regimen of 39 Gy in 26 fractions twice a day delivered for 13 treatment days.16  was assumed to be the same between patients with or without ostomy.36 Owing to the paucity of published utilities corresponding to SCRT-TNT or differing surgical methods  for the remaining health states , utilities from expert opinion based on Ness et al36 were used across all treatment groups.Utilities are quality of life scores ranging from 0 to 1, where 0 stands for death and 1 stands for perfect health. Utilities were used to discount life-years to obtain quality-adjusted life-years (QALYs). Utilities were obtained from Ness et altilities . The stu39 The Medicare severity diagnosis related groups national Medicare payment amounts were used to estimate the admission cost associated with TME.40 An annual ostomy maintenance cost was assumed for patients who underwent initial abdominoperineal resection. All costs were adjusted to 2020 US dollars using the consumer price index.42Medicare costs were used to compute the cost of radiotherapy, chemotherapy, routine surveillance, workup for tumor recurrence, and salvage therapies. The per-patient costs for treatments were defined by the Centers for Medicare & Medicaid Services outpatient payment schedule using the national costs.41 For each treatment strategy, the 3-year LRR, cumulative distant metastasis, and overall survival rates were computed from the model.Markov cohort analysis with half-cycle correction was performed to compute the total health care costs and QALYs after each treatment accumulated during the 5-year time horizon. Cost, QALYs, and utilities were discounted at an annual rate of 3%.43The incremental cost-effectiveness ratio (ICER), defined as the ratio of the incremental cost and the incremental QALY gained, was calculated to compare the cost-effectiveness of these treatment paradigms. The net monetary benefit was defined as the QALYs multiplied by the willingness to pay (WTP) per QALY gained subtracted by the total cost. The WTP threshold was defined as $50 000/QALY for strategies that were clearly cost-effective in the base case.43 Multiple 1-way sensitivity analyses were performed for the probability, utility, and cost parameters derived from 44 or had the greatest potential for fluctuations over time with improvement in technology or policy  were evaluated in 2-way sensitivity analyses. Two-way sensitivity analyses were performed by varying the influential variables determined in the 1-way sensitivity analyses. Data were analyzed from November 15, 2020, to April 25, 2021.Sensitivity analyses were conducted to test the robustness of the conclusion. In addition, WTP threshold was varied to $100 000/QALY and $150 000/QALY.16 ,45 whereas the RAPIDO trial used CAPOX for 6 cycles or FOLFOX4 for 9 cycles.16 Wright et al20 also showed that long-course TNT was cost-effective compared to LCCRT with adjuvant chemotherapy.Our results corroborate the analyses from a previously published economic study by Raldow et al,46 but it is gaining traction in the setting of increased interest in shortening treatment in the setting of the COVID-19 pandemic.47 Previous studies have suggested that SCRT might be less efficacious with less tumor downstaging compared with LCCRT48 and might result in more acute toxic effects.49 However, the Stockholm III trial51 showed greater tumor downstaging and decreased postoperative complications in patients treated with SCRT and delayed surgery compared with long-course radiotherapy (without concurrent chemotherapy) and delayed surgery. Delaying surgery after SCRT also decreased the rate of postoperative complications compared with immediate surgery.50 The phase 3 RAPIDO trial16 recently showed that SCRT followed by consolidation chemotherapy and TME increased the rate of pathological complete response , decreased disease-related treatment failure , and decreased distant metastatic disease  at 3 years compared with LCCRT followed by TME with or without adjuvant chemotherapy.At present, SCRT is underused (<1%) in the US,52 higher rates of clinical complete response and pathological complete response, increased tumor regression that could enhance complete (R0) resection rates,13 and early introduction of systemic treatment to address micrometastases that may translate to disease-free survival benefits.11 Together, optimization of adaptive treatment strategies through TNT allows for patient selection for potential organ preservation via nonoperative management,57 which is another emerging paradigm for the management of rectal cancer.58Compared with conventional treatment strategies using adjuvant chemotherapy, TNT is hypothesized to be advantageous owing to the decreased rate of toxic effects and increased tolerability,59 The indications for TNT are less clear for patients with lower-risk disease .54 Short-Course Radiotherapy Versus Chemoradiotherapy, Followed by Consolidation Chemotherapy, and Selective Organ Preservation for MRI-Defined Intermediate and High-Risk Rectal Cancer Patients (ACO/ARO/AIO-18.1), an ongoing study,60 aims to compare TNT with SCRT vs LCCRT in the nonoperative setting for patients with a clinical complete response to neoadjuvant therapy. Although our study suggests that SCRT-TNT is cost-saving compared with LCCRT, future studies are necessary to improve risk stratification, optimize TNT regimens, and evaluate the long-term oncologic and quality of life outcomes after SCRT-TNT.Current societal consensus guidelines include a conditional recommendation for TNT, with stronger evidence for patients with risk factors for recurrence .To our knowledge, this decision analytical model is the first reported economic evaluation of SCRT-TNT and LCCRT. We performed detailed time-dependent modeling of health states using randomized clinical trial data published in the modern era and included a comprehensive microcosting analysis. The results of this study support future exploration of SCRT-TNT in the management of locally advanced rectal cancer. Adoption of this treatment paradigm should also await quality of life and patient-reported outcomes data as well as maturing, long-term oncologic survival data.61 and is still being assessed in ongoing trials for the management of locally advanced rectal cancer.60 No quality of life or patient-reported outcome measures from these TNT studies have been published to date. The definition of locally advanced rectal cancer of cT3 to cT4 or node-positive disease in this study encompasses more patients than those enrolled in the RAPIDO trial with high-risk factors such as cT4a, cT4b, or cN2 disease, extramural vascular invasion, involved mesorectal fascia , or enlarged lateral lymph nodes considered to be metastatic.16 In terms of data sources, the tumor recurrence and survival outcomes were primarily based on a single phase 3 study (RAPIDO), and the cost was entirely derived from US-based Medicare data. Although these factors could potentially limit the broader applicability and generalizability of the study, the conclusions were upheld in the sensitivity analyses that were performed.This study also has multiple limitations. The model compared conventional LCCRT with a novel and emerging TNT-based regimen, which was only recently reported in phase 3 trials16 The conclusion that SCRT-TNT was cost-saving was upheld whether compared with LCCRT with or without adjuvant chemotherapy. In the extreme scenario wherein the locoregional and distant recurrence rates were assumed to be the same and all patients were assumed to have received adjuvant chemotherapy, SCRT-TNT was found to result in an even greater magnitude of cost saving while achieving a similar amount of QALYs as LCCRT.As for the model structure, the Markov model relied on simplification of disease processes and costs and was limited by the quality of data used to generate probabilities, utilities, and costs. The use of adjuvant chemotherapy in the LCCRT group was left to the discretion of the participating hospitals in the RAPIDO trial, which resulted in some treatment heterogeneity, although subgroup analysis demonstrated similar oncologic outcomes between these 2 groups.The findings of this decision analytical model suggest that SCRT followed by TNT and TME was associated with superior oncologic outcomes and lower cost compared with conventional LCCRT followed by TME with or without adjuvant chemotherapy. In the context of large randomized clinical trial data demonstrating superiority of SCRT-TNT to LCCRT, the presented data support the exploration of SCRT-TNT as a new cost-saving treatment paradigm in the management of locally advanced rectal cancer.


Background: The association of coronavirus disease 2019 (COVID-19) with hypertension has been one of the frequently discussed topics in current studies since hypertension was identified as a risk factor for coronavirus disease. However, no studies seem to be focused on the BP (blood pressure) in patients with hypertension after COVID-19. Report: This report presents the cases of five frail geriatric patients (avg. age 78.3 (±6.4) years) with sarcopenia and controlled hypertension (office BP < 140 mmHg) who were diagnosed with SARS-CoV-2. Findings: Control ABPM performed after COVID-19 showed that these hypertensive patients were hypotensive and that the previously well-established therapy was suddenly too intensive for them. Conclusions: These findings suggest that BP control after COVID-19 is needed and that ABPM is, particularly in frail geriatric patients, by no means a luxury but a necessity. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In many people, it has led to serious health complications and death. COVID case-fatality rates suggest that the individuals aged 60 years or older are most at risk. The highest case-fatality rate occurs in patients of 80 years and older , posing According to studies, hypertension and cardiovascular disease are among common comorbidities in patients with COVID-19 increasing the likelihood of hospitalization and death. Ran et al.  suggest To the best of our knowledge, there is no study focusing on blood pressure (BP) control in hypertensive patients after COVID-19. In this report, we describe the decrease of BP values in five polymorbid frail geriatric hypertensive patients with sarcopenia after COVID-19. The objective of this case report is to inform about the necessity to control the effectiveness of BP treatment after COVID-19, preferably by ABPM.This case report presents five frail geriatric patients with sarcopenia treated for arterial hypertension for more than 5 years. These patients tested positive for COVID-19 (PCR tests). The age range of patients was 65–85 years and two of five patients were men. Basic clinical parameters of the five patients before and after COVID-19 are presented in Patients had controlled hypertension before COVID-19, and their office BP was <140/90 mmHg . The offTwenty-four-hour ABPM was performed in patients during 2018–2019, i.e., less than a year before they tested positive for COVID-19 (PCR tests). ABPM showed satisfactory target values . PatientAfter COVID-19, their BP was monitored in the office, and well-controlled BP was shown in all patients . ThereafThere was no change in the lifestyle, treatment regimens or medication adjustment since the last BP compensation control performed by ABPM during 2018–2019. COVID-19 was not treated with drugs influencing BP .As for hypertension therapy, patients were treated with ACE inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics and beta-blockers. Their distribution can be seen in There was no change in antihypertensive medication between the two ABPMs. Before and after COVID-19, preparation and usage of medication were in the control of families or carers. During the hospitalization, when patients had a fever, they were taken off diuretics and an adequate intake of liquids was ensured by IV rehydration. When their hospitalization finished, they started to use diuretics regularly again as they did before the fever. No patients had contraindications. During the febrile state, the intermittent deterioration of chronic kidney disease in the context of pre-renal failure was observed. However, after careful hydration of patients, the renal functions were stable and within the same range . We did Patients had the following medical history: ischemic heart disease (2/5), stroke/TIA (1/5), diabetes mellitus and prediabetes (IGT) (2/5), atrial fibrillation (1/5), obstructive pulmonary disease (1/5) and chronic kidney disease (3/5).There was no difference in BP in smokers, ex-smokers and non-smokers.Patients 1–5 were hospitalized with COVID-19 for 36, 28, 38, 43 and 45 days, respectively. During hospitalization, Patients 1 and 3 required supplemental oxygen but did not require oxygen delivery through a high-flow device. They had dexamethasone therapy. Patient 2 had mild to moderate COVID-19  and was provided supportive care . After COVID, we observed loss of weight that can be attributed to the reduction of muscle mass caused by hypomobility and to disease-related malnutrition (DRM), which we monitored in a comprehensive geriatric assessment (CGA).As shown in the ABPM , the detWe are not aware of any factors that could contribute to BP lowering in these five patients. After COVID-19, the patients faced common post-COVID complications such as long-COVID fatigue, faintness, low performance/productivity and sometimes vertigo.To the best of our knowledge, no study has focused on the BP in patients with hypertension after they recovered from COVID-19, especially not in frail geriatric patients with sarcopenia. During the BP measuring in the office after COVID-19, the patients were normotensive, and the therapy seemed to be set well. Nevertheless, after routine control of the effectiveness of the treatment (24 h ABPM), we detected hypotension in our patients. This suggests we cannot only rely on the office BP measurement since one-off measurements may not accurately reflect the BP of a patient, but we should use the 24 h ABPM as a complementary measurement (as suggested by ESC/ESH Guidelines ), if notAccording to 2018 ESC/ESH Guidelines, the desired SBP target range for all patients aged >65 years is 130–139 mmHg and diastolic blood pressure (DBP) of <80 mmHg if tolerated, and treated SBP values of <130 mmHg should be avoided [Since ABPM in our patients showed hypotension (both SBP and DBP were much lower), the therapy and medication intake had to be adjusted to avoid potential risks because “the lower the better” does not seem to be valid for elderly patients. Results of the PARTAGE study show that frail patients (>80 years) with very low SBP (<130 mmHg) who are taking multiple antihypertensives (two or more) have an increased risk of mortality . SimilarCurrent findings from Sheppard et al.  show thaABPM measuring was performed 3–6 months after the patients left the hospital; therefore, we assume BP-lowering to be a tardive effect. Current guidelines [To assess frailty, we used the frailty index for its complexity and precision. Nevertheless, frailty is a complex phenomenon with a multifactorial etiology; therefore, there is no diagnostic standard, and the aging phenotypes and gender dimorphism should be taken into account ,14. FraiAs a consequence of COVID-19, patients are facing disruption of muscle function, and the total amount of muscle mass is reduced (sarcopenia) due to hypomobility and disease-related malnutrition. Their disability progresses, and they are dealing with even more self-care limitations in activities of daily living (ADL) and instrumental activities of daily living (iADL). Geriatric hypomobility syndrome, deconditioning and muscle weakness contribute to the BP lowering as mentioned for example in the study of Joyner and Masuki . The hosNevertheless, we expect there is also another factor or mechanism influencing the BP. We presume that this decrease in BP is associated with ACE (Angiotensin-converting-enzyme) inhibitors and beta-blockers, which are currently discussed as drugs influencing the risk of COVID-19 and its severity. At the beginning of the pandemic, using ACE inhibitors was hypothesized to present an increased risk of developing COVID-19 disease with a severe course due to the presumed higher expression of the ACE2 enzyme in the lung cells. The SARS-CoV-2 virus uses the enzyme ACE2 to enter cells . Based on the assumption that hypertensive patients taking ACE inhibitors have increased expression of this enzyme, some authors have suggested that when these patients are infected with the SARS-CoV-2 virus, the virus will extensively enter primarily into the lungs and that this treatment means an increased risk of developing COVID-19 and a more severe course. However, as Hippisley-Cox et al.  showed, SARS-CoV-1 and SARS-CoV-2, which have been responsible for the SARS epidemic and the COVID-19 pandemic, respectively, interface with the renin–angiotensin–aldosterone system (RAAS) through ACE2, an enzyme that modulates the effects of the RAAS but is also the primary receptor for both SARS viruses [SARS-CoV-2 binds and degrades ACE2, thereby potentially reducing its counter-regulatory effects . If ACE2Our patients were also taking beta-blockers. Data of Reynolds et al.  suggesteSome of our patients are ex-smokers and smokers. Smoking may cause increased ACE2 mRNA expression in human lung much as ACE inhibitors or ARBs are believed to, suggesting a possible common protective mechanism for severe COVID-19 disease , and posHypotension after COVID-19 may be presented in a lower number of hypertensive patients, but we would like to bring attention to it, especially when hypertension occurs in frail geriatric patients who have a higher mortality risk and are prone to the progression of cognitive frailty. Low BP, both diastolic and systolic, in the populations of the elderly is correlated with worse cognitive performance. Hypotension and excessive treatment of hypertension may induce cerebral hypoperfusion, ischemia  and hypoxia, leading to neurodegenerative processes that speed up the clinical manifestations of cognitive impairment and dementia .Our case report shows that there might be an increased risk which hypertensive patients may face after COVID-19: overmedication. It also highlights the importance of ABPM. Changes in BP values which are often not detected by common office BP measuring but are revealed by ABPM suggest its key role in the therapy and treatment management of hypertensive patients.These findings suggest that BP control after COVID-19 is needed and that ABPM is by no means a luxury but rather a necessity, especially in frail geriatric patients. Therefore, it is recommended to proceed with a more profound BP check than office BP measurement, particularly in frail geriatric patients.


Objective: The burden of suicidal behavior is anticipated to increase as a sequela of the COVID-19 pandemic. However, there is limited evidence on suicidal behavior among healthcare workers, an at-risk population. Our study aimed to investigate suicidal ideation in terms of the rate and associated factors in a sample of Malaysian healthcare workers during the early-phase of the COVID-19 pandemic.Methods: A subpopulation analysis (N = 171) was conducted within a larger, nation-wide cross-sectional study of Malaysian healthcare worker psychological distress from March 18–21, 2020. Current suicidal ideation was measured with item 9 of the Patient Health Questionnaire-9 (PHQ-9). The following independent variables were assessed: socio-demographic profile, occupation and service-related factors, health-anxiety , lifetime anxiety disorder and severity of depression (PHQ-9).Results: The proportion of healthcare workers with current suicidal ideation (19/171) and clinical depression (17/171) were 11.1 and 9.9%, respectively. Multivariable analysis showed that clinical depression was the most significant factor associated with current suicidal ideation  followed by mild (subthreshold) depression . Service duration of more than 10 years was associated with significantly less suicidal ideation .Conclusions: Depression  and early-career status (<10 years in service) may be target areas of early intervention for reduction of suicidal ideation amongst healthcare workers who have served during the COVID-19 pandemic. Further research is warranted to elucidate specific occupational stressors related to COVID-19 work conditions to tailor appropriate suicide preventive strategies in this population. Suicidal behavior has been projected to increase globally  as a seqThe myriad stressors faced by HCWs worldwide in their personal and professional spheres are currently compounded by unprecedented challenges due to the COVID-19 pandemic. A meta-analysis showed that the mental health impact of the COVID-19 pandemic on healthcare workers was more severe compared to the general population . SignifiNepalese healthcare workers who felt stigmatized, had a history of receiving psychiatric medication, and reported insufficient preventive measures at work seemed to be at higher risk of experiencing mental health problems . Among aPublished systematic research in terms of the pandemic's effect specific to suicidal behavior  in this high-risk population (HCWs) is limited. Anecdotal reports have linked the recent suicide deaths amongst frontline HCWs with the collective experience of fear, hopelessness, helplessness, and moral injury in the line of duty during the COVID-19 pandemic , 4. ThesWith regards to the spectrum of suicidal behavior, it is important to identify risk factors of suicidal ideation which can be distinct from predictors of more severe spectrum of suicidal behaviors  –15. ThouTherefore, the objectives of this study are to investigate the rate of suicidal ideation and the association between suicidal ideation with the following factors: socio-demographic profile, depression, health anxiety and lifetime anxiety disorder, and occupation and service-related factors, amongst a heterogenous and culturally diverse sample of Malaysian HCWs during the early phase of the COVID-19 pandemic.N = 763) nationwide, cross-sectional study on psychological distress among Malaysian HCWs; during the early phase of the COVID-19 pandemic. Ethics approval was obtained from the Medical Research and Ethics Committee, MREC: NMRR-20-1036-53864 and The National University of Malaysia Ethics Committee, UKM: FF 2020-130). According to the Malaysian Ministry of Health (MOH), frontliners are defined in the context of the COVID-19 pandemic as “individuals with high risks of contracting and transmitting Covid-19 infection i.e., those who are directly exposed to an infected individual, an individual at high risk of being infected, a patient sample or an environment that has the potential to be the source of the infection.” Healthcare workers (HCWs) are categorized by the Malaysian health ministry as frontline essential workers during the pandemic  aged between 18 and 60 years-old and (ii) able to read and write in the English language. Data collection was done through an online survey (Google Form). Advertisements for recruitment were sent or posted via email, social media platforms  among the networks of the research team, and via organizational/institutional email listserv/mailing lists/websites. The online survey Google Form included a study information sheet, informed consent form, declaration of anonymity and confidentiality as well as information on how to access crisis helplines. Participants were also given the option of including their contact information if they agreed to be contacted and offered online psychological support. Eligible Malaysian health care workers who gave informed consent were subsequently directed to the self-report questionnaire section in the online survey.The self-report questionnaire section consists of four components: socio-demographic and occupational/service-related data, Health Anxiety Inventory (HAI), presence or absence of lifetime anxiety disorder, and severity of depression (PHQ-9).The following data were collected from respondents: age, gender, ethnicity, educational level, marital status, type of HCW occupation (physician/non-physician), working hours, and duration of service. Self-reported data on the absence or presence of lifetime anxiety disorder was also collected.For this study, the very-short version of HAI was used. This screening instrument assessed health anxiety independently of physical health status with 14 items. Items assess worries about health, awareness of bodily sensations or changes, and feared consequences of having an illness. The very-short version HAI has demonstrated good reliability, criterion validity, and sensitivity to treatment . A cut-oThe PHQ-9 is a self-administered questionnaire which measures the frequency of symptoms of depression using nine items on a 4-point Likert-scale ranging from 0  to 3 (nearly every day). It has demonstrated good construct validity . A totalt-tests. The dependent variable of suicidal ideation (PHQ item 9) was analyzed as a dichotomous (yes/no) variable. The following variables were analyzed as categorical independent variables: gender, relationship status (single vs. married), lifetime anxiety disorder (yes/no), ethnicity , education level (low: diploma level and below/high: degree level and above), occupation (physician/non-physician), severity of depression , working hours per week (<40 h/40 to 50 h/> 50 h) and service duration (years: 1–3/4–6/7–10/>10). Health anxiety (HAI) scores were analyzed as a continuous independent variable (assumption of linearity was met for HAI scores with the outcome dependent variable). Values for 10 cases with missing data on continuous predictors were imputed using median. After deletion of 4 cases with missing values either on gender, relationship status, ethnicity, occupation, and having anxiety disorder, data from 171 respondents were available for analysis. Likelihood ratio test was used to determine which independent variables were included into the multivariable logistic regression model. According to Peduzzi et al. , Malay ethnicity (78.4%), married (62%), and with an educational level of a bachelor's degree or higher (70.2%). Most of the participants were physicians (56.2%), mainly working between 40 and 50 h per week (56.1%), and with a service duration of 7–10 years (36.8%). Eighty-three percent of study participants were healthcare workers in hospitals or healthcare facilities that were designated as COVID-19 treating or screening healthcare facilities. Cronbach alpha for HAI and PHQ were 0.879 and 0.873, respectively. Current clinical depression and lifetime anxiety disorder were present in 9.9% (17/171) and 11.1% (19/171) of participants, respectively. Nineteen out of 171 healthcare workers (11.1%) reported current suicidal ideation in the past 2 weeks. Fifty three percent (10/19) of those with suicidal ideation did not meet criteria for clinical depression (no or subthreshold depressive symptoms). Fifty three percent (9/17) of healthcare workers with clinical depression reported suicidal ideation. There was no multicollinearity between the independent variables. The correlation between the independent variables was 0.45 (<0.8).p = 0.017), higher levels of health anxiety (p = 0.234), and higher severity of depression (p < 0.001). Participants with more than 10 years of service duration had a significantly lower rate of current suicidal ideation (p = 0.013). Multivariable logistic regression model  followed by mild depression . Service duration of more than 10 years was associated with significantly less suicidal ideation .From bivariate analysis , factorson model  showed tThe burden and risk factors of suicidal behavior among health care workers in low- and middle-income countries have not been well-established . Our preDepression is a well-established risk factor for suicidal behavior  among medical physicians and nurses , 38. OurOur study demonstrated that a longer duration of service (more than 10 years) appeared to be protective against suicidal ideation in Malaysian HCWs during the early phase of the COVID-19 pandemic. This finding remained significant after controlling for age, gender, marital status, ethnicity, educational level, type of health care occupation and medical specialty, working hours as well as self-reported clinical depression, health anxiety or other anxiety disorders. Previous research findings have been somewhat mixed in terms of the significance of seniority and suicidal behavior among physicians. The level of seniority was not significantly associated with suicide among physicians in England and Wales . Being iFindings from our study echo a signal of increased vulnerability to suicidal ideation in early career compared to senior HCWs. The exact mechanisms underlying the interaction between suicidal behavior and stressors  encountered by HCWs in tandem with their level of work experience; are beyond the scope of this study. Nevertheless, previous research highlighted that physician burn-out can contribute to the complex issue of suicidal behavior in the medical profession .Burn-out has been conceptualized as an occupational phenomenon that is separate from a medical condition . This isOften, clinicians in the early phases of their careers inadvertently end up at the frontline of critical health care provision as part of their training. A study from Singapore reported that COVID-19 frontline HCWs mainly comprised of residents . The hieData from the general population during the current pandemic have shown that British young adults (18–29 years) have a heightened risk for suicidal ideation compared to middle-aged and older adults . In the In view of depression being a significant factor associated with suicidal ideation, early identification of depression as a target for intervention is a potential suicide preventive strategy  among HCHealthcare workers with less seniority in service appear to be a more at-risk population for suicidal ideation during this pandemic. Current models have recommended pre-frontline deployment training that emphasize resilience building, especially for medical staff that are more junior and less experienced in frontline crisis and disaster health services , 62. PreThis study is susceptible to type II error due to the relatively small sample size. We acknowledge that our study is limited by cross-sectional design which is unable to determine causality of suicidal ideation found in healthcare workers in the context of the COVID-19 pandemic. The generalizability of findings from this study is limited by the non-random sampling of HCWs in Malaysia. Item 9 of the PHQ was used to assess current suicidal ideation in this study. Previous research has supported the utility of Item 9 of the PHQ-9 as an initial screening measure for risk of suicidal acts at the individual patient-level . HoweverOur study has highlighted that depression, both at the subthreshold level and particularly in the clinical range, may be associated with suicidal ideation, while a longer service duration is potentially protective against suicidal ideation amongst Malaysian HCWs. Identification and treatment of depression, as well as a focus on early-/mid-career HCWs as a target population for early intervention may be potential areas for suicide prevention amongst HCWs who have been exposed to the COVID-19 pandemic working environment.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Medical Research and Ethics Committee. The patients/participants provided their written informed consent to participate in this study.NRNJ (P.I. and grant-holder of this study), HMSS, and LFC conceptualized this study. HMSS and FHAR was involved in the database collection and organization of this study. HMSS, TIMD, LFC, SAS, FHAR, and NRNJ were responsible for data analysis, interpretation of study results, and involved in the writing and review of the final draft of this manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Rates of invasive aspergillosis (IA) among COVID-19 ICU patients seem to reach over 30% in certain settings. At Vienna General Hospital (VGH), all rooms in COVID-19 ICUs were put under negative pressure as a protective measure, thus increasing the risk of exposure to environmental pathogens for patients. Even though all ICU patients are surveilled for healthcare-associated infections (HAI), there were concerns that the routine protocol might not be sufficient for IA detection. We reviewed the electronic patient charts of all patients with COVID-19 admitted to ICUs between 1 March 2020 and 31 July 2021 for fungal co- or superinfections, comparing four diagnostic algorithms based on different recommendations for the diagnosis of IA  to our routine surveillance protocol. We found that out of 252 patients who were admitted to the ICU during the study period, 25 (9.9%) fulfilled the criteria of probable or possible IA of at least one algorithm. The IAPA definitions detected 25 and the CAPA definition 23 probable and 2 possible cases, out of which only 16 were classified as hospital-acquired IA by routine surveillance. In conclusion, adjustment of the routine protocol using a classification system especially designed for respiratory viral illness seems useful for the surveillance of IA in a highly vulnerable patient cohort. Aspergillus fumigatus [Invasive aspergillosis (IA), which is most commonly caused by umigatus ,2,3, is umigatus ,5. It alumigatus ,2.Although reports on IA rates among COVID-19 ICU patients vary, some authors have reported rates of over 30% ,7. TheseDiagnosis of IA is still a challenge despite considerable advances in the last few decades. Diagnosis is mainly based on cultural techniques, histopathology and biomarkers. It is additionally supported by typical radiological signs and by the presence of pre-existing conditions that increase susceptibility to IA.In COVID-19 ICU patients, however, diagnosis of IA is particularly challenging due to COVID-19-damaged lungs and the associated lesions in CT scans masking IA. It is further hampered by the reluctance to obtain invasive or bronchoscopic specimens from the lower respiratory tracts of highly infectious patients ,13. ColoAt VGH, patient rooms in ICU units are usually designed to function as a protective environment. They have a ventilation system equipped with high-efficiency particulate air (HEPA) or even ultra-efficiency particulate air (ULPA) filters and relative positive room pressure to reduce the exposure to particles and spores. In contrast, at the beginning of the pandemic, rooms in ICUs that treated COVID-19 patients were converted into makeshift airborne infection isolation rooms (AIIR) that lacked anterooms but offered certain protection to staff and other patients through reversed airflow and relative negative pressure . HoweverAdditionally, from July until October 2020, demolition of one of the oldest buildings of VGH , BT83 waEven though all ICU patients at VGH are under continuous surveillance for healthcare-associated infections (HAI) according to the European Centers of Disease Prevention and Control (ECDC) HAI-Net ICU protocol (including different types of pneumonia) , we wereWe conducted an observational study on the incidence of IA in COVID-19 patients admitted to the ICU and retrospectively compared four diagnostic algorithms based on different recommendations for the diagnosis of IA as an add-on to our routine surveillance protocol.Vienna General Hospital is a 1740-bed academic hospital providing treatment for 347,926 outpatients and 59,454 inpatients in 2020. There are 15 intensive care units with 134 beds at the hospital, comprising three surgical units, one cardiothoracic surgery unit, one vascular surgery unit, one neurosurgical unit, one burn unit, one transplant unit, three internal medicine units, three pediatric units and one psychiatric unit. During the COVID-19 pandemic, VGH mainly served as a reference center for patients with severe COVID-19, requiring intensive care including extracorporeal membrane oxygenation (ECMO). During the first national lockdown in the spring of 2020, all non-urgent patient care at VGH was postponed in order to avoid an overload of ICUs and normal wards alike. By summer 2020, routine medical operation was gradually resumed.We retrospectively analyzed data of SARS-CoV-2 intensive care patients with filamentous fungal co- and superinfections at a tertiary care center. The study was approved by the Medical University of Vienna’s ethics committee (EK Nr. 1388/2021).VGH’s HVAC system for the ICUs uses 100% fresh air. The ventilation apertures are situated on the 12th floor of the main hospital building , BT10 beAir change rates in the patient rooms range from 10 to 26 per hour, with the highest air change rates achieved on the burn unit and units that care for patients immediately after organ transplantation.All ICU rooms are designed as protective environment rooms, where the airflow creates a mild positive differential pressure of 10 to 15 Pa with respect to adjacent rooms in order to protect vulnerable individuals from airborne pathogens. In the early stages of the COVID-19 pandemic, the airflow at ICUs caring for COVID-19 patients was adjusted so that the resulting negative differential pressure would protect HCW and fellow patients from aerosols dispersed by COVID-19 patients.All patients admitted to ICUs due to severe COVID-19 between 1 March 2020 and 31 July 2021 were included in the study. Electronic patient charts of all identified patients were reviewed in order to establish the diagnosis of a fungal co- or superinfection. Apart from information on fungal infection, we gathered data on laboratory results , length of stay (LOS), ventilation and outcome. For patients with IA, data on severity of disease (SAPS score), hospital stay , SARS-CoV-2 infection (including ECMO and intubation) and medication  were collected additionally.Since 2017, routine surveillance of healthcare-associated infections for ICU patients has been in place at 14 out of 15 ICUs at VGH. Surveillance is conducted using the ECDC HAI-Net ICU protocol, version 2.2 [In order to evaluate the performance of the HAI-Net ICU protocol for IA in COVID-19 patients, we compared it to the diagnostic criteria defined by the following publications: the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG); the modified version for diagnosing invasive pulmonary aspergillosis in critically ill patients (BM-AspICU) ; the defAll algorithms require culture from sterile material or histopathology for the classification of proven cases, whereas they differ regarding the patients’ underlying diseases that are accepted as host factors for probable IA. According to EORTC/MSG, a probable case of IA requires at least one host factor reflecting severe immunosuppression , which are not generally present in ICU patients. BM-AspICU is designed for ICU patients and uses chronic diseases such as chronic obstructive pulmonary disease (COPD), viral respiratory diseases including SARS-CoV2 infection, hepatic insufficiency, diabetes, chronic alcohol abuse and other chronic diseases in addition to the EORTC/MSG host factors. IAPA focuses on influenza patients; therefore, a positive influenza PCR or antigen test in patients presenting with influenza-like illness is the only host factor . Correspondingly, according to CAPA, only patients with COVID-19 needing intensive care are included. CAPA also allows classification of possible in addition to probable cases when culture, PCR or antigen tests are positive in non-bronchoscopically obtained specimens only.For probable or possible IA, all algorithms additionally require some form of clinical or radiological sign and a mycological sign . Main features are shown in ®, Brain-Heart Infusion Agar slants and Sabouraud Glucose broth  and incubated at both 35–37 °C and 28–30 °C for up to three weeks. Upon cultural growth, fungi were further identified by macroscopic and microscopic assessment and MALDI-TOF . Resistance testing was performed using E-test® on RPMI agar. Minimal inhibitory concentrations (MIC) were interpreted according to the clinical breakpoints issued by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). For antigen detection, Platelia™ Aspergillus Ag  and Fungitell® Assay  were used for aspergillus-galactomannan  and (1-3)-β-D-Glucan (serum), respectively.Mechanically ventilated patients were routinely screened for filamentous fungal infection using culture and galactomannan assay out of bronchoalveolar lavage upon intubation. In case of clinical deterioration, galactomannan assay out of respiratory specimens or serum was repeated and β-D-Glucan assay out of serum was conducted. The Division of Clinical Microbiology at VGH further processed respiratory specimens using standard microbiologic methods. For cultural detection of fungi, specimens were set onto Sabouraud Dextrose agar, CHROMagarCandidaStatistical analysis was conducted using IBM SPSS Statistics software 26.0 , Microsoft Excel 2016  and RStudio version 4.0.2 . Descriptive statistics are presented as absolute numbers and percentages for categorical variables and as either mean and 95%CI or median and IQR for continuous variablesDuring our study period, 252 COVID-19 patients were admitted to the ICU. Median age was 57 (IQR: 46–65) and 32.1% were female. Most of the patients were mechanically ventilated  and nearly a third died during their ICU stay . Median length of stay at ICU was 26 days (IQR: 11.8–41.3). Further characteristics are shown in Out of those 252 COVID-19 patients at the ICU, 172 were screened for fungal infection using the β-D-Glucan assay (68.3%), 163 using the galactomannan assay (64.7%) and 104 using fungal culture from respiratory specimens (41.3%). We identified 36 patients with positive fungal culture, galactomannan assay or β-D-Glucan assay. Of those 36 patients, eleven patients were excluded, not meeting any of the criteria for invasive aspergillosis, e.g., when culture was positive for fungi other than aspergillus or when only β-D-Glucan was positive. Characteristics of the resulting 25  patients with IA and COVID-19 are summarized in Out of 25 patients, 17 were male (68%), and the median age was 60 (IQR: 54–68), ranging from 44 to 84 years. The majority of patients were transferred either from another hospital to the ICU  or from a regular ward at VGH , and only one patient was admitted directly from home (4%). Diagnosis of COVID-19 was established before admission for all but two patients . Median SAPS II score on admission was 41 (IQR: 32.5–49), reflecting a 25% probability of in-hospital death . All patResults for different diagnostic algorithms are displayed in n = 22), the time from diagnosis of COVID-19 to diagnosis of IA (date of diagnostic sample collection) ranged from seven to 37 days . We did not identify any polymicrobial infections. Resistance testing was performed for 12 isolates . All isolates were susceptible to amphotericin B, itraconazole, voriconazole and isavuconazole, except A. terreus and A. nidulans, which are considered poor targets for amphotericin B. Five out of ten isolates were considered susceptible at increased exposure to posaconazole, while the rest were susceptible.For patients with a known start date of COVID-19 infection n = , the timOf 16 cases classified as PN3, nine died within the observation period (56.3%). Four patients  who had probable IA according to EORTC/MSG died, 12  according to BM-AspICU. All patients who did not survive the study period were probable cases according to IAPA and CAPA.Pseudomonas aeruginosa as the causative agent for pulmonary superinfection and regarded Aspergillus fumigatus as a contaminant.Diagnosing IA in ventilated COVID-19 patients is notoriously challenging. Clinical presentation and radiological findings of pulmonary aspergillosis may be very similar to those of COVID-19 ARDS, particularly if CT scans cannot be easily obtained due to the severe clinical condition of these patients. Only 10 of our patients underwent CT scanning, which mostly revealed pulmonary infiltrates that were not pathognomonic for IA. One patient had a cavitary lesion that was attributed to IA and one showed signs that the radiologist described as congruent with fungal pneumonia. Surprisingly, the latter patient did not receive antifungal therapy despite repeated positive aspergillus cultures and galactomannan assays from BAL and was eventually discharged after more than 70 days in the ICU. Clinicians probably suspected All other patients had regular chest X-rays at the ICU, where mostly dense infiltrates and ground glass opacities were described. Infiltrates that cannot be attributed to other causes allow classification as probable cases according to IAPA and CAPA as well as HAI-ICU, which may reduce specificity and leaves room for interpersonal differences in interpretation when bacteria are recovered from respiratory specimens as well as aspergillus.All patients underwent bronchoscopy multiple times in spite of concerns regarding staff safety , thus reducing the probability of mere aspergillus colonization of the upper airways, which has to be considered when only sputum or tracheal aspirate can be analyzed. This may largely be due to the fact that 80% of our patients were transferred from other ICUs and may therefore no longer have been considered highly infectious by the time of admission at VGH, which reflects VGH’s role as a referral center for the most severe cases of COVID-19 ARDS.We were surprised to find that only one out of 23 patients (4.3%) who were screened for GM in serum had a positive result, compared to fifteen out of 23 (65.2%) that were positive for BDG. This corresponds to earlier findings of low sensitivity in immunosuppressed ventilated patients, where the sensitivity of serum GM was 35% compared to 88% for BDG , as wellSome experts have expressed concerns of overtreatment with antifungals when applying highly sensitive criteria that are mainly based on mycological evidence . In our When comparing the different diagnostic algorithms, influenza-specific (IAPA) and COVID-specific (CAPA) algorithms lead to similar results. Using EORTC/MSG and BM-AspICU criteria, fewer patients were classified as probable cases, due to the lack of immunosuppression in a traditional sense. In any case, cultures from lower respiratory tract specimens remained the main pillar for the presumptive diagnosis of IA. A publication by Fekkar et al.  highlighS. aureus, enterobacterales and nonfermenting gram-negatives. HAI-Net ICU is obviously not designed for the surveillance of fungal infections of the lung, as purulent sputum, fever and leukocytosis may be absent in aspergillosis, but are the prerequisites for the classification of PN. Regarding nosocomial IA acquired at the ICU due to the exceptional circumstances, such as the reversed airflow and demolition work, a more focused surveillance approach will be needed. This is all the more true as the determination of the healthcare association of IA is complicated by prolonged incubation periods, though, in our setting, the minimum duration from in-hospital detection of SARS-CoV-2 until IA was one week, and the median time was 18 days, indicating the nosocomial origin for most of the infections.Only seventeen out of 25 probable or possible cases of IA were detected when applying routine surveillance according to the ECDC 2017 protocol, which aims primarily at the detection of infections caused by classical nosocomial pathogens such as n = 25/252) of all COVID-19 patients admitted to VGH’s intensive care units from March 2020 to July 2021 developed IA. This number is in line with data on patients with ARDS due to causes other than COVID-19 [Using the most sensitive algorithm, 9.9% (COVID-19 ,28. It iCOVID-19 , but sliCOVID-19 ,30,31,32Most patients had no severe underlying diseases, reflected by a non-fatal McCabe score in 92%. They rather presented with classical features of metabolic syndrome, such as obesity, non-insulin dependent diabetes mellitus and hypertension, which certainly affect a large proportion of Austrians. This again does not feed into the narrative that only the very old and very sick COVID-19 patients suffer the most severe forms of COVID-19.Our study has several limitations. Firstly, it is purely descriptive, as we could not identify a suitable control group. COVID-19 is a relatively new entity with unique pathognomonic features; therefore, comparison with other ICU patients is difficult. Patients with acute respiratory distress syndrome due to other underlying illnesses are not stringently screened for IA; therefore, retrospective comparison seemed inappropriate.Secondly, autopsy was only performed on two of the patients; for all other fatal cases, pathological workup was forgone due to staff safety concerns, the fact that the reasons for demise were conclusive for the treating clinicians and due to relatives’ preferences. This is understandable, but makes a final classification of cases and the assessment of the diagnostic algorithms’ validity in this particular collective difficult. It also impedes the establishment of a causal relationship between fungal infection and the high mortality in our collective. Lastly, when comparing IA rates between institutions, one should exercise caution due to external factors, such as geographical variation or, as in our setting, extensive construction and demolition work in the hospital surroundings.In our study, a significant proportion of patients developed IA; most of these patients had no severe underlying disease, but mortality was still comparatively very high. From an infection prevention and control perspective, for the surveillance of IA in a highly vulnerable patient cohort, such as patients with severe COVID-19, applying an algorithm especially designed for respiratory viral illness seems useful. This is particularly true when aggravating circumstances such as reversed airflow and large construction and demolition work are present.