Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Diagnostic value of synovial fluid adenosine deaminase level in tuberculous arthritis.

Although body fluid adenosine deaminase (ADA) level is useful for diagnosing tuberculosis but little is known about joint fluid ADA level in tuberculous (TB) arthritis. This study aimed to evaluate the diagnostic value of synovial fluid ADA (SF-ADA) in TB arthritis. Of 43 patients enrolled, nine had confirmed TB arthritis. Fourteen had non-TB septic arthritis, and 20 patients had non-infectious etiologies. The SF-ADA levels were significantly elevated in patients with TB arthritis compared to those with non-infectious origin (P <0.05). All SF-ADA levels were 76 ≥ U/L in TB arthritis and < 60 U/L in non-infectious synovial fluid. The ADA was not different between TB arthritis and non-TB septic arthritis (P = 0.87). The possibility of identifying synovial fluid with an ADA under 60-76 U/L of tuberculous etiology may be very low. In addition, an SF-ADA >76 U/L with negative ordinary bacterial culture results is highly suspicious for TB arthritis.

Antimicrobial Susceptibilities of Clostridium difficile Isolates from 12 Asia-Pacific Countries in 2014 and 2015.

Clostridium (Clostridioides) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including C. difficile ribotype (RT) 027 in North America and Europe and RT 017, the most common strain in Asia. Despite being the most common cause of hospital-acquired infection in high-income countries, and frequent misuse of antimicrobials in Asia, little is known about CDI in the Asia-Pacific region. We aimed to determine the antimicrobial susceptibility profiles of a collection of C. difficile isolates from the region. C. difficile isolates (n = 414) from a 2014 study of 13 Asia-Pacific countries were tested for susceptibility to moxifloxacin, amoxicillin-clavulanate, erythromycin, clindamycin, rifaximin, metronidazole, vancomycin, and fidaxomicin according to the Clinical and Laboratory Standards Institute's agar dilution method. All isolates were susceptible to metronidazole, vancomycin, amoxicillin-clavulanate, and fidaxomicin. Moxifloxacin resistance was detected in all countries except Australia, all RT 369 and QX 239 strains, and 92.7% of RT 018 and 70.6% of RT 017 strains. All C. difficile RT 012, 369, and QX 239 strains were also resistant to erythromycin and clindamycin. Rifaximin resistance was common in RT 017 strains only (63.2%) and was not detected in Australian, Japanese, or Singaporean isolates. In conclusion, antimicrobial susceptibility of C. difficile varied by strain type and by country. Multiresistance was common in emerging RTs 369 and QX 239 and the most common strain in Asia, RT 017. Ongoing surveillance is clearly warranted.

Acute Kidney Injury and Kidney Damage in COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This disease, which is quickly spreading worldwide, has high potential for infection and causes rapid progression of lung lesions, resulting in a high mortality rate. This study aimed to investigate the effects of SARS-CoV-2 infection on renal function in patients with COVID-19. METHODS: From February 21 to April 24, 2020, 66 patients diagnosed with COVID-19 at Chungnam National University Hospital were analyzed; all patients underwent routine urinalysis and were tested for serum creatinine, urine protein to creatinine ratio (PCR), and urine albumin to creatinine ratio (ACR). RESULTS: Acute kidney injury (AKI) occurred in 3 (4.5%) of the 66 patients, and 1 patient with AKI stage 3 underwent hemodialysis. Upon follow-up, all 3 patients recovered normal renal function. Compared with patients with mild COVID-19, AKI (n = 3) occurred in patients with severe COVID-19, of whom both urine PCR and ACR were markedly increased. CONCLUSION: The incidence of AKI was not high in COVID-19 patients. The lower mortality rate in SARS-CoV-2 infection compared with previous Middle East respiratory syndrome and SARS-CoV infections is thought to be associated with a low incidence of dysfunction in organs other than the lungs.

COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial Sepsis.

BACKGROUND: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a 'cytokine storm' is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). METHODS: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the pro-inflammatory cytokines/chemokines. RESULTS: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV-2 significantly increased pro-inflammatory cytokines/chemokines and S100A9 in human primary PBMCs. CONCLUSION: These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

Predictive risk factors for Listeria monocytogenes meningitis compared to pneumococcal meningitis: a multicenter case-control study.

PURPOSE: Various immunocompromised conditions increase the risk of meningitis caused by Listeria monocytogenes. However, the relative importance of these risk factors has not been well established. We determined the risk factors that predict meningitis due to L. monocytogenes compared to that caused by Streptococcus pneumoniae. METHODS: A nationwide multicenter case-control study was conducted in Korea. Cases of meningitis caused by L. monocytogenes between 1998 and 2013 were included. Patients with pneumococcal meningitis were included as controls. Multivariate logistic regression analysis was used to predict the risk factors of Listeria meningitis. RESULTS: A total of 36 cases and 113 controls were enrolled. The most significant predictive risk factor of Listeria meningitis was a prior history of receiving immunosuppressive therapy (odds ratio 8.12, 95 % CI 2.47-26.69). Chronic liver disease was the second most important predictive risk factor (OR 5.03, 95 % CI 1.56-16.22). Delaying appropriate antibiotic therapy by more than 6 h (hazard ratio 2.78) and fatal underlying disease (hazard ratio 2.88) were associated with increased mortality. CONCLUSIONS: Patients with a prior history of receiving immunosuppressive therapy within 1 month and chronic liver disease have 8.1-fold and 5-fold increased risk of meningitis by L. monocytogenes compared to S. pneumoniae, respectively.

Catheter-related bacteremia caused by Kocuria salsicia: the first case.

We report the first case of catheter-related bacteremia caused by Kocuria salsicia in a patient with short bowel syndrome. The pathogen was initially identified as Kocuria varians by a Vitek 2-based assessment, but its 16S rRNA gene sequence showed 100% similarity to K. salsicia. The patient was successfully treated with vancomycin and removal of the catheter.

The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study.

BACKGROUND: We estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea. METHODS: To evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity. RESULTS: Three hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US $20,494 for MRSA-BSI and $6,914 for MSSA-BSI. Total additional annual cost of nosocomial SA-BSI was $67,192,559. CONCLUSION: In view of the burden of nosocomial SA-BSI, a national strategy for reducing nosocomial SA-BSI is urgently needed in South Korea.

Mortality of community-acquired pneumonia in Korea: assessed with the pneumonia severity index and the CURB-65 score.

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.

Administering Antibiotics for Less Than Four Weeks Increases the Risk of Relapse in Culture-Positive Septic Arthritis of Native Joints.

(1) Objectives: This study investigated the optimal duration of antibiotic therapy and determined the risk factors associated with relapse in patients with culture-proven septic arthritis of native joints. (2) Methods: A retrospective review was conducted on patients aged ≥18 years diagnosed with native joint septic arthritis, with bacteria isolated from joints and/or blood. The exclusion criteria were prosthetic joint infections and cases with no identified microorganisms. The outcomes were assessed in the remission and relapse groups. (3) Results: Among 479 patients with native joint septic arthritis, 137 met the inclusion criteria, with a median follow-up duration of 2.7 years. The relapse rate was 9.5%, which mainly occurred within 30 days after antibiotic treatment completion. Compared with the remission group, the relapse group showed a significantly higher proportion of cases that received antibiotic therapy for ≤ 4 weeks (4.8% vs. 46.2%, p < 0.001), synovial fluid white blood cell (WBC) counts ≥150 × 103/mm3 (25.3% vs. 60.0%, p = 0.030), acute kidney injury (19.2% vs. 50%, p = 0.024), and extended-spectrum beta-lactamases-producing Enterobacteriaceae (0.8 vs. 15.4%, p = 0.024). Independent risk factors for relapse were determined as antibiotic therapy duration of ≤ 4 weeks (odds ratio (OR), 25.47; 95% confidence interval (CI), 1.57-412.33; p = 0.023) and synovial fluid WBC counts ≥150 × 103/mm3 (OR, 17.46; 95% CI, 1.74-175.62; p = 0.015). (4) Conclusions: Patients with native joint septic arthritis require vigilant monitoring for relapse, particularly when treated with antibiotic regimens administered for less than four weeks or when synovial aspirates exhibit elevated WBC counts at diagnosis.

Methicillin Resistance Increased the Risk of Treatment Failure in Native Joint Septic Arthritis Caused by Staphylococcus aureus.

This study aimed to compare clinical characteristics and outcomes in patients with native joint septic arthritis (NJSA) due to methicillin-resistant Staphylococcus aureus (MRSA) in comparison to methicillin-sensitive S. aureus (MSSA) and identify treatment failure risk factors. We conducted a multi-center retrospective study on adult NJSA patients at three teaching hospitals in South Korea from 2005 to 2017. Among 101 patients diagnosed with S. aureus NJSA, 39 (38.6%) had MRSA strains. Compared to MSSA, patients with MRSA had a higher prevalence of nosocomial infections (17.9% vs. 1.6%; p = 0.005) and received inappropriate antibiotics within 48 h more frequently (74.4% vs. 0%; p < 0.001). In total, twenty patients (19.8%) experienced treatment failure, which encompassed five patients (5.0%) who passed away, nine (8.9%) requiring repeated surgical drainage after 30 days of antibiotic therapy, and seven (6.9%) with relapse. The MRSA group showed a higher rate of overall treatment failure (33.3% vs. 11.3%; p = 0.007) with a notably increased frequency of requiring repeated surgical interventions after 30 days of antibiotic therapy (17.9% vs. 3.2%, p = 0.026), in contrast to the MSSA group. Independent risk factors for treatment failure included Charlson comorbidity score, elevated CRP levels, and methicillin resistance. Methicillin resistance is an independent risk factor for treatment failure, emphasizing the need for vigilant monitoring and targeted interventions in MRSA-related NJSA cases.

Guidelines for Infection Control and Burnout Prevention in Healthcare Workers Responding to COVID-19.

During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare workers (HCWs) suffered more distress from the possibility of contracting the virus, quarantine, social stigma, and prejudice against their families. Many studies have investigated the impact of the pandemic on HCWs; however, studies or guidelines presenting strategies to overcome these challenges are lacking. As part of a 2020 research project supported by the Ministry of Health and Welfare, titled "Health impact assessment of healthcare workers undertaking coronavirus disease 2019 treatment and management in Korea: Identifying problems and researching effective solutions" (HC20C0003), we created guidelines to respond to serious problems posed by infection control. and burnout among HCWs during COVID-19 response measures throughout the extended pandemic period. We formulated the guidelines by means of a systematic review and collated them with the latest literature. The guidelines will highlight the gravity and impact of infection control and burnout among HCWs responding to COVID-19 and include potential prevention strategies, and they can be used as a reference in the event of another emerging infectious disease outbreak in the future.

Corrigendum: Differential association of viral dynamics with disease severity depending on patients' age group in COVID-19.

[This corrects the article DOI: 10.3389/fmicb.2021.712260.].

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Post-influenza pneumonia caused by the USA300 community-associated methicillin-resistant Staphylococcus aureus in Korea.

Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.

Dysregulated thrombospondin 1 and miRNA-29a-3p in severe COVID-19.

Although nearly a fifth of symptomatic COVID-19 patients suffers from severe pulmonary inflammation, the mechanism of developing severe illness is not yet fully understood. To identify significantly altered genes in severe COVID-19, we generated messenger RNA and micro-RNA profiling data of peripheral blood mononuclear cells (PBMCs) from five COVID-19 patients (2 severe and 3 mild patients) and three healthy controls (HC). For further evaluation, two publicly available RNA-Seq datasets (GSE157103 and GSE152418) and one single-cell RNA-Seq dataset (GSE174072) were employed. Based on RNA-Seq datasets, thrombospondin 1 (THBS1) and interleukin-17 receptor A (IL17RA) were significantly upregulated in severe COVID-19 patients' blood. From single-cell RNA-sequencing data, IL17RA level is increased in monocytes and neutrophils, whereas THBS1 level is mainly increased in the platelets. Moreover, we identified three differentially expressed microRNAs in severe COVID-19 using micro-RNA sequencings. Intriguingly, hsa-miR-29a-3p significantly downregulated in severe COVID-19 was predicted to bind the 3'-untranslated regions of both IL17RA and THBS1 mRNAs. Further validation analysis of our cohort (8 HC, 7 severe and 8 mild patients) showed that THBS1, but not IL17RA, was significantly upregulated, whereas hsa-miR-29a-3p was downregulated, in PBMCs from severe patients. These findings strongly suggest that dysregulated expression of THBS1, IL17RA, and hsa-miR-29a-3p involves severe COVID-19.

Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia.

INTRODUCTION: De-escalation therapy is a strategy currently used for the management of nosocomial pneumonia. In this study, we evaluated clinical outcomes and risk factors related to de-escalation therapy in patients with intensive care unit (ICU)-acquired pneumonia. METHODS: This was a retrospective observational cohort study of ICU patients who developed pneumonia more than 48 hours after admission to the ICU at Samsung Medical Center from September 2004 to December 2007. RESULTS: The 137 patients comprised 44 (32.1%) who received de-escalation therapy and 93 in the non-de-escalation group. The de-escalation group showed a lower pneumonia-related mortality rate than the non-de-escalation group by day 14 (2.3% vs. 10.8%, respectively; P = 0.08) and by day 30 (2.3% vs. 14%, respectively; P = 0.03) after the diagnosis of pneumonia. The variables independently associated with ICU-acquired pneumonia-related mortality included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the modified Clinical Pulmonary Infection Score (CPIS) after 5 days with pneumonia. The non-de-escalation group had significantly higher APACHE II score and modified CPIS after 5 days with ICU-acquired pneumonia compared to the de-escalation group. Among all patients, 20.4% (28 of 137) had negative cultures for pathogens, and 42.9% (12 of 28) received de-escalation therapy. The latter 12 patients received de-escalation therapy and survived 30 days after the diagnosis of pneumonia. CONCLUSIONS: Patients in the de-escalation group showed a significantly lower mortality rate compared to patients in the non-de-escalation group. De-escalation therapy can be safely provided to patients with ICU-acquired pneumonia if they are clinically stable by day 5, even in those whose respiratory specimen cultures yield no specific pathogens.

Experimental and Mathematical Optimization of a Pooling Test for Detection of SARS-CoV-2 in a Population with Low Viral Load.

BACKGROUND: A pooling test is a useful tool for mass screening of coronavirus disease 2019 (COVID-19) in the pandemic era. We aimed to optimize a simple two-step pooling test by estimating the optimal pool size using experimental and mathematical validation. MATERIALS AND METHODS: Experimental pools were created by mixing one positive respiratory sample with various numbers of negative samples. We selected positive samples with cycle threshold (Ct) values greater than 32 to validate the efficiency of the pooling test assuming a high likelihood of false-negative results due to low viral loads. The positivities of the experimental pools were investigated with a single reverse-transcription polymerase chain reaction (RT-PCR) using the U-TOP™ COVID-19 Detection Kit Plus (Seasun Biomaterials, Daejeon, Korea). We used the Dorfman equation to calculate the optimal size of a pooling test mathematically. RESULTS: Viral RNA could be detected in a pool with a size up to 11, even if the Ct value of a positive sample was about 35. The Dorfman equation showed that the optimal number of samples in a pool was 11 when the prevalence was assumed to be 0.66% based on the test positivity in Daejeon, Korea from April 1, 2020 to November 10, 2020. The efficiency of the pooling test was 6.2, which can save 83.9 of 100 individual tests. CONCLUSION: Eleven samples in a pool were validated optimal experimentally assuming a prevalence of 0.66%. The pool size needs modification as the pandemic progresses; thus, the prevalence should be carefully estimated before pooling tests are conducted.

Differential Association of Viral Dynamics With Disease Severity Depending on Patients' Age Group in COVID-19.

Despite a clear association of patient's age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of viral load dynamics with patient's age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients' plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.

Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19.

Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.