• Diversity of Functionally Distinct Clonal Sets of Human Conventional Memory B Cells That Bind Staphylococcal Protein A

      Institute of Genomic and Evolutionary Medicine (iGEM) (Temple University) (2021-04-28)
      Staphylococcus aureus, a common cause of serious and often fatal infections, is well-armed with secreted factors that disarm host immune defenses. Highly expressed in vivo during infection, Staphylococcal protein A (SpA) is reported to also contribute to nasal colonization that can be a prelude to invasive infection. Co-evolution with the host immune system has provided SpA with an Fc-antibody binding site, and a Fab-binding site responsible for non-immune superantigen interactions via germline-encoded surfaces expressed on many human BCRs. We wondered whether the recurrent exposures to S. aureus commonly experienced by adults, result in the accumulation of memory B-cell responses to other determinants on SpA. We therefore isolated SpA-specific class-switched memory B cells, and characterized their encoding VH : VL antibody genes. In SpA-reactive memory B cells, we confirmed a striking bias in usage for VH genes, which retain the surface that mediates the SpA-superantigen interaction. We postulate these interactions reflect co-evolution of the host immune system and SpA, which during infection results in immune recruitment of an extraordinarily high prevalence of B cells in the repertoire that subverts the augmentation of protective defenses. Herein, we provide the first evidence that human memory responses are supplemented by B-cell clones, and circulating-antibodies, that bind to SpA determinants independent of the non-immune Fc- and Fab-binding sites. In parallel, we demonstrate that healthy individuals, and patients recovering from S. aureus infection, both have circulating antibodies with these conventional binding specificities. These findings rationalize the potential utility of incorporating specially engineered SpA proteins into a protective vaccine.
    • Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-12-24)
      Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be used for the differential diagnosis of SARS-CoV-2 infection. There have been cases of transmission from people with COVID-19 to pets such as cats and dogs. In addition, wild felines were infected. All These animals were either asymptomatic or mildly symptomatic and recovered spontaneously. Experimental studies showed cats and ferrets to be more susceptible to COVID-19. COVID-19 positive dogs and felines do not transmit the infection to humans. In contrast, minks at farms were severely infected from people with COVID-19. A SARS-Cov-2 variant in the Danish farmed mink that had been previously infected by COVID-19 positive workers, spread to mink workers causing the first case of animal-to-human infection transmission that causes a moderate decreased sensitivity to neutralizing antibodies. Thus, more investigations are necessary. It remains important to understand the risk that people with COVID-19 pose to their pets, as well as wild or farm animals so effective recommendations and risk management measures against COVID-19 can be made. A One Health unit that facilitates collaboration between public health and veterinary services is recommended.
    • Duolingo English Test, Revised Version July 2019

      Wagner, Elvis; 0000-0003-2332-3323 (2020-06-28)
      The Duolingo English Test (DET) is a computer adaptive test of English proficiency that is increasingly used for English-medium university admissions purposes. During the COVID-19 pandemic of 2020, test centers were shut down in many countries, and major tests including the TOEFL iBT and IELTS could not be administered. The DET is an “at home” test, and thus many universities began accepting DET scores as ameasure of applicants’ English proficiency. Because a revised version of the DET was launched in July, 2019, and because of the large increase in universities accepting DET scores, a critical review of the DET is warranted. The current review lauds the accessibility of the test (e.g., it is an inexpensive “at home” test that can be taken anywhere, in less than an hour, with scores returned in 48 hours). However, the test has multiple shortcomings: the test tasks have little in common with the types of language tasks university students engage in; the test does not assess test takers’ academic language ability, discourse level competence, or interactional competence; it is susceptible to cheating and test preparation; and it has a potential for negative washback on learners and learning systems. In addition, there is a lack of independent research validating the use of DET scores for admissions. Given these shortcomings, the use of DET scores cannot be recommended for university admissions purposes.
    • Easing of Regulatory Barriers to Telemedicine Abortion in Response to COVID-19

      Skuster, Patty; Dhillon, Jina; Li, Jessica (2021-11-24)
      For many people seeking abortion during the continuing COVID-19 pandemic, telemedicine abortion is the safest and most acceptable method, posing lower risk of exposure to the virus. In addition, by reducing in-person visits with health care providers, increased use of telemedicine for abortion can reduce pressure on overburdened health systems. Given the benefits of telemedicine during the pandemic, government agencies in several countries took measures to temporarily allow telemedicine abortion. We conducted key-word English-language searches to identify examples of government action to remove regulatory barriers to the practice of telemedicine abortion in response to the pandemic. We found instances of government agencies in eight countries taking steps to ease regulatory barriers to telemedicine abortion. Telemedicine abortion is safe, cost-effective, and may be the preferred method of abortion during acute periods of COVID-19 transmission, as well as after the pandemic has abated. As one step to expanding access to abortion with medicine where abortion is legal, health agencies and other regulatory bodies can take steps to remove barriers specific to telemedicine abortion.
    • Editorial: Metabolic Regulation of Cardiac and Vascular Cell Function: Physiological and Pathophysiological Implications

      Center for Metabolic Disease Research (Temple University) (2022-02-15)
      This Research Topic gathers a collection of five original and review articles that provide recent summaries and novel information regarding the role of metabolism in regulating cardiac and vascular cell function. The mammalian heart is a pump that requires a constant supply of energy to maintain function. Cardiac metabolism plays a pivotal role in driving molecular and cellular changes in the heart in response to physiological and pathological stresses. The adult heart generates >95% of its ATP primarily by oxidative phosphorylation in the mitochondria while the remaining 5% comes from glycolysis, or to a lesser extent from the citric acid cycle. In contrast, during development cardiac tissue relies on glycolysis to meet its energy demands during development. However, the postnatal heart undergoes a rapid shift in metabolism to oxidative phosphorylation in response to changes in oxygen tension and maturation. Injury to the adult heart is accompanied by a shift from fatty acid oxidation to glucose use, like a fetal metabolic state, promotes oxygen efficiency for ATP synthesis, considered to be beneficial particularly under ischemic cardiac injury where oxygen supply is limited. Recently, metabolism has been linked to the regulation of gene expression in cardiac cells with levels of several metabolites altered in response to physiological and pathological stresses in the heart.
    • Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity

      Center for Cardiovascular Research (Temple University); Center for Metabolic Disease Research (Temple University) (2021-12-17)
    • Effects of COVID-19 Syndemic on Sport Community

      Sbarro Institute for Cancer Research and Molecular Medicine (2022-02-07)
    • Effects of the COVID‐19 Pandemic on Patients Living With Vasculitis

      Vasculitis Patient‐Powered Research Network (2020-12-08)
      This study aimed to analyze the concerns and health‐related behaviors in patients with vasculitis during the early phase of the coronavirus disease 2019 (COVID‐19) pandemic in North America. Patients with vasculitis in North America were invited to complete an online survey through the Vasculitis Patient‐Powered Research Network in collaboration with the Vasculitis Foundation and the Relapsing Polychondritis Foundation. Questions focused on concerns and behaviors related to doctors’ visits, tests, medication, and telehealth use. Factors affecting their concern and health‐related behaviors were determined. Data from 662 patients were included: 90% of patients were White, 78% were women, 83% expressed moderate or high levels of concern about COVID‐19, and 87% reported that their vasculitis moderately or extremely affected their level of concern. Older age, female sex, lung disease, and immunosuppression were associated with greater concern. Doctors’ visits, laboratory tests, and other tests were avoided by 66%, 46%, and 40% of patients, respectively. Younger age, urban location, higher income, higher concern levels, and prednisone use (>10 mg/day) were associated with greater likelihood of avoiding visits or tests. Ten percent of patients on immunosuppressive therapy stopped their medication. Twenty‐nine percent patients on rituximab avoided an infusion. Forty‐four percent of patients had telehealth visits; more visits were reported for younger patients, for patients on glucocorticoids, and in Canada versus the United States. During the COVID‐19 pandemic, patients with vasculitis have high levels of concern and exhibit potentially harmful health‐related behaviors. Health care use varies across different demographic groups and geographic regions. Specific strategies are warranted to facilitate engagement of these patients with the health care system during the pandemic.
    • Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19: A Randomized Clinical Trial

      Sarilumab-COVID-19 Study Team (2022-03-21)
      Background: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti–IL-6R therapies in hospitalized patients with COVID-19 receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti–IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19. Methods: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 (ClinicalTrials.gov: NCT04315298) received intravenous sarilumab or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation randomized to sarilumab 400 mg or placebo. The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22. Results: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving mechanical ventilation (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving mechanical ventilation) at day 22 was 43.2% in sarilumab and 35.5% in placebo (risk difference +7.5%; 95% CI, –7.4 to 21.3; P = .3261), a relative risk improvement of 21.7%. In post-hoc analyses pooling phase 2 and 3 critical patients receiving mechanical ventilation, the hazard ratio for death in sarilumab versus placebo was 0.76 (95% CI, .51–1.13) overall and 0.49 (95% CI, .25–.94) in patients receiving corticosteroids at baseline. Conclusions: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post-hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids.
    • Elite Athletes and COVID-19 Lockdown: Future Health Concerns for an Entire Sector

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-05-07)
      In this editorial, we focused our attention on elite athletes during the COVID-19 lockdown. A high level of physical fitness is required by elite athletes irrespective of the specific type of sport. Generally speaking, elite athletes avoid long periods of rest during and at the end of the competitive season. Normally, elite athletes stop training or reduce training volume and intensity for a period that ranges from two weeks to a maximum of four weeks.
    • Embracing Diversity in Dermatology: Creation of a Culture of Equity and Inclusion in Dermatology

      Desai, Seemal R.; Khanna, Rayva; Glass, Donald; Alam, Murad; Barrio, Vicky; French, Lars E.; Gohara, Mona; McKinley-Grant, Lynn; Harvey, Valerie; Heath, Candrice; Mariwalla, Kavita; Pentland, Alice; Piliang, Melissa; Pourciau, Crystal; Taylor, Susan; Wu, Peggy; Grimes, Pearl; Lim, Henry W.; Heath|0000-0002-2687-5468 (2021-08-05)
    • EMS prehospital response to the COVID-19 pandemic in the US: A brief literature review

      Ventura, Christian Angelo I.; Denton, Edward E.; David, Jessica A.; Schoenfelder, Brianna J.; Mela, Lillian; Lumia, Rebecca P.; Rudi, Rachel B.; Haldar, Barnita (2022-03-13)
      This study aimed to analyze prehospital Emergency Medical Services (EMS) response to the COVID-19 pandemic in the US through a brief systematic review of available literature in context with international prehospital counterparts. An exploration of the NCBI repository was performed using a search string of relevant keywords which returned n=5128 results; articles that met the inclusion criteria (n=77) were reviewed and analyzed in accordance with PRISMA and PROSPERO recommendations. Methodical quality was assessed using critical appraisal tools, and the Egger’s test was used for risk of bias reduction upon linear regression analysis of a funnel plot. Sources of heterogeneity as defined by P < 0.10 or I^2 > 50% were interrogated. Findings were considered within ten domains: structural/systemic; clinical outcomes; clinical assessment; treatment; special populations; dispatch/activation; education; mental health; perspectives/experiences; and transport. Findings suggest, EMS clinicians have likely made significant and unmeasured contributions to care during the pandemic via nontraditional roles, i.e., COVID-19 testing and vaccine deployment. EMS plays a critical role in counteracting the COVID-19 pandemic in addition to the worsening opioid epidemic, both of which disproportionately impact patients of color. As such, being uniquely influential on clinical outcomes, these providers may benefit from standardized education on care and access disparities such as racial identity. Access to distance learning continuing education opportunities may increase rates of provider recertification. Additionally, there is a high prevalence of vaccine hesitancy among surveyed nationally registered EMS providers. Continued rigorous investigation on the impact of COVID-19 on EMS systems and personnel is warranted to ensure informed preparation for future pandemic and infectious disease response.
    • Endothelial Immunity Trained by Coronavirus Infections, DAMP Stimulations and Regulated by Anti-Oxidant NRF2 May Contribute to Inflammations, Myelopoiesis, COVID-19 Cytokine Storms and Thromboembolism

      Centers of Cardiovascular Research, Inflammation, Translational & Clinical Lung Research (Temple University); Metabolic Disease Research, Thrombosis Research (Temple University) (2021-06-25)
      To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19). The expressions of IGs are modulated in 21 human EC transcriptomic datasets by various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia and oxLDL. Upregulation of many IGs such as nucleic acid sensors are shared between ECs infected by MERS-CoV and those stimulated by PAMPs and DAMPs. Human heart EC and mouse aortic EC express all four types of coronavirus receptors such as ANPEP, CEACAM1, ACE2, DPP4 and virus entry facilitator TMPRSS2 (heart EC); most of coronavirus replication-transcription protein complexes are expressed in HMEC, which contribute to viremia, thromboembolism, and cardiovascular comorbidities of COVID-19. ECs have novel trained immunity (TI), in which subsequent inflammation is enhanced. Upregulated proinflammatory cytokines such as TNFα, IL6, CSF1 and CSF3 and TI marker IL-32 as well as TI metabolic enzymes and epigenetic enzymes indicate TI function in HMEC infected by MERS-CoV, which may drive cytokine storms. Upregulated CSF1 and CSF3 demonstrate a novel function of ECs in promoting myelopoiesis. Mechanistically, the ER stress and ROS, together with decreased mitochondrial OXPHOS complexes, facilitate a proinflammatory response and TI. Additionally, an increase of the regulators of mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis in ECs infected with MERS-CoV and the upregulation of pro-thrombogenic factors increase thromboembolism potential. Finally, NRF2-suppressed ROS regulate innate immune responses, TI, thrombosis, EC inflammation and death. These transcriptomic results provide novel insights on the roles of ECs in coronavirus infections such as COVID-19, cardiovascular diseases (CVD), inflammation, transplantation, autoimmune disease and cancers.
    • Entangling COVID-19 associated thrombosis into a secondary antiphospholipid antibody syndrome: Diagnostic and therapeutic perspectives (Review)

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-06-25)
      The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a novel β coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID‑19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID‑19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID‑19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID‑19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D‑dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS‑CoV‑2 infection may represent a secondary anti‑phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID‑19 infection. Diagnostic and therapeutic implications of this are also discussed.
    • Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

      Liu, Jinbiao; Bodnar, Brittany; Meng, Fengzhen; Khan, Adil I.; Wang, Xu; Saribas, Sami; Wang, Tao; Lohani, Saroj Chandra; Wang, Peng; Wei, Zhengyu; Luo, Jinjun; Zhou, Lina; Wu, Jianguo; Luo, Guangxiang; Li, Qingsheng; Hu, Wenhui; Ho, Wenzhe; Bodnar|0000-0003-0467-5219 (2021-08-31)
      Background: As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Results: We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. Conclusions: These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.
    • Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling

      Center for Substance Abuse Research (Temple University) (2021-03-23)
      Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca2+ from acidic organelles through the activation of two-pore channels (TPCs) to regulate endolysosomal trafficking events. NAADP action is mediated by NAADP-binding protein(s) of unknown identity that confer NAADP sensitivity to TPCs. Here, we used a “clickable” NAADP-based photoprobe to isolate human NAADP-binding proteins and identified Jupiter microtubule-associated homolog 2 (JPT2) as a TPC accessory protein required for endogenous NAADP-evoked Ca2+ signaling. JPT2 was also required for the translocation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus through the endolysosomal system. Thus, JPT2 is a component of the NAADP receptor complex that is essential for TPC-dependent Ca2+ signaling and control of coronaviral entry.
    • Etoposide as Salvage Therapy for Cytokine Storm due to COVID-19

      COVID-19 Research Group (Temple University) (2020-09-12)
      Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality because of a lack of effective therapies. Therapeutic strategies under investigation target the overactive cytokine response with anti-cytokine or immunomodulators therapies. We present a unique case of severe cytokine storm resistant to multiple anti-cytokine therapies, but eventually responsive to etoposide. Thus, etoposide may have a role as salvage therapy in treatment of cytokine storm in COVID-19. To our knowledge, this is the first reported case of use of etoposide in COVID-19.
    • Evaluating the neutralizing ability of a CpG-adjuvanted S-2P subunit vaccine against SARS-CoV-2 Variants of Concern

      Lien, Chia-En; Kuo, Tsun-Yung; Lin, Yi-Jiun; Lian, Wei-Cheng; Lin, Meei-Yun; Liu, Luke Tzu-Chi; Chou, Yu-Chi; Chen, Charles (2021-03-22)
      Vaccination is currently the best weapon to control the COVID-19 pandemic. However, an alarming number of novel variants termed Variants of Concern (VoC) were found to harbor mutations that diminished the neutralizing capacity of antibodies elicited by the vaccines. We have investigated the neutralizing titers of antibodies from sera of humans and rats immunized with the MVC-COV1901 vaccine against pseudoviruses coated with the wildtype, D614G, B.1.1.7, or B.1.351 spike proteins. Rats vaccinated with two doses of adjuvanted S-2P retained neutralization activities against the B.1.351 variant, albeit with a slight reduction compared to wildtype. Phase 1 vaccinated subjects showed more reduced neutralization abilities against the B.1.351 variant. The study is among the first, to our knowledge, to demonstrate dose-dependent neutralizing responses against VoCs, particularly against B.1.351, from different doses of antigen in a clinical trial for a subunit protein COVID-19 vaccine. The appearance of vaccine escape variants is a growing concern facing many current COVID-19 vaccines and therapeutics. Strategies should be adopted against the ever-changing nature of these variants. The observations of this study grant us valuable insight into preemptive strikes against current and future variants.
    • Evaluation of Albumin Kinetics in Critically Ill Patients With Coronavirus Disease 2019 Compared to Those With Sepsis-Induced Acute Respiratory Distress Syndrome

      Su, Chang; Hoffman, Katherine L.; Xu, Zhenxing; Sanchez, Elizabeth; Siempos, Ilias I.; Harrington, John S.; Racanelli, Alexandra C.; Plataki, Maria; Wang, Fei; Schenck, Edward J.; Su|0000-0003-4019-6389 (2021-12)
      OBJECTIVES: This report aims to characterize the kinetics of serum albumin in critically ill patients with coronavirus disease 2019 compared with critically ill patients with sepsis-induced acute respiratory distress syndrome. DESIGN: Retrospective analysis. SETTING: We analyzed two critically ill cohorts, one with coronavirus disease 2019 and another with sepsis-induced acute respiratory distress syndrome, treated in the New York Presbyterian Hospital-Weill Cornell Medical Center. PATIENTS: Adult patients in the coronavirus disease 2019 cohort, diagnosed through reverse transcriptase-polymerase chain reaction assays performed on nasopharyngeal swabs, were admitted from March 3, 2020, to July 10, 2020. Adult patients in the sepsis-induced acute respiratory distress syndrome cohort, defined by Sepsis III criteria receipt of invasive mechanical ventilation and a Pao2/Fio2 ratio less than 300 were admitted from December 12, 2006, to February 26, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated serial serum albumin levels within 30 days after ICU admission in each cohort. We then examined the albumin progression trajectories, aligned at ICU admission time to test the relationship at a similar point in disease progression, in survivors and nonsurvivors. Albumin trajectory in all critically ill coronavirus disease 2019 patients show two distinct phases: phase I (deterioration) showing rapid albumin loss and phase II (recovery) showing albumin stabilization or improvement. Meanwhile, albumin recovery predicted clinical improvement in critical coronavirus disease 2019. In addition, we found a deterioration and recovery trends in survivors in the sepsis-induced acute respiratory distress syndrome cohort but did not find such two-phase trend in nonsurvivors. CONCLUSIONS: The changes in albumin associated with coronavirus disease 2019 associated respiratory failure are transient compared with sepsis-associated acute respiratory distress syndrome and highlight the potential for recovery following a protracted course of severe coronavirus disease 2019.