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Worldwide excess mortality (EM) data have the potential to provide a better estimation of the impact of the pandemic. This study aims to investigate and map the inequalities in EM in Istanbul during the pre-vaccination era of the COVID-19 pandemic in 2020 and its association with selected demographic and socio-economic variables at the neighborhood level according to gender. This ecological study was conducted with the EM data of Istanbul. The EM data were obtained from the Istanbul Metropolitan Municipality (IMM) and analyzed according to socio-demographic indicators (gender, age), neighborhood-level indicators (population density, educational attainment) and neighborhood vulnerability (socio-economic and transportation) for the 808 neighborhoods, then presented separately according to gender to examine gender-specific factors. Socio-economic and transportation vulnerability indexes are provided the IMM. The excess mortality rate per 1000 (EMR) in 2020 has been calculated by using the number of deaths in the years 2018-2019. We have mapped EMRs of each neighborhood and used linear regression analysis in three datasets to examine gender specific factors. EMRs in Istanbul showed two peaks one in April and one in November. Male EMRs were higher compared to females in Istanbul during the pre-vaccination era of the pandemic. Higher EMRs were observed in neighborhoods with a higher share of 50+ year old age groups and higher neighborhood socio-economic vulnerability scores. Neighborhood socio-economic vulnerability was significantly associated with EMRs in males but not in females. Unequal distribution of EM between neighborhoods underlines the need for gender-specific pandemic measures to alleviate the burden of the COVID-19 pandemic, especially in socio-economically vulnerable settings. Increased use of area-based indicators with a gender perspective can enhance pandemic measures.
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The development of effective methods for the surveillance of seasonal respiratory viruses is required for the timely management of outbreaks. We aimed to survey Influenza-A, Influenza-B, RSV-A, Rhinovirus and SARS-CoV-2 surveillance in a tertiary hospital and a campus over 5 months. The effectiveness of air screening as an early warning system for respiratory viruses was evaluated in correlation with respiratory tract panel test results. The overall viral positivity was higher on the campus than in the hospital (55.0% vs. 38.0%). Influenza A was the most prevalent pathogen in both locations. There were two influenza peaks (42nd and 49th weeks) in the hospital air, and a delayed peak was detected on campus in the 1st-week of January. Panel tests indicated a high rate of Influenza A in late December. RSV-A-positivity was higher on the campus than the hospital (21.6% vs. 7.4%). Moreover, we detected two RSV-A peaks in the campus air (48th and 51st weeks) but only one peak in the hospital and panel tests (week 49). Although rhinovirus was the most common pathogen in panel tests, rhinovirus positivity was low in air samples. The air screening for Influenza-B and SARS-Cov-2 revealed comparable positivity rates with panel tests. Air screening can be integrated into surveillance programs to support infection control programs for potential epidemics of respiratory virus infections except for rhinoviruses.
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COVID-19 , Rhinovirus , SARS-CoV-2 , Humanos , Rhinovirus/isolamento & purificação , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/virologia , Aerossóis/análise , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/diagnóstico , Microbiologia do Ar , Influenza Humana/epidemiologia , Influenza Humana/virologia , Poluição do Ar em Ambientes Fechados/análise , Vírus da Influenza A/isolamento & purificação , Estações do Ano , Epidemias , Monitoramento Ambiental/métodos , Vírus da Influenza B/isolamento & purificação , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genéticaRESUMO
Objective: Vaccine hesitancy among healthcare workers (HCWs) represents a significant challenge and threat in pandemics. This study aims to identify the predictive factors influencing COVID-19 vaccine hesitancy among HCWs and offer strategies to increase the COVID-19 vaccination rate in healthcare settings. Materials and Methods: This study constitutes the qualitative portion (second part) of a mixed-methods doctoral thesis employing an explanatory design. It was conducted in two distinct pandemic hospitals and involved 23 vaccine-hesitant HCWs. To conduct the interviews, the researchers developed a semi-structured interview form based on the Health Belief Model (HBM). Results: Upon analyzing the in-depth interviews, we identified six primary reasons for vaccine hesitancy and four different sub-reasons that reinforce vaccine hesitancy. We also collected four key suggestions from vaccine-hesitant HCWs that could potentially persuade them to receive the COVID-19 vaccine. Conclusion: This study's findings, which encompass the identification of reasons for COVID-19 vaccine hesitancy, clarification of underlying factors contributing to hesitancy towards the COVID-19 vaccines, and gathering suggestions from HCWs on how to persuade them to get vaccinated, hold significant value for guiding vaccination campaigns during potential future pandemics.
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This study examines the effects of the bundle of antimicrobial stewardship measures for prophylactic antibiotics among thoracic surgery patients. A local protocol, based on current guidelines starting from December 2014, was developed by the Infection Control and Thoracic Surgery Teams. The effects of this protocol were assessed by monitoring a total of 1380 patients before and after its implementation from January 1, 2011, to December 31, 2022.
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Antibacterianos , Farmacorresistência Bacteriana , Fluoroquinolonas , Infecções por Salmonella , Salmonella , Humanos , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Infecções por Salmonella/microbiologia , Infecções por Salmonella/epidemiologia , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Salmonella/genética , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: The evidence on the prevalence of Lyme borreliosis (LB) is limited, but there is a suspicion of overdiagnosis of LB in recent years. We reviewed the LB diagnosis and treatment-related data in Türkiye, based on the Infectious Diseases Society of America (IDSA) 2020 and European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis (ESGBOR) 2018 guidelines. By detecting the disagreements between these two, we outlined the areas to be improved for future guidelines. METHODS: We performed a literature search according to the PRISMA guidelines in PubMed, Ovid-Medline, Web of Science, Turkish Medline, Scopus, CINAHL, ULAKBIM TR Index, Google Scholar and Cochrane Library databases. We included the published cases in a database and evaluated according to IDSA and ESGBOR guidelines. We outlined the reasons for misdiagnoses and inappropriate uses of antibiotics. RESULTS: We included 42 relevant studies with 84 LB cases reported from Türkiye between 1990 and December 2022. Among 84 cases, the most common clinical findings were nervous system findings (n = 37, 44.0%), erythema migrans (n = 29, 34.5%) and ophthalmologic findings (n = 15, 17.9%). The IDSA 2020 and ESGBOR 2018 guidelines agreed on the diagnosis of 71 (84.5%) cases; there was an agreement that 31 cases (36.9%) were misdiagnosed and 40 cases (47.6%) were correctly diagnosed, and there was disagreement for 13 cases (15.5%). Serum immunoglobulin M (IgM), IgG measurements by ELISA and western blot were widely performed, and they were effective in definitive diagnosis merely when used according to guidelines. Inappropriate use of antibiotics was detected in 42 (50.0%) of cases which were classified in the following categories: incorrect LB diagnosis, inappropriate choice of antibiotic, inappropriate route of drug administration and prolonged antibiotic treatment. CONCLUSION: Overdiagnosis and non-adherence to guidelines is a common problem. The discordance between seroprevalence and clinical studies necessitates a consensus over the best clinical approach.
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Doença de Lyme , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Doença de Lyme/tratamento farmacológico , Humanos , Turquia/epidemiologia , Antibacterianos/uso terapêuticoRESUMO
Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.
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Neoplasias Pulmonares , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias Pulmonares/terapia , EritrócitosRESUMO
BACKGROUND: In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. METHODS: Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. RESULTS: A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). CONCLUSIONS: Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate.
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Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
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We described the secondary bacterial infections (SBI) among COVID-19 patients in comparison with non-COVID-19 patients. We performed a retrospective case-control study between January 01, 2020 and April 01, 2022. Including the adult patients, who stayed ≥ 72 h in intensive care unit (ICU). In total 405 patients were included, 135 had (33.3%) COVID-19, with similar age and gender. The length of stay in ICU was not different (11.4 vs 8.2, p = 0.109), however mean intubation days were higher among COVID-19 cases (6.5 vs 3.8, p = 0.005), SBI were more common among COVID-19 cases (34% vs 10.7%, p < 0.001). Among the patients with pneumonia, the rate of gram-positive bacteria was higher in COVID-19 group than the control group (39% vs 5%, p = 0.006). The predictors for SBI were having COVID-19 (OR: 2.3, Cl 1.25-4.32, p = 0.008), days of intubation (OR: 1.05, Cl 1.01-1.10, p = 0.004), and being male (OR: 2, Cl 1.12-3.58, p = 0.018). The predictors of mortality were COVID-19 (OR: 2.38, Cl 1.28-4.42, p = 0.006), days of intubation (OR: 1.06, Cl 1.03-1.09, p < 0.001), active hematologic malignancy (OR: 3.1, Cl: 1.33-7.28, p = 0.09), active solid tumors (OR: 2.44, Cl 1.21-4.91, p = 0.012), and coronary artery diseases (OR: 1.8, Cl 1.01-3.52, p = 0.045). The most common SBI in COVID-19 patients were methicillin-sensitive Staphylococcus aureus. No carbapenem-resistant Enterobacterales related infections were detected in COVID-19 patients.
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COVID-19 , Coinfecção , Adulto , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Estudos Retrospectivos , Carbapenêmicos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. METHODS: A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. RESULTS: Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24-26 mm) for all isolates and 18 mm (IQR 15-21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. CONCLUSIONS: Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.
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Antibacterianos , Klebsiella , Humanos , Antibacterianos/farmacologia , Klebsiella/genética , Cefalosporinas/farmacologia , Testes de Sensibilidade Microbiana , CefiderocolRESUMO
After the devastating earthquake in Türkiye and Syria in February, 2023, the long-term failure to meet the need for shelter, unfavourable living conditions in tent settlements, poor access to clean drinking water, water suitable for personal hygiene, and sanitary facilities, as well as interruptions in provision of primary health-care services, have emerged as the most important risk factors contributing to the spread of infectious diseases. 3 months after the earthquake, most of these problems persist in Türkiye. Data on the control of infectious diseases are scarce according to the reports prepared by medical specialist associations based on observations of health-care providers working in the region and statements made by the local health authorities. According to these unsystematised data, and considering the conditions in the region, faecal-oral transmissible gastrointestinal infections, as well as respiratory and vector-borne infections, are the main challenges. Vaccine-preventable diseases, such as measles, varicella, meningitis, and polio can be spread in temporary shelters due to interrupted vaccine services and crowded living conditions. In addition to controlling risk factors for infectious diseases, sharing data on the status and control of infectious diseases in the region with the community, health-care providers, and relevant expert groups should be a priority to improve the understanding of the effects of interventions and prepare for possible infectious disease outbreaks.
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Doenças Transmissíveis , Terremotos , Humanos , Doenças Transmissíveis/epidemiologia , Surtos de Doenças , Serviços de Saúde , SíriaRESUMO
Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.
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Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Coroa de Proteína , Humanos , Vírus Oncolíticos/genética , Terapia Viral Oncolítica/métodos , Adenoviridae/genética , Neoplasias/terapia , Anticorpos NeutralizantesRESUMO
BACKGROUND: During the coronavirus disease (COVID-19) pandemic, vaccination of healthcare workers (HCWs) has a critical role because of their high-risk exposure and being a role model. Therefore, we aimed to investigate vaccine hesitancy and the role of mandatory polymerase chain reaction (PCR) testing and education for vaccine uptake. METHODS: We conducted an explanatory sequential designed observational mixed-methods study, including quantitative and qualitative sections consecutively in two different pandemic hospitals between 15 September 2021 and 1 April 2022. The characteristics of vaccinated and unvaccinated HCWs were compared. The vaccine hesitancy scales were applied, and the effect of nudging, such as mandatory PCR and education, were evaluated. In-depth interviews were performed to investigate the COVID-19 vaccine hesitancy among HCWs according to Health Belief Model. RESULTS: In total, 3940 HCWs were included. Vaccine hesitancy was more common among males than females, the ancillary workers than other health professions, and nonmedical departments than other departments. After the mandatory weekly PCR request nudge, 83.33â¯% (130/156) vaccine-hesitant HCWs were vaccinated, and 8.3â¯% (13/156) after the small group seminars and mandatory PCR every two days. The rate of COVID-19 vaccination was raised from 95.5â¯% to 99.67 â¯% (3927/3940). At the end of in-depth interviews (n = 13), the vaccine hesitancy determinants were distrust, fear of uncertainty, immune confidence and spirituality, the media effect, social pressure, and obstinacy. CONCLUSIONS: The nudging interventions such as mandatory PCR testing and small group seminars helped raise the rate of COVID-19 vaccination; the most effective one is mandatory PCR.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Masculino , Humanos , COVID-19/prevenção & controle , Pessoal de Saúde , Vacinação , EscolaridadeRESUMO
PURPOSE: Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to be detailed. We performed a systematic review and meta-analysis to define its effect among severely ill but non-intubated cases with COVID-19. METHODS: We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Medrxiv, and Biorxiv until February 13, 2022, for non-intubated cases, and included randomized-controlled trials (RCT) based on bias assessment. The primary outcomes were the requirement of invasive mechanical ventilation and mortality. Random effect and fixed-effect models were used. The heterogeneity was measured using the χ2 and I2 statistics, with χ2 p ≤ 0.05 and I2 ≥ 50% indicating the presence of significant heterogeneity. We registered the study to the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021232575. RESULTS: Among 261 articles, 11 RCTs were included. The pooled analysis of the 11 RCTs demonstrated that the rate of mortality was significantly lower in the tocilizumab group than in the control group (20.0% and 24.2%, OR: 0.84, 95% CI 0.73-0.96, and heterogeneity I2 = 0%. p = 0.82.). The mechanical ventilation rate was lower in the tocilizumab group than the control group (27% vs 35.2%, OR: 0.76, 95% CI 0.67-0.86, and heterogeneity I2 = 6%. p = 0.39). CONCLUSION: Among non-intubated severe COVID-19 cases, tocilizumab reduces the risk of invasive mechanical ventilation and mortality compared to standard-of-care treatment.
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COVID-19 , Humanos , Tratamento Farmacológico da COVID-19 , Anticorpos Monoclonais Humanizados/uso terapêutico , Respiração ArtificialRESUMO
The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.
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BACKGROUND: Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. OBJECTIVES: To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis. METHODS OF DATA SYNTHESIS: Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality. DATA SOURCES: PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE. STUDY ELIGIBILITY CRITERIA: Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022. PARTICIPANTS: Adults who developed mucormycosis during or after COVID-19. INTERVENTIONS: Patients with and without individual clinical variables were compared. ASSESSMENT OF RISK OF BIAS: Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies. RESULTS: Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780). CONCLUSION: Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.
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COVID-19 , Coinfecção , Mucormicose , Adulto , Humanos , Idoso , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Pandemias , COVID-19/complicações , COVID-19/epidemiologia , HospitalizaçãoRESUMO
PURPOSE: Coronavirus disease 2019 (COVID-19) continues to threaten public health globally. Severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection-dependent alterations in the host cell signaling network may unveil potential target proteins and pathways for therapeutic strategies. In this study, we aim to define early severity biomarkers and monitor altered pathways in the course of SARS-CoV-2 infection. EXPERIMENTAL DESIGN: We systematically analyzed plasma proteomes of COVID-19 patients from Turkey by using mass spectrometry. Different severity grades (moderate, severe, and critical) and periods of disease (early, inflammatory, and recovery) are monitored. Significant alterations in protein expressions are used to reconstruct the COVID-19 associated network that was further extended to connect viral and host proteins. RESULTS: Across all COVID-19 patients, 111 differentially expressed proteins were found, of which 28 proteins were unique to our study mainly enriching in immunoglobulin production. By monitoring different severity grades and periods of disease, CLEC3B, MST1, and ITIH2 were identified as potential early predictors of COVID-19 severity. Most importantly, we extended the COVID-19 associated network with viral proteins and showed the connectedness of viral proteins with human proteins. The most connected viral protein ORF8, which has a role in immune evasion, targets many host proteins tightly connected to the deregulated human plasma proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma proteomes from critical patients are intrinsically clustered in a distinct group than severe and moderate patients. Importantly, we did not recover any grouping based on the infection period, suggesting their distinct proteome even in the recovery phase. The new potential early severity markers can be further studied for their value in the clinics to monitor COVID-19 prognosis. Beyond the list of plasma proteins, our disease-associated network unravels altered pathways, and the possible therapeutic targets in SARS-CoV-2 infection by connecting human and viral proteins. Follow-up studies on the disease associated network that we propose here will be useful to determine molecular details of viral perturbation and to address how the infection affects human physiology.