In flammatory Representation of COVID-19 at the Time of Hospitalization: An Insight into the Mild, Moderate, Severe and Critical COVID-19 Disease

Background. The ongoing state of the COVID-19 pandemic necessitates the characterization of the biological basis of disease severity. We aimed to correlate the clinical severity of illness upon hospitalization with inflammatory sero-biomarker levels. Methods. A single-center prospective cohort study was conducted at a 776-bed tertiary care urban academic medical center in Detroit, Michigan. Adults with con-firmed reverse-transcriptase-polymerase-chain-reaction assay for COVID-19 were recruited in equal numbers into four disease severity categories, as defined by the WHO, upon hospital admission from January 8th, 2021 to September 1st, 2021. Electronic medical charts were reviewed. In addition to clinical markers, cytokines and chemokines were assessed to gain detailed understanding of COVID-19 pathology. Results. We included 200 patients with 50 patients each in the mild, moderate, severe and critical illness. The mean age of the cohort was 58.6. +/-15.9 yrs, 104 (52%) were males, and 135(67.5%) were blacks. The common comorbidities were hypertension (67.5%), diabetes (37%) and chronic lung diseases (26.5%). At the time of admission, oxygen therapy was needed in 49.5% but intubation in only 0.5%. Conclusion. We noted COVID-19 severity dependent changes in the clinical representation as well as the biomarker profiles. Clinical markers such as CRP, LDH, D-dimer and Ferritin were relatable to COVID-19 severity. Inflammatory cytokines and chemokines such as CCL-2, CXCL-10, IL-1ra, IL-6 and TNF-alpha also varied with the severity of disease. Our results provide a system level insight into the inflammatory state of COVID-19 at the time of hospital representation.

Association of SARS-CoV-2 Viral load in COVID-19 at the hospital representation

Background. The SARS-CoV-2 viral load and its association with COVID-19 severity remain a widely discussed topic with a little or no consensus. With these considerations we aimed to investigate SARS-CoV-2 viral load in the saliva/sputum in COVID-19 patients with varying severity levels. Methods. A single-center prospective cohort study at Ascension St John Hospital, Detroit, MIchigan was conducted during early January 2021 and September 2021. We recruited 200 subjects with a PCR-confirmed COVID-19 and 18 year of age and older. Further these subjects were divided into mild, moderate, severe and critical cohorts based on WHO defined criteria. Further we collected sputum/saliva samples and measured them for SARS-CoV-2 viral load. . Results. We recruited 50 patients in each cohort totaling to 200 patients.Our study cohort was made up of 104 (52%) males and 96 (48%) females. We note severity level differences matching with the COVID-19 severity at the hospital presentation. Conclusion. These results were interesting to provide an insight into COVID-19 severity and clinical representation.

Tocilizumab: a retrospective multi-center cohort study of critically ill patients with COVID-19

Background: Coronavirus disease 19 (COVID-19) can have a severe presentation characterized by a dysregulated immune response requiring admission to the intensive care unit (ICU) [mmunomodula- tory treatments like tocilizumab were found to improve inflammatory markers and lung injury over time. We aim to evaluate the effectiveness of toeilizumab treatment 011 critically ill patients with severe COVID-19. Materials and methods: We conducted a multi-center retrospective cohort study of 154 adult patients admitted to the ICU for severe COVID-1 9 pneumonia between March 1 5 and May 8.2020. Data were obtained by electron- ic medical record (EMR) review. The primary outcome of interest was mortality.

Clinical Features of and Risk Factors for 30-day Readmission after an Initial Hospitalization with COVID-19

Background. Little is known about risk factors for readmission after COVID-19 hospitalizations. Knowledge of these factors may help to identify patients at increased risk and may help to prevent these rehospitalizations. Methods. This historical cohort study was conducted at a tertiary care academic medical center. We included COVID-19 cases diagnosed by reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay between March 8th and June 14th, 2020. Patients readmitted within 30 days were identified. Using the electronic medical record, we collected data on demographic and clinical information. Data were analyzed using Student's t-test, the chi-squared test and multivariable logistic regression. Results. We included 391 patients who survived after the index hospitalization for COVID-19. The readmission rate was 13.3% (52/391). The mean time to readmission was 9.2 ± 7.9 days. The mean age (±SD) was 66.3 ± 18.6 years, 44.2% were male, and 78.8% were black/African-American. The most common presenting complaint was shortness of breath (50%). The most frequent diagnosis during the readmission was infectious process (57.7%). The mortality rate on readmission was 11.5%. Patients with a 30-day readmission were older than those not readmitted, mean age (±SD) 66.3 ± 18.6 vs. 61.0 ± 16.0, respectively (p=0.03). Readmitted patients also had a higher prevalence of heart failure and renal disease as comorbidities. Elevated alanine aminotransferase (AST) and low albumin level were also associated with readmission (Table 1). Intensive care unit (ICU) admission or mechanical ventilation during the index admission did not increase the risk of readmission. From multivariable analysis, independent predictors of 30-day readmission were higher Charlson score (p=0.004), higher creatinine on admission in the index hospitalization (p=0.009), and presence of rhabdomyolysis during the index hospitalization (p=0.039) (Table 2). Table 2. Multivariable Analysis of Predictors for Readmission within 30 days from COVID-19 Infection Conclusion. In our cohort, infectious etiologies were common among those readmitted within 30 days of COVID-19. A higher Charlson score, acute renal failure, and rhabdomyolysis during the index admission were independent predictors of a 30-day readmission. Further studies are required to investigate these contributing factors.

Six-Month Post-Acute Sequelae of COVID-19: High Self-Reported Morbidity among Women and Younger Adults

Background. Long term sequelae across multiple medical domains, including the respiratory, psychiatric, and neurocognitive have been reported after COVID-19. Studies evaluating the impact of this symptom burden, however, are lacking. We aimed to describe the self-reported occurrence of symptoms and their effect on patient functioning six months after their acute hospitalization for COVID-19. Methods. From a historical cohort study of patients hospitalized for COVID-19 between March 8, and June 14, 2020, we identified patients discharged home. The purpose of the study was explained, and they were asked to consent to a telephone questionnaire. We used a modified version of a previously validated general symptom questionnaire (GSQ-30) to assess multi-system symptom burden. The Patient Health Questionnaire-2 (PHQ-2) was used to screen for major depression. Results. Of the original 565 patients, 258 patients were discharged home (45%). Of these, 57 (22%) patients were able to be contacted and agreed to participate in the survey. The mean (SD) age of the respondents was 55.1 (14.8) years, and 37 (64.9%) were female. The most common symptoms at follow-up were fatigue (60.0%), dyspnea (57.1%), feeling irritable, sad or decreased pleasure (56.4%), and memory difficulty (56.4%). Females had a significantly higher GSQ score (0.02) than males. Patients ages < 60 years tended to experience similar, if not greater, impaired functioning (p=0.07) compared with those ages ≥ 60 years (Table 1). Females were more likely to be irritable or sad (p=0.007), not feel rested on awakening (p=0.04), have shooting, stabbing and burning pain (p=0.02), have discomfort with normal light and sound (p=0.04), and have memory difficulty (p=0.04) than males (Table 2). Conclusion. Our study describes the clinical burden of post-acute sequelae of COVID-19 (PASC) in four core domains: fatigue, neurologic, neuro-psychiatric and viral-like symptoms. Over 45% of patients ages < 60 years suffered impaired functioning, compared with 21.1% of patient's ages 60 years and above. Females had significantly higher GSQ scores than men which strongly corelates with the functional impairment among the females. Larger studies are needed to further validate our findings.

Sex-Related Differences in Mortality from COVID-19: Survival Analysis of Patients from an Urban Hospital

Background. Mortality from COVID-19 is associated with male sex, older age, black race, and comorbidities including obesity. Our study identified risk factors for in-hospital mortality from COVID-19 using survival analysis at an urban center in Detroit, MI. Methods. This was a single-center historical cohort study. We reviewed the electronic medical records of patients positive for severe acute respiratory syndrome coronavirus 2 (the COVID-19 virus) on qualitative polymerase-chain-reaction assay, who were admitted between 3/8-6/14/20. We assessed risk factors for mortality using Kaplan-Meier analysis and Cox proportional hazards models. Results. We included 565 patients with mean age (standard deviation) 64.4 (16.2) years, 52.0% male (294) and 77.2% (436) black/African American. The overall mean body mass index (BMI) was 32.0 (9.02) kg/m2. At least one comorbidity was present in 95.2% (538) of patients. The overall case-fatality rate was 30.4% (172/565). The unadjusted mortality rate among males was 33.7% compared to 26.9% in females (p=0.08);the median time to death (range) for males was 16.8 (0.3, 33.9) compared to 14.2 (0.32, 47.7) days for females (p=0.04). Univariable survival analysis with Cox proportional hazards models revealed that age (p=< 0.0001), admission from a facility (p=0.002), public insurance (p< 0.0001), respiratory rate ≥ 22 bpm (p=0.02), lymphocytopenia (p=0.07) and serum albumin (p=0.007) were additional risk factors for mortality (Table 1). From multivariable Cox proportional hazards modeling (Table 2), after controlling for age, Charlson score and qSofa, males were 40% more likely to die than females (p=0.03). Conclusion. After controlling for risk factors for mortality including age, comorbidity and sepsis-related organ failure assessment, males continued to have a higher hazard of death. These demographic and clinical factors may help healthcare providers identify risk factors from COVID-19.

Is Antibody to Nucleocapsid More Prevalent in Individuals with Severe COVID-19?

Background. Virus-specific antibodies help to understand the prevalence of infections and the course of the immune response. Humans produce antibodies against the spike and nucleocapsid proteins of SARS-COV-2 virus. Patients with COVID-19 who recover from the infections have higher levels of antibodies to spike proteins. Our study aimed to find the levels of antibodies to spike and nucleocapsid proteins in severe COVID-19. Methods. A single center prospective study was done at Ascension St John Hospital, Detroit, MI. We included COVID-19 cases diagnosed by reverse-transcriptase polymerase-chain-reaction (RT-PCR). Quantitative measurements of plasma or serum antibodies to nucleocapsid and spike proteins were done in hospitalized patients with acute COVID-19. Using the electronic medical record, we collected data on demographic and clinical information. Results. A total 24 patients were studied. Of which, 15 patients were suffering from severe and critical COVID 19 and 9 patients were suffering from mild to moderate COVID 19. The mean age (standard deviation) of our cohort was 69 ± 10 years and 60% were males. Common comorbid conditions were hypertension, obesity, and type 2 diabetes. We also noted that severe to critical COVID 19 expressed higher level of antibody to nucleocapsid. Conclusion. These results display the seroconversion in COVID 19 patients. Our study shows antibody level remain high in severe COVID 19 patients but those are against nucleocapsid protein instead of spike protein.

Clinical and Immunological Assessment of Patients with Sars-Cov-2 Infections

[Formula presented] Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced coronavirus disease-2019 (COVID-19) has presented humanity with unprecedented challenges. Severe disease is associated with acute respiratory distress syndrome (ARDS), use of mechanical ventilation, ICU stay and prolonged hospitalization, The role of the immune system in the pathogenesis of COVID-19 disease is still unclear, which imposes limitations on identifying potential immunotherapy that can improve care for acute and chronic phases of COVID-19 in conjunction with current therapies. Research efforts are ongoing for more than 1 year to identify key immunological mechanisms involved in the disease process. While insightful, this knowledge is still incomplete and can be complemented with the assessment of immune response kinetics. Such assessment will help with the identification of early interventional modalities of immune cell regulation. With these considerations in mind, we aimed to assess several parameters of immune system regulation during the current medical care of patients with COVID-19. Methods: This is a pre-clinical prospective cohort study which involved laboratory-based assessments of blood samples obtained from COVID-19 patients and healthy volunteers. The study population was divided into three cohorts. Our first cohort included 18 years and older COVID-19 patients with respiratory complaints, oxygen (O2) saturations of less than or equal to 92 and pulmonary infiltrates on an imaging study or who were critically ill and required ventilatory support. Second cohort included 18 years and older COVID-19 patients who were hospitalized and did not require ventilatory support. Third cohort included participants with no prior diagnosis of COVID-19, or any recent viral respiratory symptoms including fever, cough or shortness of breath for the last 2 weeks. Patients with an established diagnosis of cancer or immunologic disorders were excluded. Blood specimens were collected over the period of hospitalization: specimen number 1 on day 1-3 of hospitalization, specimen number 2 on days 3-4 of hospitalization, specimen number 3 on days 5-7 of hospitalization, and specimen number 4 on 7-30 days after discharge. We performed capillary electrophoresis for serology and automated ELISA for cytokine measurement. We collected clinical data on patient demographic, clinical characteristics such as presence of any acute and chronic comorbidities and serum inflammatory markers C-Reactive Protein, D-Dimer and Ferritin. Results: We had 15 patients in cohort 1, 10 in cohort 2 and 15 in cohort 3. Patients in cohort 1 were older and had higher comorbidities. Males constituted a substantially high percentage of patients in cohort 1 and 2 (60% and 70% respectively). Patients had similar BMI in cohort 1 and 2. Total antibody levels were highest in cohort 1 but an upward trend over the course of hospitalization was noted in all cohorts. Most interesting pattern was noted in the context of antibodies against spike protein S1 receptor-binding domain (S1RBD) where patients in cohort 2 developed minimal S1RBD antibodies. Cohort 1 on average had higher levels of Interleukin 6(IL-6), Interleukin 8(IL-8), C-X-C motif chemokine ligand 10 (CXCL10) and other inflammatory cytokines except Interferon gamma (IFN-gamma) compared to Cohort 2. Remarkable difference in CXCL-10 levels was noted between the groups and healthy volunteers had the lowest levels. No significant difference in IFN-gamma was noted between cohorts and the levels quickly depleted over the course of the infection. Conclusion: Our analysis confirms that neutralizing antibodies do not correlate with lessened COVID-19 disease severity. Severe COVID-19 infection is secondary to ineffective innate immunity associated with immune overshoot. CXCL10 serves as a major component in triggering the cytokine storm that is a hallmark of SARS-CoV-2 infections. Our findings show an association between high levels of CXCL10 and more severe COVID-19 infection. There does not seem to be any s gnificant correlation with disease severity and IFN-gamma levels. [Formula presented] Disclosures: No relevant conflicts of interest to declare.