Early Cytokine Signatures of Hospitalized Mild and Severe COVID-19 Patients: A Prospective Observational Study.

Background: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test. Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines. Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-É£ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital. Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

Chemokine Levels among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality due to intense pulmonary inflammation. Enhanced chemokine-mediated leukocyte infiltration in lungs has been linked with unfavorable outcomes with respect to the disease. This cross-sectional study assessed the levels of chemokines among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 healthy controls using a customized Luminex human chemokine magnetic multiplex panel. The plasma levels of interferon-inducible protein (IP)-10 (568.5 ± 114.7 vs. 55.19 ± 5.85 pg/mL; p < 0.0001), macrophage inflammatory protein (MIP)-1 alpha (MIP-1A) (30.78 ± 2.81 vs. 18.16 ± 0.91 pg/mL; p < 0.0001), MIP-1B (36.63 ± 4.25 vs. 25.26 ± 1.51 pg/mL; p < 0.003), monocyte chemoattractant protein (MCP)-1 (1267 ± 309.5 vs. 390.0 ± 35.51 pg/mL; p < 0.0002), and monokine-induced gamma interferon (MIG) (28.96 ± 3.93 vs. 16.29 ± 1.69 pg/mL; p < 0.001), interleukin (IL)-8 (147.9 ± 21.57 vs. 84.63 ± 10.62 pg/mL; p < 0.004) were significantly higher in symptomatic patients than healthy controls. Likewise, the levels of IP-10 (247.6 ± 80.09 vs. 55.19 ± 5.85 pg/mL; p < 0.0002) and MCP-1 (650.7 ± 149 pg/mL vs. 390 ± 35.51 pg/mL; p < 0.02) were also significantly higher in asymptomatic patients compared to healthy controls. However, no differences were observed in the plasma levels of MIP-1A, MIP-1B, MIG, and IL-8 between asymptomatic patients and uninfected controls. Conversely, the mean plasma levels of regulated on activation normal T cell expressed and secreted (RANTES) (3039 ± 301.0 vs. 4390 ± 223 pg/mL; p < 0.001) and eotaxin (176.9 ± 30.20 vs. 296.2 ± 28.11 pg/mL; p < 0.01) were significantly lower in symptomatic MERS-CoV-infected patients compared to healthy controls. Likewise, the levels of eotaxin (162.7 ± 21.60 vs. 296.2 ± 28.11 pg/mL; p < 0.01) were also significantly lower in asymptomatic patients. Interestingly, the level of MCP-1 (2139 ± 548.2 vs. 776.5 ± 165.3 pg/mL; p < 0.004) was significantly higher in deceased symptomatic patients compared to recovered symptomatic patients. MCP-1 was the only chemokine associated with a higher risk of mortality. Symptomatic MERS-CoV-infected patients had a significant elevation of plasma chemokines and elevated MCP-1 levels were found to be associated with fatal outcomes.

Assessment of Proinflammatory Cytokines Among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality. This study was performed to assess the proinflammatory cytokines profile among MERS-CoV patients. A total of 46 MERS-CoV-infected patients (27 symptomatic and 19 asymptomatic) were assessed and compared with 52 normal healthy controls for plasma levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-17, IL-7, IL-6, interferon (IFN)-α, and IL-15 using a customized luminex kit. Whereas asymptomatic MERS-CoV patients and controls were no different; the mean plasma levels among MERS-CoV symptomatic patients were significantly higher than the normal controls: IL-1ß (16.89 ± 1.23 vs. 12.80 ± 0.59 pg/mL; p < 0.001), TNF-α (14.04 ± 0.93 vs. 10.35 ± 0.29 pg/mL; p < 0.0001), IL-17 (14.3 ± 0.89 vs. 11.47 ± 0.61 pg/mL; p < 0.001), IL-7 (21.56 ± 1.00 vs. 16.31 ± 0.30 pg/mL; p < 0.0001), IL-6 (156.5 ± 37.90 vs. 18.60 ± 1.59 pg/mL; p < 0.0001), and IFN-α (68.73 ± 13.06 vs. 23.57 ± 1.05 pg/mL; p < 0.0001). The mean plasma levels of IL-7 (24.81 ± 1.63 vs. 19.79 ± 0.94 pg/mL; p < 0.01), IL-6 (312.7 ± 94.67 vs. 101.2 ± 25.67 pg/mL; p < 0.01), and IFN-α (89.00 ± 18.97 vs. 51.05 ± 8.68 pg/mL; p < 0.05) were significantly elevated among MERS-CoV symptomatic patients with fatal outcome compared with MERS-CoV symptomatic patients who survived. Only IL-7 was found to have a higher risk ratio of mortality (4.76, 95% confidence interval: 1.5-14.94; p < 0.01). No differences were observed in IL-15 levels among the groups. Significantly elevated proinflammatory cytokines among symptomatic MERS-CoV-infected patients may contribute to manifestations of cytokine storm frequently observed among critically ill MERS-CoV patients and IL-7 may serve as a marker for disease activity.

Clinical and biochemical characteristics of people experiencing post-coronavirus disease 2019-related symptoms: A prospective follow-up investigation.

Background: Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics. Purpose: To investigate the clinical and biochemical characteristics of people who recovered from COVID-19 after 6 months of discharge from the hospital. Methods: This was a prospective follow-up investigation of hospitalized and discharged COVID-19 patients. Adult patients admitted to King Saud University Medical City, Riyadh, Saudi Arabia, with laboratory-confirmed COVID-19 and discharged were recruited. The baseline demographic information, comorbidities, vital signs and symptoms, laboratory parameters, COVID-19 therapy, and outcomes were collected from the medical records. Blood samples were collected for cytokines estimation. A detailed interview about signs and symptoms was undertaken during the follow-up. Results: Half of the followed-up people reported experiencing at least one of the COVID-19-related symptoms. The mean blood pressure was found higher in follow-up. People with the symptoms were characterized by low lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without any post-COVID-19 symptoms. Cytokines IL-8, VEGF, and MCP-1 were higher in people with the most frequent symptoms. Conclusion: People with post-COVID-19 symptoms were characterized by lower lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without symptoms. Individuals with the most frequent post-COVID-19 symptoms had higher baseline pro-inflammatory, chemotactic, and angiogenic cytokines.

Clinical and biochemical characteristics and outcomes of suspected COVID-19 hospitalized patients: RT-PCR swab positive and negative comparison.

BACKGROUND: COVID-19 is diagnosed using RT-PCR assays of samples from nasal and oropharyngeal swabs. People with negative RT-PCR often presented with clinical manifestations of COVID-19. The data on such patients are lacking. The present study aims to characterize the patients who were suspected COVID-19 cases and tested negative in RT-PCR compared to patients who had been tested RT-PCR positive. METHODS: This is a retrospective, observational study of adult suspected and confirmed patients of COVID-19 admitted to King Saud University Medical City, Riyadh, Saudi Arabia, from 1st March 2020 until 30th November 2020. Laboratory confirmation is done through nasal/pharyngeal swab specimens, tested positive in RT-PCR assay. Patients with initial negative RT-PCR test results were assessed again within 48-72 h to avoid false-negative results. Patient data were extracted from the electronic medical files of each included patient using a predesigned case report form. RESULTS: The study included 488 (80.93%) patients with RT-PCR swab results positive, and 115 (19.07%) patients who were negative. Respiratory rate and diastolic blood pressure were higher among the swab-positive cases. More number of swab-negative patients had comorbidities such as coronary heart disease, chronic kidney disease, and carcinoma. Fever, cough, and shortness of breath were reported higher among the swab-positive cases. ALT and AST, and LDH levels were found higher among RT-PCR-positive patients. Serum creatinine, blood urea nitrogen and troponin were more elevated in RT-PCR-negative patients. Antibiotics, anticoagulants, and corticosteroids were used more by swab-positive patients. Significantly higher number of RT-PCR-positive patients required proning, high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation. Acute cardiac ischemia and death were found to be similar among the patients. However, deaths occurred significantly earlier among the swab-positive cases when compared to the swab-negative group. CONCLUSION: Distinctive symptoms and markers of COVID-19 are more frequent among patients who had RT-PCR-positive results.

Assessing the Detection of Middle East Respiratory Syndrome Coronavirus IgG in Suspected and Proven Cases of Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease with significant mortality. Two testing methods are currently used for MERS-CoV diagnostics: nucleic acid detection (the gold standard) and serological analysis. In this study, we evaluated the detection of MERS-CoV-IgG in suspected and proven cases of MERS-CoV infection. We enrolled 174 patients: 113 had respiratory symptoms/suspected MERS-CoV infection, 31 had confirmed influenza A or B infection, 23 had a recent confirmed MERS-CoV infection, and 7 had confirmed MERS-CoV infection 1 year before. All underwent MERS-CoV RNA and MERS-CoV-IgG testing. Thirty patients were found to be MERS-CoV RNA positive; however, during serological analysis, only 6 (3.4%) patients were positive for MERS-CoV-IgG, 1 (0.6%) patient was equivocal, and 167 (96%) patients were negative. Among the serological positives, four were recently MERS-CoV RNA positive and two were MERS-CoV RNA negative. No cross-reactivity to influenza A or B was detected. Based on the lack of correlation between nucleic acid and serological analysis, we conclude that MERS-CoV-IgG testing may not be suitable for diagnosing acute infection or estimating its prevalence during an outbreak. In addition, our findings show that MERS-CoV-IgG may not have significant value in determining disease severity or prognosis.