Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.

Clinical characteristics and predictors of mortality among COVID-19 patients in Saudi Arabia.

BACKGROUND: The new coronavirus disease (COVID-19) has caused more than 1.8 million deaths, with a fatality rate of 2.5% in more than 200 countries as of January 4, 2021. Analysis of COVID-19 clinical features can help predict disease severity and risk of mortality, early identification of high-risk patients, and provide knowledge to inform clinical interventions. OBJECTIVE: The purpose of this study is to investigate the clinical characteristics and possible predictors associated with mortality in patients with COVID-19 admitted to King Fahad (KFH), Ohood, and Miqat hospitals in Madina, Saudi Arabia. METHODS: This retrospective observational study to investigate the clinical characteristic and possible predictors associated with mortality for those 119 mild, moderate, or critically ill patients confirmed by laboratory results to have COVID-19 who were admitted to three hospitals in Madina, Saudi Arabia, from March 25, 2020, to July 30, 2020. Data were collected from December 1, 2020, to December 14, 2020. RESULTS: Of the 119 patients included in the study, the mean age was 54.2 (±15.7) years, with 78.2% survivors and 21.8% non-survivors. The demographic analysis indicated that the likelihood of mortality for patients in the older age group (i.e., ≥65 years) was five times higher than those in the younger age group (OR = 5.34, 95% CI 1.71-16.68, p = 0.004). The results also indicated those patients who admitted to the intensive care unit (ICU) was approximately seven times higher odds of mortality compare with those who were not admitted (OR = 6.48, 95% CI 2.52-16.63, p < 0.001). In addition, six laboratory parameters were positively associated with the odds of mortality: white blood cell count (OR = 1.11, 95% CI 1.02-1.21, p = 0.018), neutrophil (OR = 1.11, 95% CI 1.02-1.22, p = 0.020), creatine kinase myocardial band (OR = 1.02, 95% CI 1.00-1.03, p = 0.030), C-reactive protein (OR = 1.01, 95% CI 1.00-1.01, p = 0.002), urea (OR = 1.06, 95% CI 1.01-1.11, p = 0.026), and lactate dehydrogenase (OR = 1.00, 95% CI 1.00-1.01, p = 0.020). CONCLUSIONS: In this cohort, COVID-19 patients within the older age group (≥65 years) admitted to the ICU with increased C-reactive protein levels in particular, were associated with increased odds of mortality. Further clinical observations are warranted to support these findings and enhance the mapping and control of this pandemic.

Influenza co-infection associated with severity and mortality in COVID-19 patients.

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

Enzyme-Linked Immunosorbent Assay for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgM/IgA and IgG Antibodies Among Healthcare Workers.

Background The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading rapidly across the world. A nucleic acid real-time quantitative polymerase chain reaction (RQ-PCR) test of nasopharyngeal samples is the standard method for the diagnosis of an active SARS-CoV-2 infection. However, many limitations of the RQ-PCR tests make them unsuitable for the simple and rapid diagnosis of COVID-19 patients. Moreover, some individuals with COVID-19 present an asymptomatic infection. Thus, assessing the asymptomatic transmission of COVID-19, especially in healthcare workers (HCWs), is crucial for evaluating the efficiency of the current preventive measures. Serological tests such as enzyme-linked immunosorbent assay (ELISA) are needed to quickly identify a large number of asymptomatic carriers to prevent the further spread of the virus and assess level of possible serological immunity in a community. Method Between April 18 and June 17, 2020, 330 HCWs from five Madinah region-affiliated hospitals underwent a seroprevalence screening for anti-SARS-CoV-2 antibodies (immunoglobulin [Ig]M/IgA and IgG) using indirect ELISA testing. Result Among the 330 samples, 80 (24.24%) were positive for SARS-CoV-2 IgM/IgA and/or IgG antibodies. There were no significant differences observed in the seroprevalence among the different occupations of the HCWs (excluding the pharmacists) with respect to the percentage of their seropositive samples. Conclusion The current study presented the seroprevalence of anti-SARS-CoV-2 IgM/IgA and IgG antibodies in HCWs. The regular screening of HCWs for these antibodies is necessary; subsequently, a molecular test is recommended for those with seropositive (IgM, IgA, and IgG) samples to assess their viral load and potential shedding.