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J Clin Immunol ; 41(7): 1607-1620, 2021 10.
Article in English | MEDLINE | ID: covidwho-1298388


The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Complement C3a/metabolism , Complement C5a/metabolism , Coronavirus Infections/diagnosis , Interleukin-8/metabolism , Lung/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Aged , Biomarkers/metabolism , Complement C3a/genetics , Complement C5a/genetics , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Female , Humans , Interleukin-8/genetics , Male , Middle Aged , Prognosis , Severity of Illness Index , Survival Analysis , Up-Regulation
Virol J ; 18(1): 127, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1269882


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.

COVID-19/mortality , Coinfection/mortality , Influenza, Human/mortality , Adult , Aged , Bacterial Infections/epidemiology , Bacterial Infections/mortality , Bacterial Infections/pathology , COVID-19/epidemiology , COVID-19/pathology , Coinfection/epidemiology , Coinfection/pathology , Female , Hospitalization , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/epidemiology , Influenza, Human/pathology , Intensive Care Units , Male , Middle Aged , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , SARS-CoV-2/isolation & purification , Saudi Arabia/epidemiology