ABSTRACT
Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.
ABSTRACT
[This corrects the article DOI: 10.1186/s41182-020-00203-0.].
ABSTRACT
BACKGROUND: The Philippines has been one of the most affected COVID-19 countries in the Western Pacific region, but there are limited data on COVID-19-related mortality and associated factors from this setting. We aimed to describe the epidemiological and clinical characteristics and associations with mortality among COVID-19-confirmed individuals admitted to an infectious diseases referral hospital in Metro Manila. MAIN TEXT: This was a single-centre retrospective analysis including the first 500 laboratory-confirmed COVID-19 individuals admitted to San Lazaro Hospital, Metro Manila, Philippines, from January to October 2020. We extracted clinical data and examined epidemiological and clinical characteristics and factors associated with in-hospital mortality. Of the 500 individuals, 133 (26.6%) were healthcare workers (HCW) and 367 (73.4%) were non-HCW, with HCW more likely presenting with milder symptoms. Non-HCW admissions were more likely to have at least one underlying disease (51.6% vs. 40.0%; p = 0.002), with hypertension (35.4%), diabetes (17.4%), and tuberculosis (8.2%) being the most common. Sixty-one (12.2%) died, comprising 1 HCW and 60 non-HCW (0.7% vs. 16.3%; p < 0.001). Among the non-HCW, no death occurred for the 0-10 years age group, but deaths were recorded across all other age groups. Compared to those who recovered, individuals who died were more likely to be older (p < 0.001), male (p = 0.015), report difficulty of breathing (p < 0.001), be HIV positive (p = 0.008), be intubated (p < 0.001), categorised as severe or critical (p < 0.001), have a shorter mean hospital stay (p < 0.001), or have an additional diagnosis of pneumonia (p < 0.001) or ARDS (p < 0.001). CONCLUSION: Our analysis reflected significant differences in characteristics, symptomatology, and outcomes between healthcare and non-healthcare workers. Despite the unique mix of cohorts, our results support the country's national guideline on COVID-19 vaccination which prioritises healthcare workers, the elderly, and people with comorbidities and immunodeficiency states.
ABSTRACT
BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient's condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.