Profiles of Independent-Comorbidity Groups in Senior COVID-19 Patients Reveal Low Fatality Associated with Standard Care and Low-Dose Hydroxychloroquine over Antivirals.

Introduction: The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose: To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods: Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results: A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion: The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.

Molecular evolutionary model based on phylogenetic and mutation analysis of SARS-CoV-2 spike protein sequences from Asian countries: A phylogenomic approach.

The lethal pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused the COVID-19 pandemic, posing serious risks to people. The clove-like spike (S) protein that distinguishes coronaviruses from other viruses is important for viral pathogenicity, evolution, and transmission. The investigation of the unique structural mutations of the SARS-CoV-2 spike protein among 34 Asian countries, as well as the resulting phylogenetic relationship, provided critical information in understanding the pathogenesis. This can be utilized for the discovery of possible treatments and vaccine development. The current study analyzed and depicted phylogenetic and evolutionary models useful for understanding SARS-CoV-2 human-human transmission dynamics in Asian regions with shared land borders. Further, integrated bioinformatics analysis was performed to predict the pathogenic potential and stability of 53 mutational positions among 34 coronavirus strains. Mutations at positions N969K, D614G and S884F have deleterious effects on protein function. These findings are crucial because the Asian mutations could potentially provide a vaccine candidate with co-protection against all SARS-CoV-2 strains. This region is vulnerable because of the high population density and the volume of domestic and international travel for business and tourism. These discoveries would also aid in the development of plans for governments and the general populace to implement all required biocontainment protocols common to all countries.

Molecular and Source-Specific Profiling of Hospital Staphylococcus aureus Reveal Dominance of Skin Infection and Age-Specific Selections in Pediatrics and Geriatrics.

Staphylococcus aureus is a major human-associated pathogen that causes a wide range of clinical infections. However, the increased human dynamics and the changing epidemiology of the species have made it imperative to understand the population structure of local ecotypes, their transmission dynamics, and the emergence of new strains. Since the previous methicillin-resistant S. aureus (MRSA) pandemic, there has been a steady increase in global healthcare-associated infections involving cutaneous and soft tissue and resulting in high morbidities and mortalities. Limited data and paucity of high-quality evidence exist for many key clinical questions about the pattern of S. aureus infections. Using clinical, molecular, and epidemiological characterizations of isolates, hospital data on age and infection sites, as well as antibiograms, we have investigated profiles of circulating S. aureus types and infection patterns. We showed that age-specific profiling in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients > 50 years; most of which were MRSA (81.99%). However, specific distributions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, the age groups 0−20 years showed uniquely similar MRSA patterns in ICU and non-ICU patients (13.9% and 9.7%, respectively) and MSSA in ICU (11.6%). The similar frequencies of both lineages in youth at both settings is consistent with their increased socializations and gathering strongly implying carriage and potential evolutionary replacement of MSSA by MRSA. However, in age groups 20−50 years, MRSA was two-fold higher in non-ICU (35%) than ICU (18.6%). Interestingly, a highly significant association was found between infection-site and age-groups (p-value 0.000). Skin infections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while respiratory infections were lower in pediatrics (14.3%) and adults (17%) while it was highest in seniors (38%). Blood and "other" sites in pediatrics were recorded (28.6%; 25%, respectively), and were slightly lower in adults (18.6%; 8.6%) and seniors (14%; 22.8%), respectively. Furthermore, a significant association existed between infection-site and MRSA (Chi-Square Test, p-value 0.002). Thus, the common cutaneous infections across all age-groups imply that skin is a significant reservoir for endogenous infections; particularly, for geriatrics MRSA. These findings have important clinical implications and in understanding S. aureus profiles and transmission dynamics across different age groups that is necessary for strategic planning in patient management and infection control.

The Frequency and Patterns of Post-COVID-19 Vaccination Syndrome Reveal Initially Mild and Potentially Immunocytopenic Signs in Primarily Young Saudi Women.

Vaccination is the most promising approach for ending or containing the SARS-CoV-2 pandemic. However, serious post-COVID-19 vaccine reactions, including immunocytopenia (ITP) syndrome, have been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of widely available specific therapeutics, vigilance is important while more studies are needed. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 vaccine side effects on febrile patients after administration three major vaccines. Results indicated that the majority of respondents administered Pfizer BioNtech vaccine (81%, n = 809); followed by AstraZeneca (16%, n = 155); and Moderna (3%, n = 34). Overall 998 participants, 74% (n = 737) showed no serious symptoms; however, 26.2% (n = 261) revealed typical syndromes. In a focused group of 722 participants, the following rates were identified: shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent among those who showed typical symptoms. The onset time was mostly between 1-3 days in 49% (n = 128), followed by 4-7 days in 21.8% (n = 57), 8-14 days in 16.5% (n = 43), and more than a month in 12.6% (n = 33). The onsets occurred mostly after the first, second, or both doses, 9%, 10%, and 7% of participants, respectively. The frequency of symptoms was significantly higher after Moderna® vaccine (p-value = 0.00006) and it was significantly lower in participants who received Pfizer (p-value = 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, sex, education, and nationality had no influence on the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID-19 vaccine syndrome.

Molecular Diagnosis, Antimicrobial Resistance Profiles and Disease Patterns of Gram-Positive Pathogens Recovered from Clinical Infections in Major Ha’il Hospitals

Nosocomial resistance in staphylococci and enterococci is challenging. The aim of this work was to conduct a multipoint study using molecular detections, antimicrobial resistances profiles, patient demographics and disease patterns for objective assessments of Staphilococcus aureus and other Gram-positive pathogens recovered from clinical infections in the Ha’il region. We have surveyed 188 non-duplicate Gram-positives against 22 antimicrobials for molecular-differentiation, resistance, patient demographics, and disease patterns from January–April 2021. According to definitions for acquired resistance, Staphylococcus aureus was the most frequent with multidrug resistant (65.4%), where MRSA was 60% (n = 72 out of 121). In age-identified patients, 43% were seniors ≥50 years, 38% 21–49 years, and 19% 0–20 years. In gender-identified patients, 63% were males, and 37% were females. While 25% of specimens were from the ICU, the majority (60%) of specimens were from surgical infection in other wards. Staphylococcus epidermidis was the second (15.4%) species of infection identified with 81% from bloodstream infections at the ICU and other wards. The majority of S. epidermidis patients (69%) were seniors ≥50 years, while other age groups 0–20 and 21–49 each had 14% isolates. Although S. epidermidis was multidrug-resistant, it was susceptible to many drugs. Enterococcus faecalis (13%) ranked third with two major infections;bloodstream (64%) and urinary-tract infections (36%) in mainly seniors (86%). Its isolates were fully resistant to oxacillin, penicillin, cefoxitin, and cefotaxime but nearly 100% susceptible to seven others. Other Gram-positive bacteria (6%) were susceptible to many antibiotics. The use of combinations of objective criteria is a well thought out approach in infection control. While the low-frequency of Gram-positives is an impressive achievement, future large-scale investigations should include all private hospitals, clinics and other cities over a longer sampling time to gain more insights. Although geriatric susceptibility can be justified by age and comorbidities, the staphylococcal infections in young adults and children is a global concern and warrants more vertical studies.

Selective COVID-19 Coinfections in Diabetic Patients with Concomitant Cardiovascular Comorbidities Are Associated with Increased Mortality.

Coinfections and comorbidities add additional layers of difficulties into the challenges of COVID-19 patient management strategies. However, studies examining these clinical conditions are limited. We have independently investigated the significance of associations of specific bacterial species and different comorbidities in the outcome and case fatality rates among 129 hospitalized comorbid COVID-19 patients. For the first time, to best of our knowledge, we report on the predominance of Klebsiella pneumoniae and Acinetobacter baumannii in COVID-19 non-survival diabetic patients The two species were significantly associated to COVID-19 case fatality rates (p-value = 0.02186). Coinfection rates of Klebsiella pneumoniae and Acinetobacter baumannii in non-survivors were 93% and 73%, respectively. Based on standard definitions for antimicrobial resistance, Klebsiella pneumoniae and Acinetobacter baumannii were classified as multidrug resistant and extremely drug resistant, respectively. All patients died at ICU with similar clinical characterisitics. Of the 28 major coinfections, 24 (85.7%) were in non-survivor diabetic patients, implying aggravating and worsening the course of COVID-19. The rates of other comorbidities varied: asthma (47%), hypertension (79.4%), ischemic heart disease (71%), chronic kidney disease (35%), and chronic liver disease (32%); however, the rates were higher in K. pneumoniae and were all concomitantly associated to diabetes. Other bacterial species and comorbidities did not have significant correlation to the outcomes. These findings have highly significant clinical implications in the treatment strategies of COVID-19 patients. Future vertical genomic studies would reveal more insights into the molecular and immunological mechanisms of these frequent bacterial species. Future large cohort multicenter studies would reveal more insights into the mechanisms of infection in COVID-19.

COVID-19 Clinical Profiles and Fatality Rates in Hospitalized Patients Reveal Case Aggravation and Selective Co-Infection by Limited Gram-Negative Bacteria.

Bacterial co-infections may aggravate COVID-19 disease, and therefore being cognizant of other pathogens is imperative. We studied the types, frequency, antibiogram, case fatality rates (CFR), and clinical profiles of co-infecting-pathogens in 301 COVID-19 patients. Co-infection was 36% (n = 109), while CFR was 31.2% compared to 9.9% in non-co-infected patients (z-value = 3.1). Four bacterial species dominated, namely, multidrug-resistant Klebsiella pneumoniae (37%, n = 48), extremely drug-resistant Acinetobacter baumannii (26%, n = 34), multidrug-resistant Eschericia. coli (18.6%, n = 24), and extremely drug-resistant Pseudomonas aeruginosa (8.5%, n = 11), in addition to other bacterial species (9.3%, n = 12). Increased co-infection of K. pneumoniae and A. baumannii was associated with increased death rates of 29% (n = 14) and 32% (n = 11), respectively. Klebsiella pneumoniae was equally frequent in respiratory and urinary tract infections (UTI), while E. coli mostly caused UTI (67%), and A. baumannii and P. aeruginosa dominated respiratory infections (38% and 45%, respectively). Co-infections correlated with advance in age: seniors ≥ 50 years (71%), young adults 21-49 years (25.6%), and children 0-20 years (3%). These findings have significant clinical implications in the successful COVID-19 therapies, particularly in geriatric management. Future studies would reveal insights into the potential selective mechanism(s) of Gram-negative bacterial co-infection in COVID-19 patients.

A Multi-Point Surveillance for Antimicrobial Resistance Profiles among Clinical Isolates of Gram-Negative Bacteria Recovered from Major Ha'il Hospitals, Saudi Arabia.

The devastating nosocomial resistance is an on-going global concern. Surveillance of resistance is crucial for efficient patient care. This study was aimed to conduct a surveillance in four major Ha'il Hospitals from September to December 2020. Using a multipoint program, records of 621 non-duplicate Gram-negative cultures were tested across 21 drugs belonging to different categories. Major species were Klebsiella pneumoniae (n = 187, 30%), E. coli (n = 151, 24.5%), Pseudomonas aeruginosa, (n = 84, 13.6%), Acinetobacter baumannii (n = 82, 13.3%), and Proteus mirabilis (n = 46, 7%). Based on recent resistance classifications, A. baumanni, P. aeruginosa, and enteric bacteria were defined as pan-resistant, extremely resistant, and multi-drug resistant, respectively. A. baumannii (35%) and K. pneumoniae (23%) dominated among coinfections in SARS-CoV2 patients. The "other Gram-negative bacteria" (n = 77, 12.5%) from diverse sources showed unique species-specific resistance patterns, while sharing a common Gram-negative resistance profile. Among these, Providencia stuartii was reported for the first time in Ha'il. In addition, specimen source, age, and gender differences played significant roles in susceptibility. Overall infection rates were 30% in ICU, 17.5% in medical wards, and 13.5% in COVID-19 zones, mostly in male (59%) senior (54%) patients. In ICU, infections were caused by P. mirabilis (52%), A. baumannii (49%), P. aeruginosa (41%), K. pneumoniae (24%), and E. coli (21%), and most of the respiratory infections were caused by carbapenem-resistant A. baumannii and K. pneumoniae and UTI by K. pneumoniae and E. coli. While impressive IC, hospital performances, and alternative treatment options still exist, the spread of resistant Gram-negative bacteria is concerning especially in geriatric patients. The high selective SARS-CoV2 coinfection by A. baumannii and K. pneumoniae, unlike the low global rates, warrants further vertical studies. Attributes of resistances are multifactorial in Saudi Arabia because of its global partnership as the largest economic and pilgrimage hub with close social and cultural ties in the region, especially during conflicts and political unrests. However, introduction of advanced inter-laboratory networks for genome-based surveillances is expected to reduce nosocomial resistances.