Comparison of risk factors and outcome of patients with and without COVID-19-associated pulmonary aspergillosis from Pakistan: A case-control study.

BACKGROUND: Early identification of COVID-19-associated pulmonary aspergillosis (CAPA) is particularly challenging in low- middle-income countries where diagnostic capabilities are limited, and risk factors for CAPA have not been identified. It is also essential to recognise CAPA patients who are likely to have a poorer outcome to decide on aggressive management approaches. Therefore, this study aimed to identify risk factors and outcomes for CAPA among admitted moderate to critical COVID-19 patients at our centre in Pakistan. METHODS: An unmatched case-control study with ratio of 1:2 was conducted on hospitalised adult patients with COVID-19 from March 2020-July 2021. Cases were defined according to European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Controls were defined as patients hospitalised with moderate, severe or critical COVID-19 without CAPA. RESULTS: A total of 100 CAPA cases (27 probable CAPA; 73 possible CAPA) were compared with 237 controls. Critical disease at presentation (aOR 5.04; 95% CI 2.18-11.63), age ≥ 60 years (aOR 2.00; 95% CI 1.20-3.35) and underlying co-morbid of chronic kidney disease (CKD) (aOR 3.78; 95% CI 1.57-9.08) were identified as risk factors for CAPA. Patients with CAPA had a significantly greater proportion of complications and longer length of hospital stay (p-value < .001). Mortality was higher in patients with CAPA (48%) as compared to those without CAPA (13.5%) [OR = 6.36(95% CI 3.6-11)]. CONCLUSIONS: CAPA was significantly associated with advanced age, CKD and critical illness at presentation, along with a greater frequency of complications and higher mortality.

Contagion of coronavirus disease-the first family cluster of Pakistan: a case series.

Coronavirus Disease has resulted in public health crisis all over the world. We describe the case series of a family, who travelled together to a mass gathering in Iraq, toured Syria, Lebanon, and Doha and returned to Karachi. The data describes the demographic and clinical features of these six members. There were three males and three females. One developed severe disease and died. Incubation period was between 8-14 days. Four patients were symptomatic, had diabetes mellitus and hypertension; and presented with fever. They also had bilateral airspace opacifications on chest X-ray. Our study describes familial clustering of SARS-CoV-2 and its person-to-person transmission.

Risk factors for bacterial infections in patients with moderate to severe COVID-19: A case-control study.

Adverse outcomes in coronavirus infection disease-19 (COVID-19) patients are not always due to the direct effects of the viral infection, but often due to bacterial coinfection. However, the risk factors for such bacterial coinfection are hitherto unknown. A case-control study was conducted to determine risk factors for bacterial infection in moderate to critical COVID-19. Out of a total of 50 cases and 50 controls, the proportion of cases with severe/critical disease at presentation was 80% in cases compared to 30% in controls (p < 0.001). The predominant site was hospital-acquired pneumonia (72%) and the majority were Gram-negative organisms (82%). The overall mortality was 30%, with comparatively higher mortality among cases (42% vs. 18%; p = 0.009). There was no difference between procalcitonin levels in both groups (p = 0.883). In multivariable logistic regression analysis, significant independent association was found with severe/critical COVID-19 at presentation (AOR: 4.42 times; 95% CI: 1.63-11.9) and use of steroids (AOR: 4.60; 95% CI: 1.24-17.05). Notably, 64% of controls were administered antibiotics despite the absence of bacterial coinfection or secondary infection. Risk factors for bacterial infections in moderate to critically ill patients with COVID-19 include critical illness at presentation and use of steroids. There is widespread empiric antibiotic utilization in those without bacterial infection.

C. auris and non-C. auris candidemia in hospitalized adult and pediatric COVID-19 patients; single center data from Pakistan.

We compared candidemia due to Candida auris and other non-C.auris cases in hospitalized COVID-19 patients over a period of 9 months at our institution. Candidemia cases in all admitted patients (with or without COVID-19) from April to December 2020 were identified. Electronic records were accessed to record clinical data of COVID-19 patients with candidemia. For statistical analysis, independent samples Mann-Whitney U test was used for continuous and Fisher's exact test was used for categorical variables.A total of 26 candidemia cases (four C.auris, 22 non-C.auris) in 2438 admitted COVID-19 (10.7 per 1000 admissions) and 59 candidemia cases (six C.auris, 53 non-C.auris) in admitted non-COVID patients (8.2 per 1000 admission) were identified. The proportion of C.auris candidemia in COVID-19 and non-COVID-19 patients was 15.4 and 10%, respectively. 4/26 of COVID-19 candidemia patients were aged ≤ 15 years (10 months--15 years). Comparison of C.auris and non-C. auris candidemia cases reveal significant difference in prior antifungal exposure, present in 100% C. auris candidemia versus 27% non-C. auris candidemia patients (P-value 0.014). Although not statistically significant, C. auris candidemia patients had a longer stay in hospital before candidemia (20 vs. 9 days), higher isolation rate of multidrug resistant bacteria (100 vs. 50%), increased rate of prior colonization of Candida species (50 vs. 14%) and lower mean beta-d-glucan levels (48.73 pg/ml vs. 138.146 pg/ml). Both C. auris and non-C. auris COVID-19 patients had similar mortality rate (67 vs. 65%). A significant number of critically ill COVID-19 patients developed candidemia in our study highlighting the need for prompt diagnosis and management. LAY SUMMARY: 26 candidemia cases (4 Candida auris;22 non-C. auris) in COVID-19 patients (April-December 2020) are reported from Pakistan. Compared to non-C. auris, C. auris candidemia patients had higher prior antifungal exposure, longer hospital stay, higher rates of MDR bacteria and Candida colonization.

Role of awake prone positioning in patients with moderate-to-severe COVID-19: an experience from a developing country.

There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.

COVID-19-associated pulmonary aspergillosis (CAPA) in patients admitted with severe COVID-19 pneumonia: An observational study from Pakistan.

BACKGROUND: Invasive aspergillosis is a well-known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID-19 pneumonia, named as COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A retrospective observational study was conducted in patients with severe COVID-19 pneumonia from February 2020 to April 2020. Patients ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID-19 by RT-PCR for SARS-CoV-2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma, and descriptive analysis was performed using Stata ver 12.1. RESULTS: A total of 147 patients with confirmed COVID-19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients, and of these, five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonisation. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51-85), and 3/5 patients were male. The most frequent co-morbid was diabetes mellitus (4/5). The overall fatality rate of COVID-19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all three patients with CAPA, and the median length of stay was 16 days (IQR: 10; Range 6-35 days). CONCLUSION: This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID-19 and the need for screening for fungal infections in severe COVID-19 patients with certain risk factors.

Mortality In Patients With Respiratory And Nonrespiratory Carbapenem Resistant-Multidrug Resistant Acinetobacter Infections.

BACKGROUND: Mortality from carbapenem-multi-drug resistant Acinetobacter infections may vary according to site of infection. The objective of this study was to compare mortality in respiratory vs. non-respiratory infection with Carbapenem-Multi-drug Resistant Acinetobacter (C-MRAB). METHODS: We conducted a prospective cohort study to compare mortality rate in patients with respiratory vs. nonrespiratory infection (n=30 each). RESULTS: Results showed that mortality was 40% in the respiratory group compared to 23% in non-respiratory group; the difference was not statistically significant (p=0.165, RR=1.71, CI=0.73-3.75). There was a significantly higher prior admission rate in patients with respiratory infection (p=0.028). Logistic regression did not reveal any modifier effect from other variables. CONCLUSIONS: This study showed no significant difference in mortality in patients with carbapenem-multi-drug resistant acinetobacter respiratory vs. non-respiratory infections.

An Unusual Pathogen Causing Native Valve Endocarditis.

We present the case of a gentleman who was being evaluated for restrictive lung disease and was incidentally found to have mitral valve stenosis on an HRCT. During the surgical procedure for valve replacement, he was found to have an abscess around the native mitral valve which was drained. Pus from the abscess as well as the valve tissue grew Propionibacterium acnes after holding the cultures long. The patient was treated with IV ceftriaxone with good response to therapy. While Propionibacterium acnes is known to cause prosthetic valve infections there are rare case reports with native valves. This is the first case to be reported from our country.

Hair dye poisoning and rhabdomyolysis.

Hair dye ingestion is a rare cause of toxicity in Pakistan. We are presenting the case report of a 55 year old male who presented with accidental hair dye ingestion and developed laryngeal oedema requiring emergent tracheostomy. He had also developed aspiration pneumonitis and chemical oesophagitis. However, the most alarming manifestation was rhabdomyolysis. Hair dye toxicity can be fatal if not recognized early. There is no antidote available. Rhabdomyolysis is a complication and needs to be managed aggressively in order to prevent long term morbidity.

Mortality in Sepsis and its relationship with Gender.

BACKGROUND AND OBJECTIVE: Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20-50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients. METHODS: This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNFα) levels and patients were followed up for clinical outcome. RESULTS: There were 54% males and 46% females, with no significant difference of age or comorbids between genders. Respiratory tract infection was the commonest source of sepsis, and was more common in females (60%) compared to males (39%) (p=0.034). Males had a higher mortality (p=0.048, RR 1.73) and plasma IL-6 level(p=0.040) compared to females. Mean IL-6 plasma level was significantly (p<0.01) higher in patients who died vs. who recovered. CONCLUSION: Our study shows that males with sepsis have a 70% greater mortality rate, and mortality is associated with a higher IL-6 plasma level.

Predictors of Mortality in Crimean-Congo Hemorrhagic Fever Patients Admitted at a Tertiary Care Hospital in Pakistan over the Last 10 Years: A Case-Control Study.

The objective was to identify predictors of mortality in hospitalized patients with Crimean-Congo hemorrhagic fever (CCHF). A case-control study was conducted on patients hospitalized with CCHF from 2012 to 2022. Risk factors for mortality in CCHF patients were analyzed using logistic regression. A total of 86 patients with a median age of 36 years (interquartile range [IQR], 27-36 years) were included, and the majority were males (78, 90.7%). Thirty-one patients (36%) were cases, whereas 55 (64%) were control patients. Based on univariate logistic regression analysis, patients who were in an age group of ≥40 years (odds ratio [OR]: 4.85; 95% CI: 1.8-12.4) or with presence of gum bleeding (OR: 2.66; 95% CI: 1.0-6.8), unit increase in white blood cell count (WBC) (OR: 1.09; 95% CI: 1.00-1.07), serum glutamate-pyruvate transaminase of ≥500 U/L (OR: 3.68; 95% CI: 1.4-9.3), serum glutamic-oxaloacetic transaminase (SGOT) of ≥1,000 U/L (OR: 8.72; 95% CI: 2.6-28.3), prothrombin time (PT) of ≥120 seconds (OR: 9.85; 95% CI: 3.2-29.8), international normalized ratio of ≥5 (OR: 15.8; 95% CI: 2.0-125.3), or acute respiratory distress syndrome (ARDS) (OR: 28.27; 95% CI: 5.84-136.9) were found to be significantly associated with mortality in CCHF. Factors found to be independently associated with mortality on multivariate analysis included ARDS (adjusted OR [aOR]: 27.7; 95% CI: 4.0-190.5), unit increase in WBC (aOR: 1.02; 95% CI: 1.02-1.26), SGOT of ≥1,000 U/L (aOR: 23.6; 95% CI: 2.32-241.7), and PT of ≥120 seconds (OR: 10.2; 95% CI: 2.00-52.4). CCHF is a rare but fatal disease, and patients with ARDS and increased WBC, high SGOT level, and increased PT indicative of liver injury and coagulopathy at the time of hospitalization are at high risk for mortality.

Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications.

COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.

Shift in SARS-CoV-2 variants of concern from Delta to Omicron was associated with reduced hospitalizations, increased risk of breakthrough infections but lesser disease severity.

BACKGROUND: COVID-19 epidemiology changed with the emergence of SARS-CoV-2 variants of concern (VOC). Pakistan administered mostly inactivated vaccines. We investigated the association between VOC and breakthrough infections in a mixed-vaccination-status population of Karachi. METHODS: We investigated SARS-CoV-2 VOC tested in 392 respiratory specimens collected between May and December 2021. Data for age, sex, hospital admission, vaccinations, together with CT values of the diagnostic PCR test were analyzed. RESULTS: The median age of COVID-19 cases tested was 40 (27-57) years and 43.4% were female. Delta variants were most common (56.4%) followed by Alpha (15.9%), Omicron (12.2%), Beta/Gamma (11.3%), and others (4.3%). Eighteen percent of cases were hospitalized whereby, predominant VOC were Beta/Gamma (40.8%), Alpha (35.2%) and Delta (22.5%). Overall, 55.4% of individuals were fully vaccinated, 7.4% were partially vaccinated and 37.2% were unvaccinated. Most (74.6%) inpatients were unvaccinated. Vaccines comprised inactivated (85.34%), single-shot vector (8.62%), two-shot vector (3.02%) and mRNA (3.02%) types. Omicron variants showed lower viral loads as compared to Alpha, Beta/Gamma, and Delta (p = 0.017). The risk of infection with Delta and Omicron variants was higher, 8 weeks after vaccination. The majority of those with breakthrough infections after receiving inactivated vaccines acquired COVID-19 within 4 months of vaccination. CONCLUSION: Our data highlights the shifting of VOC from Delta to Omicron during 2021 and that COVID-19 vaccinations reduced both hospitalizations and viral transmission. It informs on the increased risk of breakthrough infection within 8 weeks of vaccination, indicating the need for booster vaccinations.

Risk factors for mortality in hospitalized COVID-19 patients across five waves in Pakistan.

This retrospective cohort study aims to describe the clinical characteristics and outcomes and assess risk factors for mortality across the epidemic waves in hospitalized COVID-19 patients in a major tertiary-care center in Pakistan. A total of 5368 patients with COVID-19, hospitalized between March 2020 and April 2022 were included. The median age was 58 years (IQR: 44-69), 41% were females, and the overall mortality was 12%. Comparative analysis of COVID-19 waves showed that the proportion of patients aged ≥ 60 years was highest during the post-wave 4 period (61.4%) and Wave 4 (Delta) (50%) (p < 0.001). Male predominance decreased from 65.2% in Wave 2 to 44.2% in Wave 5 (Omicron) (p < 0.001). Mortality rate was lowest at 9.4% in wave 5 and highest at 21.6% in the post-wave 4 period (p = 0.041). In multivariable analysis for risk factors of mortality, acute respiratory distress syndrome (ARDS) was most strongly associated with mortality (aOR 22.98, 95% CI 15.28-34.55, p < 0.001), followed by need for mechanical ventilation (aOR 6.81, 95% CI 5.13-9.05, p < 0.001). Other significant risk factors included acute kidney injury (aOR 3.05, 95% CI 2.38-3.91, p < 0.001), stroke (aOR 2.40, 95% CI 1.26-4.60, p = 0.008), pulmonary embolism (OR 2.07, 95% CI 1.28-3.35, p = 0.003), and age ≥ 60 years (aOR 2.45, 95% CI 1.95-3.09, p < 0.001). Enoxaparin use was associated with lower mortality odds (aOR 0.45, 95% CI 0.35-0.60, p < 0.001. Patients hospitalized during Wave 4 (aOR 2.22, 95% CI 1.39-3.56, p < 0.001) and the post-wave 4 period (aOR 2.82, 95% CI 1.37-5.80, p = 0.005) had higher mortality odds compared to other waves. The study identifies higher mortality risk in patients admitted in Delta wave and post-wave, aged ≥ 60 years, and with respiratory and renal complications, and lower risk with anticoagulation during COVID-19 waves.

Utility of neutrophil to lymphocyte ratio to predict acute respiratory distress syndrome in COVID-19: short communication.

Acute respiratory distress syndrome (ARDS) is the most severe and devastating form of acute lung injury. Neutrophil to lymphocyte ratio (NLR) and C-reactive protein have been used to predict severity and prognosis of certain viral illnesses. Methods: A retrospective cohort study was conducted in hospitalized COVID-19 patients. Serial measurements of NLR and C-reactive protein were recorded and patients were followed for development of ARDS. Results: Out of 388 patients admitted with COVID-19, 43 patients developed ARDS compared with 345 patients who did not develop ARDS. The median NLR at presentation was significantly higher in patients who developed ARDS (8.89 vs. 4.25) compared with those who did not develop ARDS (P<0.001). Moreover, serial measurement of NLR at presentation, day 3, day 5 and day 7 was significantly associated with development of ARDS (P<0.001). In multivariable analysis, age of greater than or equal to 50 years (adsjusted odds ratio=3.28; 95% CI=1.40-7.69) and unit increase in NLR at presentation (adsjusted odds ratio=1.07; 95% CI=1.03-1.11) were independently associated with development of ARDS. Conclusion: Serial measurement of NLR can predict patients who are at a greater risk for developing ARDS in COVID-19.

The CalculAuthor: determining authorship using a simple-to-use, fair, objective, and transparent process.

Authorship determination on a research article remains a largely subjective process. Existing guidelines on authorship taxonomy lack objectivity and are more useful in determining who deserves authorship rather than determining the order of authors. To promote best practices in authorship taxonomy, we developed an authorship rubric that provides a fair, objective, and transparent means of crediting authorship. We christened this tool the "CalculAuthor". The following steps are to be undertaken to create a scoring system based on the requirements of the projects: determining creditable criteria, assigning credit weightages, deciding levels of contribution, determining each author's contribution, calculating authorship scores and ranking. These must be performed by or in close collaboration with the primary investigator (PI), with conflicts being resolved at the PI's discretion. All team members should be informed about the authorship determination process early in the project and their agreement regarding its use must be obtained. While the CalculAuthor was developed to be used in medical research, its customizability enables it to be employed in any field of academia. We recommend that the CalculAuthor be piloted within institutions before its mainstream adoption, and any institution-specific factors should be considered to make the process more efficient and suitable.

Clinical manifestations and outcome of patients with primary amoebic meningoencephalitis in Pakistan. A single-center experience.

Primary amoebic meningoencephalitis (PAM) is a rapidly progressing central nervous system (CNS) infection caused by Naegleria fowleri, a free-living amoeba found in warm freshwater. The disease progression is very rapid, and the outcome is nearly always fatal. We aim to describe the disease course in patients admitted with PAM in a tertiary care center in Karachi, Pakistan between the periods of 2010 to 2021. A total of 39 patients were included in the study, 33 males (84.6%). The median age of the patients was 34 years. The most frequent presenting complaint was fever, which was found in 37 patients (94.9%) followed by headache in 28 patients (71.8%), nausea and vomiting in 27 patients (69.2%), and seizures in 10 patients (25.6%). Overall, 39 patients underwent lumbar puncture, 27 patients (69.2%) had a positive motile trophozoites on CSF wet preparation microscopy, 18 patients (46.2%) had a positive culture, and 10 patients had a positive PCR. CSF analysis resembled bacterial meningitis with elevated white blood cell counts with predominantly neutrophils (median, 3000 [range, 1350-7500] cells/µL), low glucose levels median, 14 [range, 1-92] mg/dL), and elevated protein levels (median, 344 [range, 289-405] mg/dL). Imaging results were abnormal in approximately three-fourths of the patients which included cerebral edema (66.7%), hydrocephalus (25.6%), and cerebral infarctions (12.8%). Only one patient survived. PAM is a fatal illness with limited treatment success. Early diagnosis and prompt initiation of treatment can improve the survival of the patients and reduce mortality.

Post-COVID-19 Pneumocystis pneumonia cases from Pakistan: an observational study.

Background. Concurrent coronavirus disease 2019 (COVID-19) and Pneumocystis jirovecii pneumonia (PJP) has been described in various reports, with a recent study describing a 9.3 % P. jirovecii detection rate in critically ill COVID-19 patients. Methods. Patients with PCR-confirmed PJP following COVID-19 infection who were admitted to Aga Khan University Hospital, Karachi, Pakistan from March 2020-June 2021 were identified through a laboratory database. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was performed by RT-PCR Cobas SARS-CoV-2 qualitative assay. P. jirovecii PCR was performed using the RealStar Pneumocystis jirovecii PCR kit. Clinical, radiological and laboratory data for PJP patients were recorded. Results. During the study period, 3707 patients were admitted with COVID-19 at our hospital. P. jirovecii PCR was requested for 90 patients and was positive in 10 (11 %). Five out of 10 patients were discharged from the hospital and later developed cough and dyspnoea. Five patients remained hospitalized with severe COVID-19 and developed PJP. Eight patients in our study received systemic steroids. The trends of lymphocyte counts of all patients showed a lymphocyte count of <1000 mm-3 (<1.0×106 cells µl-1) in the week of PJP diagnosis. Four patients did not survive; one of these patients did not receive co-trimoxazole due to late diagnosis, one patient had concomitant nosocomial pneumonia and bacteraemia with multidrug-resistant Acinetobacter species, and two patients had concomitant aspergillosis. Conclusion. In summary, invasive fungal infections such as PJP should be considered as a complication in COVID-19 patients, with prompt evaluation and management.

Exploring the relationship between SARS-CoV-2 variants, illness severity at presentation, in-hospital mortality and COVID-19 vaccination in a low middle-income country: A retrospective cross-sectional study.

Background and Aims: COVID-19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS-CoV-2 variants of concern (VOC) with COVID-19 severity and mortality among hospitalized patients in Pakistan. Methods: A retrospective review of clinical, laboratory, and vaccination data of 197 COVID-19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS-CoV-2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID-19 outcomes. Results: The median age of cases was 55 years and 51.8% were males. Twenty-four percent of females were pregnant. Of COVID-19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS-CoV-2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID-19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45-13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82-9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11-0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23-0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92-13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45-17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10-0.53]). Conclusion: Our study describes the relationship between the severity of COVID-19, in-hospital mortality in relation to SARS-CoV-2 variants, and the impact of COVID-19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID-19.