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.

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.

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.

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.

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.

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.

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.

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.

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.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

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.

VITT with inactivated SARS-CoV-2 vaccine - index case.

We report a case of vaccine-induced immune thrombotic thrombocytopenia (VITT) in a 73-year-old gentleman who presented with pulmonary embolism and thrombocytopenia, two weeks after receiving inactivated COVID-19 vaccine. He responded well to nonheparin anticoagulation with complete resolution of symptoms and platelet count.

The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries.

Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India.

Clinical outcomes of immunomodulatory therapies in the management of COVID-19: A tertiary-care experience from Pakistan.

The pharmacological management of COVID-19 has evolved significantly and various immunomodulatory agents have been repurposed. However, the clinical efficacy has been variable and a search for cure for COVID-19 continues. A retrospective cohort study was conducted on 916 patients hospitalized with polymerase chain reaction (PCR)-confirmed COVID-19 between February 2020 and October 2020 at a tertiary care academic medical center in Karachi, Pakistan. The median age was 57 years (interquartile range (IQR) 46-66 years). The most common medications administered were Methylprednisolone (65.83%), Azithromycin (50.66%), and Dexamethasone (46.6%). Majority of the patients (70%) had at least two or more medications used in combination and the most frequent combination was methylprednisolone with azithromycin. Overall in-hospital mortality was 13.65% of patients. Mortality was found to be independently associated with age greater than or equal to 60 years (OR = 4.98; 95%CI: 2.78-8.91), critical illness on admission (OR = 13.75; 95%CI: 7.27-25.99), use of hydrocortisone (OR = 12.56; 95%CI: 6.93-22.7), Ferritin> = 1500(OR = 2.07; 95%CI: 1.18-3.62), Creatinine(OR = 2.33; 95%CI: 1.31-4.14) and D-Dimer> = 1.5 (OR = 2.27; 95%CI: 1.26-4.07). None of the medications whether used as monotherapy or in combination were found to have a mortality benefit. Our study highlights the desperate need for an effective drug for the management of critical COVID-19 which necessitates usage of multiple drug combinations in patients particularly Azithromycin which has long term implications for antibiotic resistance particularly in low-middle income countries.

Long Term Impact on Lung Function of Patients With Moderate and Severe COVID-19. A Prospective Cohort Study.

Background: In Pakistan, the cases of COVID-19 have declined from 6000 per day in June to 600 in September 2020. A significant number of patients continue to recover from the disease, however, little is known about the lung function capacity among survivors. We aim to determine the long-term impact on lung function capacity in patients who have survived moderate or severe COVID-19 disease in a resource-poor setting. Methods: This prospective cohort study will be conducted at Aga Khan University Hospital (AKUH), Karachi Pakistan. Patients 15 years and above who have survived an episode of moderate or severe COVID-19, have reverse transcriptase-polymerase chain reaction (RT-PCR) positive for COVID 19 (nasopharyngeal or oropharyngeal) will be included. Patients with a pre-existing diagnosis of obstructive or interstitial lung disease, lung fibrosis, lung cancers, connective tissue disorders, autoimmune conditions affecting the lungs, underlying heart disease, history of syncope and those who refuse to participate will be excluded from the study. Pulmonary function will be assessed using spirometry and diffusion lung capacity for carbon monoxide (DLCO) at 3- and 6-months interval from the time of discharge from the hospital. Additionally, a chest X-ray and CT-chest will be performed if clinically indicated after consultation with the study pulmonologist or Infectious Disease (ID) physician. Echocardiogram (ECHO) will be performed to look for pulmonary hypertension at the 3 month visit and repeated at 6 months in case any abnormality is identified in the initial ECHO. Data analysis will be performed using standard statistical software. The study was approved by the Ethical Review Committee (ERC) of the institution (ERC reference number 2020-4735-11311). Strengths and Limitations of the Study: This cohort study will provide evidence on the long-term impact on lung function among COVID-19 survivors with moderate to severe disease. Such data will be key in understanding the impact of the disease on vital functions and will help devise rehabilitative strategies to best overcome the effects of disease. However, this will be a single-center, study recruiting only a limited number of COVID-19 survivors.

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.

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.