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.

Acute physiology and chronic health evaluation score and mortality of patients admitted to intermediate care units of a hospital in a low- and middle-income country: A cross-sectional study from Pakistan.

Background: Intermediate care units (IMCUs) serve as a bridge between general wards and intensive care units by providing close monitoring and rapid response to medical emergencies. We aim to identify the common acute medical conditions in patients admitted to IMCU and compare the predicted mortality of these conditions by acute physiology and chronic health evaluation-II (APACHE-II) score with actual mortality. Methods: A cross-sectional study was conducted at a tertiary care hospital from 2017 to 2019. All adult internal medicine patients admitted to IMCUs were included. Acute conditions were defined as those of short duration (<3 weeks) that require hospitalization. The APACHE-II score was used to determine the severity of these patients' illnesses. Results: Mean (standard deviation [SD]) age was 62 (16.5) years, and 493 (49.2%) patients were male. The top three acute medical conditions were acute and chronic kidney disease in 399 (39.8%), pneumonia in 303 (30.2%), and urinary tract infections (UTIs) in 211 (21.1%). The mean (SD) APACHE-II score of these patients was 12.5 (5.4). The highest mean APACHE-II (SD) score was for acute kidney injury (14.7 ± 4.8), followed by sepsis/septic shock (13.6 ± 5.1) and UTI (13.4 ± 5.1). Sepsis/septic shock was associated with the greatest mortality (odds ratio [OR]: 6.9 [95% CI (confidence interval): 4.5-10.6]), followed by stroke (OR: 3.9 [95% CI: 1.9-8.3]) and pneumonia (OR: 3.0 [95% CI: 2.0-4.5]). Conclusions: Sepsis/septic shock, stroke, and pneumonia are the leading causes of death in our IMCUs. The APACHE-II score predicted mortality for most acute medical conditions but underestimated the risk for sepsis and stroke.

COVID-19 and thrombotic thrombocytopenic purpura: A case report.

The clinical presentation of COVID-19 varies from being asymptomatic to developing acute respiratory distress syndrome and multi-organ dysfunction. The diffuse microvascular thrombi in multiple organs seen in the autopsy of COVID-19 patients are similar to that of thrombotic microangiopathy (TMA). TMA is characterised by thrombus formation in the microvasculature with laboratory findings of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. A 49-year-old male presented to the Aga Khan University Hospital, Karachi. with fever, diarrhoea, altered level of consciousness, and a positive nasopharyngeal swab for SARS-CoV-2. He developed severe thrombocytopenia, MAHA with 5.8% schistocytes, and worsening renal function on the sixth day of admission. Diagnosis of thrombotic thrombocytopenic purpura (TTP) was established based on PLASMIC score, and he was successfully treated with intravenous (IV) Methylprednisolone, therapeutic plasma exchange and IV Rituximab. The case emphasises the need to keep TTP in the differential diagnosis when a patient with COVID-19 develops severe thrombocytopenia, acute renal failure, or impaired level of consciousness, since prompt diagnosis and treatment is necessary to gain favourable outcome.

A retrospective review of antiphospholipid syndrome from a South Asian country.

Objectives: This study aims to investigate clinical presentations, antiphospholipid antibody patterns and their levels, therapeutic regimens, and outcomes in patients with antiphospholipid syndrome (APS) admitted to a tertiary care hospital of a South Asian country. Patients and methods: Between January 2009 and December 2019, a total of 216 patients with APS (8 males, 208 females; median age: 35.7±6.9 years; range, 20 to 76 years) who either fulfilled the modified Sydney criteria or those who satisfied only clinical criteria along with positive antiphospholipid antibody on at least one occasion (probable APS) were retrospectively analyzed. Results: The majority of the patients (n=183, 84.7%) had obstetric complications, followed by venous thrombosis in 23 (10.8%) patients. Recurrent early abortions in 126 (58.6%) and deep venous thrombosis in 16 (7.4%) patients were the most prevalent obstetrical and venous events, respectively, whereas limb gangrene in seven (3.3%) and ischemic stroke in seven (3.3%) were the most common arterial events. A total of 190 (88%) patients had primary APS, while 26 (12%) had secondary APS. Systemic lupus erythematosus was the frequent association with secondary APS found in 19 (73%) patients. Immunoglobulin M (IgM) anticardiolipin antibody was present in 173 (65.0%) patients, being the most commonly reported antibody. Probable catastrophic APS was found in four (1.9%) patients. Majority of the patients (n=190, 87.9%) were treated with a combination of acetylsalicylic acid and low-molecular-weight heparin. Single mortality was observed in our study population due to complications related to catastrophic APS. Conclusion: Antiphospholipid syndrome has a wide range of thrombotic and obstetrical manifestations with important variations in different regions of the world. There is a significant morbidity and mortality related to APS, despite treatment with anticoagulation and; therefore, describing prognostic markers and optimal therapeutic interventions is pivotal to prevent complications.

Lower limb axonal mononeuropathies as sequelae of COVID-19: a case report and review of literature.

BACKGROUND: Neurological symptoms and complications of Coronavirus disease 2019 (COVID-19) were seldom discussed in the literature initially. Neurological symptoms such as headache, dizziness, anosmia, hypogeusia, and neuralgia are, however, now being reported commonly. Mononeuropathies are rare complications of COVID-19, with most cases associated with prolonged intensive care stay. CASE PRESENTATION: A 61-year-old gentleman with prior history of well-controlled diabetes and hypertension was recently treated for COVID-19 pneumonia with supplemental oxygen and positive pressure ventilation. He now presented with left-sided foot weakness two weeks after recovering from the viral illness. On examination he had normal bulk and tone and a power of 4/5 in proximal and distal muscles of bilateral lower limbs except for ankle dorsiflexion on the left which was 2/5. He also had absent ankle and knee reflexes bilaterally with bilateral flexor plantar reflexes. Since the patient had no back pain and the sensory system was normal, the lesion was localized to the peripheral nerves and a Nerve Conduction Studies and Electromyography (NCS/EMG) was done. NCS/EMG showed findings suggestive of axonal mononeuropathies. Relevant workup done to identify the cause of mononeuropathy was negative including infectious and autoimmune workup. Since diabetes was well-controlled and he had no intensive care stay his findings were presumed to be associated with resolving COVID-19 infection. The patient underwent aggressive daily physical therapy and has started to show improvement in symptoms. CONCLUSIONS: Complications such as mononeuropathies should be kept in mind in patients recovering from COVID-19 infection, since timely diagnosis can improve clinical outcomes in patients.

Discrepancy between PCR based SARS-CoV-2 tests suggests the need to re-evaluate diagnostic assays.

OBJECTIVE: We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays. RESULTS: Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was conducted using the TaqPath™ COVID19 PCR. Eight of ten samples were positive for SARS-CoV-2 on the TaqPath assay. Further, Spike gene target failures (SGTF) were identified in three of these eight cases. Discrepancy between the three PCR assays could be due to variation in PCR efficiencies of the amplification reactions or, variation at primer binding sites. Strains with SGTF indicate the presence of new SARS-CoV-2 variant strains. Regular modification of gene targets in diagnostic assays may be necessary to maintain robustness and accuracy of SARS-CoV-2 diagnostic assays to avoid reduced case detection, under-surveillance, and missed opportunities for control.

SHORT COMMUNICATION-Inappropriate use of proton pump inhibitor for stress ulcer prophylaxis in a tertiary care hospital in Karachi, Pakistan.

The use of proton pump inhibitors (PPI) has been expanded inappropriately. PPI are among the most selling drugs in the world. There is growing evidence that PPI are associated with significant adverse effects along with undue financial burden. Inappropriate prescription of PPI is common in inpatients. The objective is to determine the frequency of inappropriate use of proton pump inhibitors for stress ulcer prophylaxis. This prospective observational study was conducted in the Department of Medicine of The Aga Khan University Hospital Karachi. 151 adult patients admitted in the hospital were included. All those patients who received PPI due to a condition mentioned by American Gastroenterology Association (AGA) as an indication for PPI, were labeled as PPI appropriately indicated. While those patients who received PPI without a condition mentioned by AGA as an indication for PPI, were labeled as PPI inappropriately indicated. Mean age was 57.2±18.2 years. Route of administration was oral in 110 (72.8%) and IV in 41 (27.2%) patients. Out of 151 patients, 100 (66.2%) patients were receiving PPI without any specific indication while 51 (33.8%) patients were receiving PPI with appropriate indications. Our study showed that inappropriate use of PPI is quite common among admitted patients.

A Fatal Case of Primary Amoebic Meningoencephalitis (PAM) Complicated with Diabetes Insipidus (DI): A Case Report and Review of the Literature.

Naegleria fowleri is a highly infective free-living amoeba usually isolated from soil and fresh water and is primarily found to infect the central nervous system (CNS) resulting in primary amoebic meningoencephalitis (PAM). PAM as a cause of meningitis is often overlooked for other, more common causes of meningitis. Despite all the advances in antimicrobial therapy and supportive care systems, the mortality rate of this rare infection remains above 95% with the bulk of the cases being found in developed countries. We are presenting a case of a 44-year-old male with fever, worsening headache, and generalized weakness. Lumbar puncture showed a raised leucocyte count of 1100/µL with predominant polymorphonuclear cells, and wet mount prep for Naegleria fowleri was positive further confirmed with PCR. The patient was started Intravenous (IV) and intrathecal amphotericin-B, Per Oral (PO) miltefosine, IV rifampin, IV fluconazole, and IV dexamethasone. However, the patient started producing urine at 300-500 ml/hour. The patient's sodium levels increased from 144 to 175 mmol/L in 12 hours with raised serum osmolality and decreased urine osmolality and urine sodium. The patient was started on PO desmopressin of 0.2 micrograms twice daily after which his urine output dropped to 60-80 ml/hour and sodium decreased from 175 to 162 and, later 155 mmol/L; however, the patient expired. PAM is a rare and extremely fatal illness, but with increasing incidence now being reported in developing countries as a result of better diagnostics. DI is a very rare complication reported in these patients leading to poor outcome. The complication of diabetes insipidus (DI) has not been extensively studied in patients having PAM. Only three cases have been reported with this complication. No mechanism has been mentioned in the literature behind the development of DI in these patients, and no study has mentioned laboratory details of DI as mentioned in this report.