Difference in presentation, outcomes, and hospital epidemiologic trend of COVID-19 among first, second, and third waves: a review of hospital records and prospective cohort study.

This study aimed to examine the differences in epidemiologic and disease aspects among patients with coronavirus disease-19 (COVID-19). Methods: The authors reviewed the hospital records between April 2020 and September 2021 and followed up on the patients for post-COVID complications. Findings: Older adult patients were predominantly affected during the third wave, and middle-aged patients were predominantly affected during the first and second waves. Men were predominantly admitted, considering the three waves, although more women were admitted in the second wave. Cough was more common in the second and third waves than in the first wave 522 (59.7%). Respiratory distress was the most common in the third wave, 251(67.1%), and least common in the first wave, 403 (46.1%). Anosmia was more common in the third wave 116 (31.2%). In the third wave, patients presenting in a critical state 23 (6.2%) and with severe disease 152 (40.8%) were more common. The hospital admission median (IQR) was longer in the first wave, 12 (8-20), than in other waves. More patients were admitted in the first wave (52%) than in the other waves, and patients received more oxygen in the third wave (75%) than in the other waves. Death occurred more commonly in the first wave (51%) than in the other waves. The positivity rate was higher in the third wave (22.8%) than in the other waves. In the third wave, the positivity rate was higher in women (24.3%) than in men. Post-COVID cough increased in the second wave, and fatigue was higher in the third wave than in the other waves. Tiredness and memory loss were greater during the second wave than in other waves. Conclusion: The authors found differences in the presentation, outcomes, and hospital epidemiologic trend of COVID-19 among the three waves.

Post-discharge quality of life of COVID-19 patients at 1-month follow-up: A cross-sectional study in the largest tertiary care hospital of Bangladesh.

There is increasing evidence of the post-COVID-19 suffering and decreased quality of life in the COVID-19 patients. This study aimed to assess the quality of life and associated factors of COVID-19 patients at one month after discharge from the hospital. This was a cross-sectional study that was conducted at the post-covid clinic of Dhaka Medical College Hospital (DMCH) where RT-PCR-confirmed adult COVID-19 recovered patients were enrolled one month after discharge from the same hospital. They were consecutively selected from January 01 to May 30. A pretested semi-structured questionnaire was used for the data collection for clinical variables. The generic multi-attributable utility instrument EQ-5D-5L was used for assessing health-related quality of life (HRQoL). A total of 563 patients were enrolled in the study. The patients had a mean age with standard deviation (±SD) of 51.18 (±13.49) years and 55.95% were male. The mean (SD) EQ-5D-5L index score and EQ-VAS scores were 0.78 (±0.19) and 70.26 (±11.13), respectively. Overall, 45.77%, 50.99%, 52.79%, 55.14% and 62.16% had problems (slight to extreme) in the mobility, self-care, usual activities, pain/discomfort and anxiety/depression dimensions, respectively. Patients aged ≥60 years had significant problem in mobility (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.07-9.77). Female participants were 5.50 times (95% CI: 2.22-13.62) more likely to have problems in their usual activities. In comparison to urban area, living in a peri-urban setting was significantly associated with problems in mobility (OR 1.89, 95% CI: 1.13-3.20), pain/discomfort (OR 1.82, 95% CI: 1.04-3.12) and anxiety/depression (OR 2.16, 95% CI: 1.22-3.84). Comorbid patients were 1.75 times (95% CI: 1.07-2.85) more likely to report problems in the pain/discomfort dimension. Presence of symptom(s) was associated with problems in self-care (OR 3.27, 95%CI: 1.31-8.18), usual-activity (OR 3.08, 95%CI: 1.21-7.87), pain/discomfort dimensions (OR 2.75, 95%CI: 1.09-6.96) and anxiety/depression (OR 3.35, 95%CI: 1.35-8.30). Specific management strategies should be planned to address the factors associated with low health-related quality of life in post-acute care of COVID-19 patients.

Systemic lupus erythematosus with acute ischemic optic neuropathy complicated with neuromyelitis optica: a case report.

BACKGROUND: Neuromyelitis optica is a relapsing-remitting disease characterized by a recurrent attack of optic neuritis and transverse myelitis; sometimes associated with acute brainstem syndrome. Systemic lupus erythematosus is an autoimmune multisystem disorder in which ocular involvement such as acute ischemic optic neuropathy is a rare manifestation. However, neuromyelitis optica can be associated with systemic lupus erythematosus. CASE PRESENTATION: A 24-year-old Bangladeshi woman was admitted to the hospital with complaints of sudden, progressive, painless vision loss in both eyes, and progressive weakness in both lower limbs for 48 hours. She also gave a history of arthralgia, a photosensitive skin rash, intermittent fever, oral ulcerations, and alopecia for the last 2 months. On examination, the fundus was suggestive of bilateral acute ischemic neuropathy, and examinations of the lower limb revealed spastic paraparesis with sensory abnormality. Laboratory investigations revealed the presence of positive anti-aquaporin 4 antibody, strongly positive antinuclear antibody, and anti-ds DNA with the longitudinally extensive lesion on magnetic resonance imaging of the spinal cord. She was treated with methylprednisolone, hydroxychloroquine, and mycophenolate, and was discharged with improvement of her paraparesis. However, her vision did not improve substantially. CONCLUSION: The importance of this report is to shed some light on the occurrence of two devastating complications that is, bilateral acute ischemic optic neuropathy in systemic lupus erythematosus complicated by neuromyelitis optica, as well as evidence of rare presentations for systemic lupus erythematosus and treatment modalities of ischemic optic neuropathy with systemic lupus erythematosus.

Acute Hemorrhagic Leucoencephalitis (AHLE): A Rare CNS Presentation of Mycoplasma pneumoniae.

Acute hemorrhagic leucoencephalitis (AHLE) is a rare inflammatory disease of the brain. Literature on the presentation and management of this rare disease is limited. A Mycoplasma pneumoniae infection is considered a possible trigger for acute hemorrhagic leucoencephalitis (Weston-Hurst syndrome). We report a case of a 58-year-old man presenting with an altered level of consciousness following a history of acute respiratory tract infection. He had also clinical and laboratory features of disseminated intravascular coagulation (DIC). Brain imaging was suggestive of hemorrhagic encephalitis involving both the fronto-temporo-parieto-occipital lobes involving the cortical, subcortical, and splenium of the corpus callosum and the posterior limb of the right internal capsule. Antibodies against Mycoplasma were strongly positive in serum. The patient was treated with fresh frozen plasma, broad-spectrum antibiotics, and methylprednisolone. However, the patient died after 17 days of hospitalization probably due to multiorgan failure and brain herniation.

Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many anti-inflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1ß) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality. METHODS AND FINDINGS: This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes were also recorded on day 28. The primary endpoint was met by 9 (6.2%) patients in the placebo group and 4 (2.7%) patients in the colchicine group (P = 0.171), which corresponds to a hazard ratio (95% CI) of 0.44 (0.13-1.43). Additional analysis of the outcomes on day 28 revealed significantly lower clinical deterioration (defined as a decrease by two or more points) in the colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098-0.917], (P = 0.035). Despite a 56% reduction in the need for mechanical ventilation and death with colchicine treatment on day 14, the reduction was not statistically significant. On day 28, colchicine significantly reduced clinical deterioration measured as the need for mechanical ventilation and all-cause mortality. CONCLUSION: Colchicine was not found to have a significant beneficial effect on reducing mortality and the need for mechanical ventilation. However, a delayed beneficial effect was observed. Therefore, further studies should be conducted to evaluate the late benefits of colchicine. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: ClinicalTrials.gov Identifier: NCT04527562 https://www.google.com/search?client=firefox-b-d&q=NCT04527562.

Health hazards related to using masks and/or personal protective equipment among physicians working in public hospitals in Dhaka: A cross-sectional study.

BACKGROUND: Wearing masks or personal protective equipment (PPE) has become an integral part of the occupational life of physicians due to the coronavirus disease 2019 (COVID-19) pandemic. Most physicians have been developing various health hazards related to the use of different protective gears. This study aimed to determine the burden and spectrum of various health hazards associated with using masks or PPE and their associated risk factors. METHODS: This cross-sectional survey was conducted in Dhaka Medical College from March 01-May 30, 2021, among physicians from different public hospitals in Dhaka, Bangladesh. We analyzed the responses of 506 physicians who completed case record forms through Google forms or hard copies. FINDINGS: The mean (SD) age of the respondents was 35.4 [7.7], and 69.4% were men. Approximately 40% were using full PPE, and 55% were using N-95 masks. A total of 489 (96.6%) patients experienced at least one health hazard. The reported severe health hazards were syncope, severe dyspnea, severe chest pain, and anaphylaxis. Headache, dizziness, mood irritation, chest pain, excessive sweating, panic attack, and permanent facial disfigurement were the minor health hazards reported. Extended periods of work in the COVID-19-unit, reuse of masks, diabetes, obesity, and mental stress were risk factors for dyspnea. The risk factors for headaches were female sex, diabetes, and previous primary headaches. Furthermore, female sex and reusing masks for an extended period (> 6 h) were risk factors for facial disfigurement. The risk factors for excessive sweating were female sex and additional evening office practice for an extended period. CONCLUSIONS: Healthcare workers experienced several occupational hazards after using masks and PPE. Therefore, an appropriate policy is required to reduce such risks.

Presentation, Etiology, Outcome, and Differentiation of Visual Semiology of Adult Occipital Epilepsy From Visual Aura of Migraine Headache: A Prospective Study in a Tertiary Care Center in Bangladesh.

BACKGROUND: Occipital epilepsy is an uncommon and likely underdiagnosed type of epilepsy that is often misdiagnosed as a migraine with aura. High clinical suspicion and subsequent electroencephalogram (EEG) and brain imaging lead to early diagnosis.  Methods: We recruited patients with occipital epilepsy based on visual semiology, structural abnormalities in the occipital region, or EEG changes who visited the Department of Neurology of Dhaka Medical College from June 2019 to January 2020. We documented the presentations, etiology, and outcomes at the 12-month follow-up. Additionally, we compared the clinical features of patients with occipital epilepsy (n = 10) and those with migraine with aura (n = 18). RESULTS: We identified three and seven cases of idiopathic and symptomatic occipital epilepsy, respectively, all presenting with visual semiology. Symptomatic occipital epilepsy occurred due to space-occupying lesions, post-hypoxic damage, post-stroke encephalomalacia, gyral calcification from Sturge-Weber syndrome, and Wilson's disease. Age, sex, illness duration, headache severity, and associated features were similar between the migraine with aura and epilepsy groups. In occipital epilepsy, the median (IQR) age was 22 (15-47) years, and the patients were predominantly female (8, 80%). The visual auras lasted 35 (3-375) seconds and included colored dots or light flashes that persisted for seconds (50%) before (60%), during (30%), and after (10%) the headache. Compared to migraines, the headaches were global (90%), compressive (90%), and of shorter duration (210 minutes, IQR: 150-630). Except for nausea or osmophobia, vomiting (80%), photophobia (80%), and phonophobia (70%) occurred. Most cases had associated focal or bilateral tonic-clonic seizures (60%; p-value < 0.001). In contrast, the visual auras in migraine were scotomas, white or golden dots, or light flashes lasting for minutes (83.3%; p-value = 0.02) before the headache. The headaches lasted longer (720 minutes, IQR: 345-1,440, p-value < 0.03), were unilateral (44%) or bilateral (50%), and throbbing (72%; p-value = 0.003). Headache was associated with photophobia (94.4%; p-value = 0.28), phonophobia (88.9%; p-value 0.31), and osmophobia (38.9%; p-value 0.03); no associated convulsions occurred. At the 12-month follow-up, most occipital epilepsy patients (9, 90%) responded well to carbamazepine. CONCLUSIONS: Patients with transient and distinct elementary visual hallucinations headache characteristics different from migraines with associated convulsions warrant evaluation for occipital epilepsy.

Subcortical Band Heterotopia Presented With Refractory Epilepsy and Reversible Aphasia.

Subcortical band heterotopia (SBH) is a rare neurodevelopmental disorder due to mutation in the DCX or LIS1 gene. It is predominantly a disease of females. Its presentation varied widely, ranging from mild epilepsy and mental retardation to refractory epilepsy and severe mental retardation. Here, a case of a 22-year-old lady with refractory seizure is reported. She also had expressive aphasia which had reversed after adjustment of the anti-epileptic drugs and control of the seizure. Her MRI of the brain revealed a band of complete gray matter deep to the pachygyric cortex and an electroencephalogram (EEG) revealed bi-frontal slow waves.

Acute Ischemic Stroke With Central Retinal Artery Occlusion as a Rare Presentation of COVID-19 Disease.

In this report, we present a case where the patient developed a border-zone ischemic stroke with central retinal artery occlusion (RAO) following coronavirus disease 2019 (COVID-19) disease. The COVID-19 disease has been described to induce inflammatory changes that predispose to thrombotic disease in both venous and arterial circulation. Angiotensin-converting enzyme 2 (ACE2) receptor expression in the blood vessel with which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds is the cornerstone of inflammation although the pathogenesis of central RAO is multifactorial. The effects of COVID-19 inflammatory and pro-coagulant state on cerebral and retinal vascular systems are still inadequately understood. Combined presentation of central RAO with ischemic stroke has not been documented in the literature yet. As of now, no guidelines exist regarding treatment modalities to be employed in such instances. Hence, further research is warranted regarding the treatment of this condition with respect to the association with COVID-19.

Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial.

OBJECTIVE: We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. METHODS: This was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR. RESULTS: Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4-10, treatment group) and 9 (5-12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60-0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04-0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. CONCLUSIONS: Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523831. DATA REPOSITORY ID: Dryad. doi:10.5061/dryad.qjq2bvqf6.

Association of ABO blood groups with presentation and outcomes of confirmed SARS CoV-2 infection: A prospective study in the largest COVID-19 dedicated hospital in Bangladesh.

BACKGROUND: Globally, studies have shown conflicting results regarding the association of blood groups with SARS CoV-2 infection. OBJECTIVE: To observe the association between ABO blood groups and the presentation and outcomes of confirmed COVID-19 cases. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of patients with mild-to-moderately severe COVID-19 infections who presented in the COVID-19 unit of Dhaka Medical College Hospital and were enrolled between 01 June and 25 August, 2020. Patients were followed up for at least 30 days after disease onset. We grouped participants with A-positive and A-negative blood groups into group I and participants with other blood groups into group II. RESULTS: The cohort included 438 patients; 52 patients were lost to follow-up, five died, and 381 completed the study. The prevalence of blood group A [144 (32.9%)] was significantly higher among COVID-19 patients than in the general population (p < 0.001). The presenting age [mean (SD)] of group I [42.1 (14.5)] was higher than that of group II [38.8 (12.4), p = 0.014]. Sex (p = 0.23) and co-morbidity (hypertension, p = 0.34; diabetes, p = 0.13) did not differ between the patients in groups I and II. No differences were observed regarding important presenting symptoms, including fever (p = 0.72), cough (p = 0.69), and respiratory distress (p = 0.09). There was no significant difference in the median duration of symptoms in the two group (12 days), and conversion to the next level of severity was observed in 26 (20.6%) and 36 patients (13.8%) in group I and II, respectively. However, persistent positivity of RT-PCR at 14 days of initial positivity was more frequent among the patients in group I [24 (19%)] than among those in group II [29 (11.1%)]. CONCLUSIONS: The prevalence of blood group A was higher among COVID-19 patients. Although ABO blood groups were not associated with the presentation or recovery period of COVID-19, patients with blood group A had delayed seroconversion.

Post-COVID-19 syndrome among symptomatic COVID-19 patients: A prospective cohort study in a tertiary care center of Bangladesh.

BACKGROUND: Post-coronavirus disease (COVID-19) syndrome includes persistence of symptoms beyond viral clearance and fresh development of symptoms or exaggeration of chronic diseases within a month after initial clinical and virological cure of the disease with a viral etiology. We aimed to determine the incidence, association, and risk factors associated with development of the post-COVID-19 syndrome. METHODS: We conducted a prospective cohort study at Dhaka Medical College Hospital between June 01, 2020 and August 10, 2020. All the enrolled patients were followed up for a month after clinical improvement, which was defined according the World Health Organization and Bangladesh guidelines as normal body temperature for successive 3 days, significant improvement in respiratory symptoms (respiratory rate <25/breath/minute with no dyspnea), and oxygen saturation >93% without assisted oxygen inhalation. FINDINGS: Among the 400 recruited patients, 355 patients were analyzed. In total, 46% patients developed post-COVID-19 symptoms, with post-viral fatigue being the most prevalent symptom in 70% cases. The post-COVID-19 syndrome was associated with female gender (relative risk [RR]: 1.2, 95% confidence interval [CI]: 1.02-1.48, p = 0.03), those who required a prolonged time for clinical improvement (p<0.001), and those showing COVID-19 positivity after 14 days (RR: 1.09, 95% CI: 1.00-1.19, p<0.001) of initial positivity. Patients with severe COVID-19 at presentation developed post-COVID-19 syndrome (p = 0.02). Patients with fever (RR: 1.5, 95% CI: 1.05-2.27, p = 0.03), cough (RR: 1.36, 95% CI: 1.02-1.81, p = 0.04), respiratory distress (RR: 1.3, 95% CI: 1.4-1.56, p = 0.001), and lethargy (RR: 1.2, 95% CI: 1.06-1.35, p = 0.003) as the presenting features were associated with the development of the more susceptible to develop post COVID-19 syndrome than the others. Logistic regression analysis revealed female sex, respiratory distress, lethargy, and long duration of the disease as risk factors. CONCLUSION: Female sex, respiratory distress, lethargy, and long disease duration are critical risk factors for the development of post-COVID-19 syndrome.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.

Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer.

BACKGROUND: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). METHODS: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. RESULTS: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. CONCLUSIONS: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.