Background
There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.
Objective
We ...performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.
Methods
Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.
Results
We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use RR 0.98 95% CI 0.66–1.46, time to fever resolution (mean difference − 0.54 days (− 1.19–011)) or clinical deterioration/development of ARDS with HCQ RR 0.90 95% CI 0.47–1.71. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ RR 1.46 95% CI 1.04 to 2.06. The quality of evidence was graded as very low for these outcomes.
Authors’ Conclusion
The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in ...the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the ...effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.
We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%.
Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61).
This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.
None.
For the Hindi translation of the abstract see Supplementary Materials section.
Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical ...entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.
Objectives
To study whether a trained convolutional neural network (CNN) can be of assistance to radiologists in differentiating Coronavirus disease (COVID)–positive from COVID-negative patients ...using chest X-ray (CXR) through an ambispective clinical study. To identify subgroups of patients where artificial intelligence (AI) can be of particular value and analyse what imaging features may have contributed to the performance of AI by means of visualisation techniques.
Methods
CXR of 487 patients were classified into 4 categories—normal, classical COVID, indeterminate, and non-COVID by consensus opinion of 2 radiologists. CXR which were classified as “normal” and “indeterminate” were then subjected to analysis by AI, and final categorisation provided as guided by prediction of the network. Precision and recall of the radiologist alone and radiologist assisted by AI were calculated in comparison to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. Attention maps of the CNN were analysed to understand regions in the CXR important to the AI algorithm in making a prediction.
Results
The precision of radiologists improved from 65.9 to 81.9% and recall improved from 17.5 to 71.75 when assistance with AI was provided. AI showed 92% accuracy in classifying “normal” CXR into COVID or non-COVID. Analysis of attention maps revealed attention on the cardiac shadow in these “normal” radiographs.
Conclusion
This study shows how deployment of an AI algorithm can complement a human expert in the determination of COVID status. Analysis of the detected features suggests possible subtle cardiac changes, laying ground for further investigative studies into possible cardiac changes.
Key Points
• Through an ambispective clinical study, we show how assistance with an AI algorithm can improve recall (sensitivity) and precision (positive predictive value) of radiologists in assessing CXR for possible COVID in comparison to RT-PCR.
• We show that AI achieves the best results in images classified as “normal” by radiologists. We conjecture that possible subtle cardiac in the CXR, imperceptible to the human eye, may have contributed to this prediction.
• The reported results may pave the way for a human computer collaboration whereby the expert with some help from the AI algorithm achieves higher accuracy in predicting COVID status on CXR than previously thought possible when considering either alone.
Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a multisystem disorder characterised by bilateral salivary gland enlargement and/or xerostomia in patients with Human Immunodeficiency Virus ...(HIV) infection. A 16 year old young male patient, presented with bilateral painless parotid swelling for five years. On evaluation, he was found to have oral thrush and bilateral cervical lymphadenopathy. He turned out to be positive for HIV with a cluster of differentiation 4 (CD4) count of 237/mcl. On Positron Emission Tomography- Contrast Tomography (PET-CT), a multiloculated thymic cyst (13×9×6 cm) was noted. He was diagnosed to have DILS with a large multiloculated thymic cyst. The patient was managed with tenofovir, lamivudine and efavirenz along with cotrimoxazole prophylaxis and fluconazole and was followed uptil nine months for the regress of the conditions. The case highlights the rare association between DILS and thymic cyst.
Lymph node tuberculosis is one of the most common forms of extrapulmonary tuberculosis worldwide. The study aimed to evaluate the role of positron emission tomography-computed tomography (PET-CT) in ...determining post-treatment response in lymph node tuberculosis. A PET-CT was done in all treatment naïve tubercular lymphadenitis adults at baseline and after six months of therapy. The post-treatment clinical response was compared with the metabolic response on PET-CT. Of the 25 patients with tubercular lymphadenitis, 9/25 patients showed a complete metabolic response (CMR) at six months, while 16 patients had a partial metabolic response (PMR). All patients with CMR had a good clinical response. However, discordance between clinical and PET findings was noticed in those with PMR. The role of PET-CT in evaluating post-treatment response in patients with tubercular lymphadenitis needs further evaluation with a larger sample size.
Resource-limited settings like India need a simple, quick, and temperature-independent point-of-care diagnostic test that can diagnose tuberculous meningitis (TBM) at the earliest.
A prospective ...study was carried out at a tertiary care center in North India wherein 50 subjects suspected of TBM were recruited and followed up for six months between January 2019 and December 2020. The aim was to evaluate the performance of loop-mediated isothermal amplification (TB-LAMP) in diagnosing TBM as compared to a composite reference standard (CRS), mycobacteria growth indicator tube 960 (MGIT 960) culture, and GeneXpert
.
Out of 50 patients, 32 were TBM cases (64%), and 18 were non-TBM cases (36%). The sensitivity of TB-LAMP and GeneXpert
for TBM diagnosis against CRS was 53% (17/32) for both, and the specificity was 78% (14/18) and 89% (16/18), respectively. On comparing TB-LAMP against GeneXpert
for TBM diagnosis, the two methods had almost perfect agreement (Cohen's kappa=0.83) with statistical significance (p<0.001).
The performance of TB-LAMP assay is comparable to GeneXpert
in diagnosing TBM, and it may be used as a substitute for CSF GeneXpert
in resource-limited settings.
BackgroundIndia has a disproportionately lower rate of coronavirus disease 2019 (COVID-19) severe disease and lower death rates with respect to other parts of the world. It has been proposed that ...malaria-endemic countries such as India are relatively protected against severe COVID-19 disease and deaths.MethodsThis was a cross-sectional, analytical, observational study conducted from August 2020 to July 2021 at a tertiary care COVID-19-designated center in New Delhi, India. It aimed to study the association between antimalarial antibody levels and COVID-19 disease severity and outcomes.ResultsOne hundred forty-six patients were included in the final analysis. The mean (standard deviation {SD}) age of the study population was 44.6 (17.2) years, and there were 85 (58.2%) males. Sixty-five patients had mild disease, 14 patients had moderate disease, and 67 patients had severe disease at the time of enrolment in the study. Forty-six patients expired during the hospital stay. For the antimalarial antibody, there was a statistically significant difference between mild and moderate (p=0.018), mild and severe (p=0.016), and mild and combined moderate and severe diseases (p=0.013). However, there was no difference between the patients who survived and those who did not.ConclusionAntimalarial antibody levels may not be associated with the outcomes of COVID-19 during hospital stay. However, this study has provided some insights into the relationship between the severity and outcomes of COVID-19 and the levels of antimalarial antibodies.
Calcium has been shown to play a vital role in the pathophysiology of severe acute respiratory syndrome-coronavirus-2 and middle east respiratory syndrome coronavirus diseases, but less is known ...about hypocalcemia in coronavirus disease 2019 (COVID-19) patients and its association with the disease severity and the final outcome. Therefore, this study was conducted with an aim to assess clinical features in COVID-19 patients having hypocalcemia and to observe its impact on COVID-19 disease severity and the final outcome.
In this retrospective study, consecutive COVID-19 patients of all age groups were enrolled. Demographical, clinical, and laboratory details were collected and analyzed. On the basis of albumin-corrected calcium levels, patients were classified into normocalcemic (
= 51) and hypocalcemic (
= 110) groups. Death was the primary outcome.
The mean age of patients in the hypocalcemic group was significantly lower (
< 0.05). A significantly higher number of hypocalcemic patients had severe COVID-19 infection (92.73%;
< 0.01), had comorbidities (82.73%,
< 0.05), and required ventilator support (39.09%;
< 0.01) compared with normocalcemic patients. The mortality rate was significantly higher in the hypocalcemic patients (33.63%;
< 0.05). Hemoglobin (
< 0.01), hematocrit (
< 0.01), and red cell count (
< 0.01) were significantly lower with higher levels of absolute neutrophil count (ANC;
< 0.05) and neutrophil-to-lymphocyte ratio (NLR;
< 0.01) in the hypocalcemic patients. Albumin-corrected calcium levels had a significant positive correlation with hemoglobin levels, hematocrit, red cell count, total protein, albumin, and albumin-to-globulin ratio and a significant negative correlation with ANC and NLR.
The disease severity, ventilator requirement, and mortality were considerably higher in hypocalcemic COVID-19 patients.
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