Cycle threshold values of SARS-CoV-2 RNA in conjunctival swabs and nasopharyngeal secretions: a comparative study from a tertiary care center in India.

PURPOSE: To detect the viral RNA load of SARS-CoV-2 in conjunctival swabs of COVID-19 patients, and compare with nasopharyngeal swabs. METHODS: Conjunctival swabs of COVID-19 patients (with PCR positive nasopharyngeal swabs) were subjected to quantitative reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 RNA. The cycle threshold (Ct) values of Open Reading Frame 1 (ORF 1 Ab gene) and nucleoprotein (N gene) PCRs were used to assess the viral RNA load, and compare them with the baseline values of nasopharyngeal swabs. RESULTS: Of 93 patients, 17 (18.27%) demonstrated SARS-CoV-2 RNA in conjunctival swabs. Baseline nasopharyngeal swabs were collected at a median of 2 days; while, the conjunctival swabs were collected at median 7 days, from onset of illness (p < 0.001). Despite a significant delay in conjunctival swab collection than nasopharyngeal swabs, the Ct values (ORF or N gene PCRs) were comparable between nasopharyngeal swab and conjunctival swab samples. Subsequently, during the recovery period, in four of these 17 patients (with conjunctival swab positivity), when the second nasopharyngeal swab was 'negative', the conjunctival swab was 'positive'. CONCLUSION: The conjunctival swabs demonstrated SARS-CoV-2 RNA in 17 (18.27%) of 93 COVID-19 patients. Our results may suggest a delayed or a prolonged shedding of the virus/viral RNA on the ocular surface than in nasopharyngeal mucosa.

Determinants of post discharge mortality among hospitalized COVID-19 patients.

Background & objectives: The post-acute effects of COVID-19 are continually being updated. This investigation was conducted to evaluate the determinants of post discharge mortality in hospitalized COVID-19 patients, especially 18-45 yr of age. Methods: A series of three nested case-control analyses was conducted on follow up data collected in the National Clinical Registry for COVID-19 between September 2020 and February 2023 from 31 hospitals. Matching (1:4) was done by the date of hospital admission ±14 days for the following comparisons: (i) case-patients reported as dead vs. controls alive at any contact within one year follow up; (ii) the same in the 18-45 yr age group and (iii) case-patients reported as dead between the first and one year of follow up vs. controls alive at one year post discharge. Results: The one year post discharge mortality was 6.5 per cent (n=942). Age [≤18 yr: adjusted odds ratio (aOR) (95% confidence interval [CI]): 1.7 (1.04, 2.9); 40-59 yr: aOR (95% CI): 2.6 (1.9, 3.6); ≥60 yr: aOR (95% CI): 4.2 (3.1, 5.7)], male gender [aOR (95% CI): 1.3 (1.1, 1.5)], moderate-to-severe COVID-19 [aOR (95% CI): 1.4 (1.2, 1.8)] and comorbidities [aOR (95%CI): 1.8 (1.4, 2.2)] were associated with higher odds of post-discharge one-year mortality, whereas 60 per cent protection was conferred by vaccination before the COVID-19 infection. The history of moderate-to-severe COVID-19 disease [aOR (95% CI): 2.3 (1.4, 3.8)] and any comorbidities [aOR (95% CI): 3 (1.9, 4.8)] were associated with post-discharge mortality in the 18-45-yr age bracket as well. Post COVID condition (PCC) was reported in 17.1 per cent of the participants. Death beyond the first follow up was associated with comorbidities [aOR (95%CI): 9.4 (3.4, 26.1)] and reported PCC [aOR (95% CI): 2.7 (1.2, 6)]. Interpretation & conclusions: Prior vaccination protects against post discharge mortality till one year in hospitalized COVID-19 patients. PCC may have long term deleterious effects, including mortality, for which further research is warranted.

Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-ß (TGF-ß) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-ß levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-ß should be evaluated further as a biomarker.

Factors associated with unexplained sudden deaths among adults aged 18-45 years in India - A multicentric matched case-control study.

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Virus related acute pancreatitis and virus superinfection in the 'Dual disease' model of acute pancreatitis and SARS-Co-V2 infection: A multicentre prospective study.

BACKGROUND: SARS-CoV-2 can cause acute pancreatitis (AP) and SARS-CoV-2 superinfection can occur in patients with AP during prolonged hospitalisation. Our objective was to characterize SARS-CoV-2 related AP and study the impact of SARS-CoV-2 superinfection on outcomes in AP. METHODS: In this multicentre prospective study, all patients with AP and SARS-CoV-2 infection between August 2020 and February 2021 were divided into two groups: SARS-CoV-2-related AP and superadded SARS-CoV-2 infection in patients with AP. The two groups were compared with each other and the whole cohort was compared with a non-COVID AP cohort. RESULTS: A total of 85 patients with SARS-CoV-2 and AP (SARS-CoV-2-related AP; n = 18 and AP with SARS-CoV-2 superadded infection; n = 67) were included during the study period. They had a higher mortality [28 (32.9%) vs. 44 (19.1%), aOR 2.8 (95% CI, 1.5-5.3)] than 230 propensity matched non-COVID AP patients. Mortality in SARS-CoV-2 and AP patients was due to critical COVID. SARS-CoV-2-related- AP (n = 18) had a higher but statistically insignificant mortality than SARS-CoV-2 superinfection in AP [8/18 (44.4%) vs 20/67 (29.8%), p = 0.24]. On multivariable analysis, infection with SARS-CoV-2 (aHR 2.3; 95% CI, 1.43.7) was a predictor of in-hospital mortality in addition to organ failure (OF) in patients with AP. CONCLUSION: Patients with AP and SARS-CoV-2 infection had a higher mortality than matched non-COVID AP patients which was largely attributable to the severity of COVID-19. SARS-CoV-2 related AP had higher OF and in-hospital mortality.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Incidence & outcomes of clinically significant bleeding events in critically ill COVID-19 patients receiving Therapeutic dose AntiCoagulanTs: A retrospective cohort study (INTerACT study).

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.

Risk factors for mortality in kidney transplant recipients with COVID-19: a single centre experience and case-control study.

BACKGROUND: COVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India. METHODS: A matched case-control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188). RESULTS: A high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes. CONCLUSIONS: The mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections.

The clinical association between Periodontitis and COVID-19.

OBJECTIVES: The study aimed to clinically assess the association between periodontitis and COVID-19-related outcomes. MATERIAL AND METHODS: Data pertaining to patient demographics, medical history, blood parameters, periodontal clinical examination and aMMP-8 point-of-care diagnostics (both site-level and patient-level) was recorded for eighty-two COVID-19-positive patients. COVID-19-related outcomes such as COVID-19 pneumonia, death/survival, types of hospital admission and need of assisted ventilation were also assessed. RESULTS: Males were predominantly afflicted with COVID-19, with advanced age exhibiting a greater association with the presence of periodontitis. Higher severity of periodontitis led to 7.45 odds of requiring assisted ventilation, 36.52 odds of hospital admission, 14.58 odds of being deceased and 4.42 odds of COVID-19-related pneumonia. The aMMP-8 mouthrinse kit was slightly more sensitive but less specific than aMMP-8 site-specific tests. CONCLUSIONS: Based on the findings of the present study, periodontitis seems to be related to poorer COVID-19-related outcomes. However, within the constraints of this work, a direct causality may not be established. Periodontitis, by means of skewing the systemic condition for a number of comorbidities, may eventually influence COVID-19 outcomes in an indirect manner. CLINICAL RELEVANCE: The study is the first to clinically, and by means of a validated point-of-care diagnostic methodology, assess the association between periodontal health and COVID-19-related outcomes. Assessment of the periodontal status of individuals can aid in the identification of risk groups during the pandemic along with reinforcing the need to maintain oral hygiene and seeking periodontal care.

Symptoms and psychosocial effects following hospitalization for Covid-19: A sequential, mixed-methods study from northern India.

Background It is reported that patients who have recovered from Covid-19 continue to experience various symptoms and adverse outcomes. However, this aspect has not been studied well. We aimed to evaluate these variables and the perceived impact of Covid-19 among patients discharged from a Covid hospital in northern India. Methods We conducted this study among patients discharged from a Covid-19 hospital in northern India in June 2020. As per the official policy at that time, patients detected to have Covid-19 (symptomatically or via contact tracing) were mandatorily admitted. A sequential, mixed-methods design was followed. Patients discharged from the hospital were contacted telephonically, and the cross-sectional prevalence of symptoms, the prevalence of depression and anxiety and the social consequences of admission were assessed. A subgroup of patients was interviewed for qualitative assessment of their experience. Results A total of 274 patients provided consent and were assessed, of which 8 patients underwent detailed interviews. The prevalence of somatic symptoms was 3.4%; 36.2% of the patients had depressive and 12% of the patients had anxiety symptoms. A majority of patients experienced adverse social and economic consequences of hospitalization for Covid-19. These themes were reinforced by a qualitative analysis of in-depth interviews. Conclusions Our study population experienced a high prevalence of adverse psychosocial consequences of Covid-19. These included depression and anxiety symptoms, stigma and economic and occupational consequences. These deserve more recognition and study.

Hydroxychloroquine in Treatment of Asymptomatic and Mildly Symptomatic COVID-19: A Multi-Centre Cohort Study.

BACKGROUND: Although hydroxychloroquine (HCQ) lacks benefit in patients with moderate-to-severe COVID-19, its role in asymptomatic and mildly symptomatic disease needs better elucidation. METHODS: This multi-centre cohort study included asymptomatic and mildly symptomatic, RT-PCR confirmed COVID-19 cases between 30 March and 20 May, 2020. Patients were categorized into two groups (HCQ-treated and untreated) based on exposure to HCQ. Dose of HCQ used was 400 mg twice daily (day one) followed by once daily for seven days. HCQ-untreated patients were managed supportively without any active antiviral or immunomodulatory therapy. Nasopharyngeal SARS-CoV-2 clearance by RT-PCR (primary outcome) was compared between HCQ-treated and untreated patients using Kaplan-Meier analysis and Cox proportional-hazards regression. Clinical efficacy and safety profile of HCQ were assessed (secondary outcomes). RESULTS: 162 patients [84 (51·9%) males; mean age 38·2 (15·2) years] were included. Forty-four (27·2%) patients had mild disease, rest 118 (72·8%) were asymptomatic. Seventy-five (46·3%) patients received HCQ. Median time to virological negativity was lesser in HCQ-treated (13 days) versus untreated patients (15 days) (logrank<0·001) in both asymptomatic and mildly symptomatic patients. Treatment with HCQ was the only independent predictor of virological negativity (hazardratio=2·24; adjusted p-value<0·001). Two (5·4%) mildly symptomatic patients progressed to severe disease within 24 hours (two doses) of HCQ initiation, compared to none in the HCQ-untreated group. Five HCQ-treated patients developed minor gastrointestinal side effects, not requiring drug discontinuation. CONCLUSION: HCQ reduced the time to virologic negativity (by 2 days) in asymptomatic and mildly symptomatic COVID-19, without any serious adverse events. However, no obvious clinical benefit was noted.

Secondary Hemophagocytic Lymphohistiocytosis: Think of the Devil Lurking!

How to cite this article: Pannu AK, Bhalla A. Secondary Hemophagocytic Lymphohistiocytosis: Think of the Devil Lurking! Indian J Crit Care Med 2022;26(5):545-546.

Comparison of high-pitch prospective electrocardiogram-gated pulmonary CT angiography with standard CT pulmonary angiography on dual-source CT for detection of subsegmental pulmonary embolism in patients suspected of acute pulmonary embolism.

Purpose: Objective of this study was to compare high-pitch prospective electrocardiogram (ECG)-gated computed tomography (CT) pulmonary angiography (HP-PECG-gated CTPA) with standard-pitch non-ECG-gated CT pulmonary angiography (SP-NECG-gated CTPA) on 128-slice dual-source CT (DSCT) for the detection of subsegmental pulmonary embolism (SSPE) in patients suspected of acute pulmonary embolism (APE) with radiation and contrastoptimized protocols. Cardiac-related motion artefacts, lung image quality, and quantitative parameter (pulmonary arterial enhancement, radiation exposure, and contrast) volumes were also compared. Material and methods: This prospective study enrolled 87 patients clinically suspected of APE and randomly distributed to either group by software. Two radiologists blinded to each other interpreted the images for assessment of SSPE, image quality, and quantitative parameters. Results: SSPE was diagnosed in 15/44 (34.09%) patients in HP-PECG-gated CTPA, in comparison to 8/43 (18.60%) patients in SP-NECG-gated CTPA. Cardiac motion-related artefacts (blurring of bronchovascular structures and double-line artefacts) were statistically significantly less, with p-value < 0.05. Lung image quality was also better, with p-value < 0.001. Effective radiation dose and contrast volume in HP-PECG-gated CTPA were (2.54 ± 0.80 mSv, 45.05 ± 6 ml) versus SP-NECG-gated CTPA (3.17 ± 1.20 mSv, 74.19 ± 7.63 ml) with p-values of 0.007 and 0.001, respectively. Conclusions: Radiation and contrast volume-optimized HP-PECG-gated CTPA provides reduced cardiac motion related artefacts of pulmonary arteries, which allows enhanced detection of SSPE. It also provides better image quality of lung and parenchyma with lower radiation exposure and less contrast volume.

Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial.

BACKGROUND & AIMS: There is controversy regarding the inclusion of granulocyte colony stimulating factor (G-CSF) in the treatment of decompensated cirrhosis. Previous studies tested only a single cycle of G-CSF administration or were underpowered to detect changes in survival time. We performed an adequately powered study to determine whether multiple cycles of G-CSF increased the survival of patients 1 year after the start of therapy. METHODS: We conducted an open-label trial of 100 patients with decompensated cirrhosis without acute-on-chronic liver failure at a tertiary center from July 2016 through June 2018. The patients were assigned randomly to a group given 5 days of G-CSF every 3 months, with standard medical therapy, in 4 cycles (group A, n = 50), or standard medical therapy alone (group B, n = 50). The primary outcome was survival for 12 months after treatment began. Secondary outcomes were an increase in the number of CD34+ cells at day 6 compared with day 0, along with reductions in Child-Turcotte-Pugh and model for end-stage liver disease scores, increased control of ascites, reduced decompensation and episodes of infection, fewer hospitalizations, lower liver stiffness measurements, increased quality of life and nutrition, fulfilment of liver transplant criteria, and fewer adverse events at 12 months after the start of treatment. RESULTS: Groups A and B were comparable at baseline. Survival at 12 months after initiation of treatment was significantly higher in group A (74%) than in group B (42%) (P < .001). Blood samples from patients in group A had significantly more CD34+ cells on day 6 than on day 0 (P < .001); there was no significant change in group B. Compared with patients in group B, patients in group A had significant reductions in Child-Turcotte-Pugh and model for end-stage liver disease scores, increased ascites control, fewer infections and hospitalizations, lower liver stiffness measurements, an increased quality of life, and a lower number fulfilled the liver transplant criteria (P < .05). There was no improvement in nutrition in either group compared with baseline. G-CSF was safe and well tolerated. CONCLUSIONS: Administration of multiple cycles of G-CSF increases the numbers of hematopoietic stem cells and survival of patients with decompensated cirrhosis receiving standard medical treatment. The addition of G-CSF to medical treatment might provide a bridge to liver transplantation for these patients. ClincialTrials.gov no: NCT03415698.

Evaluation of a First Responders Course in Rural North India.

BACKGROUND: Most mortality in trauma occurs in prehospital settings when the golden hour is spent accessing healthcare facilities rather than resuscitating and stabilizing. Assessments performed in the rural community of Nanakpur, India demonstrated a significant paucity of, and limited access to healthcare facilities. To address deficiencies in prehospital care, the All-India Institute of Medical Sciences (AIIMS) constructed the Basic Emergency Care Course (BECC). This study evaluated the BECCs efficacy in Nanakpur. METHODS: The first responder courses took place in 2017 in Nanakpur. Local community health workers, known as Accredited Social Health Activists (ASHAs) were recruited as participants. Participants completed both a pre- and post-course evaluation to assess baseline knowledge and improvement. Participants then took a one-year post-course assessment to evaluate retention. RESULTS: The course included 204 individuals, and over half (109/204) were ASHAs. Pre- and post-course test results were available for 70 participants and demonstrated a significant improvement in knowledge (P < 0.0001). The one-year knowledge retention assessment was completed by 48.6% (n = 53/109) of the original ASHAs. Comparisons between both the pre- and post-course assessment tests with the 12-mo retention assessment revealed a significant decay in knowledge (P < 0.0001). CONCLUSIONS: This study demonstrates the feasibility of utilizing BECC to train ASHAs in Nanakpur as first responders. Participants demonstrated a significant improvement in knowledge immediately after the course. After one year, there was a significant loss in knowledge, highlighting the need for refresher courses. These data suggest potential for the use of BECC for training ASHAs countrywide to strengthen India's prehospital care system.

Demographic & clinical profile of patients with COVID-19 at a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic emerged as a major public health emergency affecting the healthcare services all over the world. It is essential to analyze the epidemiological and clinical characteristics of patients with COVID-19 in different parts of our country. This study highlights clinical experience in managing patients with COVID-19 at a tertiary care centre in northern India. METHODS: Clinical characteristics and outcomes of consecutive adults patients admitted to a tertiary care hospital at Chandigarh, India, from April 1 to May 25, 2020 were studied. The diagnosis of SARS-CoV-2 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on throat and/or nasopharyngeal swabs. All patients were managed according to the institute's consensus protocol and in accordance with Indian Council of Medical Research guidelines. RESULTS: During the study period, 114 patients with SARS-CoV-2 infection were admitted. The history of contact with COVID-19-affected individuals was available in 75 (65.8%) patients. The median age of the patients was 33.5 yr (13-79 yr), and there were 66 (58%) males. Of the total enrolled patients, 48 (42%) were symptomatic. The common presenting complaints were fever (37, 77%), cough (26, 54%) and shortness of breath (10, 20.8%). Nineteen (17%) patients had hypoxia (SpO2<94%) at presentation and 36 (31%) had tachypnoea (RR >24). Thirty four (29.8%) patients had an accompanying comorbid illness. Age more than 60 yr and presence of diabetes and hypertension were significantly associated with severe COVID-19 disease. Admission to the intensive care unit (ICU) was needed in 18 patients (52%), with three (2.6%) patients requiring assisted ventilation. Mortality of 2.6 per cent (3 patients) was observed. INTERPRETATION & CONCLUSIONS: Majority of the patients with COVID-19 infection presenting to our hospital were young and asymptomatic. Fever was noted only in three-fourth of the patients and respiratory symptoms in half of them. Patients with comorbidities were more vulnerable to complications. Triaged classification of patients and protocol-based treatment resulted in good outcomes and low case fatality.

Importance of pesticides for lethal poisoning in India during 1999 to 2018: a systematic review.

BACKGROUND: Poisoning is a major problem in India. However, there is little systematic information on the key poisons responsible for most deaths by geographical area and over time. We aimed to review the literature to identify the poison classes causing the greatest number of deaths in India over the last 20 years. METHODS: We performed a systematic literature review in Medline, Embase and Google Scholar (1999-2018), and Indian online medical journals, to find papers that reported deaths from all forms of poisoning in India, with last search 20 April 2020. We included epidemiological studies, observational studies, randomised trials, interventional studies, and case series published from 1999 to 2018 that showed the number of deaths and autopsy studies indicating the specific poisons or poison classes. Studies providing the case fatality for specific poisons or classes, which enabled calculation of the number of deaths, were also included. We excluded deaths due to animal bites and stings, ethanol or methanol poisoning, and gas inhalation as well as papers reporting a single death (case study of single patient). We grouped the papers into 5-year intervals and identified the two most common poison classes in each paper. We used descriptive statistics to summarise the findings over time based on the causative poison and the location of the study. RESULTS: We identified 186 papers reporting 16,659 poisoning deaths between 1999 and 2018. The number of publications per 5-year interval showed no clear trend over the period (48, 38, 67, and 36 for consecutive periods). Half of the deaths (n = 8338, 50.0%) were reported during the first 5 years of the study (1999-2003), the number of deaths declining thereafter (to n = 1714 in 2014-2018). Deaths due to pesticide poisoning (94.5%) were dominant across the study period compared to other classes of poison [hair dye paraphenylenediamine poisoning (2.6%), medicine overdose (1.4%) or plant poisoning (1.0%)]. Among the pesticides, aluminium phosphide was the most important lethal poison during the first 10 years before declining markedly; organophosphorus insecticides were important throughout the period, becoming dominant in the last decade as aluminium phosphide cases declined. Unfortunately, few papers identified the specific organophosphorus insecticide responsible for deaths. CONCLUSION: Use of the published literature to better understand the epidemiology of lethal poisoning in India has clear limitations, including secular variation in publishing practices and interest in poisoning. Unfortunately, there are no long-term detailed, combination hospital and community studies from India to provide this information. In their absence, our review indicates that pesticides are the most important poison in India, with organophosphorus insecticides replacing aluminium phosphide as the key lethal poison after government regulatory changes in 2001 reduced the latter's lethality. Plant and hair dye poisoning and medicines overdose caused few deaths. Aluminium phosphide deaths mostly occurred in northern Indian states, whereas deaths from organophosphorus insecticide poisoning occurred throughout India. Paraquat poisoning has become a clinical problem in the last 10 years. Lethal pesticide poisoning remains alarmingly common, emphasising the need for additional regulatory interventions to curtail the burden of pesticide poisoning deaths in India. More detailed reporting about the specific pesticide involved in lethal poisoning will be helpful to guide regulatory decisions.

Absence of SARS-CoV-2 infection in the semen of men recovering from COVID-19 infection: An exploratory study and review of literature.

The effect of COVID-19 on the male reproductive tract has been sparsely studied. This exploratory study was designed to determine the presence of SARS-CoV-2 in the semen of men recovering from COVID-19. A systematic literature review was also performed as per PRISMA guidelines to gather perspective on this topic. The prospective study included men 21 years and older recovering from COVID-19 with nasopharyngeal swab negative for SARS-CoV-2 or at least two weeks from the last COVID RT-PCR positivity. After clinical evaluation, freshly ejaculated semen sample by masturbation was collected in a sterile container. Samples were processed for the detection of SARS-CoV-2 by RT-PCR. Twenty-one patients were contacted for the study, 11 of which consented to provide a semen sample. The mean age of the cohort was 29.72 ± 4.52 years. None of the patients gave a history of epididymo-orchitis or sexual dysfunction at the time of assessment. None of the semen samples demonstrated SARS-CoV-2 on RT-PCR. Median duration of semen sample collection from the COVID positivity was 44 days (Range 19-59 days). Detailed literature review revealed that SARS-CoV-2 is not found in patients recovering from COVID-19 infection. We conclude that SARS-CoV-2 is not found in the semen of patients recovering from COVID-19.

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature.

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.