Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Diagnostic Values of Laboratory Biomarkers in Predicting a Severe Course of COVID-19 on Hospital Admission.

Objective: We intend to identify differences in the clinicodemographic and laboratory findings of COVID-19 patients to predict disease severity and outcome on admission. Methods: This single-centred retrospective study retrieved laboratory and clinical data from 350 COVID-19 patients on admission, represented as frequency tables. A multivariate regression model was used to assess the statistically significant association between the explanatory variables and COVID-19 infection outcomes, where adjusted odds ratio (AOR), p value, and 95% CI were used for testing significance. Results: Among the 350 COVID-19 patients studied, there was a significant increase in the WBC count, neutrophils, aggregate index of systemic inflammation (AISI), neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte and platelet ratio (NLPR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), D-dimer, interleukin-6 (IL-6), ferritin, lactate dehydrogenase (LDH), prothrombin time (PT), glucose, urea, urea nitrogen, creatinine, alanine phosphatase (ALP), and aspartate aminotransferase (AST) and a significant decrease in lymphocytes, eosinophils, total protein, albumin, prealbumin serum, and albumin/globulin (A/G) ratio in the severe group when compared with the mild and moderate groups. However, after adjusting their age, gender, and comorbidities, WBC count (adjusted odds ratio (AOR) = 6.888, 95% CI = 1.590-29.839, p = 0.010), neutrophils (AOR = 5.912, 95% CI = 2.131-16.402, p = 0.001), and urea (AOR = 4.843, 95% CI = 1.988-11.755, p = 0.001) were strongly associated with disease severity. Interpretation and Conclusion. On admission, WBC count, neutrophils, and urea, with their cut of values, can identify at-risk COVID-19 patients who could develop severe COVID-19.

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.

A challenging case of pyrexia of unknown origin: adrenal histoplasmosis mimicking tuberculosis in a patient with chronic hepatitis C.

We present an unusual case of fever of unknown origin with bilateral adrenal masses in a patient with compensated chronic liver disease (compensated) due to hepatitis C who had been treated elsewhere with four months of anti-tuberculous therapy for suspected disseminated tuberculosis (TB). At our institution, he underwent a CT-guided biopsy of the adrenal lesion which to our surprise did not reveal any evidence of TB but a close mimic.

An unusual cause for rib osteomyelitis in the tropics: Cryptococcal osteomyelitis.

The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. We report an unusual case of fungal osteomyelitis due to Cryptococcus. The patient was a young man who had been adequately treated for pulmonary tuberculosis three years prior. Three months before, he sustained a minor road-traffic accident with only minor abrasions. He presented with subacute chest pain of 15 days' duration and was found to have radiological evidence of a lytic lesion of the fifth rib. Given prior tuberculosis, he was thought to have a relapse of disease with tuberculous osteomyelitis. Surprisingly, a biopsy revealed evidence of fungal osteomyelitis with Cryptococcus. An evaluation for primary immunodeficiency revealed low CD4 cell counts with undetectable serum IgA and IgM levels. Genetic sequencing proved a genetic mutation consistent with primary T-cell immunodeficiency. The patient responded well to treatment and is asymptomatic on follow-up.

An unusual case of tropical pyomyositis: cryptococcal pyomyositis.

The more common manifestations of cryptococcal infections are restricted to the central nervous system and lungs. A young man, suffering from idiopathic dilated cardiomyopathy with a left ventricular ejection fraction of 20%, presented with subacute, painful tender swelling in both legs initially attributed to congestive cardiac failure. No response to diuretics was achieved. Metabolically active lesions in the muscles of both lower limbs suggestive of muscle abscesses were found. A diagnosis of tropical pyomyositis was therefore made, but aspiration surprisingly revealed gram-positive yeast cells, staining of which on India ink and culture confirmed Cryptococcus. A good response to a combination of liposomal amphotericin B and flucytosine was obtained, but nevertheless the patient died from heart failure after induction of antifungal therapy.

Pacemaker Lead Endocarditis Due to Trichosporon Species.

Pacemaker-related fungal endocarditis is an uncommon and unexpected complication. It is associated with high mortality rates. Due to nonspecific clinical symptoms, negative blood culture and delays in obtaining appropriate imaging studies; late diagnosis is common with fungal endocarditis. Hereby we are reporting a rare case of pacemaker lead endocarditis due to Trichosporon species. In literature we did not find any case of pacemaker-related endocarditis due to Trichosporon species.