A clinico-epidemiological profile, coinfections and outcome of patients with Influenza Like Illnesses (ILI) presenting to the emergency department during the COVID-19 pandemic.

Background: During the COVID-19 pandemic, many patients presented to the emergency department (ED) with features of Influenza-like illnesses (ILI) and with other atypical presentations. This study was done to determine the etiology, co-infections, and clinical profile of patients with ILI. Methods: This prospective observational study included all patients presenting to the ED with fever and/or cough, breathing difficulty, sore throat, myalgia, gastrointestinal complaints (abdominal pain/vomiting/diarrhea), loss of taste and altered sensorium or asymptomatic patients who resided in or travelled from containment zones, or those who had contact with COVID-19 positive patients during the first wave of the pandemic between April and August 2020. Respiratory virus screening was done on a subset of COVID-19 patients to determine co-infection. Results: During the study period, we recruited 1462 patients with ILI and 857 patients with the non-ILI presentation of confirmed COVID-19 infection. The mean age group of our patient population was 51.4 (SD: 14.9) years with a male predominance (n-1593; 68.7%). The average duration of symptoms was 4.1 (SD: 2.9) days. A sub-analysis to determine an alternate viral etiology was done in 293 (16.4%) ILI patients, where 54 (19.4%) patients had COVID 19 and co-infection with other viruses, of which Adenovirus (n-39; 14.0%) was the most common. The most common symptoms in the ILI-COVID-19 positive group (other than fever and/or cough and/or breathing difficulty) were loss of taste (n-385; 26.3%) and diarrhea (n- 123; 8.4%). Respiratory rate (27.5 (SD: 8.1)/minute: p-value < 0.001) and oxygen saturation (92.1% (SD: 11.2) on room air; p-value < 0.001) in the ILI group were statistically significant. Age more than 60 years (adjusted odds ratio (OR): 4.826 (3.348-6.956); p-value: <0.001), sequential organ function assessment score more than or equal to four (adjusted OR: 5.619 (3.526-8.957); p-value: <0.001), and WHO critical severity score (Adjusted OR: 13.812 (9.656-19.756); p-value: <0.001) were independent predictors of mortality. Conclusion: COVID-19 patients were more likely to present with ILI than atypical features. Co-infection with Adenovirus was most common. Age more than 60 years, SOFA score more than or equal to four and WHO critical severity score were independent predictors of mortality.

The economic impact of a COVID-19 illness from the perspective of families seeking care in a private hospital in India.

Background: The Covid-19 pandemic had a tremendous impact that caused significant morbidity, mortality, and financial stress for families. Our study aimed to determine the Out-of-pocket expenses and economic impact of a Covid-19 illness for households where patients were admitted to a private hospital in India. Methodology: This was a cost-of-illness study from a tertiary care academic institute where adult patients diagnosed with COVID-19 from May 2020 to June 2021 were included. Patients with an admission of less than one day or who had any form of insurance were excluded. The clinical and financial details were obtained from the hospital information system and a cross-sectional survey. This was stratified across three clinical severity levels and two epidemiological waves. Results: The final analysis included 4445 patients, with 73 % admitted in Wave 1 and 99 patients interviewed. For patients with severity levels 1, 2 and 3, the median admission days were 7, 8 and 13 days respectively. The total cost of illness (general category) was $934 (₹69,010), $1507 (₹111,403) and $3611 (₹266,930) and the direct medical cost constituted 66%, 77% and 91% of the total cost for each level respectively. Factors associated with higher admission costs were higher age groups, male gender, oxygen use, ICU care, private admission, increased duration of hospital stay and Wave 2. The median annual household income was $3247 (₹240,000) and 36% of families had to rely on more than one financial coping strategies, loans with interest being the commonest one. The lockdown period affected employment and reduced income for a considerable proportion of households. Conclusion: A Covid admission of higher severity was a significant financial burden on families. The study reaffirms the need for collaborative and sustainable health financing systems to protect populations from hardships.$-US Dollar; ₹- Indian Rupees.

Evaluation of Remdesivir to the outcomes of hospitalized patients with COVID-19 infection in a tertiary-care hospital in southern India.

INTRODUCTION: Remdesivir was the only antiviral used in the treatment of COVID-19 in the first wave of the COVID-19 pandemic, following the adaptive COVID-19 treatment trial-1 interim analysis report. However, its use in moderate to critical hospitalized COVID-19 patients continues to be controversial. METHODOLOGY: In a cohort of 1,531 moderate to critical COVID-19 patients, we retrospectively performed a nested case-control study where 515 patients on Remdesivir were compared to 411 patients with no Remdesivir. Cases and controls were matched for age, sex and severity. The primary outcome was in-hospital mortality and secondary outcomes were duration of hospital stay, need for intensive care unit (ICU), progression to oxygen therapy, progression to non-invasive ventilation, progression to mechanical ventilation, and duration of ventilation. RESULTS: Mean age of the cohort was 57.05 + 13.5 years. 75.92% were males. Overall, in-hospital mortality was 22.46% (n = 208). There was no statistically significant difference in all-cause mortality among cases and controls (20.78% vs. 24.57%, p = 0.17). Progression to non-invasive ventilation was lower in the Remdesivir group (13.6% vs 23.7%, p < 0.001), however progression to mechanical ventilation was higher in the Remdesivir group (11.3% vs 2.7%, p value < 0.001*). In a subgroup analysis of critically ill patients, the use of Remdesivir lowered mortality (OR 0.32 95% CI: 0.13 - 0.75). CONCLUSIONS: Remdesivir did not decrease the in-hospital mortality in moderate to severe COVID-19 but decreased progression to non-invasive ventilation. Its mortality benefit in critically ill patients needs further evaluation. Remdesivir may be useful if given early in the treatment of patients with moderate COVID-19.

Retrospective study of comparison of clinical severity and outcome of hospitalised COVID-19 patients during the first and second waves of the pandemic in India.

OBJECTIVES: To compare the clinical severity and outcome of hospitalised patients during the two waves of the COVID-19 pandemic in India. SETTING: A tertiary care referral hospital in South India. PARTICIPANTS: Symptomatic SARS CoV-2 reverse transcriptase PCR positive patients presenting to the emergency department during the two waves were recruited. The first wave spanned between April and December 2020 and the second wave between April and May 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of interest was mortality. Secondary outcomes included illness severity at presentation, need for oxygen therapy, non-invasive ventilation (NIV) and hospital or intensive care unit admission. RESULTS: The mean (SD) age of the 4971 hospitalised patients in the first wave was similar to the 2293 patients in the second wave (52.5±15.4 vs 52.1±15.1 years, p=0.37). When compared with the first wave, during the second wave, a higher proportion of patients presented with critical illness (11% vs 1.1%, p<0.001) and needed supplemental oxygen therapy (n=2092: 42.1% vs n=1459: 63.6%; p<0.001), NIV (n=643; 12.9% vs n=709; 30.9%; p<0.001) or inotropes/vasoactive drugs (n=108; 2.2% vs n=77: 3.4%; p=0.004). Mortality was higher during the second wave (19.2% vs 9.3%; p<0.001). On multivariable regression analysis, age >60 years (risk ratio, RR 2.80; 95% CI 2.12 to 3.70), D-dimer >1000 ng/mL (RR 1.34; 95% CI 1.15 to 1.55), treatment with supplemental oxygen (RR 14.6; 95% CI 8.98 to 23.6) and presentation during the second wave (RR 1.40; 95% CI 1.21 to 1.62) were independently associated with mortality. CONCLUSION: The second wave of the COVID-19 pandemic in India appeared to be associated with more severe presentation and higher mortality when compared with the first wave. Increasing age, elevated D-dimer levels and treatment with supplemental oxygen were independent predictors of mortality.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Impact of prior vaccination with CovishieldTM and Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in South India during April and May 2021: a cohort study.

BACKGROUND: COVID-19 vaccines were authorised for emergency use to mitigate the impact of the pandemic. This study evaluated the effect of prior vaccination with either Oxford Astra Zeneca's Covishield™ or Bharath Biotech's Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in India. METHODOLOGY: In this cohort study comprising of RT-PCR confirmed symptomatic COVID-19 patients presenting during April and May 2021, the effect of prior vaccination on mortality (primary outcome), need for hospitalization, oxygen therapy, non-invasive ventilation (NIV) and intensive care unit (ICU) admission were assessed and expressed as risk ratio (RR) with 95% confidence intervals (CI). RESULTS: The mean (SD) age of the cohort (n = 4183) was 46.3 (15.5) years; 17.9% (748/4183) had received at least one dose of Covishield™ and 4.8% (201/4183) had received Covaxin®. Mortality was 0.2% (95% CI: 0.2% - 0.7%), 3.5% (1.9-5.2%), 6.2% (0.3-12%) and 12.9% (11.8-14.1%) among fully vaccinated (>2 weeks after two doses), partially vaccinated (>2 weeks after one dose or <2 weeks after two doses), indeterminate (<2 weeks after one dose) and unvaccinated patients respectively. The difference in mortality among unvaccinated vs. fully vaccinated was 12.7% (95% CI: 11.4-13.9%), unvaccinated vs. partially vaccinated was 9.4% (7.4-11.4%) and unvaccinated vs. indeterminate vaccinated was 6.8% (0.8-12.7%). On adjusted analysis, as compared to unvaccinated patients, at least one dose of vaccine reduced the need for hospitalization (RR: 0.40; 95% CI: 0.35-0.47), oxygen (0.33; 0.27-0.40), NIV (0.23; 0.17-0.32), ICU admission (0.18; 0.12-0.27) and mortality (0.18; 0.11-0.29). CONCLUSION: Among symptomatic COVID-19 patients, prior vaccination with Covishield ™ or Covaxin® impacted the severity of illness and reduced mortality during a period of widespread delta variant circulation. Full vaccination conferred greater protection than partial vaccination.

Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.

The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage-defining mutations were analyzed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X), and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore leading to well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount in the coming months, the task of mapping viral mutations and recording their impact on key viral proteins should be crucial to preemptively catch any escape mechanism for which SARS-CoV-2 may evolve. IMPORTANCE Since its initial isolation in Wuhan, China, large numbers of SARS-CoV-2 genome sequences have been shared in publicly accessible repositories, thus enabling scientists to do detailed evolutionary analysis. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed the phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast-expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage-defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines that have recently been approved or are in development. In this vein, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.

Genomic evolution of severe acute respiratory syndrome Coronavirus 2 in India and vaccine impact.

Recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent containment procedures have impacted the world as never seen before. Therefore, there is considerable curiosity about the genome evolution related to the origin, transmission and vaccine impact of this virus. We have analysed genome sequences of SARS-CoV-2 isolated from Indian patients to gain an in-depth understanding of genomic evolution and transmission in India. Phylogenetic analysis and mutation profiling revealed major lineages being evolved by characteristic mutations. As the mutation frequency in spike protein is comparatively lesser, the candidate vaccines expected to have wide coverage worldwide including India.