Modeling the relative influence of socio-demographic variables on post-acute COVID-19 quality of life: an application to settings in Europe, Asia, Africa, and South America (preprint)

Long-term COVID-19 complications are a globally pervasive threat, but their plausible social drivers are often not prioritized. Here, we use data from a multinational consortium to quantify the relative contributions of social and clinical factors to differences in quality of life among participants experiencing long COVID and measure the extent to which social variables impacts can be attributed to clinical intermediates, across diverse contexts. In addition to age, neuropsychological and rheumatological comorbidities, educational attainment, employment status, and female sex were identified as important predictors of long COVID-associated quality of life days (long COVID QALDs). Furthermore, a great majority of their impacts on long COVID QALDs could not be tied to key long COVID-predicting comorbidities, such as asthma, diabetes, hypertension, psychological disorder, and obesity. In Norway, 90% (95% CI: 77%, 100%) of the effect of belonging to the highest versus lowest educational attainment quintile was not attributed to intermediate comorbidity impacts. The same was true for 86% (73%, 100%) of the protective effects of full-time employment versus all other employment status categories (excluding retirement) in the UK and 74% (46%,100%) of the protective effects of full-time employment versus all other employment status categories in a cohort of four middle-income countries (MIC). Of the effects of female sex on long COVID QALDs in Norway, UK, and the MIC cohort, 77% (46%,100%), 73% (52%, 94%), and 84% (62%, 100%) were unexplained by the clinical mediators, respectively. Our findings highlight that socio-economic proxies and sex may be as predictive of long COVID QALDs as commonly emphasized comorbidities and that broader structural determinants likely drive their impacts. Importantly, we outline a multi-method, adaptable causal machine learning approach for evaluating the isolated contributions of social disparities to long COVID quality of life experiences.

Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting virus-specific enzymes (preprint)

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules against virus-specific proteins that play a role in viral inflammation and simultaneous act on the host pathways participating in viral inflammation, will provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50) values ranging from 1.42 to 32.7 M. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin exhibit potent antiviral activity with half-maximum effective concentration (EC50) values of 21.73 M and 31.19 M, respectively. The anti-inflammatory role of azadirachtin and withanolide_A when assessed using HEK293T cells were found to significantly reduce the levels of CXCL10, TNF, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2 specific enzymes and also host immune pathways involved in virus mediated inflammation.

Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India (preprint)

Introduction: The COVID19 pandemic has posed a serious threat to global health, with developing nations like India being amongst the worst affected. Chest CT scans play a pivotal role in the diagnosis and evaluation of COVID19, and certain CT features may aid in predicting the prognosis of COVID19 illness. Methods: This was a single center, hospital based, cross sectional study conducted at a tertiary care center in Northern India during the second wave of the COVID19 pandemic from May June 2021. The study included 473 patients who tested positive for COVID-19. A high resolution chest CT scan was performed within five days of hospitalization, and patientrelated information was extracted retrospectively from medical records. Univariable and Multivariable analysis was done to study the predictors of poor outcome. Results: A total of 473 patients were included in the study, with 75.5% being males. The mean total CT score was 29.89 {+/-} 9.06. Fibrosis was present in 17.1% of patients, crazy paving in 3.6%, pneumomediastinum in 8.9%, and pneumothorax in 3.6%. Males had a significantly higher total score, while the patients who survived (30.00 {+/-} 9.55 vs 35.00 v 6.21, p value <.001), received Steroids at day 2 (28.04 {+/-} 9.71 vs 31.66 {+/-} 7.12, p value 0.002) or Remdesivir had lower total scores (28.04 {+/-} 9.71 vs 31.66 {+/-} 7.12, p value 0.002). Total CT score (aHR 1.05, 95% CI 1.02 1.08, p 0.001), pneumothorax (aHR 1.38, 95 % CI 0.67 2.87, p 0.385), pneumomediastinum (aHR 1.20, 95% CI 0.71 2.03, p 0.298) and cardiovascular accident (CVA, aHR 4.75, 95% CI 0.84 26.72, p 0.077) were associated with increased mortality, but the results were not significant after adjusting with other variables on multiple regression analysis. Conclusion: This study identifies several radiological parameters, including fibrosis, crazy paving, pneumomediastinum, and pneumothorax, that are associated with poor prognosis in COVID19. These findings highlight the role of CT thorax in COVID19 illness and the importance of timely identification and interventions in severe and critical cases of COVID19 to reduce mortality and morbidity.

Predictors of mortality among post-COVID-19 discharged patients in Northern India (preprint)

Background: The one-year postdischarge allcause mortality rate of COVID19 disease is 7.87 % with the majority of patients readmission and mortality occurring within the first 30 days postdischarge. Objective: Understanding predictors of mortality will help in prioritising patient care and preventive approaches. Methods: Ours a single centre unmatched case control study at a tertiary care centre in northern India, conducted from April 2020 to September 2022. The data was extracted retrospectively from the electronic hospital medical records of patients and by trained physicians using standardised data extraction sheet. Results: A total of 184 patients were enrolled with 92 cases and 92 controls. The mean age of patients was 49.3 {+/-} 17.53 years. The mortality group had a higher mean age (53.24 {+/-} 18.53 yrs) as compared to the control group (45.37 {+/-} 15.58 yrs) [p, 0.002]. Bivariate analysis revealed a significant difference in the two groups with respect to O2 saturation at admission [Case, 91.12 {+/-} 12.49 %, control, 95.46 {+/-} 5.01 %, p, 0.003); Maximum O2 flow rate [L/min] (Case, 11.01 {+/-} 22.2, Control, 6.41 {+/-} 13.31, P, 0.04); ICU need (p, 0.005), Cancer (p, 0.001), O2 need at discharge (p, 0.001) and AKI (p, 0.007). On multiple regression analysis, Cancer (aOR, 2.469; 95% CI, 1.183-5.150, p,0.016), ICU admission (aOR, 2.446; 95% CI, 1.212-4.938, p, 0.013), Oxygen at discharge (aOR, 2.340; 95% CI, 0.971-5.640, p, 0.0586) and Acute kidney injury (aOR, 5.6; 95% CI, 2.351-13.370, p, 0.00) only found to be significant. Conclusion: Oxygen requirement at discharge (2.3 times), Malignancy (2.4 times), ICU admission (2.4 times), and Acute Kidney Injury (5.6 times) were risks of death among COVID19 recovered patients, post discharge. The presence of these variables would warrant a close follow up for these patients in order to decrease post COVID mortality.

Knowledge, attitude, and practices of ward attendant and housekeeping staffs towards dead body care of COVID-19 patients at tertiary care hospital : A cross sectional study (preprint)

Background : Healthcare workers worked untiringly during entire pandemic period and taken efforts to protect individuals, families and communities in adverse situations with stretched resources. Among health care workers role of ward attendant and housekeeping staffs have been very significant particularly in infection control practices and dead body management. Present study aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of ward attendant and housekeeping staffs towards dead body management. Methods: Hospital-based cross-sectional study design was conducted among ward attendant and housekeeping staffs working in COVID units. A total of 62 participants were selected using simple random sampling technique. Self-administered questionnaire was used to collect data. Binary logistic regression model was used to see association between outcome and independent variables. Result: Present study found mean knowledge, attitude and practice score of participants were 6.1, 49.9 and 12.28 indicates good knowledge, positive attitude and inappropriate practice towards dead body care. Study result also shows that odds of good knowledge were not significantly associated with demographic variables. However, the participants who did not receive any training on dead body care were found to have positive attitude towards dead body care(AOR=3.90,95%CI=1.092-13.92), whereas gender (AOR=1.85,95%CI=.430-7.96), working experience in COVID units (AOR=99.5,95%CI=.913-98.8) and educational qualification (AOR=30.33,95%CI=1.5-577) were significantly associated with practice of dead body care of COVID-19 patients. Conclusion: The study found that majority of participants were having good knowledge, positive attitude and inappropriate practice towards dead body care of COVID-19 patients. Hospital administration should conduct regular training of dead body care of COVID-19 patients for all the housekeeping staffs and ward attendant to minimise the risk of exposure to infections and better management of dead bodies.

Knowledge practice gap of nurses towards COVID-19 patients dead body care in a tertiary care hospital. (preprint)

Abstract Title: Knowledge practice gap of nurses towards COVID-19 patients dead body care in a tertiary care hospital. Authors: Girraj Saini, Mahendra Singh, Prasan Kumar Panda, Manish Kumar Sharma, Pankaj Punjot, Raviprakash Meshram, Puneet Kumar Gupta. Aim: To know the dead body care of COVID 19 patients. Objective: 1.To determine health care professionals, knowledge, attitude, and practice towards Covid-19 dead body care. 2. To find the association of knowledge, attitude, practice with selected demographic variables. Background: COVID -19 was a global pandemic and it was a serious note for health care professionals from many aspects. The virus was infective and causes serious infections to patients which were easily transmitted, hence specific dead body care is required for such kinds of patients. To keep this background in mind the study was conducted to identify the knowledge, practice and attitude towards COVID-19 dead body care among nurses. Methodology: A cross sectional survey based study was done on 282 samples.Quantitative research design with purposive sampling technique data was collected for knowledge,attitude, and practice. Result: Knowledge, attitude and practice were assessed and association was done with demographic profile. Hence the good knowledge, attitude and practice were observed in experienced and trained nurses (p value<0.005. Whereas no significant changes were observed with age, gender and education qualification. Conclusion: Overall knowledge, attitude and practice regarding COVID -19 dead body care were moderate to good. But it was important to identify the gap as it was a global pandemic and higher chances of spreading of infection. Keywords: Contact transmission, Corona virus disease 2019, Dead body, Healthcare workers, and Questionnaire study.

Clinical profile of scrub typhus patients during COVID pandemic: A sub-Himalayan single center experience (preprint)

Introduction Scrub typhus is tropical zoonotic disease, commonly presented with multi organ dysfunction and high mortality rate in untreated patients. This study was done to identify clinical features commonly associated with scrub typhus during COVID pandemics, parameters associated with severe scrub typhus and mortality. Methods This retrospective study was done in a tertiary care hospital with a total of 52 admitted scrub typhus positive patients in October 2020 to February 2022. Diagnosis was established by scrub IgM ELISA or Rapid antigen test. The clinical and laboratory data, duration of hospital stay and outcomes were collected. Common clinical and laboratory findings were of descriptive analysis. Factors associated with mortality were analysed using Chi-square test. Results Fever was the most common presenting symptoms on admission (94.2%) followed by respiratory abnormalities (38.46%). Acute kidney injury was the most common organ failure on admission (67.3%), followed by acute liver injury (46.2%) and thrombocytopenia (32.7%). MODS was seen in 46.15%. Of the total, 30.8% were admitted in ICU. Mortality was seen in 7.7% of all patients. On Chi-square analysis, altered mental status and coagulopathy were associated with significant mortality with p value <0.05. Conclusion Scrub typhus can manifest with potentially life-threatening complications such as acute kidney injury, acute liver injury, thrombocytopenia and MODS. The overall case-fatality rate was 7.7%, and presence of altered mental status and coagulopathy were associated with higher mortality. As per literature, COVID has changed few clinical profiles of scrub typhus compared to same center experience before.

SARS-CoV-2 IgM and IgG serology and clinical outcomes in COVID-19 patients (preprint)

BackgroundThe SARS-CoV-2 virus has become pandemic for the last 2 years. Inflammatory response to the virus leads to organ dysfunction and death. Predicting the severity of inflammatory response helps in managing critical patients using serology tests IgG and IgM. We conducted a longitudinal study to correlate serum SARS-CoV-2 IgM and IgG serology with clinical outcomes in COVID-19 patients. MethodsWe analyzed patient data from March to December of 2020 for those who were admitted at AIIMS Rishikesh. Clinical and laboratory data of these patients were collected from the e-hospital portal and analysed. Correlation was seen with clinical outcomes and was assessed using MS Excel 2010 and SPSS software. ResultsOut of 494 patients, the mean age of patients was 48.95 {+/-} 16.40 years and there were more male patients in the study (66.0%). The patients were classified into 4 groups; mild-moderate 328 (67.1%), severe 131 (26.8%) and critical 30 (6.1%). The mean duration from symptom onset to serology testing was 19.87 {+/-} 30.53 days. In-hospital mortality was observed in 25.1% patients. The seropositivity rate (i.e., either IgG or IgM >10 AU) was 50%. There was a significant difference between the 2 groups in terms of IgM Levels (AU/mL) (W = 33428.000, p = <0.001) and IgG Levels (AU/mL) (W = 39256.500, p = <0.001), with the median IgM/ IgG Levels (AU/mL) being highest in the RT-PCR-Positive group. There was no significant difference between the groups in terms of IgM Levels and IgG levels with all other clinical outcomes (disease severity, septic shock, Intensive care admission, mechanical ventilation and mortality). ConclusionSerology (IgM and IgG) levels are high in RTPCR positive group compared to clinical COVID-19. However, serology cannot be useful for the prediction of disease outcomes except few situations. The study also highlights the importance of doing serology at a particular time as antibody titres vary with the duration of the disease.

Utility of IL-6 in the diagnosis, treatment and prognosis of COVID-19 patients: A longitudinal study (preprint)

Introduction: Covid-19 has caused devastating effects worldwide ever since its origin in December, 2019. Till date, there is no definitive treatment for it. Deaths due to Covid-19 has largely been attributed to cytokine storm and organ dysfunctions, mainly ARDS. Therefore, the focus has been on using inflammatory markers as a marker of severity of the disease. IL-6 is one such marker which has been increasingly used in the management of Covid-19. We conducted a longitudinal study to investigate the role of IL-6 in diagnosis, treatment and prognosis of Covid-19 related cytokine storm. Methodology: Patients with Covid-19, who were admitted at AIIMS Rishikesh from March to December, 2020 were included in the study. Patients with no baseline IL-6 value at admission and for whom clinical data was not available were excluded. Clinical and laboratory data of these patients were collected from the e-hospital portal and entered in excel sheet. The correlation was seen with other inflammatory markers and outcomes were assessed using MS Excel 2010 and SPSS software. Results: At total of 131 patients were included in the study. Majority were males (74.8%), mean age of the subjects being 55.03+13.57 years, with a mean duration from symptom onset being 6.69+6.3 days. Most of them belonged to the WHO severe category (82.4%), with 46.56% having severe hypoxia at presentation and 61.8% of them having some comorbidity- diabetes mellitus being the commonest. Spearman Rank Correlation coefficient of IL-6 with D-dimer was 0.203, with LDH was -0.005, with Ferritin was 0.3, and with Uric acid was 0.123. 11 patients received Tocilizumab at a mean duration from symptom onset of 18.09 days, and 100% mortality was observed. Deaths were reported more in the group with IL-6 more than 40pg/ml (57.1% vs 40.2%,p=0.06). Similarly, ICU admissions and ventilator requirement were reported more in the IL-6 more than 40pg/ml group (95.9% vs 91.4%,p=0.32 and 55.1% vs 37.8%,p=0.05). Conclusion: The study showed that IL-6 can be used as a possible thrombotic cytokine marker. Higher values of IL-6 (>40pg/ml) are associated with more deaths, ICU admissions and ventilator requirement.

Comparative study between first and second wave of COVID-19 deaths in India - a single center study (preprint)

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving and many mutant variants of the virus are circulating in the world. Recurrent waves of COVID-19 have caused enormous mortality all over the world. It is of utmost importance for a health expert to understand the demographic and clinical attributes between the first and second waves of COVID-19 induced deaths. Method This was a hospital record based comparative study of baseline demographic, clinical and laboratory parameters of the first and second wave of COVID-19 in a tertiary care hospital in Uttarakhand, India. The study included all deceased patients admitted to the hospital during the first and second wave of COVID-19, i.e., between March 2020 to January 2021 and between March 2021 to June 2021, respectively. Result The study showed that there were more casualties in the second wave compared to the first, 475 (19.8%) and 424 (24.1%) respectively. There was no significant difference in terms of age. A male preponderance of mortality was evident in both the waves. The median duration of hospital stay was 5 (3-10) days in the second wave, which is significantly different from the corresponding duration in first wave (pConclusion In both the first and second COVID-19 waves, older males (>45 years) with comorbidities like HTN and DM were most susceptible for COVID-19 related mortality. The study also demonstrated that most of the baseline demographic and clinical characteristics which are attributed to the mortality were more common during the second wave of COVID-19.

Ribavirin antiviral combination therapy in COVID 19, a single-center experience (preprint)

Background COVID 19 infection has a similar clinical spectrum of disease presentation such as SARS and MERS in the past. These led to the assumption of the possibility to treat COVID 19 infection with antivirals which had been used to treat SARS and MERS. Methods A retrospective analysis was done on the data of SEV COVID Trial in symptomatic adult patients of COVID 19 infection with objectives to explore whether ribavirin antiviral combinations reduces the need of both noninvasive and invasive ventilators in treatment of COVID 19 infections. Results The patients were categorized as Cohort A consisting of 40 patients and Cohort B of 61 patients as Cohort A being the group of patients who received the standard therapy and Cohort B the group of patients who received the ribavirin combination therapy. Conclusion The study concluded that there was no statistically significant difference in regard to the need of noninvasive ventilation and invasive ventilation and also the development of multiorgan dysfunction in between the two Cohorts. Also, with progress of time, the proportion of patients with single organ dysfunctions in the two cohorts showed gradual recovery without any statistically significant differences.

Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study (preprint)

BackgroundSince the outbreak of COVID-19 pandemic, the world began a frantic search for possible prophylactic options. While trials on hydroxychloroquine (HCQ) prophylaxis are ongoing, concrete evidence is lacking. The study aimed to determine the relative efficacy of various doses of oral HCQ in prophylaxis and mitigating the severity of COVID-19 in healthcare workers. MethodsThis was a prospective cohort with four arms (high, medium, low dose, and control) of HCQ prophylaxis, used by healthcare workers at a tertiary care center in India. Participants were grouped as per their opting for any one arm on a voluntary basis as per institute policy under the Government guidance. The outcomes studied were COVID-19 positivity by RT-PCR and its severity assessed by WHO COVID-19 severity scale. ResultsTotal 486 participants were enrolled, of which 29 (6%) opted for low dose, 2 (<1%) medium dose, and none for high dose HCQ while 455 (93.6%) were in the control arm. Of the 164 participants who underwent RT-PCR, 96 (58.2%) tested positive. Out of these 96 positive cases, the majority of them (79 of 96 [82.3%]) were ambulatory and were managed conservatively at home. Only 17.7% (17 of 96) participants, all of them from the control group, required hospitalization with the mild-moderate disease. None of the participants had severe disease, COVID-related complications, ICU stay, or death. The difference in the outcome assessed amongst the various arms was statistically insignificant (p value >0.05). ConclusionThis single-center study demonstrated that HCQ prophylaxis in healthcare workers does not cause a significant reduction in COVID-19 as well as mitigating its severity in those infected. At present, most of the trials have not shown any benefit. The debate continues to rage, should HCQ prophylaxis be given to healthcare workers for chemoprophylaxis?

Descriptive epidemiology of COVID-19 deaths during the first wave of pandemic in India - a single center experience (preprint)

BackgroundWith the looming threat of recurrent waves of COVID-19 in the presence of mutated strains, its of paramount importance to understand the demographic and clinical attributes of COVID-19 related mortalities in each pandemic waves. This could help policy makers, public health experts, and clinicians to better plan preventive and management strategies to curb COVID-19 related mortality. MethodThis was a hospital record based, retrospective cross-sectional descriptive study, at a tertiary care hospital in Rishikesh, India. The study included all deceased patients between March 2020 and January 2021 (first wave) who tested positive for SARS-CoV-2 by RT-PCR and were hospitalized. The study was done to describe demography, clinical presentation, laboratory parameters, treatment given and associated complications of all COVID-19 deaths. ResultOut of 424 mortalities, 298 (70.38%) were males and 126 (29.62%) were females. Mean age of patients was 55.85 {+/-} 16.24 years, out of which 19.5 percent were less than 45 years old, 33.6 percent were 45 to 60 years old and 41.8% were more than 60 years old. Comorbidity in the form of type 2 diabetes mellitus was present in 41.4% [95% CI (41.4-51.1)], hypertension in 39.8% [95% CI (35.1-44.6)], and coronary artery disease in 15.2% [95% CI (11.8-18.8)]. At the time of presentation, shortness of breath was present in 73.6% [95% CI (69.1 -77.7)], fever in 64.92% [95% CI (60.1-69.4)], and cough in 46.1%, [95% CI (41.1-50.8)]. Deranged laboratory parameters were lymphopenia in 90.2% [95% CI (86.8-92.7)], transaminitis in 59.7% [95% CI (54.8-64.3)], and hypercreatinemia in 37.7% [95% CI (33.1-42.5)]. Complications manifested were acute respiratory distress syndrome in 78.3% [95% CI (74-82.1)] and shock in 54.7% [95% CI (49.8-59.5)]. Median time duration between onset of symptom and hospital admission was 5 days (IQR = 3 - 5 days) and median length of hospital stay was 9 days (IQR = 4 - 14 days). ConclusionDuring first pandemic wave, COVID-19 related mortality was 2.37 times higher among males, 2.14 times in age group >60 than <45 years. Most common associated comorbidities (>40%) were type 2 diabetes mellitus and hypertension. Most common associated symptoms (>60%) were shortness of breath and fever. Lymphopenia was seen in >90% cases while liver involvement in 60% and kidney in 38% cases. Median hospital stay was doubled the pre-hospital illness.

Tocilizumab fails survival benefit in severe Covid-19 – a retrospective cohort study (preprint)

Background: Anti IL-6 monoclonal antibody Tocilizumab has produced mixed results in clinical trials for effectiveness against COVID-19. We conducted a retrospective cohort study to compare outcomes at 28 days of a cohort of patients with severe Covid-19 treated with Tocilizumab and standard care, with those receiving standard care only. Methods In this record based retrospective cohort study, patients hospitalized with Covid-19 were classified into non-severe and severe disease as per institutional protocol. One cohort received Tocilizumab with standard care and the second cohort received only standard care. Few patients also received high dose steroids as ‘pulse’ steroids on initial clinical deterioration. Data was collected for the treatment given including oxygen interface, steroids, antimicrobials, duration of hospital stay in survivors, requirement of mechanical ventilation and day of intubation from symptom onset. Results There was statistically significant mortality in Tocilizumab cohort as compared to standard care alone (HR 2.43, 95%CI 1.54–3.89). The need for mechanical ventilation was more in Tocilizumab cohort (85% vs 18%, P-value 

Hyper-eosinophilic syndrome with myocarditis after inactivated SARS-CoV-2 vaccination: A case study (preprint)

A young man without any co-morbidities presented with persistent periorbital baggy swelling along with itchy swelling over fingers, resting tachycardia and exertional breathlessness following first dose of an inactivated SARS-CoV-2 vaccination (COVAXIN). On investigation, patient had elevated blood eosinophils and myocarditis. He was successfully treated with steroid and supportive treatment.

Mixed invasive molds among COVID-19 patients (preprint)

PurposeDue to surge in COVID cases during the second wave of the COVID pandemic, the healthcare system collapsed in India with shortage of hospital beds, injudicious use of steroids and other immunomodulators, and poor glycaemic monitoring among a population with pre-existing risk of diabetes. Fungal epidemic was announced amid COVID pandemic with several cases of COVID-associated mucormycosis and aspergillosis being reported. But, there is no data regarding mixed fungal infections in COVID patients. Materials and MethodsThe study presented a series of ten consecutive cases with dual invasive molds in patients infected with SARS-CoV-2. Among patients hospitalized with the diagnosis of COVID in May 2021 at a tertiary care center in North India, ten microbiologically confirmed dual/mixed COVID-associated mucor-aspergillosis (CAMA) were evaluated. ResultsAll patients were diabetics with the majority having severe COVID pneumonia (6/10, 60%) either on admission or in the past one month, whilst two were each of moderate (20%) and mild (20%) categories of COVID. The patients were managed with amphotericin-B along with surgical intervention. In this case series, 70% of all CAMA (Rhizopus arrhizus with Aspergillus flavus in seven and Aspergillus fumigatus in three patients) patients survived, connoting the critical importance of a high index of clinical suspicion and accurate microbiological diagnosis for managing invasive molds. ConclusionsMixed fungal infections i.e. CAMA during COVID and post-COVID periods may be an emerging disease. This outbreak is seen particularly in such patients with uncontrolled diabetes, on steroids, or cocktail therapy, or living in unhygienic environments.We believe that our findings would help gain a better insight into the risk and progression of invasive fungal mixed infections among COVID patients and thus play a pivotal role in diagnosing, classifying, and implementing an effective management strategy for treating similar cases in the future.

Seroprevalence of Antibodies against SARS COV- 2 among Health Care Workers at Tertiary Care Hospital, Uttarakhand: A Retrospective study (preprint)

Background: The number of confirmed SARS-CoV-2 infections is vastly underestimated. In this context, Seroprevalence surveys are of utmost importance to assess the proportion of the population that has already developed antibodies against the virus and might potentially be protected against subsequent infection. Health care workers face greater risk of developing SARS-CoV-2. Therefore, present retrospective study was undertaken to estimate the prevalence of antibodies against SARS-CoV-2 among healthcare workers at tertiary care institute, Uttarakhand. Material: and Methods : Data was gathered from Hospital records of 704 healthcare workers admitted at COVID 19 Unit and attended Covid-OPD of tertiary care institute, Uttarakhand in-between 15th July to 14th Aug 2020. Result: Out of the 704 recruited participants, 14 (1.99%) were seropositive for IgG antibodies against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive RT-PCR) was 4.40%. Conclusion: The present study shows a low prevalence of SARS-CoV-2 IgG antibodies among health care workers. In addition, posting in COVID-19-positive areas was not associated with increased seropositivity. More studies are warranted to assess IgG/IgM antibodies against SARS-CoV-2 among those HCW who are exposed to COVID-19 patients.

A Retrospective analysis of DIC score and SIC score in prediction of COVID-19 severity (preprint)

Background: The novel Disseminated Intravascular Coagulation (DIC) score [platelet count, prolonged prothrombin time, D-dimer, and fibrinogen] and Sepsis Induced Coagulopathy (SIC) score [platelet count, International normalized ratio, and Sequential organ failure assessment score] are markers of coagulopathy, which, for the first time, are explored in line with the COVID-19 disease outcomes. The correlation of D-dimer with these findings is also studied. Patients and methods: A retrospective analysis of hospital-based records of 168 COVID-19 patients. Data including D-dimer, routine investigations, DIC and SIC scorings (all within three days of admission) were collected and correlated with the outcomes. The study was conducted in a tertiary care center catering to population of North India. Results: Higher DIC score (1{middle dot}59 {+/-} 1{middle dot}18 v/s 0{middle dot}96 {+/-} 1{middle dot}18), SIC score (1{middle dot}60 {+/-} 0{middle dot}89 v/s 0{middle dot}63 {+/-} 0{middle dot}99), and D-dimer titers (1321{middle dot}33 {+/-} 1627{middle dot}89 v/s 583{middle dot}66 {+/-} 777{middle dot}71 ng/ml) were significantly associated with severe COVID-19 disease (P<0{middle dot}05). DIC score and SIC score [≥] 1, and D-dimer [≥] 1315 ng/ml for severe disease; DIC score [≥] 1, SIC score [≥] 2, and D-dimer [≥] 600 ng/ml for Pulmonary Embolism (PE); and DIC score and SIC score [≥] 1, and D-dimer level [≥] 990 ng/ml for mortality were the respective cut-off values we found from our study. Conclusion: Higher DIC scores, SIC scores, and D-dimer values are associated with severe COVID-19 disease, in-hospital mortality, and PE risk. They can serve as easily accessible early markers of severe disease and prioritize hospital admissions in the presently overburdened scenario, and may be used to develop prognostic prediction models.

Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial) (preprint)

Background Definitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried. Methods A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report. Results Total 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05). Conclusions The results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.

Comparing India's second COVID wave with the first wave, a single center experience (preprint)

Background The COVID-19 pandemic has resurfaced in India in the form of a hard-hitting second wave. This study aims to compare the clinical profile of the first wave (April-June 2020) and the second wave (March-May 2021) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a single tertiary care center of India. This will help prioritize the target population group and management strategies in the upcoming third wave if any. Methods In this retrospective observational study, we examined the demographic profile, symptoms at presentation, the severity of illness, baseline investigations, treatments received, underlying comorbidities, and outcomes of the COVID-19 patients belonging to the first (W1) and the second wave (W2) of the pandemic in India. Findings Among 106 patients in W1 and 104 patients in W2, the age group affected most was 37.1 (SD=16.9) years compared with 50.5 (SD=17.7) years respectively. The baseline oxygen saturation is lower in W2, being 84.0 (13.4) % compared with 91.9 (7.4) % in W1. 70.2 % of the cases belonged to the severe category in W2 compared to 37.5% in W1. W2 patients demonstrated higher transaminase levels [SGOT, 108.3 (99.3) v/s 54.6 (69.3); SGPT, 97.6 (82.3) v/s 58.7 (69.7)] with respect to W1. Similarly, the CT severity score for W2 [29.5 (6.7)] was higher than W1 [23.2 (11.5)][All P<0.05]. The proportion of patients requiring oxygen (81.8% v/s 11.2%), high flow nasal cannula (11.4% v/s 5.6%), non-invasive ventilation (41.2% v/s 1.5%), invasive ventilation (24.5% v/s 0.9%), as well as ICU/HDU admissions (56.4% v/s 12.0%) was higher for W2 as compared with W1. The measured case fatality rate varies from 29% for W2 to 9.6% for W1. Interpretation Higher age, oxygen requirement, ventilator requirement, ICU admission, and organ impairment are more prevalent in the admitted COVID-19 cases during the second wave that has hit India compared to the first wave and associated with more fatalities. Strategy for another wave should be planned accordingly.