Coronavirus disease 2019-associated mucormycosis - a syndemic

Coronavirus disease 2019 (COVID-19) and COVID-associated mucormycosis (CAM) came as a syndemic that not only severely increased morbidity and mortality but also posed a serious challenge for the healthcare system of a developing country like India. Although mucormycosis is a rare disease with a worldwide incidence of 0.43 cases per million population/year, these two COVID-19 waves caused a total of more than 14,000 cases in India itself. Mucormycosis is an angio-invasive fungal infection with rapid progression. The three major modalities of treatment involve early surgical debridement, initiation of antifungal therapy and controlling the predisposing risk factor. A complex interplay of factors, including pre-existing disease such as diabetes mellitus, use of immunosuppressants and immunomodulators, risk of hospital-acquired infection and immune dysregulation post-COVID-19, may all predispose to the development of CAM. Future research regarding the efficiency of newer antifungal with lower side effect profiles and evidence-based establishment of risk factors for adopting preventing strategies is the need of the hour. The disease is known to have high mortality despite the best treatment. We review in this article the aetiopathogenesis, various diagnostic modalities and treatment considerations for this disease.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in admitted patients at a tertiary referral centre in North India (preprint)

Background: Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate true burden of infection in a given population. Serosurveys, though being conducted in different parts of India, are not readily published in entirety and often do not report on the different characteristics of the population studied. In this present study, we aimed to serially estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody over 11 months at one of the largest government hospital in India. Method In this cross-sectional study which was conducted between 9th June 2020 and 27th April 2021, consecutive patients admitted to medicine wards or intensive care units, who were negative for SARS-CoV-2 by RT-PCR or CBNAAT were included. The clinic-demographic features of the subjects were recorded in pre-formed questionnaires. Anti-SARS-CoV2 antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method. Results A total of 916 patients were recruited over 11 months with mean age(plus/minus SD) 39.79 plus/minus 14.9 of years and 55% of population being males. In total 264(28.8%) patients were found to be seropositive. Residency in Delhi and non-smoking status conferred a higher risk for seropositivity. The adjusted odds ratio for seropositivity with regards to no smoking and residence out of Delhi were .31 plus/minus .09 (Odds ratio plus/minus S.E) and .65 plus/minus .1 (Odds ratio plus/minus S.E) respectively. No other factors like age, socio-economic status, contact history etc. showed significant relationship with seropositivity. Conclusion The seropositivity rate among hospitalized patients was found to increase with time (from 8.45% to 38%) over a period of 9 months. Residence in Delhi and non-smokers had higher risk for seropositivity on multivariate analysis.

Efficacy of Influenza Like Illness (ILI) Screening OPD for COVID-19 at a High-Volume Centre: Unlocking Routine OPD (preprint)

Background: The Impact of COVID-19 pandemic over non-essential health services has been massive. We initiated Influenza Like Illness (ILI) screening for resumption of out-patient services at a tertiary care centre and this study attempted to gauge its efficacy in effectively pruning out COVID-19. Methods: We included all the patients who had visited for an OPD appointment during the study period. Patient details and ILI symptoms were noted. Patients were then followed up telephonically after 2 weeks. The telephonic follow up was to ensure RT-PCR status and complaints of any newly developed ILI post OPD visit (within the last 14 days). Results: : Out of the 957 patients who were enrolled, 929 patients were successfully followed up telephonically after 14 days. Only 13 who were screened out as ‘possible ILI’, were either RT-PCR negative or did not follow up with a confirmatory test. The telephonic follow up to ensure RT-PCR status and complaints of any newly developed ILI post OPD visit (within the last 14 days) was noted in the rest of the patients. Only 1 participant out of 957 screened, tested positive for COVID-19. Conclusion: The period in which the study was held the national positivity rate was low (around 3%). Therefore, in a resource limited country such as India it is astute to restart the OPD services in the pre-existing setup using basic precautions and a verbal questionnaire during the slope of the pandemic.

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality (preprint)

The precise molecular mechanisms behind severe life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant "classical" signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing "Cytokine Release Syndrome" (CRS) showed upregulation of IL1 cytokines such CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Gordonia bronchialis in "classical" patients and Staphylococcus warneri in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.

Impact of COVID-19 on the patients' income and work in Delhi, India.

BACKGROUND: Currently, there is no data on the impact of COVID-19 on patients' income and work in India. METHODS: We conducted a cross-sectional study at a tertiary hospital in New Delhi. We included all the patients who were ≥18 years of age and consecutively diagnosed with COVID-19 between the 1st of May 2020 to 31st July 2020. Patients were interviewed by a physician using a semi-structure questionnaire. Data were collected on socio-economic status, occupation, income loss, leaves taken, decrease in work efficiency (self-perceived) and about-facing any stigma/discrimination at the workplace. RESULTS: Out of 245 patients, 190 patients were employed. A total of 126 patients (66.3%) self-reported their work was affected due to COVID-19 disease. A total of 30.5% of patients (n = 58/190) reported deduction in their salary. The median amount of salary loss was INR 10,000 (IQR 9000-25000). Decrease in income and work efficiency (self-perceived) was found to be 37.3% (n = 71) and 12.1% (n = 23), respectively. A total of 47 patients (37.3%) took personal leaves (median number - 17 days (IQR 14-25), and discrimination/stigma related to the COVID-19 at the workplace was faced by 22.6% of patients. CONCLUSION: Income and work of a substantial number of patients was affected due to COVID-19, as there was a decrease in income and work efficiency. Patients also had to take personal leaves and face stigma in the workplace. This will inform the policymakers to formulate strategies to mitigate the impact of COVID-19.

Determination of utility of 3 minute and 6 minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary hospital in North India (preprint)

Introduction: There have been 214 million confirmed cases of COVID-19 worldwide with a total death tally of 4.4 million. The current study aims to determine the predictive value of 3 minute and 6-minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary care hospital in North India. Methods: The study population consisted of adults (age more than 18 years) with a confirmed diagnosis of Covid-19 by RT-PCR on nasopharyngeal specimens. Patients with only mild illness were enrolled. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, vital signs and laboratory parameters were recorded. The 3 and 6 minute walk test was performed daily from admission till discharge or progression of severity of COVID-19 and it was used to calculate BDS and NEWS2 scores. Results: Our study consisted of 50 patients with 34 (68%) males and the mean (SD) age of the patient population being 28.1 (6.4) years. The most common symptoms were fever, sore throat, and cough. All laboratory parameters were within normal ranges for all the patients. 96% recovered without progression, while only 4% of them progressed to moderate illness. Results of the 3 and 6 minutes walk tests, BDS and NEWS2 scores showed improvement over the course of hospital stay. Conclusions: Although the walk tests and the scores improved over time, they failed to predict the disease progression.

The effectiveness of SARS-CoV-2 vaccination in preventing severe illness and death – real-world data from a cohort of patients hospitalized with COVID-19 (preprint)

Background Due to the unprecedented speed of SARS-CoV-2 vaccine development, their efficacy trials and issuance of emergency use approvals and marketing authorizations, additional scientific questions remain that need to be answered regarding vaccine effectiveness, vaccination regimens and the need for booster doses. While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited, studies on breakthrough infections help us understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. Methods This observational cohort study aimed at comparing the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1,464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Results Completing the course of vaccination protected individuals from developing severe COVID-19 as evidence by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. Conclusion With a current rate of only 9.5% of the Indian population being fully vaccinated, efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources. Research in context Evidence before this study The Government of India started vaccinating its citizens from the 16 th of January 2021, after emergency use authorization had been received for the use of two vaccines, BBV152, a COVID-19 vaccine based on the whole-virion SARS-CoV-2 vaccine strain NIV-2020-770, (Covaxin) and the recombinant replication-deficient chimpanzee adenovirus vector encoding the spike protein ChAdOx1 nCoV-19 Corona Virus Vaccine (Covishield). These have been approved by the Indian regulatory authority based on randomized controlled studies. In these studies, was found that the vaccines led to more than 90% reduction in symptomatic COVID-19 disease. However, there is scarce evidence of the efficacy of these vaccines in real-world scenarios. A few studies have looked at vaccinated cohorts such as health care workers in whom the vaccines had an efficacy similar to the RCTs. In a study of patients with SARS-CoV-2 infection admitted to a tertiary care hospital in New Delhi, it was found that mortality in fully vaccinated patients was 12.5% as compared to 31.5% in the unvaccinated cohort. Added-value of this study This cohort of hospitalized patients with SARS-CoV-2 infection was studied during the peak of the second wave of COVID-19 in India during which the delta variant of concern was the predominant infecting strain and had 26% patients who were partially vaccinated and 71.4% who were unvaccinated. Only 3% of the patients were fully vaccinated and developed a breakthrough infection. At the time of presentation, 13% of the individuals with breakthrough infection and 48·5% in the non-vaccinated group were hypoxic. Inflammatory markers were significantly lower in the completely vaccinated patients with breakthrough infection. The need for use of steroids and anti-viral agents such as remdesivir was also significantly low in the breakthrough infection group. A significantly less proportion of the individuals with breakthrough infection required oxygen supplementation or ventilatory support. Very few deteriorated or progressed to critical illness during their hospital stay. Only 3 individuals (5.7%) out of the 53 who developed breakthrough infection succumbed to illness while case fatality rates were significantly higher in the unvaccinated (22.8%) and partially vaccinated (19.5%) groups. Propensity score weighted multivariate logistic regression analysis revealed lower odds of developing hypoxia, critical illness or death in those who were completely vaccinated. Implications of all the available evidence The real-world effectiveness of the vaccines against SARS-CoV-2 seems to be similar to the randomized controlled trials. The vaccines are very effective in reducing the incidence of severe COVID-19, hypoxia, critical illness and death. The reduced need for oxygen supplementation, mechanical ventilation and the requirement of corticosteroids or other expensive medications such as anti-viral drugs could go a long way in redistributing scarce health care resources. All nations must move forward and vaccinate the citizens, as the current evidence suggests that ‘prevention is better than cure’.

Management of COVID-19 symptoms with Yoga and Standard treatment .

ACE2 Expression in Lungs of Severe COVID-19 Infection: A Study on Minimally Invasive Post- mortem Tissue Samples (preprint)

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India-A cohort study (preprint)

Background The second wave of the COVID-19 pandemic hit India from early April 2021 to June 2021 and more than 400,000 cases per day were reported in the country. We describe the clinical features, demography, treatment trends, baseline laboratory parameters of a cohort of patients admitted at the All India Institute of Medical Sciences, New Delhi with SARS-CoV-2 infection and their association with the outcome. Methods This was a retrospective cohort study describing the clinical, laboratory and treatment patterns of consecutive patients admitted with SARS-CoV-2 infection. Multivariate logistic regression models were fitted to identify the clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay and death. Findings A total of 2080 patients were included in the study. The case fatality rate was 19.5%. Amongst the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 Acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged 45-60 years [OR (95% CI): 1.8 (1.2-2.6)p =0.003] and those aged >60 years [OR (95%CI): 3.4 (2.3-5.2), p<0.001] had a higher odds of death as compared to the 18-44 age group. Vaccination reduced the odds of death by 30% [OR (95% CI): 0.7 (0.5-0.9), p=0.036]. Patients with hyper inflammation at baseline as suggested by leucocytosis [OR (95% CI): 2.1 (1.4-3.10), p <0.001], raised d-dimer >500 mg/dL [OR (95% CI): 3.2 (2.2-4.6), p <0.001] and raised C-reactive peptide >0.5 mg/L [OR (95% CI): 3.8 (1.1-13), p=0.037] had higher odds of death. Patients who were admitted in the second week had lower odds of death and those admitted in the third week had higher odds of death. Interpretation This is the largest cohort of patients admitted with COVID-19 from India reported to date and has shown that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Strategies should be made to improve vaccination rates and early admission of patients with moderate and severe COVID-19 to improve outcomes. Research in context Evidence before this study The COVID-19 pandemic has been ravaging the world since December 2019 and the cases in various regions are being reported in waves. We found that the case fatality rates ranging from 1.4% to 28.3% have been reported in the first wave in India. Older age and the presence of comorbidities are known predictors of mortality. There are no reports regarding the effectiveness of vaccination, correlation of mortality with the timing of admission to the health care facility and inflammatory markers in the ‘second wave’ of the COVID-19 pandemic in India. Added-value of this study This study reports the real-world situation where patients get admitted at varying time points of their illness due to the mismatch between the availability of hospital beds and the rising number of COVID-19 patients during the pandemic. It reports the odds of developing severe hypoxia necessitating oxygen therapy and death thus helping identify priority groups for admission. Implications of all the available evidence This study found increased odds of requiring oxygen support or death in patients older than 45 years of age, with comorbidities, and those who had hyper-inflammation with raised C-reactive peptide, d-dimer or leukocytosis. Patients who were admitted in the second week of illness had lower odds of death as compared to those admitted in the third week implying that treatment with corticosteroids in the second week of the illness during the ‘inflammatory phase’ could lead to reduced mortality. These findings would help triage patients and provide guidance for developing admission policy during times where hospital beds are scarce. Vaccination was found to reduce the odds of deterioration or death and should be fast-tracked to prevent further ‘waves’ of the pandemic.

Novel Risk Factors for Coronavirus Disease-Associated Mucormycosis (CAM): A Case Control Study During the Outbreak in India (preprint)

Background: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. In this study, we aimed to analyse the risk factors for CAM, in addition to those established for mucormycosis prior to COVID-19 pandemic.Methods: We performed a case-control study comparing patients diagnosed with CAM with those who had recovered from COVID-19 without developing mucormycosis. Information on comorbidities, glycaemic control, and practices related to COVID-19 prevention and management was recorded.Findings: One hundred fifty-two cases of CAM and 200 controls diagnosed with COVID-19 during April–May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean 18·9 ± 9·1 days after the symptom onset of COVID-19. All, but one patient, carried either of the conventional risk factors: diabetes and steroid use. On multivariate regression analysis, risk factors associated with increased odds of CAM included presence of diabetes (aOR 3·5, 95%CI 1·1–11), poor glycaemic control (p<0.05 for blood glucose levels >200 mg/dL), use of systemic steroids (aOR 7·7,95% CI 2·4–24·7), prolonged use of cloth and surgical masks (vs N95 masks, aOR 17·5, 95% CI 4·6-66·7), and repeated nasopharyngeal swab testing (aOR 1·6,95% CI 1·2–2·2).Interpretation: CAM is strongly associated with diabetes, poor glycaemic control, and systemic steroid use. Novel risk factors identified in our study include prolonged use of cloth and surgical masks vis-a-vis N95 masks, and repeated nasopharyngeal swab testing. Oxygen therapy and need for hospitalization for COVID-19 did not affect the risk of CAM.Funding Information: This was an investigator-initiated non-funded study.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: The study was approved by the Institute Ethics Committee, AIIMS, Delhi, India. [IECPG-353/28.05.21].

Novel risk factors for Coronavirus disease-associated mucormycosis (CAM): a case control study during the outbreak in India (preprint)

BackgroundThe epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. MethodsWe performed a case-control study comparing cases diagnosed with CAM and those who had recovered from COVID-19 without developing mucormycosis (controls). Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Results352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases carried conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95%CI 1.1-11), use of systemic steroids (aOR 7.7,95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6,95% CI 1.2-2.2). Zinc therapy, probably due to its utility in immune function, was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. ConclusionJudicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Post COVID-19 sequelae: A prospective observational study from Northern India (preprint)

Background: Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. Aim: To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. Method: This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. Results: Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. Conclusion: Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.

Use of HFNC in COVID-19 patients in non-ICU setting: Experience from a tertiary referral centre of north India and a systematic review of literature (preprint)

Introduction The rapid surge of cases and insufficient numbers of intensive care unit (ICU) beds have forced hospitals to utilise their general wards for administration of non-invasive respiratory support including HFNC(High Flow Nasal Cannula) in severe COVID-19. However, there is a dearth of data on the success of such advanced levels of care outside the ICU setting. Therefore, we conducted an observational study at our centre, and systematically reviewed the literature, to assess the success of HFNC in managing severe COVID-19 cases outside the ICU. Methods A retrospective cohort study was conducted in a tertiary referral centre where records of all adult COVID-19 patients (over 18 years) requiring HFNC support were between September and December 2020 were analysed. HFNC support was adjusted to target SpO2 over 90% and respiratory rate less than 30 per min. The clinical, demographic, laboratory, and treatment details of these patients were retrieved from the medical records and entered in predesigned proforma. Outcome parameters included duration of oxygen during hospital stay, duration of HFNC therapy, length of hospital stay and death or discharge. HFNC success was denoted when a patient did not require escalation of therapy to NIV or invasive mechanical ventilation, or shifting to the ICU, and was eventually discharged from the hospital without oxygen therapy; otherwise, the outcome was denoted as HFNC failure. Systematic review was also performed on the available literature on the experience with HFNC in COVID-19 patients outside of ICU settings using the MEDLINE, Web of Science and Embase databases. Statistical analyses were performed with the use of STATA software, version 12, OpenMeta[Analyst], and visualization of the risk of bias plot using robvis. Results Thirty-one patients receiving HFNC in the ward setting, had a median age of 62 (50 - 69) years including 24 (77%) males. Twenty-one (68%) patients successfully tolerated HFNC and were subsequently discharged from the wards, while 10 (32%) patients had to be shifted to ICU for non-invasive or invasive ventilation, implying HFNC failure. Patients with HFNC failure had higher median D-dimer values at baseline (2.2 mcg/ml vs 0.6 mcg/ml, p=0.001) and lower initial SpO2 on room air at admission (70% vs 80%, p=0.026) as compared to those in whom HFNC was successful .A cut-off value of 1.7 mg/L carried a high specificity (90.5%) and moderate sensitivity (80%) for the occurrence of HFNC failure. Radiographic severity scoring as per the BRIXIA score was comparable in both the groups(11 vs 10.5 out of 18, p=0.78 ). After screening 98 articles, total of seven studies were included for synthesis in the systematic review with a total of 820 patients, with mean age of the studies ranging from 44 to 83 years and including 62% males. After excluding 2 studies from the analysis, the pooled rates of HFNC failure were 36.3% (95% CI 31.1% - 41.5%) with no significant heterogeneity (I2 =0%, p=0.55). Conclusions Our study demonstrated successful outcomes with use of HFNC in an outside of ICU setting among two-thirds of patients with severe COVID-19 pneumonia. Lower room air SpO2 and higher D-dimer levels at presentation were associated with failure of HFNC therapy leading to ICU transfer for endotracheal intubation or death. Also, the results from the systematic review demonstrated similar rates of successful outcomes concluding that HFNC is a viable option with failure rates similar to those of ICU settings in such patients.

Seroprevalence of COVID-19 in HIV Population (preprint)

Background: seroprevalence helps us to estimate the exact prevalence of a disease in a population. More than a year since the identification of the disease, it is still not known the exact burden of the disease in the PLHA group. Seroprevalence data in this subset of the population is scarce in most part of the world, including India. The current study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among people living with HIV/AIDS. Aim: To determine the seroprevalence of SARS-CoV-2 antibodies in PLHA (People living with HIV/AIDS). Design: This was an observational prospective cohort study. Method: This cross-sectional study, conducted at a tertiary care hospital in North India, recruited HIV positive patients following at the ART centre of the institute. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the chemiluminescent immunoassay method. Results: A total of 164 patients were recruited in the study with mean age (+SD) of 41.2 (+15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 14% patients (95% C 9.1-20.3%). Conclusion: The seroprevalence of COVID-19 disease in PLHA was found to be lower than the general population.

Clinical Characteristics And Outcomes of 16 Cases With COVID19 and Mucormycosis: Experience From A Tertiary Care Center In India and Review of Literature (preprint)

Background-The sharp uptick in the cases of mucormycosis in the background of the COVID19 pandemic is a cause of concern and the reasons and it’s impact remains to be seen. We studied the clinical characteristics in patients with mucormycosis and COVID19 co-infection and performed a literature review.Methods-This retrospective study was conducted at tertiary centre in India. All patients admitted with COVID19 and mucormycosis were included, clinical details were obtained from hospital records. We did review of literatures using the terms “SARS-CoV2” OR “COVID19” AND “Mucormycosis” AND “co-infection” on Pubmed published before February 20, 2021.Results-Sixteen cases (M:F–13:3), mean age 46·5 years (24-75years), were included. Fourteen had known risk factors for mucormycosis, the most common being diabetes mellitus. Most patients (n=14) were symptomatic with mucormycosis before diagnosis of COVID19. There was delay in surgery by 22.5 days (IQR–>17.75–29.5), pending SARS-CoV-2 RT-PCR negativity. There were six deaths in this cohort, unrelated to the COVID19 severity. The literature review revealed eleven case reports on co-infection. Patients who had developed mucormycosis were found to have history of mechanical ventilation.Conclusion-The apparent increase in the incidence of mucormycosis may be due to decompensation of underlying comorbidities (decreased access to healthcare), and increased use of immunosuppressants in COVID19. Patients with co-infection were noted to have poorer outcomes. 

Clinical correlation of lung ultrasound profiles in patients with COVID-19 infection (preprint)

BackgroundLung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 patients by determining its ability to predict clinical severity and outcomes. MethodsThis was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 (respiratory rate >30/min OR SpO2<90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 related severity and outcomes. FindingsBetween October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio ({rho}= -0.7232, p<0.0001) and SpO2/FiO2 ratio ({rho}= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of [≥]6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones. InterpretationIn patients with COVID-19, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 infection. Author ApprovalAll authors have seen and approved the manuscript Competing interestsThere are no potential competing interests Data availability StatementAll data referred to in the manuscript shall be provided when asked for. DisclaimersThe authors have nothing to disclose Funding statementNo funding source was involved.

Clinical Correlation of Lung Ultrasound Profiles in Patients with COVID-19 Infection (preprint)

Background: Lung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 patients by determining its ability to predict clinical severity and outcomes.Methods: This was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 (respiratory rate >30/min OR SpO2 <90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 related severity and outcomes.Findings: Between October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio (ρ= -0.7232, p<0.0001) and SpO2/FiO2 ratio (ρ= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of ≥6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones.Interpretation: In patients with COVID-19, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 infection.Funding Statement: No funding source was involved.Declaration of Interests: The authors have nothing to discloseEthics Approval Statement: The study was reviewed and cleared by the Institute Ethics Committee (IEC).

The Association Between Hypocalcemia and Outcome in COVID-19 Patients: a Retrospective Study (preprint)

Background: Calcium has been shown to have a vital role in the pathophysiology of SARS-CoV and MERS-CoV diseases but less is known about hypocalcemia in COVID-19 patients and its association with the disease severity and the final outcome. Therefore, this study was conducted with an aim to assess the clinical features in the COVID-19 patients having hypocalcemia and to observe its impact on COVID-19 disease severity and final outcome.Method: In this retrospective study, consecutive COVID-19 patients of all age groups were enrolled. Demographical, clinical and laboratory details were collected and analysed. On the basis of albumin-corrected calcium level patients were classified into normocalcemic (n=51) and hypocalcemic (n=110). Death was the primary outcome. Results: The mean age of hypocalcemic were significantly lower (p<0.05). A significantly higher number of normocalcemic patients had severe COVID-19 disease(92.73%, p<0.01), had comorbidities (82.73%, p<0.05) and required ventilator support(39.09%, p<0.01)compared to the hypocalcemic patients. The mortality rate was significantly higher (33.63%, p<0.05) in the hypocalcemic patients when compared with the normocalcemic patients (15.69%). Haemoglobin (p<0.01), hematocrit (p<0.01) and red cell count (p<0.01) were significantly lower with higher levels of absolute neutrophil count (<0.05) and neutrophil to lymphocyte ratio (p<0.01) in the hypocalcemic patients. Albumin-corrected calcium level had a significant positive correlation with haemoglobin level, haematocrit, red cell count, total protein, albumin and albumin to globulin ratio and a significant negative correlation with absolute neutrophil count and neutrophil to lymphocyte ratio.Conclusion: The disease severity, ventilator requirement and mortality were considerably higher in hypocalcemic COVID-19 patients. 

Seroprevalence and attainment of herd immunity against SARS CoV-2: A modelling study (preprint)

Objective: The present study is aims to predict the likelihood of and likely time required to attain herd immunity against COVID-19 in New Delhi due to natural infection. Method: An ODE based mathematical model was constructed by extending the classical SEIR model to predict the seroprevalence rate in Delhi. We estimated the parameter values for Delhi using available data (reported cases and the seroprevalence rate) and used them for future prediction. We also attempted to capture the changes in the seroprevalence rate with different possibilities of reinfection. Results: Maximum seroprevalence rate obtained through our model is 31.65% and also a reduction in the seroprevalence rate was observed for the upcoming one month (month of January, 2021) due to the reduced transmission rate. After increasing the transmission rate to the value same as the third wave in New Delhi, we obtained a maximum value of 54.96%. This maximum value significantly decreased with the reduction in the reinfection possibilities. Also, a little impact of the duration of persistence of antibodies, 180 vs 105 days, was observed on the maximum seroprevalence. Conclusion: This modelling study suggests that natural infection alone, as gauged by serial sero-surveys, will not result in attainment of herd immunity in the state of Delhi.