Impact of COVID-19 infection among indian sickle cell disease patients.

Background: Sickle cell disease (SCD) is one of the most common hemoglobinopathy disorders and is widely prevalent in India, especially in the tribal population. SCD patients are prone to develop recurrent respiratory infections and related complications owing to the microvascular occlusion and impaired immunological response. Objectives: We aimed to determine the prevalence and impact of COVID-19 in SCD patients from India. Methodology: We conducted a cross-sectional study in Chandrapur district of Maharashtra, India, between August and October 2021. After taking informed consent, details of 300 SCD patients' demographic data, history of COVID-19 testing, infection, symptoms related to COVID-19 in the past 1 year, hospitalization, complications, mortality, COVID-19 vaccination, and side effects were recorded. Results: We found that 93 (31%) of SCD patients had influenza-like symptoms during the COVID-19 pandemic with symptoms of fever (81.72%), cough (35.48%), sore throat (18.27%), headache (15.05%), and breathlessness (7.52%). A total of 13 (4.33%) SCD among 300 SCD were tested as COVID positive. Majority of them were mild cases and the 1st dose of COVID-19 vaccine was received by 47 (29.37%) of SCD patients and 10 (6.02%) of the patient had received second dose of vaccine. Conclusion: Low incidence of COVID-19 and milder disease spectrum in our study cohort suggests that there is no increased risk of COVID-19 mortality and morbidity in SCD patients compared to general population. However, the reason for low COVID vaccination in our study could be due to the fear of complications of COVID vaccine.

Higher proinflammatory responses possibly contributing to suppressed cytotoxicity in patients with COVID-19 associated mucormycosis.

INTRODUCTION: COVID-19 Associated Mucormycosis (CAM), an opportunistic fungal infection, surged during the second wave of SARS Cov-2 pandemic. Since immune responses play an important role in controlling this infection in immunocompetent hosts, it is required to understand immune perturbations associated with this condition for devising immunotherapeutic strategies for its control. We conducted a study to determine different immune parameters altered in CAM cases as compared to COVID-19 patients without CAM. METHODOLOGY: Cytokine levels in serum samples of CAM cases (n = 29) and COVID-19 patients without CAM (n = 20) were determined using luminex assay. Flow cytometric assays were carried out in 20 CAM cases and 10 controls for determination of frequency of NK cells, DCs, phagocytes, T cells and their functionalities. The cytokine levels were analyzed for their association with each other as well as with T cell functionality. The immune parameters were also analyzed with respect to the known risk factors such as diabetes mellitus and steroid treatment. RESULTS: Significant reduction in frequencies of total and CD56 + CD16 + NK cells (cytotoxic subset) was noted in CAM cases. Degranulation responses indicative of cytotoxicity of T cell were significantly hampered in CAM cases as compared to the controls. Conversely, phagocytic functions showed no difference in CAM cases versus their controls except for migratory potential which was found to be enhanced in CAM cases. Levels of proinflammatory cytokines such as IFN-γ, IL-2, TNF-α, IL-17, IL-1ß, IL-18 and MCP-1 were significantly elevated in cases as compared to the control with IFN-γ and IL-18 levels correlating negatively with CD4 T cell cytotoxicity. Steroid administration was associated with higher frequency of CD56 + CD16- NK cells (cytokine producing subset) and higher MCP-1 levels. Whereas diabetic participants had higher phagocytic and chemotactic potential and had higher levels of IL-6, IL-17 and MCP-1. CONCLUSION: CAM cases differed from the controls in terms of higher titers of proinflammatory cytokines, reduced frequency of total and cytotoxic CD56 + CD16 + NK cell. They also had reduced T cell cytotoxicity correlating inversely with IFN-γ and IL-18 levels, possibly indicating induction of negative feedback mechanisms while diabetes mellitus or steroid administration did not affect the responses negatively.

Antibody profile in post-vaccinated & SARS-CoV-2 infected individuals.

Background & objectives: During the COVID-19 pandemic it was important to assess the antibody profile in individuals vaccinated with Covaxin (BBV152) and Covishield (ChAdOx1 nCoV-19) with both 28 and 84 days gaps between two doses, those infected with SARS-CoV-2 and post-COVID-19-infected individuals vaccinated with only one dose of either of the vaccines. The present study was aimed to assess these objectives. Methods: Fifty real time reverse transcription-polymerase chain reaction (qRT-PCR)-confirmed COVID-19-infected individuals, along with 90 COVID-19-naïve (BBV152 and ChAdOx1 nCov-19)-vaccinated individuals, were included in the study. Individuals who received a single dose of either vaccine with a confirmed past diagnosis of SARS-CoV-2 infection (n=15) were also included. Blood samples were collected strictly between the 4th and 5th wk after development of symptoms for SARS-CoV-2 infected individuals and after the first/second vaccination dose. Antibody profile assessment was done using whole-virus, spike-receptor binding domain (RBD) and nucleocapsid-specific ELISA kits along with neutralizing antibody kit. Results: There was an overall 97.7 per cent seropositivity rate in vaccinated individuals, and a strong correlation (R2=0.8, P<0.001) between neutralizing and spike-RBD antibodies. Among individuals who received two standard doses of ChAdOx1 nCoV-19 vaccine, the spike antibody levels developed were of higher titre with a longer prime boost interval than in those with shorter intervals (P<0.01). Individuals vaccinated with two doses as well as only one dose post-SARS-CoV-2 infection had high neutralizing and spike-specific antibodies. Interpretation & conclusions: High neutralizing and spike-specific antibodies were developed in individuals vaccinated only with one dose of either vaccine post-SARS-CoV-2 infection. With the main priority being vaccinating majority of the population in our country, single-dose administration to such individuals would be a sensible way to make the most of the limited supplies. Furthermore, neutralizing antibody levels observed in COVID-19-naïve vaccinees imply the need for booster vaccination.

Perturbations of immune landscape in COVID-19 associated mucormycosis.

BACKGROUND: A rise in secondary fungal infections during the COVID-19 pandemic necessitates a deeper understanding of the associated immunological perturbations. OBJECTIVES: To evaluate the clinical and immunological characteristics observed in patients with COVID-19 associated mucormycosis (CAM) infection. PATIENTS/ METHODS: Cases of mucormycosis with or post-COVID-19 infection were compared with cases of acute COVID-19 and convalescent COVID-19. Lymphocyte subsets, cytokines and other laboratory markers were compared between the groups. RESULTS: The frequency of proposed risk factors for CAM was diabetes mellitus (77%), recent history of steroid use (69%) and hypoxia during COVID-19 infection (52%). Iron metabolism was dysregulated in CAM patients with low TIBC and total iron. Further, CAM was accompanied with lymphopenia with drastic reduction in B cell counts; however, plasmablasts were not altered. Further, CAM patients had low immunoglobulin levels and antibodies specific to mucor peptide did not increase in CAM suggesting dysfunction in B-cell response. There was increase in activated effector cytotoxic CD8 T cells and NK cells in CAM compared with COVID-19 infection and healthy controls. Among T helper cells, Tregs were reduced and Th-1 frequency was increased in CAM compared with COVID-19 infection. A distinct cytokine signature was evident in CAM with increase in IL-1ß, IFN-γ, IL-6, IL-22, IL-17A, IL-10, IL-2, IL-8, IL-7, IL-21 and GM-CSF. CONCLUSION: This is the first study on immunophenotyping in CAM suggesting the need for long-term monitoring of B-cell function after SARS-CoV-2 in patients with dysregulated glycaemic control and the possible benefit of therapeutic supplementation with intravenous immunoglobulins in CAM.

Comparative study of clinical features and vaccination status in Omicron and non-Omicron infected patients during the third wave in Mumbai, India.

Objectives: The Omicron variant-mediated COVID-19 wave is responsible for a global tsunami of cases. There is scarce data about the clinical and epidemiological characteristic analyses of the third wave. We present the data of COVID-19 patients from Mumbai region during the early third wave by taking S-gene target failure (SGTF) as a proxy for probable Omicron cases. Methods: We collected retrospective data of RT-PCR-confirmed (COVID-19) patients, and measured the proportion of possible Omicron cases by SGTF. We segregated and analyzed the clinical and lab data of patients with outcomes such as differing symptoms, vaccination coverage, previous infection, and travel history. We also performed a trend analysis of Mumbai's COVID-19 data before and during the third wave. Results: All patients had mild clinical symptoms while few were asymptomatic. Myalgia was more significantly present in SGTF/Omicron cases compared to non-SGTF/Delta patients. Out of the total 101 COVID-positive individuals, 94 individuals (93%) had taken two doses of COVID vaccine. Among these 94 individuals, 9 (8.9%) had been previously infected with COVID 19 in the first or second waves. 77.7% of the previously infected were now infected with Omicron variant and only 22.3% by a non-Omicron variant. Conclusion: Rapid rise and fall during the third wave in Mumbai was due to Omicron cases gradually replacing Delta. The overall milder clinical spectrum in both Omicron and Delta cases imply that vaccines might not be effective against re-infection but can attenuate disease severity and mortality, as evident by high coverage of vaccination in the country.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Serosurvey for Health-Care Workers Provides Supportive Evidence for the Effectiveness of Hydroxychloroquine Prophylaxis against SARS-CoV-2 Infection.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has resulted in occupational exposure among Healthcare Workers (HCWs) and a high risk of nosocomial transmission. Asymptomatic infection and transmission of infection before the development of symptoms are well-recognized factors contributing to the spread of infection. We conducted a cross-sectional observational study to understand the seroprevalence of SARS-CoV-2 infection among HCWs and to verify the appropriateness of infection control measures, particularly Hydroxychloroquine (HCQ) prophylaxis. METHODS: A cross-sectional sero-surveillance study was conducted among 500 HCWs in Dombivli and surrounding Mumbai Metropolitan area (Maharashtra, India) between 21st July and 3rd August 2020. The vulnerability of the study participants to SARS-CoV-2 infection was ascertained through a history of (i) involvement in direct care, (ii) exposure to aerosol-generating procedures, (iii) co-morbidities, (iv) Personal Protective Equipment (PPE) use, and (v) HCQ prophylaxis. SARS-CoV-2 IgG antibodies were tested using COVID KAVACH anti-SARS-CoV-2 IgG antibody detection enzyme-linked immunosorbent assay (ELISA) from Zydus Cadila. A systematic analysis of the correlation between the development of antibodies and factors affecting vulnerability to infection was performed. RESULTS: The overall SARS-CoV-2 seroprevalence in the study population was 11%. Providing direct care to COVID-19 patients (Adjusted OR 16.4, 95% CI 3.3-126.9, p = 0.002) for long hours and irregular use of PPE (Adjusted OR 3.78, 95% CI 1.1-11.9, p = 0.02) were associated with an increased incidence of seropositivity. Prophylaxis with HCQ may have a role in reducing the vulnerability to infection as depicted by univariate and multivariate analysis (Adjusted OR 0.55, 95% CI 0.3-0.9, p = 0.047). It was also noted that those not on HCQ prophylaxis were threefold more prone to infection and developed severe disease as compared to those on HCQ prophylaxis. CONCLUSION: Prophylaxis with HCQ may have a role in mitigating the incidence and severity of SARS-CoV-2 infection. Although vaccination is the most robust strategy to safeguard against COVID-19, it will be months before vaccination percolates to the masses. In the face of the second wave of COVID-19, the use of HCQ prophylaxis in combination with use of face-masks regularly may be considered as a cost-effective measure for population dense areas like urban slums where social distancing is not possible.