Cancer care continuum at a tertiary care centre in India during the Covid-19 pandemic and nationwide lockdown: Healthcare delivery through telemedicine.

Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

Genomic Analysis of AZD1222 (ChAdOx1) Vaccine Breakthrough Infections in the City of Mumbai

Background This manuscript describes the genetic features of SARS-CoV-2 mutations, prevalent phylogenetic lineages, and the disease severity amongst COVID-19-vaccinated individuals in a tertiary cancer hospital during the second wave of the pandemic in Mumbai, India. Methods This observational study included 159 COVID-19 patients during the second wave of the pandemic from 17th March to 1st June 2021 at a tertiary cancer care centre in Mumbai. The cohort comprised of healthcare workers, staff relatives, cancer patients, and patient relatives. For comparison, 700 SARS-CoV-2 genomes sequenced during the first wave (23rd April to 25th September 2020) at the same centre were also analysed. Patients were assigned to nonvaccinated (no vaccination or <14 days from the 1st dose, n = 92), dose 1(≥14 days from the 1st dose to <14 days from the 2nd dose, n = 29), and dose 2 (≥14 days from the 2nd dose, n = 38) groups. Primary measure was the prevalence of SARS-CoV-2 genomic lineages among different groups. In addition, severity of COVID-19 was assessed according to clinical and genomic variables. Results Kappa B.1.1671.1 and delta B.1.617.2 variants contributed to an overwhelming majority of sequenced genomes (unvaccinated: 40/92, 43.5% kappa, 46/92, 50% delta;dose 1: 14/29, 48.3% kappa, 15/29, 51.7% delta;and dose 2: 23/38, 60.5% kappa, 14/38 36.8% delta). The proportion of the kappa and delta variants did not differ significantly across the unvaccinated, dose 1, and dose 2 groups (p = 0.27). There was no occurrence of severe COVID-19 in the dose 2 group (0/38, 0% vs. 14/121, 11.6%;p = 0.02). SARS-CoV-2 genomes from all three severe COVID-19 patients in the vaccinated group belonged to the delta lineage (3/28, 10.7% vs. 0/39, 0.0%, p = 0.04). Conclusions Sequencing analysis of SARS-COV-2 genomes from Mumbai during the second wave of COVID-19 suggests the prevalence of the kappa B.1.617.1 and the delta B.1.627.2 variants among both vaccinated and unvaccinated individuals. Continued evaluation of genomic sequencing data from breakthrough COVID-19 is necessary for monitoring the properties of evolving variants of concern and formulating appropriate immune response boosting and therapeutic strategies.

SARS-CoV-2 reinfection after previous infection and vaccine breakthrough infection through the second wave of pandemic in India: An observational study.

BACKGROUND: There are sparse longitudinal data on SARS-CoV-2 infection after previous infection and after partial or full vaccination. METHODS: This study of a cohort of healthcare workers used Kaplan-Meier analysis with appropriate definition of events and censoring and used Cox models to assess outcomes, with data cut-off on June 18, 2021. RESULTS: A total of 1806 individuals with median age of 32 (18-64) years, 1483 (82.1%) with at least one vaccine dose, 1085 (60.1%) with 2 vaccine doses, 408 (22.6%) with at least one episode of SARS-CoV-2 infection, and 6 (1.47%) with 2 episodes of infection were included in the analysis. At median follow-up of 38.4 weeks after first SARS-CoV-2 infection (n=408), the 52-week probability of reinfection was 2.2% (95% CI, 1.0-4.91%); and at median follow-up of 13.3 weeks after second dose, the 16-week probability of breakthrough infection was 5.6% (95% CI, 4.33-7.23%), which was significantly higher among those without previous SARS-CoV-2 infection versus with previous infection (6.4% vs 1.8%, p=0.016, adjusted Cox HR=3.49, 95% CI, 1.09-11.20, p=0.036) and females versus males (7.9% vs 3.8%, p=0.007, adjusted Cox HR=2.06, 95% CI 1.19-3.56, p=0.01). CONCLUSIONS: There was low probability of reinfection after previous SARS-CoV-2 infection and higher vaccine breakthrough infections among females and those without previous infection.

Genomic Analysis of AZD1222 (ChAdOx1) Vaccine Breakthrough Infections in the City of Mumbai.

Background: This manuscript describes the genetic features of SARS-CoV-2 mutations, prevalent phylogenetic lineages, and the disease severity amongst COVID-19-vaccinated individuals in a tertiary cancer hospital during the second wave of the pandemic in Mumbai, India. Methods: This observational study included 159 COVID-19 patients during the second wave of the pandemic from 17th March to 1st June 2021 at a tertiary cancer care centre in Mumbai. The cohort comprised of healthcare workers, staff relatives, cancer patients, and patient relatives. For comparison, 700 SARS-CoV-2 genomes sequenced during the first wave (23rd April to 25th September 2020) at the same centre were also analysed. Patients were assigned to nonvaccinated (no vaccination or <14 days from the 1st dose, n = 92), dose 1(≥14 days from the 1st dose to <14 days from the 2nd dose, n = 29), and dose 2 (≥14 days from the 2nd dose, n = 38) groups. Primary measure was the prevalence of SARS-CoV-2 genomic lineages among different groups. In addition, severity of COVID-19 was assessed according to clinical and genomic variables. Results: Kappa B.1.1671.1 and delta B.1.617.2 variants contributed to an overwhelming majority of sequenced genomes (unvaccinated: 40/92, 43.5% kappa, 46/92, 50% delta; dose 1: 14/29, 48.3% kappa, 15/29, 51.7% delta; and dose 2: 23/38, 60.5% kappa, 14/38 36.8% delta). The proportion of the kappa and delta variants did not differ significantly across the unvaccinated, dose 1, and dose 2 groups (p = 0.27). There was no occurrence of severe COVID-19 in the dose 2 group (0/38, 0% vs. 14/121, 11.6%; p = 0.02). SARS-CoV-2 genomes from all three severe COVID-19 patients in the vaccinated group belonged to the delta lineage (3/28, 10.7% vs. 0/39, 0.0%, p = 0.04). Conclusions: Sequencing analysis of SARS-COV-2 genomes from Mumbai during the second wave of COVID-19 suggests the prevalence of the kappa B.1.617.1 and the delta B.1.627.2 variants among both vaccinated and unvaccinated individuals. Continued evaluation of genomic sequencing data from breakthrough COVID-19 is necessary for monitoring the properties of evolving variants of concern and formulating appropriate immune response boosting and therapeutic strategies.

Clinical characteristics, laboratory parameters and outcomes of COVID-19 in cancer and non-cancer patients from a tertiary Cancer Centre in India.

BACKGROUND: There is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India. MATERIALS AND METHODS: This was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients. RESULTS: A total of 200 COVID-19 infection episodes were analysed of which 109 (54.5%) were patients with cancer and 91 (45.5%) were patients without cancer. The median age was 43 (interquartile range [IQR]:32-57), 51 (IQR: 33-62) and 38 (IQR: 31.5-49.3) years; of whole cohort, cancer and non-cancer patients, respectively. Comparison of outcomes showed that oxygen requirement (31.2% [95% CI: 22.6-40.7] vs. 17.6% [95% CI: 10.4-26.9]; p = 0.03), median time to discharge (11 days [IQR: 6.75-16] vs. 6 days [IQR: 3-9.75]; p < 0.001) and mortality (10.0% [95% CI: 5.2-17.3] vs. 1.1% [95% CI: 0.03-5.9]; p = 0.017) were significantly higher in patients with cancer. In univariable analysis, factors associated with higher mortality in the whole cohort included diagnosis of cancer (10.1% vs. 1.1%; p = 0.027; odds ratio [OR]: 7.04), age ≥60 (17.4% vs. 2.6%; p = 0.001; OR: 7.38), oxygen requirement (22% vs. 0.6%; p < 0.001; OR: 29.01), chest infiltrates (19.2% vs. 1.4%; p < 0.001; OR: 22.65), baseline absolute lymphocyte count <1 × 109 /L (10.8% vs. 1.9%; p = 0.023; OR:5.1), C-reactive protein >1 mg% (12.8% vs. 0%; p = 0.027; OR: 24.69), serum procalcitonin >0.05 ng/ml (22.65% vs. 0%; p = 0.004; OR: 4.49) and interleukin-6 >6 pg/ml (10.8% vs. 1.3%; p = 0.036; OR: 3.08). In multivariable logistic regression, factors significantly associated with mortality were oxygen requirement (p = 0.005; OR: 13.11) and high baseline procalcitonin level (p = 0.014; OR: 37.6). CONCLUSION: Cancer patients with COVID-19 have higher mortality and require longer hospital stay. High procalcitonin levels and oxygen requirement during admission are other factors that affect outcomes adversely.

Comprehensive immune cell profiling depicts an early immune response associated with severe coronavirus disease 2019 in cancer patients.

Recent studies have highlighted multiple immune perturbations related to severe acute respiratory syndrome coronavirus 2 infection-associated respiratory disease [coronavirus disease 2019 (COVID-19)]. Some of them were associated with immunopathogenesis of severe COVID-19. However, reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities such as cancer are scarce. We prospectively studied about 200 immune response parameters, including a comprehensive immune-cell profile, inflammatory cytokines and other parameters, in 95 patients with COVID-19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized as having a nonsevere disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune responses in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DCs) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (Tregs ), type 1 T helper (Th1) and Th9; additionally, relative expansion of effector natural killer (NK) cells were significantly associated with severe COVID-19. Compared with patients without cancer, the levels of terminal effector CD4 T cells, Tregs , Th9, effector NK cells, B cells, intermediate-type monocytes and myeloid DCs were significantly lower in cancer patients with mild and severe COVID-19. We concluded that severely depleted circulating myeloid DCs and helper T subsets in the initial phase of infection were strongly associated with severe COVID-19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID-19 in cancer patients without intensive chemo/immunotherapy.

Dynamics of viral RNA load, virus culture, seroconversion & infectivity in COVID-19 patients: Implications on isolation policy.

The ongoing SARS-CoV-2 pandemic has spread all over the world due to rapid person-to-person transmission. More information about viral load dynamics and replication is needed for clarity on duration of infectiousness of an individual, along with its implications on transmission. This is important to healthcare facilities and public health authorities in formulating guidance on the duration of isolation for patients and return to work criteria for healthcare workers. The duration of detection of viral RNA by molecular methods in the upper respiratory tract has ranged from 2 to 12 wk. Viral RNA detection by reverse transcription polymerase chain reaction (RT-PCR) does not necessarily mean that the individual is infectious to others, as the detected virus may not be replication competent. Infectious virus is generally not shed beyond 20 days of the onset of symptoms in most patients, including severely ill and immunocompromised, as indicated by failure to isolate replication-competent virus beyond this timeline in available studies. Further, detection of neutralizing antibodies in the serum, although associated with positive RT-PCR, is generally not associated with infectious virus shedding as indicated by negative viral cultures beyond this period. In this review, we analyze the current literature on the dynamics of viral load, culture, seroconversion and their implications on infectivity and the duration of isolation precautions for COVID-19 patients.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is influenced by the type of transport medium: Implications for diagnosis and monitoring.

It is unclear if the use of a molecular transport medium (MTM) containing guanidine isothiocyanate (GITC) would be advantageous over the CDC recommended, commonly used viral transport medium (VTM). We retested 70 SARS-CoV2 cases by RT-PCR in varying stages of follow-up using MTM and VTM in parallel and found discrepant results of RNase P, E and N genes. Majority (81%) patients tested positive with MTM as compared with VTM (27.1%). Even patients who were sampled 3 weeks after diagnosis demonstrated a significant discrepancy in the positivity rates between MTM vs VTM raising concerns about the clinical utility of VTM.

Clinical course of severe COVID19 treated with tocilizumab and antivirals post-allogeneic stem cell transplant with extensive chronic GVHD.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.

COVID-19 in cancer patients on active systemic therapy - Outcomes from LMIC scenario with an emphasis on need for active treatment.

BACKGROUND: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). PATIENTS AND METHODS: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. RESULTS: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. CONCLUSIONS: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.

Particle removal from air by face masks made from Sterilization Wraps: Effectiveness and Reusability.

Wearing face masks is highly recommended to prevent SARS-CoV-2 transmission in health care workers and for the general public. The demand for high quality face masks has seen an upsurge in the recent times, leading to exploration of alternative economic and easily available options, without compromising on the quality. Particle removal from air in terms of capture efficiency of the filter media or the face mask is a crucial parameter for testing and quality assurance. Short-term reusability of the face masks is also an important aspect as the demand for masks will potentially outstrip the supply in future. Sterilization Wraps, which are used to wrap sterile surgical instruments, have shown a promising performance in terms of removal of particles from air. In this study, we evaluate the particle filtration characteristics of face masks made of 2 different metric weights [45 and 60 gram per square metre (GSM)] respectively, using locally available Sterilization Wraps. The aerosol filtration characteristics were also studied after sterilisation by different techniques such as heat with 50% humidity (thermal treatment), ethylene oxide (ETO), steam and radiation dose of 30kGy. We found that 60 GSM face mask had particle capture efficiency of 94% for total particles greater than 0.3 microns and this capture efficiency was maintained even after sterilisation with ETO and thermal treatment. The cost of producing these masks was 30 US cents/mask at our institute. Our study suggests that sterilization wrap material made of non-woven polypropylene spunbond-meltblown-spunbond (SMS) fibres could be an appropriate readily available inexpensive material for making face masks or N95 respirators.

Laboratory biosafety issues related to coronavirus disease 2019

Indroduction: The outbreak of Novel Coronavirus Pneumonia SARS-CoV-2 has necessitated the reinforcement of infection control measures in the hospital and laboratory setting. Contact and droplet infection control measures are advised for handling patients diagnosed with COVID-19 and airborne precautions for procedures that generate aerosols. Pre-ananalytical Phase: Risk assessment is conducted for all steps of laboratory processes viz. preanalytical, analytical and postanalytical. Standard Precautions must be followed at all times when laboratory staff handle clinical specimens that may contain infectious microorganism. Standard precautions must include hand hygiene along with the use of personal protective equipment (PPE). All samples are collected in appropriate containers and all containers are decontaminated by 62-71% ethanol (alcohol) before transporting them to the laboratory in triple packaging. Analytical Phase: All samples should undergo initial processing in a biosafety cabinet (BSC). It should be ensured while undertaking all technical procedures that there is minimal formation of aerosols and droplets. Post-analytical Phase: All biomedical waste should be disposed as per state and national guidelines. Decontamination includes use of 1% sodium hypochlorite, 62-71% ethanol for surface disinfection or Hydrogen peroxide (0.5%). Conclusion: These laboratory biosafety measures are important to minimise the risk of laboratory transmission of COVID-19 to health care workers.

Mandatory preoperative COVID-19 testing for cancer patients-Is it justified?

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has caused substantial disruptions in routine clinical care. Emerging data show that surgery in coronavirus disease (COVID)-positive cases can be associated with worsening of clinical outcomes and increased postoperative mortality. Hence, preoperative COVID-19 testing for all patients before elective surgery was implemented in our institution. MATERIALS AND METHODS: Two hundred and sixty-two asymptomatic cancer patients were preoperatively tested for COVID-19 using reverse-transcription polymerase chain reaction technique with nasopharyngeal and oropharyngeal swabbing. All negative patients were operated within 72 hours, and positive patients were quarantined for a minimum 14 days before re-swabbing. RESULTS: In our cohort, 21 of 262 (8.0%) asymptomatic preoperative patients, who were otherwise fit for surgery, tested positive. After adequate quarantine and a negative follow-up test report, 12 of 21 (57%) had an operation. No major postoperative morbidity due to COVID-19 was noted during the immediate postoperative period before discharge from the hospital. CONCLUSION: Routine preoperative COVID-19 testing was successful in identifying asymptomatic viral carriers. There was no incidence of symptomatic COVID-19 disease in the postoperative period, and there was no incidence of morbidity attributable to COVID-19. These data suggested a beneficial role for mandatory preoperative COVID-19 testing.