Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

The contribution of dynamics to macaque body and face patch responses.

Previous functional imaging studies demonstrated body-selective patches in the primate visual temporal cortex, comparing activations to static bodies and static images of other categories. However, the use of static instead of dynamic displays of moving bodies may have underestimated the extent of the body patch network. Indeed, body dynamics provide information about action and emotion and may be processed in patches not activated by static images. Thus, to map with fMRI the full extent of the macaque body patch system in the visual temporal cortex, we employed dynamic displays of natural-acting monkey bodies, dynamic monkey faces, objects, and scrambled versions of these videos, all presented during fixation. We found nine body patches in the visual temporal cortex, starting posteriorly in the superior temporal sulcus (STS) and ending anteriorly in the temporal pole. Unlike for static images, body patches were present consistently in both the lower and upper banks of the STS. Overall, body patches showed a higher activation by dynamic displays than by matched static images, which, for identical stimulus displays, was less the case for the neighboring face patches. These data provide the groundwork for future single-unit recording studies to reveal the spatiotemporal features the neurons of these body patches encode. These fMRI findings suggest that dynamics have a stronger contribution to population responses in body than face patches.

Remarkably Corrosion Resistant Graphene Coating on Steel Enabled Through Metallurgical Tailoring.

Graphene coatings developed by chemical vapor deposition (CVD) that possess extraordinary/unique characteristics as barrier against aggressive environment can improve the corrosion resistance of Ni and Cu by up to two orders of magnitude. However, because of some compelling technical reasons, it has thus far been a nontrivial challenge to develop graphene coatings on the most commonly used engineering alloy, mild steel (MS). To circumvent the challenge simply by first electroplating MS with a Ni layer is attempted, and then developing CVD graphene over the Ni layer. However, this approach proved too simplistic and does not work. This necessitated an innovative surface modification of MS (based on basic metallurgical principles) that enabled successful CVD of graphene coating on MS. The graphene coating thus developed is demonstrated to improve the corrosion resistance of mild steel by two orders of magnitude in an aggressive chloride solution, through electrochemical testing. This improvement was not only sustained for the entire test duration of >1000 h; but there is a clear trend for the resistance to be possibly everlasting. The optimized surface modification that enabled development of CVD graphene coating on mild steel is generic in nature, and it should enable graphene coating on other alloy systems, which would otherwise not be possible.

Graphene-Coated Ni-Cu Alloys for Durable Degradation Resistance of Bi-Polar Plates for Proton Exchange Membrane Fuel Cells: Remarkable Role of Alloy Composition.

Bipolar plates, a critical component of proton exchange membrane fuel cell (PEMFC), are constructed out of alloys of Ti, Pt, Cr, or graphitic materials that have limitations. Electrical conductivity, cost, and corrosion resistance are among the critical considerations for bi-polar plate material. Graphene, which possesses impressive conductivity and toughness, is an attractive option as coating on metallic substrates of PEMFC bipolar plates. This study investigates corrosion resistance and its durability due to graphene developed by chemical vapor deposition on a pure Ni-Cu alloy and a commercial Ni-Cu alloy in 0.5 m H2 SO4 environment, with a view to exploring use of graphene coated Ni-Cu alloys for the construction of PEMFC bipolar plates. The graphene coating on the pure alloy shows remarkably superior corrosion resistance than the commercial alloy that is attributed to the former's ability to develop considerably defect-free graphene.

A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in Coronavirus Disease 2019 Patients With Regular Intravenous Immunoglobulin Therapy.

BACKGROUND: Currently, there is no specific drug for the treatment of coronavirus disease 2019 (COVID-19). Therapeutic benefits of intravenous immunoglobulin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. METHODS: An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. One hundred eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. RESULTS: Duration of hospital stay was significantly shorter in the IVIG group compared with that of SOC alone (7.7 vs 17.5 days). Duration for normalization of body temperature, oxygen saturation, and mechanical ventilation were significantly shorter in IVIG compared with SOC. Percentages of patients on mechanical ventilation in 2 groups were not significantly different (24% vs 38%). Median time to reverse-transcription polymerase chain reaction negativity was significantly shorter with IVIG than SOC (7 vs 18 days). There were only mild to moderate adverse events in both groups except for 1 patient (2%), who died in SOC. CONCLUSIONS: Intravenous immunoglobulin was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19.

A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

BACKGROUND: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. METHODS: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. RESULTS: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. CONCLUSION: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.

Role of temperature and co-infection in mediating the immune response of goldfish.

Aquatic Pathogens are expected to encounter tremendous levels of variation in their environment - both abiotic and biotic. Here we examined the change in innate immune parameters and mortality pattern of Carassius auratus during the interaction of co-infection due to an ectoparasite, Argulus and bacteria Aeromonas hydrophila, along with a temperature gradient. Experimental fish were assigned randomly to six treatment groups (T1-T6). Fish of groups T1, T3 and T5 are assigned for healthy fishes kept at 23, 28 and 33°c temperature and served as control. T2, T4 and T6 groups are the co-infected groups kept at temperature gradient. For the haematological and enzyme parameter analysis, sampling was done at 24 h, 72 h and 168 h post challenge from 4 fish in all experimental groups. A temperature dependent increase in intensity of Argulus was observed in the experimental group. Both in control group and co-infected group a temperature dependent mortality pattern was observed, showing an increased mortality of 60% in T6 and 20% in T5 group. A significant decrease of RBC, Hb, and PCV values was observed in co-infected group when compared with control fish in each of the experimental group. Also a temperature dependent increase in WBC, neutrophil and monocyte value was observed in control fish. Whereas, a significant reduction in WBC, neutrophil and monocyte was observed in co-infected fish exposed to 33 °C during the progression of infection. Furthermore, T4 group showed a significantly higher Nitroblue tetrazolium test, Myelo peroxidase and lyzozyme activity compared to other co-infection group. A significantly increased activity of Superoxide dismutase, Glutathione peroxidise and catalase activity was recorded in control fish exposed to 33 °C (T5) whereas, there was no significant difference observed in the activity of catalase and Glutathione peroxidise in the other control fish (T1 and T3 group). This result implies that increase in temperature not only accelerates the intensity of co-infection but also imbalance the health status of the fish by hampering the immunological and physiological parameters towards more detrimental side.

Dose-dependent co-infection of Argulus sp. and Aeromonas hydrophila in goldfish (Carassius auratus) modulates innate immune response and antioxidative stress enzymes.

Co-infection with parasites and bacteria is of frequent occurrence in aquaculture, leads to growth impedance otherwise mortality in fish depending on the varying degree of a load of primary pathogen either parasite or bacteria. The mechanistic regulation of immune response during co-infection in fish has merely documented. The aim of this study was to determine the impact of co-infection with Aeromonas hydrophila at three exposure doses of Argulus sp. on the innate immune responses and antioxidative stress enzymes of goldfish (Carassius auratus). The experimental fish were randomly distributed into eight treatment groups viz. T1 (control group without Argulus and A. hydrophila infection), T2 (fish exposed to a sub-lethal dose of A. hydrophila), T3 (low Argulus-infested fish), T4 (T3 + sub-lethal dose of A. hydrophila), T5 (moderate Argulus-infested fish), T6 (T5 + sub-lethal dose of A. hydrophila), T7 (high Argulus-infested fish) and T8 (T7+ sub-lethal dose of A. hydrophila) in duplicates. After distributing experimental fish into their respective treatment group, A. hydrophila was injected to T2, T4, T6 and T8. After the bacterial challenge, four fish from each experimental group were randomly sampled on 24, 72, and 168 h and subjected to the hematological, innate immune parameters and enzymatic analysis. In the co-infection group T8, a high degree of enhanced pathogenicity of A. hydrophila was noticed with increased mortalities (84.2%) in comparison to other groups. The current study shows a declining pattern in RBC, PCV and Hb values with the degree of parasite infestation without co-infection groups. Moreover, in the T8 group, exposure of a sub-lethal dose of bacteria resulted in a drastic reduction of the recorded parameters. Furthermore, a decreased value for WBC, monocyte and neutrophil was found in higher parasite group co-infected with a sub-lethal dose of bacteria relative to other co-infected groups during the experimental period. Also, a decrease in innate immune parameters and antioxidative stress enzymes were observed in the T8 group compared to T7 and T2 groups throughout the trial period. These findings indicate that a rise in the dose of Argulus infection improves A. hydrophila colonization in goldfish and contributes to suppression of the innate immune system and increased mortality.

Completeness and quality of text paging for subspecialty consult requests.

It is unclear whether previously developed frameworks for effective consultation apply to requests initiated by alphanumeric text page. We assessed a random sample of 210 text paged consult requests for communication of previously described 'essential elements' for effective consultation: reason for consult, level of urgency and requester contact information. Overall page quality was evaluated on a 5-point Likert scale. Over 90% of text paged consult requests included contact information and reason for consult; 14% indicated level of urgency. In ordinal logistic regression, reason for consult was most strongly associated with quality (OR 22.4; 95% CI 8.1 to 61.7), followed by callback number (OR 6.2; 95% CI 0.8 to 49.5), caller's name (OR 5.0; 95% CI 1.9 to 13.1) and level of urgency (OR 3.3; 95% CI 1.6 to 6.7). Results suggest that text paged consult requests often include most informational elements, and that urgency, often missing, may not be as 'essential' for text pages as it was once thought to be.

Role of Surface Preparation in Corrosion Resistance Due to Silane Coatings on a Magnesium Alloy.

Coating of an organo-silane (Bis-1,2-(TriethoxySilyl)Ethane (BTSE)) has been observed to improve the corrosion resistance of magnesium alloy AZ91D. Three different types of surface preparations have been employed before condensing the silane coating on to the substrate. Corrosion resistance was investigated using electrochemical impedance spectroscopy (EIS). A specific alkali treatment of the substrate prior to the coating has been found to improve the corrosion resistance of the coated alloy, which has been attributed to the ability of the treatment in facilitating the condensation of a relatively compact siloxane film.

Metal contaminations in sediment and associated ecological risk assessment of river Mahanadi, India.

Mahanadi is one of the major rivers of peninsular India. Like other Indian rivers, it is contaminated with sewages, industrial discharges, and agricultural runoff. Thus, necessity was felt to monitor its pollution status. Present work was part of that program and aimed to assess the sediment contamination due to the trace metals Cd, Cr, Cu, Mn, Pb, and Zn during 2012-2015. Sediment pollution status and ecological risks were evaluated calculating contamination factor (CF), geo-accumulation (Igeo), pollution load index (PLI), potential ecological risk (EiR), etc. The recorded metal concentrations were Cd BDL of flame mode of AAS; Cr BDL - 73.9; Cu BDL - 44.4; Mn 37.2 - 1887.0; Pb BDL - 29.5; and Zn BDL - 92.5 mg kg-1. As per US EPA guidelines, Cr concentrations at many locations were in the moderately polluted range. Igeo, CF, mCd, PLI, and EiR indicated low pollution levels and low ecological risks due to the trace metals assessed. The sediment quality guidelines (SQGs) indicated that Cr and Cu concentrations exceeded (16% sample) the threshold effect concentrations and may occasionally exhibit adverse biological effects. The association of sediment organic matter, conductivity and content of Cu, and their grouping in component 1 of PCA revealed that the anthropogenic input was dominant and so also the component 2 where Cr exhibited moderately good correlation with organic matter. Cluster analysis of the sampling sites based on pollution status yielded 3 groups: relatively uncontaminated (S3, S4), low to moderately contaminated (S2), and moderately contaminated (S1, S5, S6) stretches.

Modulation of fear behavior and neuroimmune alterations in house dust mite exposed A/J mice, a model of severe asthma.

Fear-associated conditions such as posttraumatic stress disorder (PTSD) and panic disorder (PD) are highly prevalent. There is considerable interest in understanding contributory risk and vulnerability factors. Accumulating evidence suggests that chronically elevated inflammatory load may be a potential risk factor for these disorders. In this regard, an association of asthma, a chronic inflammatory condition, with PTSD and PD has been reported. Symptoms of PD and PTSD are more prevalent in severe asthmatics, compared to those with mild or moderate asthma suggesting that factors that influence the severity of asthma, may also influence susceptibility to the development of fear-related disorders. There has been relatively little progress in identifying contributory factors and underlying mechanisms, particularly, the translation of severe asthma-associated lung inflammation to central neuroimmune alterations and behavioral manifestations remains unclear. The current study investigated the expression of behaviors relevant to PD and PTSD (CO2 inhalation and fear conditioning/extinction) in A/J mice using a model of severe allergic asthma associated with a mixed T helper 2 (Th2) and Th17 immune response. We also investigated the accumulation of Th2- and Th17-cytokine expressing cells in lung and brain tissue, microglial alterations, as well as neuronal activation marker, delta FosB (ΔFosB)) in fear and panic regulatory brain areas. HDM-exposed mice elicited higher freezing during fear extinction. CO2-associated spontaneous and conditioned freezing, as well as anxiety or depression-relevant exploratory and coping behaviors were not altered by HDM treatment. A significant increase in brain Th17-associated inflammatory mediators was observed prior to behavioral testing, accompanied by microglial alterations in specialized blood brain barrier-compromised circumventricular area, subfornical organ. Post extinction measurements revealed increased ΔFosB staining within the medial prefrontal cortex and basolateral amygdala in HDM-treated mice. Collectively, our data show modulation of brain immune mechanisms and fear circuits by peripheral airway inflammation, and is relevant to understanding the risk and comorbidity of asthma with fear-associated disorders such as PTSD.

Experiential learnings from the Nipah virus outbreaks in Kerala towards containment of infectious public health emergencies in India.

Nipah virus (NiV) outbreak occurred in Kozhikode district, Kerala, India in 2018 with a case fatality rate of 91% (21/23). In 2019, a single case with full recovery occurred in Ernakulam district. We described the response and control measures by the Indian Council of Medical Research and Kerala State Government for the 2019 NiV outbreak. The establishment of Point of Care assays and monoclonal antibodies administration facility for early diagnosis, response and treatment, intensified contact tracing activities, bio-risk management and hospital infection control training of healthcare workers contributed to effective control and containment of NiV outbreak in Ernakulam.

Perspectives for repurposing drugs for the coronavirus disease 2019.

The newly emerged 2019 novel coronavirus (CoV), named as severe acute respiratory syndrome CoV-2 (SARS-CoV-2), like SARS-CoV (now, SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV), has been associated with high infection rates with over 36,405 deaths. In the absence of approved marketed drugs against coronaviruses, the treatment and management of this novel CoV disease (COVID-19) worldwide is a challenge. Drug repurposing that has emerged as an effective drug discovery approach from earlier approved drugs could reduce the time and cost compared to de novo drug discovery. Direct virus-targeted antiviral agents target specific nucleic acid or proteins of the virus while host-based antivirals target either the host innate immune responses or the cellular machineries that are crucial for viral infection. Both the approaches necessarily interfere with viral pathogenesis. Here we summarize the present status of both virus-based and host-based drug repurposing perspectives for coronaviruses in general and the SARS-CoV-2 in particular.

Strategic planning to augment the testing capacity for COVID-19 in India.

Background & objectives: Nearly 5,500 tests for coronavirus disease 2019 (COVID-19) had been conducted on March 31, 2020 across the Indian Council of Medical Research (ICMR)-approved public and private laboratories in India. Given the need to rapidly increase testing coverage, we undertook an exercise to explore and quantify interventions to increase the daily real-time reverse transcription-polymerase chain reaction (qRT-PCR)-based testing capacity over the next few months. The objective of this exercise was to prepare a potential plan to scale-up COVID-19 testing in India in the public sector. Methods: Potential increase in daily testing capacity of the existing public laboratories was calculated across the three base scenarios of shifts (9, 16 and 24 h). Additional testing capacity was added for each shift scenario based on interventions ranging from procurement of additional qRT-PCR machines, leveraging spare capacity on available qRT-PCR machines not drafted into COVID-19 testing, to in-laboratory process optimization efforts. Results: Moving to a 24 h working model in the existing approved laboratories can enhance the daily testing capacity to 40,464 tests/day. The capacity can be further bolstered by leveraging qRT-PCR and nucleic acid amplification test (NAAT)-based machines available with the Multidisciplinary Research Units (MRUs), National AIDS Control Organisation (NACO) and National Tuberculosis Elimination Programme (NTEP). Using combination/multiplex kits, and provision of automated RNA extraction platforms at all laboratories could also optimize run time and contribute to capacity increase by 1.5-2 times. Interpretation & conclusions: Adopting these interventions could help increase public sector's daily testing capacity to nearly 100,000-120,000 tests/day. It is important to note that utilization of the scaled-up testing capacity will require deployment of additional workforce, procurement of corresponding commodities for testing and scale-up of sample collection and transportation efforts.

The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence.

A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.

Prudent public health intervention strategies to control the coronavirus disease 2019 transmission in India: A mathematical model-based approach.

Background & objectives: Coronavirus disease 2019 (COVID-19) has raised urgent questions about containment and mitigation, particularly in countries where the virus has not yet established human-to-human transmission. The objectives of this study were to find out if it was possible to prevent, or delay, the local outbreaks of COVID-19 through restrictions on travel from abroad and if the virus has already established in-country transmission, to what extent would its impact be mitigated through quarantine of symptomatic patients? Methods: These questions were addressed in the context of India, using simple mathematical models of infectious disease transmission. While there remained important uncertainties in the natural history of COVID-19, using hypothetical epidemic curves, some key findings were illustrated that appeared insensitive to model assumptions, as well as highlighting critical data gaps. Results: It was assumed that symptomatic quarantine would identify and quarantine 50 per cent of symptomatic individuals within three days of developing symptoms. In an optimistic scenario of the basic reproduction number (R0) being 1.5, and asymptomatic infections lacking any infectiousness, such measures would reduce the cumulative incidence by 62 per cent. In the pessimistic scenario of R0=4, and asymptomatic infections being half as infectious as symptomatic, this projected impact falls to two per cent. Interpretation & conclusions: Port-of-entry-based entry screening of travellers with suggestive clinical features and from COVID-19-affected countries, would achieve modest delays in the introduction of the virus into the community. Acting alone, however, such measures would be insufficient to delay the outbreak by weeks or longer. Once the virus establishes transmission within the community, quarantine of symptomatics may have a meaningful impact on disease burden. Model projections are subject to substantial uncertainty and can be further refined as more is understood about the natural history of infection of this novel virus. As a public health measure, health system and community preparedness would be critical to control any impending spread of COVID-19 in the country.

Severe acute respiratory illness surveillance for coronavirus disease 2019, India, 2020.

Background & objectives: Sentinel surveillance among severe acute respiratory illness (SARI) patients can help identify the spread and extent of transmission of coronavirus disease 2019 (COVID-19). SARI surveillance was initiated in the early phase of the COVID-19 outbreak in India. We describe here the positivity for COVID-19 among SARI patients and their characteristics. Methods: SARI patients admitted at 41 sentinel sites from February 15, 2020 onwards were tested for COVID-19 by real-time reverse transcription-polymerase chain reaction, targeting E and RdRp genes of SARS-CoV-2. Data were extracted from Virus Research and Diagnostic Laboratory Network for analysis. Results: A total of 104 (1.8%) of the 5,911 SARI patients tested were positive for COVID-19. These cases were reported from 52 districts in 20 States/Union Territories. The COVID-19 positivity was higher among males and patients aged above 50 years. In all, 40 (39.2%) COVID-19 cases did not report any history of contact with a known case or international travel. Interpretation & conclusions: COVID-19 containment activities need to be targeted in districts reporting COVID-19 cases among SARI patients. Intensifying sentinel surveillance for COVID-19 among SARI patients may be an efficient tool to effectively use resources towards containment and mitigation efforts.

Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19.

BACKGROUND & OBJECTIVES: Healthcare workers (HCWs) are at an elevated risk of contracting COVID-19. While intense occupational exposure associated with aerosol-generating procedures underlines the necessity of using personal protective equipment (PPE) by HCWs, high-transmission efficiency of the causative agent [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] could also lead to infections beyond such settings. Hydroxychloroquine (HCQ), a repurposed antimalarial drug, was empirically recommended as prophylaxis by the National COVID-19 Task Force in India to cover such added risk. Against this background, the current investigation was carried out to identify the factors associated with SARS-CoV-2 infection among HCWs in the country. METHODS: A case-control design was adopted and participants were randomly drawn from the countrywide COVID-19 testing data portal maintained by the ICMR. The test results and contact details of HCWs, diagnosed as positive (cases) or negative (controls) for SARS-CoV-2 using real-time reverse transcription-polymerase chain reaction (qRT-PCR), were available from this database. A 20-item brief-questionnaire elicited information on place of work, procedures conducted and use of PPE. RESULTS: Compared to controls, cases were slightly older (34.7 vs. 33.5 yr) and had more males (58 vs. 50%). In multivariate analyses, HCWs performing endotracheal intubation had higher odds of being SARS-CoV-2 infected [adjusted odds ratio (AOR): 4.33, 95% confidence interval (CI): 1.16-16.07]. Consumption of four or more maintenance doses of HCQ was associated with a significant decline in the odds of getting infected (AOR: 0.44; 95% CI: 0.22-0.88); a dose-response relationship existed between frequency of exposure to HCQ and such reductions (χ[2] for trend=48.88; P <0.001). In addition, the use of PPE was independently associated with the reduction in odds of getting infected with SARS-CoV-2. INTERPRETATIONS & CONCLUSIONS: Until results of clinical trials for HCQ prophylaxis become available, this study provides actionable information for policymakers to protect HCWs at the forefront of COVID-19 response. The public health message of sustained intake of HCQ prophylaxis as well as appropriate PPE use need to be considered in conjunction with risk homoeostasis operating at individual levels.

A cluster of SARS-CoV-2 infection among Italian tourists visiting India, March 2020.

BACKGROUND & OBJECTIVES: A cluster of SARS-CoV-2 infection occurred among Italian tourists visiting India. We report here the epidemiological, clinical, radiological and laboratory findings of the first cluster of SARS-CoV-2 infection among the tourists. METHODS: Information was collected on demographic details, travel and exposure history, comorbidities, timelines of events, date of symptom onset and duration of hospitalization from the 16 Italian tourists and an Indian with laboratory-confirmed SARS-CoV-2 infection. The clinical, laboratory, radiologic and treatment data was abstracted from their medical records and all tourists were followed up till their recovery or discharge or death. Throat and deep nasal swab specimens were collected on days 3, 8, 15, 18, 23 and 25 to evaluate viral clearance. RESULTS: A group of 23 Italian tourists reached New Delhi, India, on February 21, 2020 and along with three Indians visited several tourist places in Rajasthan. By March 3, 2020, 17 of the 26 (attack rate: 65.4%) had become positive for SARS-CoV-2 infection. Of these 17 patients, nine were symptomatic, while eight did not show any symptoms. Of the nine who developed symptoms, six were mild, one was severe and two were critically ill. The median duration between the day of confirmation for COVID-19 and RT-PCR negativity was 18 days (range: 12-23 days). Two patients died with a case fatality of 11.8 per cent. INTERPRETATION & CONCLUSIONS: This study reconfirms higher rates of transmission among close contacts and therefore, public health measures such as physical distancing, personal hygiene and infection control measures are necessary to prevent transmission.