Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU).

BACKGROUND: After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. METHODS: In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. RESULTS: Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. CONCLUSIONS: In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Diaphragmatic rupture in case of COVID-19 pneumonia- A rare presentation.

We describe the case of a male patient admitted to our emergency department during the COVID-19 pandemic with complaints of fever, severe breathlessness and dry cough associated with symptoms of gastric reflux for 5 days. Chest HRCT showed subtle multiple areas of diffuse patchy opacities with ground-glass haze with associated left subdiaphragmatic hernia and atelectasis of the left pulmonary lobe. Barium meal revealed subdiaphragmatic hernia. A nasopharyngeal swab for 2019-nCoV was positive. A diagnosis of diaphragmatic hernia in COVID-19 pneumonia was made. To our knowledge, spontaneous herniation of the diaphragm is a rare entity. Treatment for COVID-19 and empiric antibiotic therapy were promptly started and a decision of elective surgery was made.

From stress to stigma - Mental health considerations of health care workers involved in COVID19 management.

BACKGROUND: Healthcare workers (HCWs) involved in administration and patient management during COVID-19 pandemic are at high risk of developing psychological problems related to fear and stress of contacting COVID infection. This is augmented by the stigma faced at home and society, owing to the nature of their job. AIM: To assess the mental health issues and stigma amongst health care workers involved in COVID care. METHODOLOGY: We conducted a hospital based cross sectional study where 150 health care workers involved in the care of COVID-19 patients, directly and indirectly, were selected using systematic random sampling. They were assessed using Depression, Anxiety and Stress Scale (DASS-21) Hindi Version, The Impact of Event Scale - Revised scale and a Modified Stigma scale. RESULTS: Significant psychological stress, anxiety, depression and high risk for developing post-traumatic stress disorder was found in more than half of the healthcare workers, albeit more in those having direct contact with COVID patients (p < 0.05). Stigma was significantly reported in most HCWs, especially with concerns regarding public attitude and disclosure of their work profile. CONCLUSION: Healthcare Workers are at a higher risk for developing psychological disorders and post-traumatic stress disorder because of the immensely stressful work-related conditions and stigma related to working with COVID patients. This may lead to long lasting psychosocial consequences which may affect more severely than the infection itself. Early identification of psychological issues of HCWs and timely intervention is the key.

Impact of COVID-19 on (Non-COVID) chronic respiratory disease outcome survey in India (CCROS study).

BACKGROUND: India has high prevalence of chronic respiratory diseases, especially bronchial asthma and chronic obstructive pulmonary disease (COPD). Both of these are also recognized as risk factors for severity and poor outcome of COVID-19 disease. It is assumed that COVID-19 outbreak as well as an effective lockdown might have affected the incidence and outcome of some of these. METHODS: To substantiate above hypothesis, an online survey was mailed to 547 pulmonologists across the country; 314 (54.7%) responses were recorded in the given period. The survey included observations on incidence and outcome of common chronic respiratory diseases such as asthma, COPD and interstitial lung diseases (ILD) in predefined pre-COVID and during COVID period in a total of 24 questions. RESULTS: It was observed that the reduction in incidence of outpatient department cases, acute exacerbations and hospitalization for asthma, COPD and ILD was statistically significant. The outcome of acute exacerbations of these chronic respiratory diseases was analyzed in terms of discharges from hospitals after satisfactory recovery and/ or mortalities. For COPD and ILD, it was not significantly affected during the COVID period. At the same time, a relatively higher proportion of acute asthma mortality was reported. A wide variation in nebulization practices was reported during this period. The doses of inhaled corticosteroids in asthma management were not affected. A wide variety of factors including effective lockdown, better quality of air and regular use of masks were probably responsible for reduced incidence of exacerbations of these chronic respiratory diseases. CONCLUSION: We conclude that while outpatient department visits, acute exacerbations and hospitalizations were significantly reduced during COVID-19 period, outcome of asthmatics was relatively unfavorable as compared to that of COPD and ILDs.

Exploring status of emergency drugs and vaccine development in Covid-19 pandemic: an update.

COVID-19 outburst initiated from the city of Wuhan in China in December 2019 and has been declared as a public health emergency of international concern. This pandemic portrays a spectrum of clinical complications, primarily affecting the respiratory system reported to be caused by a pathogen SARS-CoV-2 belonging to the family of beta coronavirus. Currently, the main objective of the government authorities of all affected countries and research organizations is to find a potential solution in the form of a pharmacological intervention or a vaccination to eradicate the disease and to have a long-term solution to deal with the pandemic. A multitude of anti-viral regimens is proposed based on the repurposing of currently available drugs for other issues or the compassionate use of drugs to immediately control and optimize the healthcare facilities. Meanwhile, a number of agencies are proposing new drug candidates to recreate the possibility of treating the disease. Similarly, a lot of research work is going on worldwide for the development of vaccination. Currently, a good number of candidates has finally reached the borders of Clinical Trials and are expected to be launched as soon as possible. However, the regulatory framework and authorization of these candidates is the most significant aspect of the whole scenario, which needs a specific set of time for validation purposes. The present work is widely focused on the general aspects of COVID-19 and the regulatory landscape for the emergency authorization of repurposed drug candidates, compassionate use of drugs, investigational entities, and vaccine development worldwide. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00684-5.

Conventional flexible bronchoscopy during the COVID pandemic: A consensus statement from the Indian Association for Bronchology.

During the times of the ongoing COVID pandemic, aerosol-generating procedures such as bronchoscopy have the potential of transmission of severe acute respiratory syndrome coronavirus 2 to the healthcare workers. The decision to perform bronchoscopy during the COVID pandemic should be taken judiciously. Over the years, the indications for bronchoscopy in the clinical practice have expanded. Experts at the Indian Association for Bronchology perceived the need to develop a concise statement that would assist a bronchoscopist in performing bronchoscopy during the COVID pandemic safely. The current Indian Association for Bronchology Consensus Statement provides specific guidelines including triaging, indications, bronchoscopy area, use of personal protective equipment, patient preparation, sedation and anesthesia, patient monitoring, bronchoscopy technique, sample collection and handling, bronchoscope disinfection, and environmental disinfection concerning the coronavirus disease-2019 situation. The suggestions provided herewith should be adopted in addition to the national bronchoscopy guidelines that were published recently. This statement summarizes the essential aspects to be considered for the performance of bronchoscopy in COVID pandemic, to ensure safety for both for patients and healthcare personnel.

Mycobacterium W. - An unusual side effect.

OBJECTIVE: To present an interesting case of unusual side effect of Mycobacterium W. in an adult COVID 19 positive male and discuss its assessment and management. METHODS: - DESIGN: Case Report. SETTING: Tertiary care hospital. PATIENT: One. RESULTS: 70 years male was admitted with complaints of fever, persistent dry cough since 10-12 days and progressive breathlessness since 3-4 days. Patient was found COVID-19 RTPCR positive and is known case of Type-II Diabetes with CAD (Post PTCA). Patient was managed conservatively with Oxygen support, I/V antibiotics, I/V Steroids, oral Favipiravir and other supportive treatment. Patient was also given injection Mycobacterium W. in dose of 0.3 ml per day intradermally at 3 different sites (both deltoids) consecutively for three days. 7-8 days after administration, patient developed bright red pustules which later got converted into small punched out ulcerations on all nine local sites of administration, which were managed conservatively with oral analgesics and local steroids for 8-10 days which healed without any scar formation. CONCLUSION: Injection Mycobacterium W. is used in COVID 19 patients as an immunomodulator agent and has been proved to be safe in most of the cases but we encountered this unusual side effect of bright red pustules formation at all nine local sites of injection in our case most likely because of being administered subcutaneously instead of intradermally, making this an interesting case which is being reported to scientific fraternity.

DISPOSABLE COVID BOX - A new invention.

OBJECTIVE: To introduce a new method to do safe bronchoscopy, a highly aerosol generating procedure through disposable COVID box in this difficult COVID time. METHODS: We have introduced an unbelievably cheap and effective method "DISPOSABLE COVID BOX". We took an acrylic board 70 × 20 cm and attached 3 bars 32 cm long and slide it under the side of the patient. A similar contraption is used on the other side. Then, it is covered by a polypropylene sheet 2' × 2'. It makes a completely disposable airtight chamber with the polypropylene sheet. We make a 1 cm nick in the sheet and introduce the video-bronchoscope, which is further navigated into the patient without any discomfort either to the patient or Bronchoscopist. When the procedure is finished, scope is withdrawn from the patient and the polypropylene sheet is squeezed out. The polypropylene sheet is removed and disposed off with all precautions, and the acrylic boards and the bars are cleaned with 1% Sodium hypochlorite solution. This way, the cost is only of polypropylene sheet which is negligible. RESULTS: Videobronchoscopies in indicated patients were done using this novel disposable covid box. This new invention called Disposable COVID box has been practiced for the first time, it's an innovative technique about which we want the world to be known. CONCLUSION: To conclude, there are no aerosols released in atmosphere after the procedure, making it absolutely safe for bronchoscopist and at same time patient also remains safe. We are ready again in no time with fresh polypropylene sheet to do the next bronchoscopy.

An updated insight into the molecular pathogenesis, secondary complications and potential therapeutics of COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is an unprecedented disease caused by highly pathogenic SARS-CoV-2 and characterized by extreme respiratory deterrence, pneumonia and immune damage. The phylogenetic analysis demonstrated the sequence similarity of SARS-CoV-2 with other SARS-like bat viruses. The primary source and intermediate host are not yet confirmed, although transmission from human to human is universally confirmed. The new SARS-CoV-2 virus reaches cells via ACE-2 and subsequently down-regulates ACE-2, leaving angiotensin II unbalanced in affected organs primarily in the lungs, heart, brain, and kidneys. As reported recently, numerous secondary complications i.e., neurological, nephrological, cardiovascular, gastrointestinal, immune, and hepatic complications, are associated with COVID-19 infection along with prominent respiratory disease including pneumonia. Extensive research work on recently discovered SARS-CoV-2 is in the pipeline to clarify pathogenic mechanisms, epidemiological features, and identify new drug targets that will lead to the development of successful strategies for prevention and treatment. There are currently no appropriate scientifically approved vaccines/drugs for COVID-19. Nonetheless, few broad-spectrum antiviral drugs, azithromycin were tested against COVID-19 in clinical trials, and finally, FDA approved emergency use of remdesivir in hospitalized COVID-19 patients. Additionally, administration of convalescent plasma obtained from recovered COVID-19 patients to infected COVID-19 patients reduces the viral burden via immunomodulation. This review analysis therefore concentrates primarily on recent discoveries related to COVID-19 pathogenesis along with a full description of the structure, genome, and secondary complication associated with SARS-CoV-2. Finally, a short and brief clinical update has been provided concerning the development of therapeutic medications and vaccines to counter COVID-19.