Organ Involvement in COVID 19: Lung and Beyond

Coronavirus Disease 19 (COVID-19) evolved into a pandemic to torment the world since the last 15 months and has resulted in millions of individuals getting affected. It has caused significant strain on the health care systems in developed and developing countries alike. It has killed more than two million patients globally. The potential of this virus to cause multi-organ dysfunction with associated significant mortality and morbidity has made it the most formidable enemy we have faced since the great plague. COVID-19 is becoming a mystery with its plethora of typical and atypical clinical presentations. Its ability to get attached to widely distributed human angiotensin-converting enzyme-2 (hACE2) receptors, has enabled it to cause multi-organ dysfunction and extensive disease. In this chapter, we review the pulmonary and extra-pulmonary manifestations of SARS-CoV-2 and try to elucidate organ-specific patho-physiology. Organ dysfunction leading to a myriad of cardiac dysfunction, symptoms related to gut and liver, nervous system involvement, renal and ocular injury is being discussed in this chapter. An effort to raise awareness of the potential to cause long covid syndrome is being made to identify the possible burden of morbidity we might have to experience post covid 19 pandemic. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

"DOES ANYONE EVEN NOTICE US?" COVID-19'S IMPACT ON ACADEMICS' WELL-BEING IN A DEVELOPING COUNTRY

In March 2020, the President of South African announced that the nation would go into full lockdown in the wake of an increase in COVID-19 infections. Academics had, in some instances, only one day to prepare for "emergency remote teaching". Few academics had taught online before, as South Africa's internet connectivity is not guaranteed in underprivileged areas, where 80 per cent of the population reside. The online move thus necessitated an entirely novel pedagogy for most academics, with high potential for an escalation of work-related stress and related illness, outcomes we have related in the wider sphere of workplace readjustment during COVID-19, to a state of "pandemia". In this article, we report on an institutional case study where we surveyed n=136 academics from a university in the Western Cape, South Africa to learn more about impacts of COVID-19 on their work. The data analysis adopts Ryff's (1995) theory of wellbeing. Findings indicate that the enforced lockdown due to COVID-19 and the subsequent move to online teaching has had a negative impact on academics' sense of well-being. However, the emergence of positive, caring relationships between colleagues is reported as a significant outcome of the COVID-19 enforced move to online teaching.

Hydroxychloroquine in Treatment of Asymptomatic and Mildly Symptomatic COVID-19: A Multi-Centre Cohort Study

Background: Although hydroxychloroquine (HCQ) lacks benefit in patients with moderate-to-severe COVID-19, its role in asymptomatic and mildly symptomatic disease needs better elucidation. Methods: This multi-centre cohort study included asymptomatic and mildly symptomatic, RT-PCR confirmed COVID-19 cases between 30 March and 20 May, 2020. Patients were categorized into two groups (HCQ-treated and untreated) based on exposure to HCQ. Dose of HCQ used was 400 mg twice daily (day one) followed by once daily for seven days. HCQ-untreated patients were managed supportively without any active antiviral or immunomodulatory therapy. Nasopharyngeal SARS-CoV-2 clearance by RT-PCR (primary outcome) was compared between HCQ-treated and untreated patients using Kaplan-Meier analysis and Cox proportional-hazards regression. Clinical efficacy and safety profile of HCQ were assessed (secondary outcomes). Results:162 patients [84 (51·9%) males;mean age 38·2 (15·2) years] were included. Forty-four (27·2%) patients had mild disease, rest 118 (72·8%) were asymptomatic. Seventy-five (46·3%) patients received HCQ. Median time to virological negativity was lesser in HCQ-treated (13 days) versus untreated patients (15 days) (log-rank<0·001) in both asymptomatic and mildly symptomatic patients. Treatment with HCQ was the only independent predictor of virological negativity (hazard-ratio=2·24;adjusted p-value<0·001). Two (5·4%) mildly symptomatic patients progressed to severe disease within 24 hours (two doses) of HCQ initiation, compared to none in the HCQ-untreated group. Five HCQ-treated patients developed minor gastrointestinal side effects, not requiring drug discontinuation. Conclusion: HCQ reduced the time to virologic negativity (by 2 days) in asymptomatic and mildly symptomatic COVID-19, without any serious adverse events. However, no obvious clinical benefit was noted. © 2022 Journal of Association of Physicians of India. All rights reserved.

Roadblocks in the delivery of cancer care in India during COVID pandemic

The coronavirus disease (COVID) pandemic has impacted the health sector in massive proportions. Perhaps the worst affected aspect is that of oncological care. Cancer patients continue to suffer silently due to nonavailability of consultations and shortage of operating rooms. We need to brace ourselves for the impact of this backlog of nearly 18 months of neglected care of such patients.

Elevated pancreatic enzyme level in covid-19 patients: Is it a silent bystander

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) is a known respiratory pathogen, its impact on other organs including the pancreas has been reported. Only case reports and few retrospective studies have linked coronavirus disease 2019 (COVID-19) to acute pancreatitis (AP) and pancreatic injury (PI). Aims & Methods: This prospective study was planned to look at the incidence of PI in COVID-19 positive patients and its implications. All consecutive patients of established COVID-19 positive cases presenting to a tertiary care center in India between July and October 2020 were assessed. Detailed symptomatology was documented including respiratory and gastrointestinal (GI) symptoms. Prior co-morbidities, drug history and medical history were documented, and patients on pancreatic enzyme level influencing drugs were excluded. All patients, on admission, underwent blood cytology, biochemical parameters and serum inflammatory markers estimation. Pancreatic injury (PI) was defined as any abnormal value of amylase (normal 0-100 U/L) or lipase (normal 0-60 U/L). Patients having clinical AP or any pre-existing GI diseases were excluded. Outcome measures such as need for ICU, oxygen requirement, need for ventilation and mortality were noted. Results: Out of 244 patients screened, 40 were excluded. Of the 203 patients, (128 males;63.1%) studied, 72 (35.5%) had PI. Comparing patients with PI and those without (Table 1) showed that both groups had similar respiratory and/or GI symptoms profile, while asymptomatic cases had less pancreatic enzyme elevation (p=0.035). PI was noted in the older age group (49.83 vs 37.12 yrs., p=0.01) with a male predominance. PI group had a higher proportion of severe disease (29.2% vs 8.4%;p<0.0001) with significantly higher levels of serum ferritin, D-dimer, fibrinogen, procalcitonin and C-reactive protein (CRP) and higher baseline triglyceride (TG) levels. PI group showed higher ICU (p<0.0001), oxygen (p<0.0001) & mechanical ventilation (p=0.003) requirements and mortality (p=0.018). Multivariate regression analysis showed that the severity of the disease was a significant predictor (aOR-4.68;p=0.003) of PI. Diabetes was found to be higher in the PI group (p<0.0001), but not so when adjusted for disease severity. Of all PI patients, 7(3.45%) had enzyme elevation >3 times the upper limit of the normal (ULN), more in severe disease (Severe-4;12.5% vs moderate-2;4% vs mild-1;0.8%, p=0.005). Conclusion: Incidence of PI was seen in more than 1/3rd of the COVID-19 positive patients. PI is not uncommon in COVID-19 patients and is a harbinger of severe disease with greater inflammatory burst and higher intensive care requirement with poorer outcome.

'The COVID-19 crisis is not the core problem': experiences, challenges, and concerns of Irish academia during the pandemic

This article, drawing on data from an international survey - distributed in the summer of 2020 - explores the experiences and concerns of academic staff (n = 167) working in universities in Ireland and their perceptions of their institutions' early response to the pandemic. Concerns related to transitioning to remote online working, impact on research productivity and culture, and work intensification, as intersected by enhanced managerialism, are ubiquitous to their accounts. As some respondents wrote of potential positive changes, particularly in the delivery of teaching, we conclude by suggesting potential avenues for building on successes in coping with the pandemic with some recommendations for mitigating some of the harms.

Safety of remdesivir vs standard care in patients with moderate COVID-19

Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods: We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut;safety data through day 28 will be presented at the meeting. Results: 584 patients were randomized and treated (5d RDV: n=191;10d RDV, n=193;SOC: n=200). Baseline characteristics were balanced among groups;median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Conclusion: RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. (Figure Presented).

Evaluation of Gamma glutamyl-transferase (GGT) levels in COVID-19: A retrospective analysis in tertiary care centre

Many recent studies have reported that patients infected with novel coronavirus 2019 or SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) might have a liver injury. However, few studies have focussed on the levels of Gamma glutamyl-transferase (GGT) alone and the variations associated with it. We retrospectively analysed the GGT levels of 476 admitted patients with confirmed COVID-19 in a tertiary care centre, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh. Out of the total 476 COVID-19 patients studied, 35% had elevated GGT levels. ICU care was required for 51.19% (P <0.0001) of these patients and their hospital stay was of longer duration as compared to the patients with normal GGT levels. The incidence of GGT elevation was found to be more pronounced in males and elderly patients. The male population displayed higher GGT levels with 52% having raised levels compared to females where only 21.6% had elevated GGT levels. Although the number of COVID-19 cases was majorly from young age groups, the elevation in GGT levels has been reported more in elderly patients. GGT levels can therefore serve as a predictor for the extent of liver injury and severity in COVID-19 patients.

Impact of baseline alanine aminotransferase levels on the safety and efficacy of remdesivir in severe COVID-19 patients

Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat<94% Patients with screening ALT or AST> 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0.001) prior to first dose of RDV. Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1). Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented).

SARS-CoV-2 Detection in Gingival Crevicular Fluid.

Understanding the pathophysiology of the coronavirus disease 2019 (COVID-19) infection remains a significant challenge of our times. The gingival crevicular fluid being representative of systemic status and having a proven track record of detecting viruses and biomarkers forms a logical basis for evaluating the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study aimed to assess gingival crevicular fluid (GCF) for evidence of SARS-CoV-2 in 33 patients who were deemed to be COVID-19 positive upon nasopharyngeal sampling. An attempt was also made to comparatively evaluate it with saliva in terms of its sensitivity, as a diagnostic fluid for SARS-CoV-2. GCF and saliva samples were collected from 33 COVID-19-confirmed patients. Total RNA was extracted using NucliSENS easyMAG (bioMérieux) and eluted in the elution buffer. Envelope gene (E gene) of SARS-CoV-2 and human RNase P gene as internal control were detected in GCF samples by using the TRUPCR SARS-CoV-2 RT qPCR kit V-2.0 (I) in an Applied Biosystems 7500 real-time machine. A significant majority of both asymptomatic and mildly symptomatic patients exhibited the presence of the novel coronavirus in their GCF samples. Considering the presence of SARS-CoV-2 RNA in the nasopharyngeal swab sampling as gold standard, the sensitivity of GCF and saliva, respectively, was 63.64% (confidence interval [CI], 45.1% to 79.60%) and 64.52% (CI, 45.37% to 80.77%). GCF was found to be comparable to saliva in terms of its sensitivity to detect SARS-CoV-2. Saliva samples tested positive in 3 of the 12 patients whose GCF tested negative, and likewise GCF tested positive for 2 of the 11 patients whose saliva tested negative on real-time reverse transcription polymerase chain reaction. The results establish GCF as a possible mode of transmission of SARS-CoV-2, which is the first such report in the literature, and also provide the first quantifiable evidence pointing toward a link between the COVID-19 infection and oral health.