Anthropogenic ecological changes and spill over of viruses - a review

Biodiversity protects ecosystem against infectious diseases. Increased human contact with wild life have caused high impact diseases such as SARS, Novel Corona virus, Nipah Virus, Ebola fever and many more. Anthropogenic activities such as hunting, farming, human encroachments, wild life trade, introduction of domestic species, bush meat hunting, road building, mining and increased human wildlife contact rates have lead to massive decline in biodiversity and increased risk of spilling over of dangerous viruses from animals to humans primarily due to host shifts. Human preference to high meat diet is also on rise in many countries. Wet markets have significant contribution in amplifying epizootic virus transmission and increased human exposure. Species in the primate and bat orders harbor a number of zoonotic viruses. Our destruction of nature, loss of habitat and biodiversity possibly tend to promote viral emergence. Invasion of undisturbed places leads to more and more exposure and create habitat where viral transmission is easier. Interference with a natural environment/habitat can, therefore, worsen the health risks. The erosion of biodiversity may lead to proliferation of species that are most likely to transmit new diseases to humans. Preserving habitat, biodiversity and natural environment is therefore one of the essential issues that cannot be put at the back any more.

Effect of COVID-19 vaccine on long-COVID: A 2-year follow-up observational study from hospitals in north India (preprint)

IntroductionLong-COVID syndrome encompasses a constellation of fluctuating, overlapping systemic symptoms after COVID. We know that vaccination reduces the risk of hospitalization and death but not of re-infections. How these vaccines impact long-COVID is under debate. The current study was designed to analyze the patterns of long-COVID amongst vaccinated and unvaccinated hospitalized patients during the three waves in India. MethodsThe computerized medical records of the patients admitted to a group of hospitals in the National Capital Region of Delhi with a nasopharyngeal swab positive RT-PCR for SARS-CoV-2, during the three distinct COVID-19 waves, were accessed. Because of large numbers, every 3rd case from the data sheet for the wave-1 and wave-2 but all cases admitted during wave-3 were included because of small numbers (total 6676). The selected patients were telephonically contacted in April 2022 for symptoms and their duration of long-COVID and their vaccination status. Of these, 6056 (90.7%) responded. These were divided into fully vaccinated who received both doses of COVID vaccine at least 14 days before admission (913) and unvaccinated at the time of admission (4616). Others and deaths were excluded. "Symptom-weeks" was calculated as the sum of weeks of symptoms in case of two or more symptoms. The statistical significance was tested, and odds ratio (unadjusted and adjusted) were calculated by logistic regression. ResultsNearly 90% of COVID-19 patients reported at least one symptom irrespective of their vaccination status. Almost three-fourths of these had symptoms lasting up to a month but nearly 15% reported a duration a least 4 weeks including 11% even exceeding one year. During wave-3, significantly more vaccinated patients reported short term post-acute sequelae of COVID-19 than did the unvaccinated group. The cases with diabetes and hypertension had higher odds of reporting at least one symptom when the effect of vaccination, age, sex, severity, and length of stay was adjusted. The fully vaccinated cases had reduced length of stay in the hospital and had a milder disease. Most common symptoms reported by both the groups were fatigue (17.0%), insomnia (15.1%) and myalgia (15%). There were significant differences in the duration and the type of long-COVID symptoms across the three waves, and the presence of comorbidities between the vaccinated and the unvaccinated groups but overall no difference could be detected. No significant difference was seen between the cases receiving covishield and covaxin. ConclusionsNearly 15% reported symptoms of duration exceeding 4 weeks including 11% exceeding one year. There were significant differences in the specific symptoms with some more common in the vaccinated and some others more common in the unvaccinated but overall the vaccination or the type of vaccine did not significantly alter either the incidence or the duration of long COVID.

Secondary infections modify the overall course of hospitalized COVID-19 patients: A retrospective study from a network of hospitals across North India (preprint)

IntroductionSARS-CoV-2 infection increases the risk of secondary bacterial and fungal infections and contributes to adverse outcomes. The present study was undertaken to get better insights into the extent of secondary bacterial and fungal infections in Indian hospitalized patients and to assess how these alter the course of COVID-19 so that the control measures can be suggested. MethodsThis is a retrospective, multicentre study where data of all RT-PCR positive COVID-19 patients was accessed from Electronic Health Records (EHR) of a network of 10 hospitals across 5 North Indian states, admitted during the period from March 2020 to July 2021.The data included demographic profile of patients, clinical characteristics, laboratory parameters, treatment modalities, and outcome in those with secondary infections (SIs) and those without SIs. Spectrum of SIS was also studied in detail. ResultsOf 19852 RT-PCR positive SARS-CO2 patients admitted during the study period, 1940 (9.8%) patients developed SIs. Patients with SIs were 8 years older on average (median age 62.6 years versus 54.3 years; P<0.001) than those without SIs. The risk of SIs was significantly (p < 0.001) associated with age, severity of disease at admission, diabetes, ICU admission, and ventilator use. The most common site of infection was urinary tract infection (UTI) (41.7%), followed by blood stream infection (BSI) (30.8%), sputum/BAL/ET fluid (24.8%), and the least was pus/wound discharge (2.6%). As many as 13.4% had infections with more than organism and 34.1% patients had positive cultures from more than one site. Gram negative bacilli (GNB) were the commonest organisms (63.2%), followed by Gram positive cocci (GPC) (19.6%) and fungus (17.3%). Most of the patients with SIs were on multiple antimicrobials - the most commonly used were the BL-BLI for GNBs (76.9%) followed by carbapenems (57.7%), cephalosporins (53.9%) and antibiotics carbapenem resistant entreobacteriace (47.1%). The usage of emperical antibiotics for GPCs was in 58.9% and of antifungals in 56.9% of cases, and substantially more than the results obtained by culture. The average stay in hospital for patients with SIs was twice than those without SIs (median 13 days versus 7 days). The overall mortality in the group with SIs (40.3%) was more than 8 times of that in those without SIs (4.6%). Only 1.2% of SI patients with mild COVID-19 at presentation died, while 17.5% of those with moderate disease and 58.5% of those with severe COVID-19 died (P< 0.001). The mortality was highest in those with BSI (49.8%), closely followed by those with HAP (47.9%), and then UTI and SSTI (29.4% each). The mortality rate where only one microorganism was identified was 37.8% and rose to 56.3% in those with more than one microorganism. The mortality in cases with only one site of infection was 28.8%, which steeply rose to 62.5% in cases with multiple sites of infection. The mortality in diabetic patients with SIs was 45.2% while in non-diabetics it was 34.3% (p < 0.001). ConclusionsSecondary bacterial and fungal infections can complicate the course of almost 10% of COVID-19 hospitalised patients. These patients tend to not only have a much longer stay in hospital, but also a higher requirement for oxygen and ICU care. The mortality in this group rises steeply by as much as 8 times. The group most vulnerable to this complication are those with more severe COVID-19 illness, elderly, and diabetic patients. Varying results in different studies suggest that a region or country specific guideline be developed for appropriate use of antibiotics and antifungals to prevent their overuse in such cases. Judicious empiric use of combination antimicrobials in this set of vulnerable COVID-19 patients can save lives.

Profile of Mucormycosis Cases from a Network of Hospitals in North India Amidst COVID-19 Pandemic (preprint)

Incidence of mucormycosis suddenly surged in India after the second wave of COVID-19. This is a crippling disease and needs to be studied in detail to understand the disease, its course, and the outcomes. Between 1st March and 15th July 2021, our network of hospitals in North India received a total of 155 cases of COVID-associated mucormycosis cases as all of them reported affliction by COVID-19 earlier or concurrent. Their records were retrieved from the Electronic Health Records system of the hospitals and their demographics, clinical features, treatments, and outcomes were studied. More than 80% (125 cases) had proven disease and the remaining 30 were categorized as possible mucormycosis as per the EORTC criteria. More than two-thirds (69.0%) of the cases were males and the mean age was 53 years for either sex. Nearly two-thirds (64.5%) had symptoms of nose and jaws and 42.6% had eye involvement. Some had multiple symptoms. As many as 78.7% had diabetes and 91.6% gave history of use of steroids during COVID-19 treatment. The primary surgery was functional endoscopic sinus surgery (FESS) (83.9%). Overall mortality was 16.8%, which is one-and-a-half times the mortality in hospitalized COVID-19 patients in the corresponding population. Occurrence of mucormycosis was associated with diabetes and use of steroids, but mortality was not associated with either of them. Cases undergoing surgery and on antifungal had steeply lower mortality (11.9% vs. 50.0%, P < 0.001) than those who were exclusively on antifungal drugs. Treatment by different drugs did not make much of a difference in mortality.

Long Term Health Consequences of COVID-19 in Hospitalized Patients from North India: A follow up study of upto 12 months (preprint)

Purpose: Long COVID syndrome is now a real and pressing public health concern. We cannot reliably predict who will recover quickly or suffer with mild debilitating long COVID 19 symptoms or battle life threatening complications. In order to address some of these questions, we studied the presence of symptoms and various correlates in COVID 19 patients who were discharged from hospital, 3 months and up to 12 months after acute COVID 19 illness. Methods: This is an observational follow up study of RT PCR confirmed COVID 19 patients admitted at 3 hospitals in north India between April August 2020. Patients were interviewed telephonically using a questionnaire regarding the post COVID symptoms. The first tele calling was done in the month of September 2020, which corresponded to 4 to 16 weeks after disease onset. All those who reported presence of long COVID symptoms, were followed up with a second call, in the month of March 2021, corresponding to around 9 to 12 months after the onset of disease. Results: Of 990 patients who responded to the first call, 615 (62.2%) had mild illness, 227 (22.9%) had moderate and 148 (15.0%) had severe COVID 19 illness at the time of admission. Nearly 40% (399) of these 990 patients reported at least one symptom at that time. Of these 399 long COVID patients, 311 (almost 78%) responded to the second follow up. Nearly 8% reported ongoing symptomatic COVID, lasting 1 to 3 months and 32% patients having post COVID phase with symptoms lasting 3 to 12 months. Nearly 11% patients continued to have at least one symptom even at the time of the second interview (9 to 12 months after the disease onset). Overall, we observed Long COVID in almost 40% of our study group. Incidence of the symptoms in both the follow ups remained almost same across age groups, gender, severity of illness at admission and presence of comorbidity, with no significant association with any of them. Most common symptoms experienced in long COVID phase in our cohort were fatigue, myalgia, neuro psychiatric symptoms like depression, anxiety, brain fog and sleep disorder, and breathlessness. Fatigue was found to be significantly more often reported in the elderly population and in those patients who had a severe COVID 19 illness at the time of admission. Persistence of breathlessness was also reported significantly more often in those who had severe disease at the onset. The overall median duration of long COVID symptoms was 16.9 weeks with inter quartile range of 12.4 to 35.6 weeks. The duration of symptom resolution was not associated with age, gender or comorbidity but was significantly associated with severity of illness at the time of admission (P=0.006). Conclusions: Long COVID is now being recognized as a new disease entity, which includes a constellation of symptoms. Long COVID was in almost 40% of our study group with no correlation to age, gender, comorbidities or to the disease severity. The duration of symptom resolution was significantly associated with severity of illness at the time of admission (P = 0.006). In our study, all patients reported minor symptoms such as fatigue, myalgia, neuro psychiatric symptoms like depression, anxiety, brain fog and sleep disorder and persistence of breathlessness. Severe organ damage was not reported by our subjects. This might be the longest post COVID follow up study on a sample of nearly 1000 cases from India.

Differentials in the characteristics of COVID-19 cases in Wave-1 and Wave-2 admitted to a network of hospitals in North India (preprint)

Second wave of COVID 19 pandemic in India came with unexpected quick speed and intensity, creating an acute shortage of beds, ventilators, and oxygen at the peak of occurrence. This may have been partly caused by emergence of new variant delta. Clinical experience with the cases admitted to hospitals suggested that it is not merely a steep rise in cases but also possibly the case profile is different. This study was taken up to investigate the differentials in the characteristics of the cases admitted in the second wave versus those admitted in the first wave. Records of a total of 14398 cases admitted in the first wave (2020) to our network of hospitals in north India and 5454 cases admitted in the second wave (2021) were retrieved, making it the largest study of this kind in India. Their demographic profile, clinical features, management, and outcome was studied. Age sex distribution of the cases in the second wave was not much different from those admitted in the first wave but the patients with comorbidities and those with greater severity had larger share. Level of inflammatory markers was more adverse. More patients needed oxygen and invasive ventilation. ICU admission rate remained nearly the same. On the positive side, readmissions were lower, and the duration of hospitalization was slightly less. Usage of drugs like remdesivir and IVIG was higher while that of favipiravir and tocilizumab was lower. Steroid and anticoagulant use remained high and almost same during the two waves. More patients had secondary bacterial and fungal infections in Wave 2. Mortality increased by almost 40% in Wave 2, particularly in the younger patients of age less than 45 years. Higher mortality was observed in those admitted in wards, ICU, with or without ventilator support and those who received convalescent plasma. No significant demographic differences in the cases in these two waves, indicates the role of other factors such as delta variant and late admissions in higher severity and more deaths. Comorbidity and higher secondary bacterial and fungal infections may have contributed to increased mortality.

Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2. (preprint)

Immunization is expected to confer protection against infection and severe disease for vaccinees, while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies, we show that during a severe SARS-CoV2 Delta-variant outbreak in Delhi, 25.3% (95% CI 16.9 - 35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare-workers (HCW) were infected within a period of less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, IQR 374) or not (342 U/ml, IQR 497), as was induction of neutralization activity to wildtype. Most infections were unrecognized. The Delta-variant thus causes frequent unrecognized breakthrough infections in adequately immunized subjects, reducing any herd-effect of immunity, and requiring reinstatement of preventive measures such as masking.