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.

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.