Treating COVID-19: are we missing out the window of opportunity?

Severe COVID-19 is a biphasic illness, with an initial viral replication phase, followed by a cascade of inflammatory events. Progression to severe disease is predominantly a function of the inflammatory cascade, rather than viral replication per se. This understanding can be effectively translated to changing our approach in managing the disease. The natural course of disease offers us separate windows of specific time intervals to administer either antiviral or immunomodulatory therapy. Instituting the right attack at the right time would maximize the benefit of treatment. This concept must also be factored into studies that assess the efficacy of antivirals and immunomodulatory agents against COVID-19.

Immune status against diphtheria in healthy adults.

Outbreaks of diphtheria continue to occur in Kerala with an age shift to older population. Antibody seroprevalence studies are essential to understand the immune status of the community and to develop an effective immunization strategy. AIM: To assess the necessity of diphtheria vaccination among adults. SETTINGS AND DESIGN: Cross-sectional study, among 152 healthy adults (>18 years). METHODS AND MATERIALS: Diphtheria IgG antibody detection was performed by using ELISA technique. RESULTS: Out of 152 study population, 14 (9.2%) individuals had very low antibody levels, requiring basic immunization, 123 (80.9%) needed booster vaccination, 12 (7.9%) would need a booster dose in 5 years and 3 (2%) would need a booster dose in 7 years to maintain adequate antibody levels. Out of the total, 131 (86.2%) individuals had completed childhood immunization and 21 (13.8%) had incomplete or no immunization during childhood. In the population who had completed childhood immunization, 4 (3%) had very low antibody levels requiring basic immunization and 113 (86%) had antibody levels needing booster vaccine soon, with the remaining 14 (10.6%) individuals requiring a booster vaccine after 5 years and 7 years. In the partially immunized/unimmunized population, 10 (47.6%) had antibody levels requiring basic immunization and another 10 (47.6%) had antibody levels low enough to warrant a booster vaccine. CONCLUSIONS: Majority of the subjects who had completed childhood immunization showed an inadequate immunity against diphtheria during adulthood. This indicates waning immunity against diphtheria. Hence, modifying the present diphtheria vaccination strategy to include booster doses during adulthood is essential. CONTEXT: Even in developed countries where nearly 100% universal immunization is achieved, diphtheria outbreaks are known to occur. Several seroprevalence studies have been conducted in those regions to determine whether those populations have adequate levels of antibodies against diphtheria. In India, sporadic outbreaks occur, and an increasing number of diphtheria cases are being reported over the last few years. Large outbreaks in Kerala 2016 were about 533 cases. Recent outbreaks in 2019, in Trivandrum, about 175 cases were suspected and 19 cases were confirmed in laboratory. However, Indian studies to determine whether the adult population has adequate protective antibody levels are lacking. Knowing the immune status of the population and devising an appropriate strategies to prevent outbreaks of diphtheria are the integral parts of primary care. These concerns are the basis and evaluation of the seroprevalence of IgG antibody levels against diphtheria antitoxin among healthy adults in our region in this study.

Differential diagnosis of scrub typhus meningitis from tuberculous meningitis using clinical and laboratory features.

OBJECTIVES: The involvement of the central nervous system in the form of meningitis or meningoencephalitis is common in scrub typhus and is an important differential diagnosis of other lymphocytic meningitis like tuberculous meningitis (TBM). The aim of this study was to identify the clinical and laboratory parameters that may be helpful in differentiating scrub typhus meningitis from TBM. PATIENTS AND METHODS: We compared of the clinical and laboratory features of 57 patients admitted with scrub typhus meningitis or TBM during a 3-year period. Patients who had abnormal cerebrospinal fluid (CSF) and positive scrub typhus enzyme-linked immunosorbent assay serology (n=28) were included in the scrub typhus meningitis group, while the TBM group included those who satisfied the consensus diagnostic criteria of TBM (n=29). RESULTS: Compared with the TBM group, the mean duration of symptoms was less in patients with scrub typhus meningitis, who also had a lower magnitude of neurological deficits, such as altered mental status and cranial nerve and motor deficits. Patients with scrub typhus meningitis had a lower CSF white blood-cell count (WBC) than the TBM group (130.8±213 195±175 cells/mm3, P=0.002), lower CSF protein elevation (125±120 vs. 195.2±108.2mg/dl, P=0.002), and higher CSF sugar (70.1±32.4 vs. 48.7±23.4mg/dl, P=0.006). Features predictive of the diagnosis of scrub typhus meningitis included the absence of neurological impairment at presentation, blood serum glutamic-oxaloacetic transaminase>40 international units (IU)/L, serum glutamic-pyruvic transaminase>60 IU/L, total blood leukocyte count>10,000/mm3, CSF protein<100mg/dl, CSF sugar>50mg/dl, CSF WBC<100 cells/mm3. All patients with scrub typhus meningitis recovered completely following doxycycline therapy CONCLUSIONS: This study suggests that, clinical features, including duration of fever, neurological deficits at presentation and laboratory parameters such as CSF pleocytosis,CSF protein elevation, CSF sugar levels and liver enzyme values are helpful in differentiating scrub typhus meningitis from tuberculous meningits. These features with scrub IgM serology may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.