No abstract

Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

According to recent observations, there is worldwide vitamin D insufficiency (VDI) in various populations. A number of observations suggest a link between low serum levels of vitamin D and higher incidence of chronic pain. A few case reports have shown a beneficial effect of vitamin D therapy in patients with headache disorders. Serum vitamin D level shows a strong correlation with the latitude. Here, we review the literature to delineate a relation of prevalence rate of headaches with the latitude. We noted a significant relation between the prevalence of both tension-type headache and migraine with the latitude. There was a tendency for headache prevalence to increase with increasing latitude. The relation was more obvious for the lifetime prevalence for both migraine and tension-type headache. One year prevalence for migraine was also higher at higher latitude. There were limited studies on the seasonal variation of headache disorders. However, available data indicate increased frequency of headache attacks in autumn–winter and least attacks in summer. This profile of headache matches with the seasonal variations of serum vitamin D levels. The presence of vitamin D receptor, 1α-hydroxylase and vitamin D-binding protein in the hypothalamus further suggest a role of vitamin D deficiency in the generation of head pain.

The prevalence of tension-type headache and vitamin D deficiency are both very high in the general population. The inter-relations between the two have not been explored in the literature. We report 8 patients with chronic tension-type headache and vitamin D deficiency (osteomalacia). All the patients responded poorly to conventional therapy for tension headache. The headache and osteomalacia of each of the 8 patients responded to vitamin D and calcium supplementation. The improvement in the headache was much earlier than the improvements in the symptom complex of osteomalacia. We also speculate on the possible mechanisms for headache in the patients with vitamin D deficiency.

New daily persistent headache (NDPH) is a subtype of chronic daily headache (CDH) that starts acutely and continues as a daily headache from the onset. It is considered as one of the most treatment refractory of all headache syndromes. The pathophysiology is largely unknown. Viral infections, extracranial surgery, and stressful life events are considered as triggers for the onset of NDPH. A few patients may have the onset of their symptoms during an infection. Here we report nine patients with NDPH like headache. All of them had a history suggestive of extracranial infections a few weeks prior to the onset of headache. All patients received intravenous methyl prednisolone (IV MPS) for 5 days. Intravenous MPS was followed by Oral steroids for 2–3 weeks in six patients. The relief of headache started between the second and fifth days of infusion in all patients. The steady improvement in headache continued and seven patients experienced almost complete improvement within 2 weeks. Two other patients showed complete improvement between 6 and 8 weeks after initiation of IV MPS therapy. We conclude that NDPH-like headache may occur as a post infectious process following a recent infection. We also speculate on the possible mechanisms of headache in our patients.